Parkinson’s disease (PD) is a severe neurodegenerative disorder characterized by prominent motor and non-motor (e.g., cognitive) abnormalities. Notwithstanding Food and Drug Administration (FDA)-approved treatments (e.g., L-dopa), most persons with PD do not adequately benefit from the FDA-approved treatments and treatment emergent adverse events are often reasons for discontinuation. To date, no current therapy for PD is disease modifying or curative. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are central nervous system (CNS) penetrant and have shown to be neuroprotective against oxidative stress, neuroinflammation, and insulin resistance, as well as promoting neuroplasticity. Preclinical evidence suggests that GLP-1RAs also attenuate the accumulation of α-synuclein. The cellular and molecular effects of GLP-1RAs provide a basis to hypothesize putative therapeutic benefit in individuals with PD. Extant preclinical and clinical trial evidence in PD provide preliminary evidence of clinically meaningful benefit in the cardinal features of PD. Herein, we synthesize extant preclinical and early-phase clinical evidence, suggesting that GLP-1RAs may be beneficial as a treatment and/or illness progression modification therapeutic in PD.

This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 μg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 μg/ml and ≤ 1 μg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.

Myanmar is located within an important geographic corridor of prehistoric demographic and technological exchange, yet relatively few archaeological sites have been securely dated. Here, the authors present a new radiocarbon chronology for Halin, a UNESCO-listed complex in the north-central Sagaing Division of Myanmar, which contributes to the generation of nuanced regional chronologies and to improving the temporal resolution of Southeast Asia more generally. Discussion of 94 radiocarbon determinates, together with site stratigraphy and pottery traditions, provides a chronological sequence from the early third millennium BC to the early second millennium AD. Corroboration of the beginning of this sequence would place Halin as the oldest currently dated Neolithic site in Mainland Southeast Asia and would provide support for the two-layer model of Neolithic migration.

Warm ice at temperatures close to the pressure melting point is often encountered in deep ice-core drilling. The heat generated by rotary cutting can melt ice chips, which seriously threatens the safety of drilling if the chips refreeze on the drill bit or barrel. Lowering the cutting heat is an effective method to reduce the melting of ice chips. In this study, a general theoretical model was established based on heat transfer theory and the cutting mechanism to calculate and analyze the cutter temperature during the circulation of the drilling fluid. The model was validated by a series of experiments, which demonstrated reasonable agreement between the calculated data and experimental results, with a maximum error of <16%. The factors that contribute to the rise in the cutter temperature during warm ice drilling were investigated. Results suggest that the drilling fluid has excellent cooling performance, and its type and flow rate have minimal impact on the cutter temperature. To mitigate the cutter temperature rise, maximizing the rake angle and thermal conductivity of the cutter, while minimizing the rotation speed of the drill bit, cutting depth, cutter width and friction coefficient between the ice and cutter is recommended.

In this paper, a super-twisting disturbance observer (STDO)-based adaptive reinforcement learning control scheme is proposed for the straight air compound missile system with aerodynamic uncertainties and unmodeled dynamics. Firstly, neural network (NN)-based adaptive reinforcement learning control scheme with actor-critic design is investigated to deal with the tracking problems for the straight gas compound system. The actor NN and the critic NN are utilised to cope with the unmodeled dynamics and approximate the cost function that are related to control input and tracking error, respectively. In other words, the actor NN is used to perform the tracking control behaviours, and the critic NN aims to evaluate the tracking performance and give feedback to actor NN. Moreover, with the aid of the STDO disturbance observer, the problem of the control signal fluctuation caused by the mismatched disturbance can be solved well. Based on the proposed adaptive law and the Lyapunov direct method, the eventually consistent boundedness of the straight gas compound system is proved. Finally, numerical simulations are carried out to demonstrate the feasibility and superiority of the proposed reinforcement learning-based STDO control algorithm.

