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Purpose: To investigate the effect of intraoperative remimazolam sedation on postoperative sleep quality in elderly patients after total joint arthroplasty. Methods: Between May 15, 2021 and March 26, 2022, 108 elderly patients (age ≥ 65 years) who received total joint arthroplasty under neuraxial anesthesia were randomized into remimazolam group (a loading dose of 0.025–0.1 mg/kg and followed by an infusion rate of 0.1–1.0 mg/kg/h till end of surgery) or routine group (sedation was given on patient's requirement by dexmedetomidine 0.2–0.7 μg/kg/h). Primary outcome was the subjective sleep quality at surgery night which was evaluated by Richards Campbell Sleep Questionnaire (RCSQ). Secondary outcomes included RCSQ scores at postoperative first and second nights and numeric rating scale pain intensity within first 3 days after surgery. Results: RCSQ score at surgery night was 59 (28, 75) in remimazolam group which was comparable with 53 (28, 67) in routine group (median difference 6, 95% CI − 6 to 16, P = 0.315). After adjustment of confounders, preoperative high Pittsburg sleep quality index was associated worse RCSQ score (P = 0.032), but not remimazolam (P = 0.754). RCSQ score at postoperative first night [69 (56, 85) vs. 70 (54, 80), P = 0.472] and second night [80 (68, 87) vs. 76 (64, 84), P = 0.066] were equivalent between two groups. Safety outcomes were comparable between the two groups. Conclusions: Intraoperative remimazolam did not significantly improve postoperative sleep quality in elderly patients undergoing total joint arthroplasty. But it is proved to be effective and safe for moderate sedation in these patients. Clinical trial number and registry URL: ChiCTR2000041286 (www.chictr.org.cn). [ABSTRACT FROM AUTHOR]

• MET fusions represent a promising therapeutic target. • EPHB4, THAP5, TNPO3 , and DST are novel MET fusion partners in NSCLC. • Patients with MET fusions present acquired MET D1228H/N or D1246N mutations. • Tivantinib has optimal suppression efficacy in a PDO model with MET D1228N mutation. De novo mesenchymal-to-epithelial transition (MET) gene fusions in non-small cell lung cancer (NSCLC) are a promising target for MET tyrosine kinase inhibitors (TKIs). We aimed to examine the response to targeted therapy with MET TKIs and resistance mechanisms in de novo MET fusion-positive NSCLC as these have not been comprehensively explored. We examined the MET fusions in 4,429 patients with advanced-stage NSCLC using targeted next-generation sequencing and validated the results using RT-PCR. We analyzed cellular models harboring MET fusions and established a patient-derived organoid (PDO) model. We identified 13 (0.29 %, 13/4429) patients with de novo MET fusions and found EPHB4, THAP5, TNPO3 , and DST as novel MET fusion partners. The most common concomitant gene with MET fusions was TP53 mutations. Among 12 patients receiving MET TKI treatment, two achieved stable disease, six achieved partial response, and four underwent progressive disease. An in vitro study showed that EPHB4-MET is a functional driver gene. MET inhibitors significantly inhibited the proliferation and phosphorylation of downstream STAT3, AKT, and ERK1/2 in EPHB4-MET overexpressing cells. Acquired MET D1228H/N or D1246N mutations were found in patients harboring MET fusions after acquiring resistance to MET TKIs. Tivantinib showed optimal suppression efficacy in a PDO model with an acquired MET D1228N mutation. MET fusions occur in a rare subset of patients with NSCLC and represent a promising therapeutic target. MET secondary mutations D1228H/N or D1246N present the potential resistance mechanisms of MET inhibitors in patients with de novo MET fusions. [ABSTRACT FROM AUTHOR]

Purpose: To explore the effectiveness and safety of laparoscopic transhiatal complete mesenteric resection (CME) surgery compared with those of the traditional laparoscopic transhiatal approach in the treatment of Siewert II/III adenocarcinoma of the esophagogastric junction (AEG). Materials and methods: Ninety-nine patients with Siewert type II/III AEG were enrolled and divided into two groups: the laparoscopic CME transhiatal approach (CEM-TH, n = 61) group and traditional laparoscopic transhiatal (TH, n = 38) group. Intraoperative and postoperative clinical data of both groups were analyzed. Results: The laparoscopic trasihiatal surgery was technically successful in all patients. The surgical time, intraoperative bleeding, and hospital stay were all significantly (P < 0.05) reduced in the CME-TH group compared with those in the TH group. The levels of white blood cells on postoperative day (POD) 1 and 5, postoperative CRP on POD 3 and 5, and postoperative PCT were significantly (P < 0.05) lower while lymph nodes were harvested significantly (P < 0.05) more in the CME-TH group than in the TH group. Complications were not significantly (P > 0.05) different between two groups. No death occurred within 90 days. Conclusion: The CME theory could be safely and effectively applied laparoscopically to treat patients with Siewert II/III AEG. Mesogastrium and lower mesoesophagus can be completely resected together with the tumor, lymph nodes, adipose tissue, and blood vessels as an "intact package," leading to better short-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. Methods: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. Results: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference − 1; 95% CI − 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. Conclusions: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. Trial registration: www.chictr.org.cn; identifier: ChiCTR-IOR-17011994; registered on 14 July 2017. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness and clinical significance of thoracolaparoscopic esophagectomy with mesoesophagus excision. Materials and methods: Patients who underwent en bloc mesoesophageal esophagectomy through thoracoscopy combined with laparoscopy were retrospectively enrolled. Carbon nanoparticles were used in some patients to label the esophageal drainage lymph nodes. The clinical data were analyzed. Results: En bloc mesoesophageal esophagectomy was successfully performed in 135 patients (100%). The carbon nanoparticles were used in 10 patients, among which the left gastric arterial lymph nodes were labeled in all patients and excised together with the left gastric mesentery, mesoesophagus, esophageal cancer, lymph nodes, vessels, nerves, and adipose tissues as one intact package. The mean operation time was 182.5 ± 26.4 min, intraoperative blood loss 45.9 ± 17.6 ml, mean number of lymph nodes dissected 20.9 ± 8.12, extubation time of drainage tubes 7.5 ± 3.8 days, first oral feeding time 7.5 ± 1.8 days, and postoperative hospital stay 13 ± 5.11 days. Postoperatively, anastomotic leakage occurred in six patients (4.4%), anastomotic stenosis in eight (5.9%), hoarseness in seven (5.2%), and inflammation of the remnant stomach in four (3.0%), with a complication rate of 18.5%. Patients were followed up for 13–34 months (median 23). Eighteen patients presented with organ metastasis. No local recurrence or death during follow-up. Conclusion: Based on the membrane anatomy or mesoesophagus theory, thoracolaparoscopic en bloc mesoesophageal esophagectomy is safe, with decreased blood loss, and it is necessary to resect the left gastric artery lymph nodes together with the left gastric mesentery and its contents to completely remove the cancer. [ABSTRACT FROM AUTHOR]

We study timelike particles' bound orbits around renormalization group improved Schwarzschild black holes (RGISBHs), which originate from renormalization group improvement of the Einstein–Hilbert action by using the running Newton constant. By considering the secular periastron precession for the timelike particles orbiting around RGISBHs, we found that it is not feasible to distinguish such black holes from Schwarzschild ones in the weak gravitational field. However, in the strong gravitational field, periodic orbits for the particles are investigated by employing a taxonomy. This suggests that the variation of the parameters in RGISBHs can change the taxonomy. This leads to a transition from periodic motion around Schwarzschild black holes to a quasi-periodic motion around these black holes. After that, the epicyclic motions of charged particles around RGISBHs immersed in an external asymptotically uniform magnetic field are taken into account with respect to the observed twin peak quasi-periodic oscillations' frequencies. The epicyclic motions of charged particles around such black holes in the external magnetic field can give one possible explanation for the 3:2 resonance in three low-mass X-ray binaries. Our results might provide some hints to distinguish RGISBHs from the classical black holes by using periodic orbits and epicyclic motions around the strong gravitational field. [ABSTRACT FROM AUTHOR]

