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Although immune checkpoint inhibitors (ICIs) have produced remarkable responses in non-small cell lung cancer (NSCLC) patients, receivers still have a relatively low response rate. Initial response assessment by conventional imaging and evaluation criteria is often unable to identify whether patients can achieve durable clinical benefit from ICIs. Overall, there are sparse effective biomarkers identified to screen NSCLC patients responding to this therapy. A lot of studies have reported that patients with specific gene mutations may benefit from or resist to immunotherapy. However, the single gene mutation may be not effective enough to predict the benefit from immunotherapy for patients. With the advancement in sequencing technology, further studies indicate that many mutations often co-occur and suggest a drastic transformation of tumour microenvironment phenotype. Moreover, co-mutation events have been reported to synergise to activate or suppress signalling pathways of anti-tumour immune response, which also indicates a potential target for combining intervention. Thus, the different mutation profile (especially co-mutation) of patients may be an important concern for predicting or promoting the efficacy of ICIs. However, there is a lack of comprehensive knowledge of this field until now. Therefore, in this study, we reviewed and elaborated the value of cancer mutation profile in predicting the efficacy of immunotherapy and analysed the underlying mechanisms, to provide an alternative way for screening dominant groups, and thereby, optimising individualised therapy for NSCLC patients.
This study deploys RTK-GNSS in 2012, TLS in 2015 and UAV in 2018 to monitor the changes of Urumqi Glacier No. 1 (UG1), eastern Tien Shan, and analyzes the feasibility of three technologies in monitoring the mountain glaciers. DEM differencing shows that UG1 has experienced a pronounced thinning and mass loss for the period of 2012–18. The glacier surface elevation change of −0.83 ± 0.57 m w.e. a−1 has been recorded for 2012–15, whereas the changes of glacier tongue surface elevation in 2015–18 and 2012–18 were −2.03 ± 0.95 and −1.34 ± 0.88 m w.e. a−1, respectively. The glacier area shrunk by 0.07 ± 0.07 × 10−3 km2 and the terminus retreat rate was 6.28 ± 0.83 m a−1 during 2012–18. The good agreement between the glaciological and geodetic specific mass-balances is promising, showing the combination of the three technologies is suitable to monitor glacier mass change. We recommend application of the three technologies to assess each other in different locations of the glacier, e.g. RTK-GNSS base stations, ground control points, glacier tongue and terminus, in order to avoid the inherent limitations of each technology and to provide reliable data for the future studies of mountain glacier changes in western China.
The study aimed to investigate behavioural intentions to receive free and self-paid COVID-19 vaccinations (BICV-F and BICV-SP) among Chinese university students if the vaccine was 80% effective with rare mild side effects, to examine their associations with social media exposures and peer discussions regarding COVID-19 vaccination, and to explore the mediational role of perceived information sufficiency about COVID-19 vaccination. An online anonymous survey (N = 6922) was conducted in November 2020 in five Chinese provinces. Logistic regression and path analysis were adopted. The prevalence of BICV-F and BICV-SP were 78.1% and 57.7%. BICV-F was positively associated with the frequencies of passive social media exposure (adjusted odds ratio (AOR) = 1.32, P < 0.001), active social media interaction (AOR = 1.13, P < 0.001) and peer discussions (AOR = 1.17, P < 0.001). Indirect effects of the three factors on BICV-F via perceived information sufficiency were all significant (P < 0.001). The direct effect of active social media interaction on BICV-F was significantly negative (P < 0.001). Similar associations/mediations were observed for BICV-SP. The COVID-19 vaccination intention of Chinese university students needs improvement. Boosting social media exposures and peer discussions may raise students' perceived information sufficiency and subsequently increase their vaccination intention. Considering the potential negative effect of active social media interaction, caution is needed when using social media to promote COVID-19 vaccination.