Cancer remains the leading cause of death worldwide, and metastasis is still the major cause of treatment failure for cancer patients. Epithelial–mesenchymal transition (EMT) has been shown to play a critical role in the metastasis cascade of epithelium-derived carcinoma. Tumour microenvironment (TME) refers to the local tissue environment in which tumour cells produce and live, including not only tumour cells themselves, but also fibroblasts, immune and inflammatory cells, glial cells and other cells around them, as well as intercellular stroma, micro vessels and infiltrated biomolecules from the nearby areas, which has been proved to widely participate in the occurrence and progress of cancer. Emerging and accumulating studies indicate that, on one hand, mesenchymal cells in TME can establish ‘crosstalk’ with tumour cells to regulate their EMT programme; on the other, EMT-tumour cells can create a favourable environment for their own growth via educating stromal cells. Recently, our group has conducted a series of studies on the interaction between tumour-associated macrophages (TAMs) and colorectal cancer (CRC) cells in TME, confirming that the interaction between TAMs and CRC cells mediated by cytokines or exosomes can jointly promote the metastasis of CRC by regulating the EMT process of tumour cells and the M2-type polarisation process of TAMs. Herein, we present an overview to describe the current knowledge about EMT in cancer, summarise the important role of TME in EMT, and provide an update on the mechanisms of TME-induced EMT in CRC, aiming to provide new ideas for understanding and resisting tumour metastasis.

This paper asked participants to assess four selected expert-rated Taiwan International Student Design Competition (TISDC) products using four methods: Consensual Assessment Technique (CAT), Creative Product Semantic Scale (CPSS), Product Creativity Measurement Instrument (PCMI), and revised Creative Solution Diagnosis Scale (rCSDS). The results revealed that, between experts and non-experts, the ranking results by the CAT and CPSS were the same, while the ranking results of the rCSDS were different. The CAT, CPSS, and TISDC methods provided the same results indicating that raters may return the same results on creativity assessment, and the results are not affected by the selected methods.

If it is necessary to use non-experts to assess creativity and the creativity results are expected to be the same with that of experts, asking non-expert raters to use CPSS to assess creativity and then ranking the creativity score is more reliable. The study offers a contribution to the creativity domain on deciding which methods may be more reliable from a comparison perspective.

The prognostic factor for in-hospital mortality in tuberculosis (TB) patients requiring intensive care unit (ICU) care remains unclear. Therefore, a retrospective study was conducted aiming to estimate the in-hospital mortality rate and the risk factors for mortality in a high-burden setting. All patients with culture-confirmed TB that were admitted to the ICU of the hospital between March 2012 and April 2019 were identified retrospectively. Data, such as demographic characteristics, comorbidities, laboratory measures and mortality, were obtained from medical records. The Cox proportional hazards regression model was used to identify prognostic factors that influence in-hospital mortality. A total of 82 ICU patients with confirmed TB were included in the analysis, and 22 deaths were observed during the hospital stay, 21 patients died in the ICU. In the multivariable model adjusted for sex and age, the levels of serum albumin and white blood cell (WBC) count were significantly associated with mortality in TB patients requiring ICU care (all P < 0.01), the hazard ratios were 0.8 (95% confidence interval (CI): 0.7–0.9) per 1 g/l and 1.1 (95% CI: 1.0–1.2) per 1 × 109/l, respectively. In conclusion, in-hospital mortality remains high in TB patients requiring ICU care. Low serum albumin level and high WBC count significantly impact the risk of mortality in these TB patients in China.