Background: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia.Methods: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth.Results: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment.Conclusions: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined.Trial Registration: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017. [ABSTRACT FROM AUTHOR]

The neutral time-like particle's bound orbits around modified Hayward black holes have been investigated. We find that both in the marginally bound orbits (MBO) and the innermost stable circular orbits (ISCO), the test particle's radius and its angular momentum are all more sensitive to one of the parameters β. Especially, modified Hayward black holes with β = 1 0 could mimic the same ISCO radius around the Kerr black hole with the spin parameter up to a / M ≈ 0. 9 9. Small β could mimic the ISCO of small-spinning test particles around Schwarzschild black holes. Meanwhile, rational (periodic) orbits around modified Hayward black holes have also been studied. The epicyclic frequencies of the quasi-circular motion around modified Hayward black holes are calculated and discussed with respect to the observed Quasi-periodic oscillations (QPOs) frequencies. Our results show that rational orbits around modified Hayward black holes have different values of the energy from the ones of Schwarzschild black holes. The epicyclic frequencies in modified Hayward black holes have different frequencies from Schwarzschild and Kerr ones. These might provide hints for distinguishing modified Hayward black holes from Schwarzschild and Kerr ones by using the dynamics of time-like particles around the strong gravitational field. [ABSTRACT FROM AUTHOR]

We investigate neutral and charged test particles' motions around quantum-corrected Schwarzschild black holes immersed in an external magnetic field. Taking the innermost stable circular orbits of neutral timelike particles into account, we find that the black holes can mimic different ranges of the Kerr black hole's spin |a/M| from 0.15 to 0.99. Our analysis of charged test particles' motions suggests that the values of the angular momentum l and the energy E 2 are slightly higher than Schwarzschild black holes. The allowed regions of the (l , E 2) demonstrate that the critical energy E c 2 divides the charged test particle's bounded trajectory into three types. With the help of a Monte Carlo method, we study the charged particles' probabilities of falling into the black holes and find that the probability density function against l depends on the signs of the particles' charges. Finally, the epicyclic frequencies of the charged particles are considered with respect to the observed twin peak quasi-periodic oscillations frequencies. Our results might provide hints for distinguishing quantum-corrected Schwarzschild black holes from Schwarzschild ones by using the dynamics of charged test particles around the strong gravitational field. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the lymph node metastasis pattern and significance of dissection of the left gastric artery lymph nodes in radical en bloc esophagectomy for esophageal squamous carcinomas based on the lymphatic drainage pathway revealed by carbon nanoparticle labeling. Materials and methods: Patients who underwent en bloc esophagectomy endoscopically were retrospectively enrolled. Carbon nanoparticles were injected in the submucosa of upper thoracic esophagus to label the relevant draining lymph nodes. The clinical data, lymph nodes dissected, surgical technique, and complications were analyzed. Results: En bloc esophagectomy was successful in all 179 patients. Metastases to the left gastric artery lymph nodes were positive in 42 patients (23.5%) but negative in 137 (76.5%). The left gastric lymph nodes were labeled, whereas no celiac lymph nodes were labeled by carbon nanoparticles. A total of 4652 lymph nodes were resected, with 26 lymph nodes per patient. Seventy-three patients had lymph node metastasis (73/179). Seventeen patients had metastasis to the recurrent laryngeal nerve lymph nodes (9.5%). The metastasis rate of the lower thoracic esophageal cancer to the left gastric artery lymph nodes was 37.0%, significantly greater than that at the middle (15.4%) or upper (6.7%) thoracic segment. The lymph node metastasis rate was significantly (P < 0.05) increased with the length of the cancerous lesion, infiltration depth, and poor differentiation. Univariate analysis revealed that the metastasis rate to the left gastric artery lymph nodes was significantly (P < 0.05) associated with paraesophageal lymph node metastasis, para-cardial lymph metastasis, and TNM classification. Multivariate analysis indicated that cancer location (odds ratio 8.32, 95% confidence interval 2.12–32.24) was significantly (P < 0.05) associated with metastasis to the left gastric artery lymph nodes, with the cancer at the middle and lower thoracic segments significantly more than in the upper thoracic segment. Conclusion: Certain patterns exist in lymph node metastasis of esophageal cancer, and in radical esophagectomy of esophageal cancers, dissection of the left gastric artery lymph nodes is necessary to prevent possible residual or metastasis of esophageal squamous carcinomas based on the lymphatic drainage pathway of esophageal carcinomas demonstrated by carbon nanoparticle labeling. [ABSTRACT FROM AUTHOR]

Background: Depression is a common and serious complication in new mothers. We investigated the hypothesis that neuraxial labor analgesia is associated with a decreased risk of postpartum depression.Methods: In this multicenter prospective cohort study with propensity score matching, 599 nulliparous women with single term cephalic pregnancy who planned vaginal delivery were enrolled and self-selected neuraxial analgesia or not. The primary outcome was 6-week postpartum depression assessed with the Chinese version Edinburgh Postnatal Depression Scale; a score of ≥10 was set as the threshold of postpartum depression. Logistic regression models were established to assess the association between neuraxial labor analgesia and postpartum depression.Results: Of the 577 parturients who completed the study, 417 (72.3%) received neuraxial analgesia and 160 (27.7%) did not. After propensity score matching, 433 parturients were included in the analysis; of whom, 279 (64.4%) received neuraxial analgesia and 154 (35.6%) did not. The incidence of postpartum depression was lower in parturients with neuraxial analgesia than in those without (14.9% [62/417] vs. 23.8% [38/160], P=0.012 before matching; 13.3% [37/279] vs. 23.4% [36/154], P=0.007 after matching). After adjustment for confounding factors, neuraxial analgesia was associated with decreased odds of postpartum depression (odds ratio [OR] 0.50, 95% CI 0.28-0.88, P=0.015 before matching; OR 0.40, 95% CI 0.21-0.77, P=0.006 after matching).Limitations: As an observational study, unidentified confounders might influence the results.Conclusions: In nulliparae with single term cephalic pregnancy preparing to give vaginal delivery neuraxial analgesia during labor was associated with a decreased risk of 6-week postpartum depression. [ABSTRACT FROM AUTHOR]

Herein, a novel photoelectrochemical (PEC) immunoassay based on organic-inorganic BiVO 4 /rGO/FeOOH/C dot as cascade-sensitized photoactive material was fabricated for the ultrasensitive detection of β2-MG protein. Specifically, the composite BiVO 4 /rGO/FeOOH/C dot integrated the merits of high light absorption efficiency of organic material with fast electric carrier mobility of inorganic material. Additionally, the composite possessed a narrow energy level gradient, result in that the utilization of light energy improved greatly. More importantly, the composite with well-matched energy level would mediate multi-electron transport, thereby effectively promoting electron transfer and improving charge separation with an excellent photocurrent. Thereafter, through a typical sandwiched immunoreaction, quencher SiO 2 -labeled antibody that related to target was captured on electrode to decrease the initial photocurrent signal. The results showed that the proposed immunosensor exhibited high sensitivity and excellent stability in the linear range from 0.1 pg/mL to 1 μg/mL with a detection limit of 0.0383 pg/mL. This PEC biosensor offers a well-matched organic-inorganic cascade-sensitized strategy, providing novel insights to explore the high-performance photoactive material for application in early diagnosis of diseases. [Display omitted] • The BiVO 4 /rGO/FeOOH/C dot structure with well-matched energy level would mediate multielectron transport. • The typical sandwiched immunoreaction could load quencher, thereby obtaining significantly deceased PEC signal. • The proposed PEC biosensor of composites achieved ultra-sensitive detection of β2-MG protein. [ABSTRACT FROM AUTHOR]