The high overall plant-based diet index (PDI) is considered to protect against type 2 diabetes in the general population. However, whether the PDI affects gestational diabetes mellitus (GDM) risk among pregnant women is still unclear. We evaluated the association between PDI and GDM risk based on a Chinese large prospective cohort – the Tongji Maternal and Child Health Cohort. Dietary data were collected at 13–28 weeks of pregnancy by a validated semi-quantitative FFQ. The PDI was obtained by assigning plant food groups positive scores while assigning animal food groups reverse scores. GDM was diagnosed by a 75 g 2-h oral glucose tolerance test at 24–28 weeks of gestation. Logistic regression models were fitted to estimate OR of GDM, with associated 95 % CI, comparing women in different PDI quartiles. Among the total 2099 participants, 169 (8·1 %) were diagnosed with GDM. The PDI ranged from 21·0 to 52·0 with a median of 36·0 (interquartile range (IQR) 33·0–39·0). After adjusting for social-demographic characteristics and lifestyle factors etc., the participants with the highest quartile of PDI were associated with 57 % reduced odds of GDM compared with women in the lowest quartile of PDI (adjusted OR 0·43; 95 % CI 0·24, 0·77; Pfor trend = 0·005). An IQR increment in PDI was associated with 29 % decreased odds of GDM (adjusted OR 0·71; 95 % CI 0·56, 0·90). Findings suggest that adopting a plant-based diet during pregnancy could reduce GDM risk among Chinese women, which may be valuable for dietary counselling during pregnancy.
We consider the fractional elliptic problem:
where B1 is the unit ball in ℝN, N ⩾ 3, s ∈ (0, 1) and p > (N + 2s)/(N − 2s). We prove that this problem has infinitely many solutions with slow decay O(|x|−2s/(p−1)) at infinity. In addition, for each s ∈ (0, 1) there exists Ps > (N + 2s)/(N − 2s), for any (N + 2s)/(N − 2s) < p < Ps, the above problem has a solution with fast decay O(|x|2s−N). This result is the extension of the work by Dávila, del Pino, Musso and Wei (2008, Calc. Var. Partial Differ. Equ. 32, no. 4, 453–480) to the fractional case.
The aim of this study was to investigate the association between daily Se intake and postpartum weight retention (PPWR) among Chinese lactating women, and the impact of their Se nutritional status on infants’ physical development. Se contents in breast milk and plasma collected from 264 lactating Chinese women at the 42nd day postpartum were analysed with inductively coupled plasma MS. Daily Se intake was calculated based on plasma Se concentration. The dietary data of 24-h records on three consecutive days were collected. Infant growth status was evaluated with WHO standards by Z-scores. Linear regression analyses and multinomial logistic regression were conducted to examine the impact of Se disequilibrium (including other factors) on PPWR and growth of infants, respectively. The results indicated that: (1) the daily Se intake of the subjects was negatively associated with their PPWR (B = −0·002, 95 % CI − 0·003, 0·000, P = 0·039); (2) both insufficient Se daily intake (B = −0·001, OR 0·999, 95 % CI 0·998, 1·000, P = 0·014) and low level of Se in milk (B = −0·025, OR 0·975, 95 % CI 0·951, 0·999, P = 0·021) had potential associations with their infants’ wasting, and low level of Se in milk (B = −0·159, OR 0·853, 95 % CI 0·743, 0·980, P = 0·024) had a significant association with their infants’ overweight. In conclusion, the insufficient Se nutritional status of lactating Chinese women was first found as one possible influencing factor of their PPWR as well as low physical development of their offspring.