Recent evidence suggests that synchronizing eating-fasting schedules with body's circadian rhythms or day-night cycles is important for metabolic health. Besides food quantity and quality, food timing may contribute to weight regulation. However, it is unclear if this factor during pregnancy can influence maternal weight retention after childbirth. Using data from a prospective cohort, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, we examined the associations of maternal circadian eating pattern and diet quality in pregnancy with substantial postpartum weight retention (PPWR) at 18 months. We assessed 687 pregnant women for their circadian eating pattern (night-eating, night-fasting and eating episodes) and diet quality (Healthy Eating Index) based on information derived from 24-h dietary recall at 26–28 weeks’ gestation. Night-eating was defined as > 50% of total energy intake during 1900–0659 h; night-fasting duration was determined based on the longest fasting interval between consumption of a calorie-containing food or beverage during 1900–0659 h; eating episodes were defined as events that provided ≥ 210 kJ with time intervals between eating episodes of ≥ 15 min; diet quality was ascertained using the Healthy Eating Index which measures adherence to the Singapore dietary guidelines for pregnant women. PPWR was calculated by subtracting the weight at the first antenatal clinic visit from weight at 18-month postpartum. Substantial PPWR was defined as weight retention of 5 kg or more. Adjusting for maternal age, ethnicity, education, parity, night shift, mood, body mass index and total energy intake, multivariable binary logistic regression analysis was performed to estimate odds ratio (OR) of substantial PPWR in relation to circadian eating pattern and diet quality. Of 687 women, 110 (16%) had substantial PPWR. After confounders adjustment, night-eating (OR 1.95; 95% confidence interval 1.05, 3.62) and lower diet quality (1.91; 1.17, 3.10) were independently associated with higher odds of substantial PPWR. No associations with substantial PPWR were observed for night-fasting duration and number of eating episodes. During pregnancy, women with higher caloric consumption at night and lower diet quality had a greater likelihood of substantial PPWR. These findings suggest that aligning eating time with day-night cycles and adherence to dietary guidelines during pregnancy may help to alleviate overweight and obesity risk in postpartum life. There is a possibility that these eating patterns persist beyond pregnancy and pose implications for long-term obesity development. Further investigation on this area is required.

Ventricular septal defect is the most common type of CHD, and transcatheter ventricular septal defect closure has been shown to be an alternative to surgical closure with acceptable mortality and morbidity as well as encouraging results. Short-term and mid-term follow-ups have indicated the safety and efficacy of transcatheter closure, but long-term follow-up results were rare. In this report, we first found that aortic regurgitation occurred in patients 9–12 years following transcatheter closure and regurgitation were gradually increased. The findings indicate that the long-term outcome of transcatheter closure of ventricular septal defect may not be as satisfied as expected.

Maternal dietary patterns and macronutrients intake have been shown to affect the development of gestational diabetes mellitus (GDM), but the findings are inconsistent. We aimed to identify maternal dietary patterns and examine their associations with GDM risk, and to evaluate the contributions of macronutrients intake to these associations. We included 2755 Chinese pregnant women from the Tongji Maternal and Child Health Cohort. Dietary intakes were assessed using a validated semi-quantitative FFQ 2 weeks before the diagnosis of GDM. GDM (n 248) was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24–28 weeks gestation. We derived five different dietary patterns from a principal component analysis. The results showed that high fish–meat–eggs scores, which were positively related to protein intake and inversely related to carbohydrate intake, were associated with a higher risk of GDM (adjusted OR for quartile 4 v. quartile 1: 1·83; 95 % CI 1·21, 2·79; Ptrend=0·007) and higher plasma glucose levels. In contrast, high rice–wheat–fruits scores, which were positively related to carbohydrate intake and inversely related to protein intake, were associated with lower risk of GDM (adjusted OR for quartile 3 v. quartile 1: 0·54; 95 % CI 0·36, 0·83; Ptrend=0·010) and lower plasma glucose levels. In addition, dietary protein and carbohydrate intake significantly contributed to the associations between dietary patterns and GDM risk or glucose levels. These findings suggest that a dietary pattern characterised by high protein and low carbohydrate intake in pregnancy was associated with a higher risk of GDM, which may provide important clues for dietary guidance during pregnancy to prevent GDM.

Pulmonary artery sling is a congenital cardiovascular disease and is usually accompanied by tracheobronchial stenosis. Generally, infants diagnosed with pulmonary artery sling should have surgery. However, the treatment of tracheobronchial stenosis is still controversial. Our team developed a customised, degradable, three-dimensional printed splint and successfully applied it in the treatment of pulmonary artery sling associated with severe bilateral bronchus stenosis. We suggested that three-dimensional printing may be a novel and effective way to treat tracheobronchial stenosis and other diseases in children.