In this work, a novel photoelectric active material Ti 3 C 2 T x MXene/Ag 2 S with strong photocurrent signal was prepared to construct the photoelectrochemical (PEC) biosensor for ultrasensitive detection of target miRNA-141. Impressively, Ti 3 C 2 T x MXene with excellent metal conductivity could shorten the electron transmission path to prominently improve the separation of electron-hole pairs and significantly enhance the photocurrent signal of Ti 3 C 2 T x MXene/Ag 2 S nanocomposite. Meanwhile, streptavidin (SA) was used as a scaffold to assemble a DNA tetrad for constructing a spatial DNA structure by a nonlinear hybrid chain reaction (HCR) triggered via target miRNA-141, which embedded amount of thionine as a sensitizer for significantly increasing the photocurrent response. The biosensor could achieve the sensitive detection of miRNA-141 with detection limit of 34 aM. This strategy demonstrated a novel photoactive material to construct the PEC biosensor for sensitive detection of biomarkers with potential application value in disease diagnosis. • Ti 3 C 2 T x MXene can reduce electron-hole pairs recombination with excellent metal conductivity and adjustable band gap. • Ti 3 C 2 T x MXene/Ag 2 S composite with a wide light absorption range exhibited an admirable photocurrent signal. • The nonlinear HCR as an amplifier achieves the sensitive detection of miRNA-141 with a lower detection limit. [ABSTRACT FROM AUTHOR]

A black hole on a three-brane in five-dimensional spacetime was predicted by Dadhich, Maartens, Papadopoulos and Rezania (DMPR). In order to reveal some signatures for observations, we investigate a timelike particle's motion around the DMPR brane-world black holes. We find that, both in the innermost stable circular orbits (ISCO) and the marginally bound orbits (MBO), the particle's angular momentum and its radius decrease with the increase of Q, where Q is a tidal charge parameter and may be negative and positive in the brane-world black holes. From these results, the corresponding periodic orbits with different energy levels are analyzed numerically by employing a taxonomy, which is related to the adiabatic inspiral regime in the gravitational wave radiation. It clearly shows that a rational number defined by the taxonomy increases with the particle's energy. In addition, periodic orbits with Q < 0 in the DMPR brane-world black holes have higher energy in comparison to the ones with Q > 0 and in the Schwarzschild black holes. Our results might provide hints for distinguishing the DMPR brane-world black holes from other black holes by the timelike particle's periodic orbits in the future. [ABSTRACT FROM AUTHOR]

Only a few studies have investigated the brain morphology abnormalities in structural MRI in patients with drug-naïve idiopathic generalized epilepsy (IGE) and mainly focused on brain volume changes. In the present study, we aimed to investigate the changes in three morphologic measurement differences including cortical thickness, cortical volume, and surface area using FreeSurfer in a pediatric cohort of recent-onset, drug-naïve IGE. Forty-five recent-onset, drug-naïve patients diagnosed with IGE and 32 demographically matched healthy controls were recruited. All participants underwent structural MRI scans with a 3.0 T MR system. FreeSurfer, an automated cortical surface reconstruction toolbox, was applied to compare the cortical morphology between patients and controls. The brain regions with significant group differences after multiple comparison correction were extracted in common space for each patient, and then correlated with their clinical characteristics (including onset age, duration of epilepsy, and mini-mental state examination (MMSE)) using partial correlation analysis with age, sex and intracranial volume as covariates. Compared with controls, IGE patients showed decreased cortical thickness in the left rostral middle frontal gyrus, decreased cortical volume in the right cuneus and left superior frontal gyrus that extended to the precentral gyrus, and decreased surface area in the right cuneus and right inferior parietal gyrus. None of these regions showed significant relationships with clinical measurements in the patient group. Our findings suggest that cortical thickness, cortical volume, and surface area changes occurred in the early stage of IGE. These findings provide structural neuroimaging evidence underlying the pathology of IGE. [ABSTRACT FROM AUTHOR]

We investigate charged particles' motions around a hairy black hole of Horndeski's theory immersed in an external magnetic field. Although the critical energy E ∗ 2 divides the charged particle's bounded trajectory into three types just like the situation in the classical Schwarzschild black hole, it still suggests that the values of the angular momentum and the energy for the charged particle around the hairy black hole are smaller than the ones of the classical hole. The epicyclic frequencies of the charged particle around the hairy black hole immersed in the external magnetic field are compared with the results of the observed microquasars' results. It indicates that the influences of the hairy black hole best fits the data of the observations with a non-vanishing magnetic field. Our present work might provide hints for distinguishing the hairy black hole in Horndeski's theory from the classical Schwarzschild black hole by using the test charged particles' dynamics around the strong gravitational field. • The test particles' motions around a hairy black hole are investigated. • The epicyclic motions are compared with the results of the observed results. • The results best fit the data of observations with a non-vanishing magnetic field. [ABSTRACT FROM AUTHOR]

Solar System tests of a brane world, which is called DMPR model, were studied in recent works. The correction of DMPR model to the general relativity (GR) in the four-dimensional curved spacetime can be parametrized by a “tidal charge” parameter Q. The parameter Q in this model was obtained and improved as |Q|≲6.7m2 by the Earth–Mercury ranging. A new test of the DMPR model based on gravitational time advancement is proposed and investigated in this work. The advancement is a gravitational consequence on round-trip proper time duration of a photon. For ranging a distant spacecraft, it is shown that (1) the “tidal charge” parameter can make the advancement larger or smaller than the one of GR, depending on the sign of Q; (2) the superior conjunction (SC) and the inferior conjunction (IC) are all suitable for detecting the advancement; (3) the advancement can be complementary to the classical test of Shapiro time delay for detecting the brane world; and (4) the implementation of optical clocks and planetary laser ranging will provide more insights on the brane world model in the future. [ABSTRACT FROM AUTHOR]

Under gravity's rainbow, we investigate its effects on the gravitational time advancement, which is a natural consequence of measuring proper time span for a photon's round trip. This time advancement can be complementary to the time delay for testing the gravity's rainbow, because they are sensitive to different modified dispersion relations (MDRs). Its observability on ranging a spacecraft far from the Earth by two radio and a laser links is estimated at superior conjunction (SC) and inferior conjunction (IC). We find that (1) the IC is more favorable than the SC for measurement on the advancement caused by the rainbow; (2) a specific type of MDR has a significantly larger effect on the advancement than others in both SC and IC cases; and (3) a combination of available optical clocks and the realization of planetary laser ranging in the future will benefit distinguishing the gravity's rainbow from GR by measuring the gravitational time advancement. [ABSTRACT FROM AUTHOR]