The epidemic of coronavirus disease 2019 (COVID-19) began in China and had spread rapidly to many other countries. This study aimed to identify risk factors associated with delayed negative conversion of SARS-CoV-2 in COVID-19 patients. In this retrospective single-centre study, we included 169 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 15th January to 2nd March. The cases were divided into two groups according to the median time of SARS-CoV-2 negative conversion. The differences between groups were compared. In total, 169 patients had a median virus negative conversion time of 18 days (interquartile range: 11–25) from symptom onset. Compared with the patients with short-term negative conversion, those with long-term conversion had an older age, higher incidence of comorbidities, chief complaints of cough and chest distress/breath shortness and severer illness on admission, higher level of leucocytes, neutrophils, aspartate aminotransferase, creatine kinase and erythrocyte sedimentation rate (ESR), lower level of CD3+CD4+ lymphocytes and albumin and more likely to receive mechanical ventilation. In multivariate analysis, cough, leucocytes, neutrophils and ESR were positively correlated with delayed virus negative conversion, and CD3+CD4+ lymphocytes were negatively correlated. The integrated indicator of leucocytes, neutrophils and CD3+CD4+ lymphocytes showed a good performance in predicting the negative conversion within 2 weeks (area under ROC curve (AUC) = 0.815), 3 weeks (AUC = 0.804), 4 weeks (AUC = 0.812) and 5 weeks (AUC = 0.786). In conclusion, longer quarantine periods might be more justified for COVID-19 patients with cough, higher levels of leucocytes, neutrophils and ESR and lower levels of CD3+CD4+ lymphocytes.
During the detection of industrial hazardous gases, like formaldehyde (HCHO), the selectivity is still a challenging issue. Herein, an alternative HCHO chemosensor that based on the tin oxide nanoparticles is proposed, which was obtained through a facile hydrothermal method. Gas sensing performances showed that the optimal working temperature located at only 180 °C, the response value of 79 via 50 ppm HCHO was much higher than that of 35 at 230 °C. However, the compromised test temperature was selected as 230 °C, taking into account the faster response/recovery speeds than 180 °C, named 20/23versus 53/60 s, respectively. The response (35) of the SnO2 nanoparticles-based sensor to 50 ppm of HCHO is about 400% higher than that of bulk SnO2 sensor (9), especially when the gas concentration is 1 ppm, SnO2 nanoparticles also has a higher sensitivity which may possibly result from more exposed active sites and small size effect for nanoparticles than for bulk ones. The gas sensor based on SnO2 nanoparticles can be utilized as a promising candidate for practical low-temperature detectors of HCHO due to its higher gas response, excellent response–recovery properties, and perfect selectivity.
The purpose of this study was to construct a glycyrrhetinic acid (GA)-mediated, breakable, intracellular, nanoscale drug-delivery carrier via amide and esterification reactions. The structures were identified by Fourier-transformed infrared (FTIR) and 1H-nuclear magnetic resonance (1H-NMR) spectrophotometry. The compatibility and safety of the carrier were evaluated using hemolysis and cytotoxicity tests. The GA-copolymer micelle was prepared using the solvent evaporation method. FTIR and 1H-NMR detection demonstrated the successful construction of the polymer. No hemolysis occurred in any concentration of polymer within 3 h, and the hemolysis rate was less than 5%. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) experimental results showed that the novel polymer reduced the cell survival rate and had significant cytotoxic effects. The blank nanoparticles were liquid with light blue opalescence. Transmission electron microscopy revealed that the empty micelles were uniform spheres, with an average size of 62 nm and a zeta potential of −13 mV. The novel GA-mediated polymeric carrier material developed here has the potential to effectively kill human SMMC-7721 cancer cells within 3 days when the dose is above 500 ug/mL.
Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program.
In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC.
The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal.
The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention.
To investigate the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of small for gestational age (SGA) and to examine the joint effect of folic acid supplementation and dietary folate intake on the risk of SGA.
Participants were interviewed by trained study interviewers using a standardized and structured questionnaire. Information on birth outcomes and maternal complications was abstracted from medical records and dietary information was collected via a semi-quantitative FFQ before conception and during pregnancy.
A birth cohort data analysis using the 2010–2012 Gansu Provincial Maternity and Child Care Hospital.
Women (n 8758) and their children enrolled in the study.