Water-based polyurethane/alumina hollow microsphere (WPU-hAl2O3) composite films were prepared via a facile spin coating method. The pristine WPU, as the matrix of the composite films, was tailor-made by hAl2O3 with the diameter of 2–5 μm to improve the mechanical and physical properties of the films. The hardness, surface morphology, infrared emissivity, wettability, and light transmittance of the WPU-hAl2O3 films with different hAl2O3 contents were investigated. The results indicate that the Vickers hardness, coefficient of friction, infrared emissivity at the wavelength of 2–22 μm, and wetting angle of the WPU-hAl2O3 films (30 wt%) increased by 53.6%, 51.7%, 21.1%, and 19.0%, respectively, compared with the pristine WPU films. Meanwhile, with the rising of hAl2O3 content, the light transmittance decreased by 75.3% at the wavelength of 400–800 nm. This work not only designs a kind of lightweight multifunctional composite film but also provides an effective route for extending further applications of hAl2O3 in the field of composite films.

Recent results in the development of diode-driven high energy, high repetition rate, picosecond lasers, including the demonstration of a cryogenic Yb:YAG active mirror amplifier that produces 1.5 J pulses at 500 Hz repetition rate (0.75 kW average power) are reviewed. These pulses are compressed resulting in the generation of ${\sim}5~\text{ps}$ duration, 1 J pulses with 0.5 kW average power. A full characterization of this high power cryogenic amplifier, including at-wavelength interferometry of the active region under ${>}1~\text{kW}$ average power pump conditions, is presented. An initial demonstration of operation at 1 kW average power (1 J, 1 kHz) is reported.

Pedogenic alteration of illite from red earth sediments in Jiujiang in subtropical China was investigated using X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). Illite, hydroxy-interlayered vermiculite (HIV), kaolinite and mixed-layer illite-HIV (I-HIV) are present in the soils. The characteristic reflections of the clay phases were 14 Å, 10–14 Å, 10 Å, and 7 Å, respectively. After Mg-glycerol saturations, the 14 Å peak of the samples did not expand, and after heating at 350°C and 550°C it shifted to 13.8 Å and 12 Å respectively, with no residual 14 Å reflection, suggesting the occurrence of hydroxy-interlayered vermiculite. The randomly interstratified I-HIV clays were characterized by a broad peak at 10–14 Å, which did not change its position after Mg-glycerol saturation, but collapsed to 10 Å after heating at 350°C and 550°C. HRTEM analysis showed different lattice fringes of 12 Å, 10 Å and 7 Å . Mixed-layer I-HIV, HIV-K and illite-kaolinite (I-K) were observed in the HRTEM images which represented the intermediate phases during illite alteration. The merging of two 10 Å illite layers into a 12 Å HIV layer, lateral transformation of one HIV layer into one kaolinite layer and alteration of one illite layer into two kaolinite layers illustrated the mechanisms of illite-to-HIV, HIV-to-kaolinite and illite-tokaolinite transformation, respectively. The proposed pedogenic alteration of illite and the weathering sequence of the clay minerals in Jiujiang is illite → I-HIV → HIV → HIV-K → kaolinite. In addition, illite may transform directly to kaolinite.

The radiodontans, including anomalocaridids and their allies, are enigmatic stem-group euarthropods and are the most ancient apex giant predators known from the fossil record. Most studies on their feeding behaviors have emphasized their diverse and abundant raptorial frontal appendages, while the oral cone surrounding the mouth opening in these animals has attracted less attention. At present, three oral cone morphotypes are known, from Anomalocaris Whiteaves, 1892, Peytoia Walcott, 1911, and Hurdia Walcott, 1912, respectively. In this paper, we report on a novel form of radiodontan oral cone from the Guanshan Lagerstätte (Cambrian Series 2, Stage 4) in the Wulongqing Formation, eastern Yunnan, South China. This oral cone is unique in combining features seen in Peytoia/Hurdia and Anomalocaris. It possesses a Peytoia/Hurdia-type ‘tetraradial’ configuration comprising a 32-plate outer ring that consists of four perpendicularly arranged large plates and 28 small plates, in addition to furrowed folds and scale-like nodes on plate surfaces otherwise seen only in Anomalocaris. As an intermediate morphotype, the Guanshan oral cone improves our understanding of the occurrence and morphological disparity of radiodontan oral cones, illuminates future investigations on potentially variable radiodontan feeding mechanisms, and reveals possible evolutionary transformations of these peculiar feeding structures. The resolution of current radiodontan phylogeny would be potentially improved by new knowledge on other body parts apart from frontal appendages in future studies.