With the purpose of deeply understanding the fundamental interaction between the electromagnetic and gravitational fields, photons coupled to the Weyl tensor was proposed, which could be derived from the Maxwell equation with a Weyl correction. This correction with respect to general relativity in a 4-dimensional spacetime can be characterized by a coupling strength parameter α . By taking such a coupling into account, we investigate its effects on the classical tests in the Solar System, including the deflection of light, the gravitational time delay and the Cassini tracking experiment, and constrain the parameter α with new datasets. None of these works were done before and these data of the experiments are used for testing the photons coupled to the Weyl tensor for the first time. We find that the experimental upper bounds are | α | ≲ 4 × 1 0 11 − 5 × 1 0 13 m 2 , in which the strongest bound comes from the Cassini tracking. Therefore, it is expected that when more sophisticated frequency standards can be implemented in the spacecrafts tracking in the future, this bound on α will be reduced further. [ABSTRACT FROM AUTHOR]

By making use of the supplementary advances of the perihelia provided by INPOP10a and INPOP15a (France) and EPM2011 (Russia) ephemerides, we obtain improved Solar System bounds on the cosmologically viable $f(\mathcal{G})$ gravity, where $f$ is an arbitrary function of the Gauss-Bonnet invariant $\mathcal{G}$ . When we estimate new bounds on its model parameters, we consider the Lense-Thirring effect caused by the Sun's angular momentum and the uncertainty of the Sun's quadrupole moment, neither of which were included in related works before. The bounds we obtain in the present work are tighter than the previous ones by at least 5 orders of magnitude. [ABSTRACT FROM AUTHOR]

China faces multiple pressures from both global climate change and local pollution. Given that China is now taking economic growth and the improvement of people's living standards as its primary goal, it is necessary to control a variety of environmental problems synergistically to minimize adverse socio-economic impacts. Using an input–output model, this study aims to identify the important behaviors that simultaneously lead to various environmental discharges among the troika of China's economic development (consumption, investment, and exports). The results show that behaviors that have an obvious driving force behind multiple environmental discharges exist in all three final use components. Household consumption of health care, residential services and real estate; investments in construction, transport equipment, and special purpose machinery and exports of electrical machinery/equipment and electronic equipment had obvious driving effects on most of the environmental discharges examined, totally covering 25.62% (COD (chemical oxygen demand))-54.91% (soot and dust) of the corresponding environmental discharges. Household consumption of electricity and heating and investments in general purpose machinery are behaviors with obvious driving effects on CO 2 emissions, air pollutants and solid waste. Household consumption of agricultural byproducts, other processed foods, wine, drinks and refined tea, textile wearing and apparel; exports of textiles, textile wearing and apparel, raw chemical materials and chemical products had obvious driving effects on water pollutants. The characteristics of these behaviors and their roles in social and economic development are then discussed. Based on the discussions, potential ways to utilize the identified behaviors are recommended: household consumption of electricity, heating, food, wine, drinks and refined tea, textile wearing and apparel should be guided toward a more conservation-oriented approach; the structure of investments in transport equipment, special and general purpose machinery, and exports of electrical machinery/equipment, textiles, textile wearing and apparel, raw chemical materials and chemical products should be adjusted toward more high-end products; the discharge intensities of the supply chain of health care, residential services, real estate and electronic equipment should be further lowered; the investment in construction should be planned more rationally, while the unnecessary waste of high-discharge-intensive construction materials should be avoided. [ABSTRACT FROM AUTHOR]

The light time equation and frequency shift are worked out in the framework of a second parametrized post-Newtonian (2PPN) formalism in the Solar System barycentric reference system (SSBRS) developed in a recently published paper. Effects of each body's oblateness, spin and translational motion are taken into account for the light propagation. It is found that, at the second post-Newtonian (2PN) approximation, the light time and frequency shift depend on the parameter only. [ABSTRACT FROM AUTHOR]

As an extension of previous works on classical tests of a braneworld model which is called as the Dadhich, Maartens, Papadopoulos and Rezania (DMPR) solution, and as an attempt to find more stringent constraints on this model, we investigate its effects on physical experiments and astronomical observations conducted in the Solar System by modeling new observable effects and adopting new datasets. First, we investigate gravitational time delay at inferior conjunction (IC) caused by the braneworld model, which was not considered in previous works, because these measurements are not affected by the solar corona noise. Second, the Cassini superior conjunction (SC) experiment is, for the first time, used to test the DMPR model. Third, compared to previous works, we refine the model, which confronts the perihelion shift induced by the braneworld model with modern Solar System ephemerides INPOP10a (IMCCE, France) and EPM2011 (IAA RAS, Russia). The correction of DMPR solution to Einstein's general relativity (GR) in the four-dimensional spacetime can be characterized by a constant bulk 'tidal charge' parameter , which is confined in the present work. We find that time delay experiment at IC is independent of and not suitable for testing the braneworld model. However, the Cassini SC experiment and modern Solar System ephemerides can give better upper bounds on : (1) by Cassini, and (2) based on the supplementary advances of the perihelia provided by INPOP10a and based on the ones of EPM2011. The latter upper bounds are improved to be tighter than the ones of previous works by at least two orders of magnitude. Besides, the stronger constraints on the brane tension are given by the modern ephemerides, which are for INPOP10a and for EPM2011. These improved upper bounds mean that the Solar System tests can serve as a good testbed for high dimensional theories. [ABSTRACT FROM AUTHOR]

A recent model of nonlocal gravity is tested by the dynamics of the Solar System. This theory of gravity goes beyond the hypothesis of locality and includes the past history of an observer into measurements. Using the supplementary advances of the perihelia provided by INPOP10a (IMCCE, France) and EPM2011 (IAA RAS, Russia) ephemerides, we obtain the bounds on its parameters: α and λ 0 . In this investigation, we take the Lense–Thirring effect due to the Sun’s angular momentum and the uncertainty of the Sun’s quadrupole moment into account. These two factors were usually absent in previous works. We find that INPOP10a yields the Solar System’s bounds as α = ( − 0.6 ± 12 ) × 1 0 − 12 and λ 0 = ( 0.2 ± 2.1 ) × 10 5 kpc, while EPM2011 gives α = ( 0.3 ± 3.2 ) × 1 0 − 12 and λ 0 = ( − 0.4 ± 1.7 ) × 10 5 kpc. The bound of α is considerably smaller than the result based on the rotation curves of spiral galaxies and the bound of λ 0 is much larger than the one based on the rotation curves by at least 5 orders of magnitude. It makes the nonlocal gravity much weaker in the scale of the Solar System than it in the scale of galaxies, implying that a screening mechanism is required to suppress the nonlocal gravity in high density regions. [ABSTRACT FROM AUTHOR]

The relativistic theories of light propagation are generalized by introducing two new parameters ς and η in the second post-Newtonian (2PN) order, in addition to the parametrized post-Newtonian (PPN) parameters γ and β. This new 2PN parametrized (2PPN) formalism includes the nonstationary gravitational fields and the influences of all kinds of relativistic effects. The multipolar components of gravitating bodies are taken into account as well at the first post-Newtonian (1PN) order. The equations of motion and their solutions of this 2PPN light propagation problem are obtained. Started from the definition of a measurable quantity, a gauge-invariant angle between the directions of two incoming photons for a differential measurement in astrometric observation is discussed and its formula is derived. For a precision level of a few microarcsecond (μas) for space astrometry missions in the near future, we further consider a model of angular measurement, the Laser Astrometric Test of Relativity (LATOR)-like missions. In this case, all terms with aimed at the accuracy of ~1μas are estimated. [ABSTRACT FROM AUTHOR]