Folic acid supplementation was associated with a reduced risk of SGA (OR = 0·72, 95 % CI 0·60, 0·86), with the reduced risk seen mainly for SGA at ≥37 weeks of gestational age (OR = 0·70, 95 % CI 0·58, 0·85) and nulliparous SGA (OR = 0·67, 95 % CI 0·54, 0·84). There was no significant association between dietary folate intake and SGA risk.
Our study suggested that folic acid supplementation was associated with a reduced risk of SGA and the risk varied by preterm status and parity.
The present study explored the mechanism of Zn-methionine (Zn-Met) influencing eggshell quality of laying hens and investigated whether the mechanism was related to Ca deposition. Hyline grey layers (n 384, 38 weeks old) were divided into four groups: 0 mg Zn/kg, 40, 80 mg Zn/kg as Zn-Met, and 80 mg Zn/kg as zinc sulphate (ZnSO4). Eggshell quality, Zn contents, Zn-containing enzyme activities and expressions of shell matrix proteins in eggshell gland (ESG) were analysed. Zn-Met treatment at 80 mg/kg increased (P < 0·05) egg weight and eggshell strength throughout the experiments. The 80 mg/kg Zn-Met group (P < 0·05) had decreased mammillary knob width and larger relative atomic weight percentage of Ca, stronger signal intensity of Ca in linear distribution and the Ca was more evenly distributed in the transversal surface of eggshell. Zn contents (P < 0·001) in yolk and serum, Ca, albumin (Alb) levels in ESG as well as carbonic anhydrase (CA) activity in serum (P < 0·05) and mRNA levels of CA and Ca-binding protein-d28k (CaBP-D28k) (P < 0·001) in the 80 mg/kg Zn-Met group were the highest among all treatments. In conclusion, shell strength as one of eggshell qualities was mostly related to mammillary cone width in ultrastructure caused by the pattern of Ca deposition in eggshell formation. Also, the increase in Zn-Met-induced Ca deposition may be due to the increased Zn contents in serum and tissues, which were attributable to the increased CA concentrations in serum, Ca, Alb levels and up-regulated CA and CaBP-D28k mRNA levels in ESG.
Spray-painting equipments are important for the automatic spraying of long conical objects such as rocket fairing. This paper proposes a spray-painting equipment that consists of a feed worktable, a gantry frame and two serial–parallel mechanisms and investigates the optimal design of PRR–PRR parallel manipulator in serial–parallel mechanisms. Based on the kinematic model of the parallel manipulator, the conditioning performance, workspace and accuracy performance indices are defined. The dynamic model is derived using virtual work principle and dynamic evaluation index is defined. The conditioning performance, workspace, accuracy performance and dynamic performance are involved in multi-objective optimization design to determine the optimal geometrical parameters of the parallel manipulator. Furthermore, the geometrical parameters of the gantry frame are optimized. An example is given to show how to determine these parameters by taking a long object with conical surface as painted object.
Recently, we introduced an epoxy group to mebendazole by a reaction with epichlorohydrin and obtained two isoforms, mebendazole C1 (M-C1) and mebendazole C2 (M-C2). The in vitro effects of mebendazole derivatives at different concentrations on Echinococcus multilocularis protoscoleces and metacestodes as well as cytotoxicity in rat hepatoma (RH) cells were examined. The results demonstrated that the solubility of the two derivatives was greatly improved compared to mebendazole. The mortality of protoscoleces in vitro reached to 70–80% after 7 days of exposure to mebendazole or M-C2, and M-C2 showed higher parasiticidal effects than mebendazole (P > 0.05). The parasiticidal effect of M-C1 was low, even at a concentration of 30 µm. The percentage of damaged metacestodes that were treated with mebendazole and M-C2 in vitro at different concentrations were similar, and M-C1 exhibited insignificant effects on metacestodes. Significant morphological changes on protoscoleces and metacestodes were observed after treatment with mebendazole and M-C2. In addition, the introduction of an epoxy group to mebendazole also reduced its cytotoxicity in RH cells. Our results demonstrate that the introduction of an epoxy group not only improved the solubility of mebendazole, but also increased its parasiticidal effects on E. multilocularis and reduced its cytotoxicity in RH cells.