As a generalization of Einstein's general relativity (GR), the f( R, T) gravity replace the gravitational Lagrangian of GR with an arbitrary function of the Ricci scalar R and of the trace of the stress-energy tensor T. It can induce an extra acceleration a in the dynamics of massive test particles due to the physical coupling between matter and geometry. In this work, we confront this extra acceleration with planetary motions in the solar system. Using the supplementary advances in the perihelia provided by current INPOP10a and EPM2011 ephemerides, we obtain new upper limits on a when the uncertainty of the Sun's quadrupole moment and the Lense-Thirring effect due to the Sun's angular momentum are properly taken into account. These two factors were mostly absent in previous works dealing with a. We find that INPOP10a yields the upper limit as a=(−0.04±4.81)×10 m s and EPM2011 gives a=(0.06±1.58)×10 m s . Both of them are improved at least by about 10 times than previous results obtained in the solar system and they are smaller than the results given by fitting rotation curves of galaxies by about 4 orders of magnitude. This discrepancy of a on these scales seems to imply that its effects might be screened in high density regions. [ABSTRACT FROM AUTHOR]

As a power class of generalization of Einstein’s general relativity, the R 1 + δ gravity is confronted with planetary motions in the solar system. Using the supplementary advances in the perihelia provided by current INPOP10a (IMCCE, France) and EPM2011 (IAA RAS, Russia) ephemerides, we obtain new upper limits on δ in the solar system when the Lense–Thirring effect due to the Sun’s angular momentum and the uncertainty of the Sun’s quadrupole moment are properly taken into account. These two factors were mostly absent in previous works dealing with δ . We find that INPOP10a yields the upper limit as δ = ( 0.6 ± 4.4 ) × 10 - 24 and EPM2011 gives δ = ( 7.5 ± 3.4 ) × 10 - 24 . Both of them are improved by about 5 orders of magnitude than previous result. [ABSTRACT FROM AUTHOR]

The presence of autoantibodies is characteristic of autoimmune diseases. It is widely accepted that autoantibodies provide crucial diagnostic and prognostic information for autoimmune diseases. Indeed, numerous studies have demonstrated that the appearance of autoantibodies precedes the clinical onset of autoimmune diseases. We performed a literature review regarding the appearance of autoantibodies that preceded the clinical onset of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, primary biliary cirrhosis, inflammatory bowel disease, and multiple sclerosis. Herein we review and comment on the major findings of these studies. [ABSTRACT FROM AUTHOR]

Photocathodic biosensor has great capability in anti-interference from reductive substances, however, the low signal intensity of photoactive species with inferior detection sensitivity restricts its wide application. In this work, the P3HT-PbS nanocomposites were synthesized as signal tags, by integrating with target-trigger generated hemin/G-quadruplex nanotail as bi-enhancer to significantly apmplify the photocurrent, an ultrasensitive photocathodic biosensor was proposed for detection of β 2-microglobulin (β 2-MG). Impressively, P3HT with cathode signal is an attractive polymer consisted of substantial thiophene groups with high absorption coefficient and mobility of photo-generated holes, which could anchor with the PbS dots as sensitizer, providing a high charge mobility and strong photosensitivity. More importantly, target-trigger generated hemin/G-quadruplexes could accept the electron from illuminated photoactive species through the conversion of Fe(III)/Fe(II) in hemin, effectively reducing charge recombination rate as well as accelerating the generation of electron acceptor O 2 in the assistant of H 2 O 2. Moreover, hemin/G-quadruplexes inherited the HRP mimicking catalytic capability that further improved the produce of plentiful O 2. As a result, PEC cathode signal was significantly enhanced for sensitive analysis of β 2-MG protein with a good detection range of 0.1 pg/mL to 100 ng/mL. It would provide a path for establishing PEC platform with excellent anti-interference ability and extend the application of photoelectrochemical (PEC) biosensor in bioanalysis and early disease diagnosis. [Display omitted] • The p-typed P3HT could be sensitized by PbS dots , providing a high charge mobility and strong photosensitivity. • The hemin/G-quadruplexes could accelerate the generation of electron acceptor O 2 in the assistant of H 2 O 2. • Hemin/G-quadruplexes inherited the HRP mimicking catalytic capability that further improved the produce of plentiful O 2. • The cathode signal was enhanced significantly to improve the detection sensitivity and extend the detection range. [ABSTRACT FROM AUTHOR]

Using the supplementary advances of the perihelia provided by INPOP10a (IMCCE, France) and EPM2011 (IAA RAS, Russia) ephemerides, we obtain preliminary limits on a logarithmic correction to the Newtonian gravitational potential in the solar system. This kind of correction may originate from fundamental frameworks, like string theories or effective models of gravity due to quantum effects and the non-local gravity scheme. We estimate upper limit of Tohline-Kuhn-Kruglyak parameter λ and lower bound of Fabris-Campos parameter α, which parametrize the correction and connect each other by αλ=−1. In our estimation, we take the Lense-Thirring effect due to the Sun's angular momentum and the uncertainty of the Sun's quadrupole moment into account. These two factors were usually absent in previous works. We find that INPOP10a yields the upper limit as α=−(0.66±5.82)×10 kpc [or the lower limit as λ=(0.15±8.76)×10 kpc] while EPM2011 gives α=(0.52±1.74)×10 kpc [or the lower limit as λ=−(0.19±3.29)×10 kpc]. The limits of | λ| are greater than the result based on the rotation curves of spiral galaxies by about 3 orders of magnitude, indicating its effects might be screened in high density regions. [ABSTRACT FROM AUTHOR]

Ground-based and space-borne observatories studying exoplanetary transits now and in the future will considerably increase the number of known exoplanets and the precision of the measured times of transit minima. Variations in the transit times can not only be used to infer the presence of additional planets, but might also provide opportunities for testing new physics in the places beyond the Solar system. In this work, we take deviation from the inverse-square law of gravity as an example, focus on the fifth-force-like Yukawa-type correction to the Newtonian gravitational force which parameterizes this deviation, investigate its effects on the secular transit timing variations and analyse their observability in exoplanetary systems. It is found that the most optimistic values of Yukawa-type secular transit timing variations are at the level of ∼0.1 s per year. Those values unfortunately appear only in rarely unique cases and, most importantly, they are still at least two orders of magnitude below the current capabilities of observations. Such a deviation from the inverse-square law of gravity is likely too small to detect for the foreseeable future. Meanwhile, systematic uncertainties, such as the presence of additional and unknown planets, will likely be exceptionally difficult to remove from a signal that should be seen. [ABSTRACT FROM AUTHOR]

The Yukawa correction to the Newtonian gravitational force is accepted as a parametrization of deviations from the inverse-square law of gravity which might be caused by new physics beyond the standard model of particles and the general theory of relativity. We investigate these effects on the clock onboard a drag-free satellite: dynamics of the satellite and influence on the time transfer link. We find that the Yukawa signal in the time transfer is much more difficult to detect with the current state of clocks than those effects on the dynamics, especially the secular change of periastron, by laser ranging in the case of an artificial Earth satellite carrying a frequency standard with an orbit of a = 107 m and e = 0.01. [ABSTRACT FROM AUTHOR]

A novel class of optical breathers, called elegant Ince-Gaussian breathers, are presented in this paper. They are exact analytical solutions to Snyder and Mitchell's mode in an elliptic coordinate system, and their transverse structures are described by Ince-polynomials with complex arguments and a Gaussian function. We provide convincing evidence for the correctness of the solutions and the existence of the breathers via comparing the analytical solutions with numerical simulation of the nonlocal nonlinear Schrödinger equation. [ABSTRACT FROM AUTHOR]

Viola baoshanensis is one of the most rare cadmium (Cd) hyperaccumulators, however, it is hard to propagate. Micropropagation has been applied to solve the problems with propagation of a few heavy metal hyperaccumulators. Therefore there is a high likelihood that micropropagation may offer a suitable method for large-scale propagation of V. baoshanensis. To test this hypothesis, three types of explants were used for shoot regeneration and various combinations of four plant growth regulators were used to improve shoot regeneration efficiency from leaflet of V. baoshanensis. Best shoot regeneration efficiency was obtained by incubating leaflet in a 1/2 MS medium supplemented with 2.5 μM BA + 2.5 μM IBA, therein shoot regeneration rate was 70.9% and the number of shoots formation per explant was 22.4. Rooting was achieved from almost all regenerated shoot growing on 1/2 MS medium without plant growth regulator. Micropropagated seedlings were acclimatized under greenhouse conditions and 95% of them survived and showed no visible morphological variation compared to their donor plant. Furthermore, there were no significant differences between regenerated and seed-germinated V. baoshanensis in Cd tolerance and accumulation. These results suggested that an efficient and rapid micropropogation system was successfully developed for V. baoshanensis. [ABSTRACT FROM AUTHOR]

Abstract: Although Candida containing biofilms contribute to the development of oral candidosis, the characteristics of multi-species Candida biofilms and how oral bacteria modulate these biofilms is poorly understood. The aim of this study was to investigate interactions between Candida albicans and either Candida glabrata or Streptococcus mutans in biofilms grown on various surfaces, with or without saliva. Hydroxyapatite (HA), polymethylmetacrylate (PMMA) and soft denture liner (SL) discs were used as substratum. Counts of viable micro-organisms in the accumulating biofilm layer were determined and converted to colony forming units per unit surface area. Confocal laser scanning microscopy was used to characterize biofilms and to quantitate the number of hyphae in each condition tested. Viable counts of C. albicans and C. glabrata per mm2 decreased in the order HA>PMMA>SL (p <0.05). Biofilms grown on saliva-coated specimens harboured fewer C. glabrata than uncoated specimens (p <0.05). Glucose and the presence of S. mutans suppressed C. albicans hyphal formation. Dual Candida species biofilms did not show competitive interaction between the two species. We conclude that Candida biofilms are significantly affected by saliva, substratum type and by the presence of other micro-organisms. [Copyright &y& Elsevier]

Sedum alfredii Hance is a newly reported zinc (Zn) and cadmium (Cd) hyperaccumulator native to China. In this study, four populations of S. alfredii were collected from Yejiwei (YJW), Jinchuantang (JCT) and Qiaokou (QK) lead (Pb)/Zn mines located in Hunan Province as well as Quzhou (QZ) Pb/Zn mine located in Zhejiang Province for exploring the intraspecies difference of this plant in metal accumulation. Although they grew in the Pb/Zn spoils with relatively similar levels of Zn, Cd and Pb, remarkable differences among the four populations in tissue heavy metal concentrations were observed. The shoot Zn concentration of QZ population (11 116 mg/kg) was highest and nearly five times higher than that of the JCT population (1 930 mg/kg). Furthermore, the shoot Cd concentration observed in the QZ population (1 090 mg/kg) was also highest and 144 times higher than that found in the JCT population (7.5 mg/kg). As for Pb concentrations in the shoot of different populations, a fourfold difference between the highest and the lowest was also found. Such difference on metal accumulation was population-specific and may be significantly explained by differences in the soil properties such as pH, organic matter (OM), and electrical conductivity (EC). Taking biomass and metal concentration in plants into consideration, the QZ, YJW and QK populations may have high potential for Zn phytoremediation, the QZ population may have the highest potential in Cd phytoremediation, and the QK population may be the most useful in Pb phytoremediation. [ABSTRACT FROM AUTHOR]

Abstract: Density functional theory calculations have been performed on the structure and stability of Fe4C bulk and the corresponding low-index surfaces. It is found that the structure with octahedral interstitial carbon (Fe4C/oct) is more stable than that with tetrahedral interstitial carbon (Fe4C/tet). For Fe4C/oct, the most stable surface termination is the (100) surface with mixed carbon and iron (T Fe/C). For Fe4C/tet, the most stable surface termination is the dramatically reconstructed (110) surface with the newly formed T Fe/C surface layer. [Copyright &y& Elsevier]

In the oral cavity a balanced physiological response is essential for Streptococcus mutans to survive various types of external challenges. In this study we examined the role of the ClpP serine protease in the response of S. mutans towards sodium fluoride, sodium chloride, hydrogen peroxide, and chlorhexidine. By constructing a clpP promoter–green fluorescent protein reporter strain, we showed increased fluorescence intensities under all types of stress, indicating a need for ClpP under all these challenges. We constructed a clpP knockout mutant, which proved to be more sensitive to all the challenges than the wild-type strain. This knockout strain also displayed a reduced growth rate, hyperaggregation, and increased biofilm formation. Furthermore, an increased resistance to toxic levels of hydrogen peroxide and chlorhexidine after pre-incubation with sublethal levels of the corresponding compounds was found in the wild-type strain but not in the knockout mutant. In conclusion, ClpP is involved in the general stress response of S. mutans and assists the bacteria to resist killing through adaptation. [ABSTRACT FROM AUTHOR]

In order to testify the safe reliability, antibacterial property and wound healing ability in clinic application of the chitosan-gelatin sponge wound dressing (CGSWD), a lot of experiments were executed : (1) A series of toxicological evaluations of the CGSWD were performed. (2) The antibacterial properties of the CGSWD obtained by different dryness ways were investigated, and then compared the antibacterial properties with cefradine, ciprofioxacin and penicillin to ascertain how its antibacterial property is. (3) The animal wound model was made on the back of New Zealand rabbit, and treated respectively with vaseline sterile gauze, 0.2% (v/v) ethacridine and CGSWD. The wound skin tissues at the 3rd, 5th, 7th, 10th and 14th day after initial wounding were observed with naked eyes first, then all the skin tissues at the 14th day after initial wounding and normal skin without wounding were observed on SEM. The results showed that as a kind of surgical wound dressing, the CGSWD is of safe reliability, good antibacterial property. The antibacterial effect of CGSWD dried by vacuum dryness on Escherichia coli K88 is better than that of penicillin, and the effect on Streptococcus is also better than that of cefradine. CGSWD makes the wound contract obviously, and the wound healing time of treatment with CGSWD is shorter than that with vaseline sterile gauze. Still, the scar formed after healing did not protrude over the skin surface conspicuously. The healing effect of CGSWD superior to that by 0.2% (v/v) ethacridine. Therefore, the CGSWD is a kind of excellent wound healing material. [Copyright &y& Elsevier]

Abstract: Phosphodiesterase 4 (PDE4) isozyme plays important roles in inflammatory and immunomodulatory cells. In this study, piclamilast, a selective PDE4 inhibitor, was used to investigate the role of PDE4 in respiratory function and inflammation in a murine asthma model. Sensitized mice were challenged with aerosolized ovalbumin for 7 days, piclamilast (1, 3 and 10 mg/kg) and dexamethasone (2 mg/kg) were orally administered once daily during the period of challenge. Twenty-four hours after the last challenge, airway hyperresponsiveness to methacholine was determined by whole-body plethysmography, airway inflammation and mucus secretion by histomorphometry, pulmonary cAMP-PDE activity by HPLC, cytokine levels in bronchoalveolar lavage fluid and their mRNA expression in lung by ELISA and RT-PCR, respectively. In control mice, significant induction of cAMP-PDE activity was parallel to the increases of hyperresponsiveness, inflammatory cells, cytokine levels, mRNA expression as well as goblet cell hyperplasia. However, piclamilast dose-dependently and significantly improved airway resistance and dynamic compliance, and the maximal effect was similar to that of dexamethasone. Piclamilast treatment dose-dependently and significantly prevented the increase in inflammatory cell number and goblet cell hyperplasia, as well as production of cytokines, including eotaxin, TNFα and IL-4. Piclamilast exerted a weaker inhibitory effect than dexamethasone on eosinophils and neutrophils, had no effect on lymphocyte accumulation. Moreover, piclamilast inhibited up-regulation of cAMP-PDE activity and cytokine mRNA expression; the maximal inhibition of cAMP-PDE was greater than that exerted by dexamethasone, and was similar to dexamethasone on cytokine mRNA expression. This study suggests that inhibition of PDE4 by piclamilast robustly improves the pulmonary function, airway inflammation and goblet cell hyperplasia in murine allergenic asthma. [Copyright &y& Elsevier]