This paper reports on an atomic-scale investigation into the β′ precipitates and the long-period stacking ordered phase (LPSO) in Mg–5Y–2.5Ni–0.5Zr (at.%) alloy, using Cs-corrected high angle annular dark field-scanning transmission electron microscopy (HAADF-STEM). The results displayed that the 18R-type and 14H-type LPSO phases coexisted in the as-cast and the solid solution states, and the 18R-type and 14H-type LPSO structures were thermal stable. After aging treatment, the aging peak hardness reached 138 HV at 225 °C for 48 h. The significant increase in hardness was attributed to the formation of the metastable β′ phase. The lattice parameters of a and b axes for β′ phases are a = 0.65 nm, b = 2.20 nm, and c = 0.52 nm by HAADF-STEM. The interaction between the LPSO phase and the β′ can be found. The atomic-scale interactions between the LPSO and β′ phases are divided into two parts: under-aging and peak-aging conditions between the building blocks.
This article reports on the growth kinetics of cerium oxide (CeO2) nanoparticles prepared via a sintering method. By varying the sintering temperatures and periods of time, particle size of CeO2 nanoparticles was tuned from 11 to 100 nm. Ostwald ripening mechanism prevails in the growth process, and the growth kinetics is determined to follow an equation, D5 = 16.25 + 3.6 × 1020 exp(−344.20/RT) in the temperature range of 700 to 1000°C. After dispersing Pt on CeO2 nanoparticles, the size effect for the catalytic performance of the CO oxidation reaction was researched. When temperature and period of time are set at 700 °C and 2 h, respectively, dispersion of Pt onto CeO2 nanoparticles led to the largest quantity of chemisorbed oxygen species on the surface and the best catalytic performance. The findings reported here would provide a feasible path for the preparation of advanced catalysts in the future and moreover to discover novel size-dependent supports for many catalytic applications.
The novel visible-light-responsive direct solid-state Z-scheme g-C3N4/BiOI heterojunction has been synthesized successfully by means of a solid phase calcination method and used for the degradation of microcystin-LR (MC-LR). The layered g-C3N4 disperses on the surface of BiOI microspheres. The samples are characterized by FESEM, HRTEM, XRD, FT-IR, UV-vis spectroscopy, XPS, BET, PL, and Mott–Sckottky. The photocatalytic activity and photodegradation mechanism of the as-prepared g-C3N4/BiOI microsphere photocatalysts are conducted under visible light irradiation using MC-LR as the target pollutant. The g-C3N4/BiOI material exhibits superior photocatalytic performance when compared with pure BiOI, the possible reason is the efficient separation of photogenerated carriers at the interface between g-C3N4 and BiOI. The heterostructure is responsible for the improved separation efficiency of photogenerated electron–hole pairs and thus the higher photocatalytic activity. The possible photocatalytic mechanism is proposed based on relative band positions of these two semiconductors.
Methods for efficient variance-based global sensitivity analysis of complex high-dimensional problems are presented and compared. Variance decomposition methods rank inputs according to Sobol indices that can be computationally expensive to evaluate. Main and interaction effect Sobol indices can be computed analytically in the Kennedy and O'Hagan framework with Gaussian processes. These methods use the high-dimensional model representation concept for variance decomposition that presents a unique model representation when inputs are uncorrelated. However, when the inputs are correlated, multiple model representations may be possible leading to ambiguous sensitivity ranking with Sobol indices. In this work, we present the effect of input correlation on sensitivity analysis and discuss the methods presented by Li and Rabitz in the context of Kennedy and O'Hagan's framework with Gaussian processes. Results are demonstrated on simulated and real problems for correlated and uncorrelated inputs and demonstrate the utility of variance decomposition methods for sensitivity analysis.