Abstract: PDE4 (phosphodiesterase-4) plays a critical role in pathogenesis of allergic asthma and chronic obstructive pulmonary disease (COPD). PDE4 inhibitors are presently under clinical development for the treatment of asthma and/or COPD. Ciclamilast, a new PDE4 inhibitor, is a piclamilast (RP 73401) structural analogue, but has a more potent inhibitory effect on PDE4 and inflammation in the airway tissues and less side effects than that of piclamilast. In this study, we elucidate primarily on the roles of compound on PDE4 enzyme in physiological and pathological processes in a mouse model of asthma. The sensitized/challenged mice were reexposed to ovalbumin and airway response to inhaled methacholine was monitored. Orally administration of ciclamilast, in a dose-dependent manner, significantly inhibited changes in lung resistance and lung dynamic compliance, as well as upregulation of cAMP-PDE activity, increase of PDE4D mRNA expression, but not PDE4B from lung tissue in the murine model. In addition, the compound dose-dependently reduced mRNA expression of eotaxin, tumor necrosis factor (TNF)-α and interleukin (IL)-4, but slightly increased mRNA expression of interferon (IFN)-γ from lung tissue. Further, levels of eotaxin, TNF-α and IL-4, and eosinophil and neutrophil accumulation in bronchoalveolar lavage fluid were also significantly reduced. Pathological examination, goblet cell hyperplasia and inflammatory cells infiltration in lung tissue were suppressed by treatment with ciclamilast. A significant correlation was observed between the increases in PDE4D mRNA expression and airway hyperresponsiveness. These studies confirm that inhibitory effect of ciclamilast on airway hyperresponsiveness includes its inhibiting PDE4D mRNA expression, down-modulating PDE4 activity, anti-inflammation and anti-mucus hypersecretion, and ciclamilast may have therapeutic potential for the treatment of asthma. [Copyright &y& Elsevier]

Abstract: Polydactyly is a common malformation of vertebrate limbs. Preaxial polydactyly (PPD) has been mapped in human, mouse and chicken to the syntenic region of human 7q36. Lmbr1 was thought as the critical candidate gene for human and mouse PPD. To understand the molecular mechanism underlying chicken polydactyly, we have cloned the open reading frame (ORF) of chicken Lmbr1, which contains 1467 nucleotides. Within this ORF, we found one short and one long splice forms. The short splice form has a complete deletion of exon 4. Six cSNPs were found in the chicken ORF, and two of these cSNPs, G797A and G1255A, lead to amino acid substitutions. However, G797A substitution had no significant association with polydactyly and the G1255A substitution had very low frequency in the population. The T1254C polymorphism in exon 13 was found to be strongly associated with polydactyly. Radiation hybrid mapping of a DNA fragment containing intron 13 of the chicken Lmbr1 assigned the gene to chromosome 2 between MCW071 (a marker within the EN2 gene) and ADL0270, a syntenic region to human 7q36. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate the immunomodulatory effects of the volatile oil of ginger (Zingiber officinale Roscoe) in vitro and in vivo in mice. In vitro, the volatile oil of ginger (0.001–10ng/mL) significantly inhibited T lymphocyte proliferation (P <0.01), decreased the number of the total T lymphocytes and T helper cells (P <0.01) in a concentration-dependent manner, but increased the percentage of T suppressor cells to the total T lymphocytes in the mice. In addition, the volatile oil of ginger (0.001–10ng/mL) inhibited IL-1α secretion by the mice peritoneal macrophages in a concentration-dependent manner. In vivo, oral administration of the volatile oil of ginger in the doses of 0.125, 0.25 and 0.5g/kg body weight dose-dependently weakened the delayed type of hypersensitivity response to 2,4-dinitro-1-fluorobenzene in the sensitized mice (P <0.05). These results suggest that the volatile oil of ginger influences both cell-mediated immune response and nonspecific proliferation of T lymphocyte, and may exert beneficial effects in a number of clinical conditions, such as chronic inflammation and autoimmune diseases. [Copyright &y& Elsevier]

Deng DM, Buijs MJ, ten Cate JM. The effects of substratum on the pH response of Streptococcus mutans biofilms and on the susceptibility to 0.2% chlorhexidine. Eur J Oral Sci 2004; 112: 42–47.© Eur J Oral Sci, 2004 Antimicrobial agents are now being studied in bacterial biofilms rather than in suspensions . However, no data are available whether the choice of substratum influences biofilm properties or the assessment of antimicrobial efficacy. This study compared dentin and polyacrylate (PA) grooves as substratum for biofilm formation on pH profiles after sugar challenge, as well as biofilm susceptibility to chlorhexidine. Streptococcus mutans biofilms were formed in a constant depth film fermenter (CDFF) by alternate pulsing with sucrose solutions and bacterial growth medium. Spatial and temporal pH profiles were measured using a pH microelectrode outside the CDFF in a flow reactor. Also, 15-d biofilms were treated with either water or 0.2% chlorhexidine and tested for total viable counts and organic acid content. The results show that in PA grooves, compared with dentin grooves, minimum pH was lower but recovered faster after a sucrose pulse. The pH response to sugar application decreased with the age of the biofilm more in PA than in dentin grooves. Chlorhexidine treatment in PA grooves gave greater reductions in viable counts and acid formation than in dentin. We conclude that the nature of the substratum not only affects metabolic activity of biofilms but also their susceptibility to antimicrobials. [ABSTRACT FROM AUTHOR]

China's "the Belt and Road Initiative" (BRI) is a top-level cooperation initiative among countries proposed by China, which has promoted China's cooperation with relevant countries in various aspects and fields. Research reports from think tanks and experts on the evaluation, analysis, and research conclusions of the BRI can reflect the stance, opinions, and demands of various countries abroad regarding the initiative. This paper takes the BRI reports of important think tanks in the " Global Go To Think Tank Index Report 2020" as the subject of its research, and analyzes the key points and development trends of foreign think tank research on the BRI by using text mining, topic evolution, and social network analysis. It provides reasonable suggestions and ideas for promoting the construction of the BRI and deepening related cooperation in China. Research shows that the thematic distribution of research reports on the BRI by think tanks is mainly focused on the fields of politics, economy, and military. The research areas are relatively stable, and there is not a strong trend of thematic evolution. The evolution paths are also mainly distributed in the fields of politics, economy, and military. There are not many expansions in the thematic evolution directions over the years, and there is a strong inheritance of themes. The connection between research themes and the main purpose of the BRI is somewhat inadequate, indicating a certain limitation in the understanding of the BRI. [ABSTRACT FROM AUTHOR]

Cellular senescence is an irreversible cell‐cycle arrest in response to a variety of cellular stresses, which contribute to the pathogenesis of a variety of age‐related degenerative diseases. However, effective antisenescence strategies are still lacking. Drugs that selectively target senescent cells represent an intriguing therapeutic strategy to delay aging and age‐related diseases. Thus, we thought to investigate the effects of dihydroartemisinin (DHA) on senescent cells and elucidated its mechanisms underlying aging. Stress‐induced premature senescence (SIPS) model was built in NIH3T3 cells using H2O2 and evaluated by β‐galactosidase staining. Cells were exposed to DHA and subjected to cellular activity assays including viability, ferroptosis, and autophagy. The number of microtubule‐associated protein light‐chain 3 puncta was detected by immunofluorescence staining. The iron content was assessed by spectrophotometer and intracellular reactive oxygen species (ROS) was measured by fluorescent probe dichlorodihydrofluorescein diacetate. We found that DHA triggered senescent cell death via ferroptosis. DHA accelerated ferritin degradation via promoting autophagy, increasing the iron contents, promoting ROS accumulation, thus leading to ferroptotic cell death in SIPS cells. In addition, autophagy inhibitor BafA1 preconditioning inhibited ferroptosis induced by DHA. Moreover, Atg5 silencing and autophagy inhibitor BafA1 preconditioning inhibited ferroptosis induced by DHA. We also revealed that the expression of p‐AMP‐activated protein kinase (AMPK) and p‐mammalian target of rapamycin (mTOR) in senescent cells was downregulated. These results suggested that DHA may be a promising drug candidate for clearing senescent cells by inducing autophagy‐dependent ferroptosis via AMPK/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Male‐specific wing spots are usually associated with wing displays in the courtship behavior of Drosophila and may play important roles in sexual selection. Two closely related species, D. nepalensis and D. trilutea, differ in wing spots and scissoring behavior. Here, we compare male morphological characters, pigmentation intensity of male wing spots, wing‐scissoring behavior, courtship songs, and reproductive isolation between 2 species. F1 fertile females and sterile males result from the cross between females of D. nepalensis and males of D. trilutea. The pigmentation of wing spots is significantly weaker in D. trilutea than in D. nepalensis and the F1 hybrid. Males scissor both wings in front of the female during courtship, with a posture spreading wings more widely, and at a faster frequency in D. nepalensis than in D. trilutea and the F1s. Males of D. trilutea vibrate wings to produce 2 types (A and B) of pulse songs, whereas D. nepalensis and the F1s sing only type B songs. The incidence of wing vibration and scissoring during courtship suggests that wing vibration is essential but scissoring is a facultative courtship element for successful mating in both species. The association between the darker wing spots with more elaborate scissoring might be the consequence of correlated evolution of these traits in D. nepalensis; however, D. trilutea retains wing scissoring during courtship despite having weaker pigmentation of wing spots. The genetic architecture of 2 traits differs in the F1s, consistent with maternal or sex‐linked effects for spots but nonadditive effects for scissoring. [ABSTRACT FROM AUTHOR]

In this work, a high-performance conjugated microporous polymer (CMP) decorated with BiOBr (Tr(PhXOD) 3 -CMP/BiOBr) is synthesized to application in construction of ultrasensitive photoelectrochemical (PEC) biosensor for sensing miRNA-122, by firstly coupling with efficient clip toehold-mediated allosteric bicycle strand displacement (ABSD). Notably, the Tr(PhXOD) 3 -CMP/BiOBr not only owns self-enhanced D-A-D structure that extremely shortens migration distance of photo-generated electron, but also forms Z-type heterostructure for accelerating electron-hole separation, thereby significantly enhancing the photocurrent with 10-fold higher than commonly used methods. Meanwhile, the clip toehold-mediated ABSD based on ternary linkage structure transformation avoids the attrition of invading strand, endowing the conservation of high concentration for undergoing rapid reaction with high-efficiency DNA amplification, which dramatically improves reaction time and superior target conversion. The experimental results indicate that proposed PEC biosensor had a high sensitivity to miRNA-122 with a detection limit of 0.49 fM, which provides a newly organic/inorganic photosensitive nanomaterials and efficient DNA strand displacement in bioanalytical and early clinical disease diagnosis. • Self-enhanced Tr(PhXOD) 3 -CMP/BiOBr with D-A-D structure, shortened the migration distance of photo generated electrons and enhanced the PEC response. • Cleverly combined the target with signal amplification strategy could effectively improve reaction time and superior target conversion rate. • The production of insoluble precipitates of 4-CD catalyzed by MnPP loaded nanonet used to construct signal-off photochemical biosensor. • This approach realized accurate and sensitive detection of miRNA, which provided a development and supplementation for tumor monitoring. [ABSTRACT FROM AUTHOR]

A massive particle orbiting around a regular black hole (e.g., a Bardeen one) provides a lot of information about the black hole, allowing one to investigate the problem of spacetime singularities and get an insight into quantum gravity. In the present work, the bound orbits of the particle around the Bardeen black hole have been established by using a taxonomy proposed by Levin and Perez-Giz. It clearly shows that, both in the innermost stable circular orbits (ISCO) and the marginally bound orbits (MBO), the particle's angular momentum and its radial distance decrease with k ≡ g 2 , where g is a parameter of the Bardeen model and characterizes the monopole charge of a self-gravitating magnetic field described by a nonlinear electrodynamics. In the strong gravitational field, by using the numerical method, a rational number defined by the taxonomy increases with the particle's energy, but the case of the angular momentum is opposite. The periodic motion in the Bardeen black hole has lower energy in comparison to the one in Schwarzschild black hole. It is expected that the Bardeen black hole could be identified by using the method of the taxonomy when more sophisticated observations for detecting black holes can be implemented in the future and it will give us an inspiring answer to the problems of spacetime singularities and quantum gravity. • Bound orbits around the Bardeen black hole are studied in detail. • The taxonomy in the Bardeen black hole are investigated for the first time. • The periodic motion in the Bardeen black hole has lower energy in comparison to the one in Schwarzschild black hole. • Future experiments in the strong gravitational field will impose chances for probing a regular black hole. [ABSTRACT FROM AUTHOR]

The rapid population growth in China has increased the demand for limited water, energy and food resources. Because the resource supply is constrained by future uncertainties such as climate change, it is necessary to examine the connections among water, energy and food resources from the perspective of the relevant final demands. Based on an input-output model and structural path analysis, this study aims to explore the hidden connections among water, energy and food resources by identifying important final demands and examine how these resources are embodied in upstream production and downstream consumption processes along the supply chain. The water-energy-food nexus approach in this research identifies where and how these resources intersect in economic sectors. By simultaneously considering the water, energy and food footprints, synergistic effects can be maximized among these resource systems. The results reveal that urban household consumption and fixed capital formation have large impacts on water-energy-food resources. Besides, agriculture, construction and service sectors have the largest water-energy-food footprints. For each resource, we rank the top-20 supply chain paths from the final demands to the upstream production sectors, and six critical supply chain paths are identified as important contributors to the consumption of all these resources. Compared with independent approach to manage water, energy and food resources, the nexus approach identifies the critical linkages of the water, energy and food systems and helps to formulate integrated policies to effectively manage these resources across sectors and actors. Synergistic strategies for conserving water, energy, and food resources can be achieved through avoiding unnecessary waste in end uses and improving resource use efficiency along critical supply chains. This research can help consumers, industries and the government make responsible consumption and production decisions to conserve water, energy and food resources. Unlabelled Image • The hidden connections among water, energy and food consumptions are examined. • Maximizing the synergy of the water-energy-food nexus management. • Urban household consumption and fixed capital formation have large resource impacts. • Agriculture, construction and service sectors have the largest resource footprints. • Six key supply chains that consume these resources simultaneously are recognized. [ABSTRACT FROM AUTHOR]