Explore the vast range of titles available.

Manure is a primary source of methane (CH4) emissions into the atmosphere. A large proportion of CH4 from manure is emitted during storage, but this varies with storage methods. In this research, we tested whether covering a manure heap with plastic reduces CH4 emission during a short-term composting process. A static chamber method was used to detect the CH4 emission rate and the change of the physicochemical properties of cattle manure which was stored either uncovered (treatment UNCOVERED) or covered with plastic (treatment COVERED) for 30-day periods during the four seasons? The dry matter content of the COVERED treatment was significantly less than the UNCOVERED treatment (P < 0.01), and the C/N ratio of the COVERED treatment significantly greater than the UNCOVERED treatment (P > 0.05) under high temperature. In the UNCOVERED treatment, average daily methane (CH4) emissions were in the order summer > spring > autumn > winter. CH4 emissions were positively correlated with the temperature (R2 = 0.52, P < 0.01). Compared to the UNCOVERED treatment, the daily average CH4 emission rates from COVERED treatment manure were less in the first 19 days of spring, 13 days of summer, 10 days of autumn and 30 days of winter. In summary, covering the manure pile with plastic reduces the evaporation of water during storage; and in winter, long-term covering with plastic film reduces the CH4 emissions during the storage of manure.

Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo . Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.

This phase 3 multicenter, randomized, double-blind, placebo-controlled 2-year trial compared the efficacy and safety of intravenous belimumab with those of placebo, plus standard therapy, in patients with active lupus nephritis. More patients who received belimumab had a primary efficacy renal response than those who received placebo.

A direct measurement of cosmic-ray electrons and positrons with unprecedentedly high energy resolution reveals a spectral break at about 0.9 teraelectronvolts, confirming the evidence found by previous indirect measurements. A break in the cosmic-ray spectrum The spectrum of cosmic-ray electrons and positrons that arrive at Earth potentially contains information about the sources that accelerated them, and may reveal dark-matter annihilation. The spectrum has previously been measured directly up to around 2 teraelectronvolts (TeV), and indirectly up to around 5 TeV from ground-based Cherenkov arrays, which revealed a possible break in the spectrum. The Dark Matter Particle Explorer (DAMPE) Collaboration reports a direct measurement between 25 gigaelectronvolts and 4.6 TeV, which clearly reveals a spectral break at around 0.9 TeV. High-energy cosmic-ray electrons and positrons (CREs), which lose energy quickly during their propagation, provide a probe of Galactic high-energy processes 1 , 2 , 3 , 4 , 5 , 6 , 7 and may enable the observation of phenomena such as dark-matter particle annihilation or decay 8 , 9 , 10 . The CRE spectrum has been measured directly up to approximately 2 teraelectronvolts in previous balloon- or space-borne experiments 11 , 12 , 13 , 14 , 15 , 16 , and indirectly up to approximately 5 teraelectronvolts using ground-based Cherenkov γ-ray telescope arrays 17 , 18 . Evidence for a spectral break in the teraelectronvolt energy range has been provided by indirect measurements 17 , 18 , although the results were qualified by sizeable systematic uncertainties. Here we report a direct measurement of CREs in the energy range 25 gigaelectronvolts to 4.6 teraelectronvolts by the Dark Matter Particle Explorer (DAMPE) 19 with unprecedentedly high energy resolution and low background. The largest part of the spectrum can be well fitted by a ‘smoothly broken power-law’ model rather than a single power-law model. The direct detection of a spectral break at about 0.9 teraelectronvolts confirms the evidence found by previous indirect measurements 17 , 18 , clarifies the behaviour of the CRE spectrum at energies above 1 teraelectronvolt and sheds light on the physical origin of the sub-teraelectronvolt CREs.

An intervention study on the FCR (Fasting and Calorie Restriction) dietary regime was carried out to determine its efficacy in improving mood states and depression status among ageing men. A total of 32 healthy males (Mean±SD), aged 59.7±6.3 years, with a BMI of 26.7±2.2 kg/m2 were recruited to the study. Participants were randomized to either the FCR group (and were instructed to follow a calorie restricted dietary regime with intermittent fasting) or to the control group (in which individuals were asked to maintain their current lifestyle), for a 3 month period. Mood was assessed using the Profile of Mood States and depression was assessed using Beck Depression Inventory-II and Geriatric Depression Scale-15 at baseline, week 6 and week 12 of the intervention. A total of 31 subjects completed the study (n=16, FCR and n=15, control). Significant decreases in tension, anger, confusion and total mood disturbance and improvements in vigor were observed in participants in the FCR group compared to the control group (p<0.05). No significant changes in mean depression scores were observed. Weight, BMI and percent body fat were reduced by 3.8%, 3.7% and 5.7% respectively in the FCR group. Our findings show that a FCR dietary regime is effective in improving mood states and nutritional status among ageing men.

Planetary rings are observed not only around giant planets 1 , but also around small bodies such as the Centaur Chariklo 2 and the dwarf planet Haumea 3 . Up to now, all known dense rings were located close enough to their parent bodies, being inside the Roche limit, where tidal forces prevent material with reasonable densities from aggregating into a satellite. Here we report observations of an inhomogeneous ring around the trans-Neptunian body (50000) Quaoar. This trans-Neptunian object has an estimated radius 4 of 555 km and possesses a roughly 80-km satellite 5 (Weywot) that orbits at 24 Quaoar radii 6 , 7 . The detected ring orbits at 7.4 radii from the central body, which is well outside Quaoar’s classical Roche limit, thus indicating that this limit does not always determine where ring material can survive. Our local collisional simulations show that elastic collisions, based on laboratory experiments 8 , can maintain a ring far away from the body. Moreover, Quaoar’s ring orbits close to the 1/3 spin–orbit resonance 9 with Quaoar, a property shared by Chariklo’s 2 , 10 , 11 and Haumea’s 3 rings, suggesting that this resonance plays a key role in ring confinement for small bodies. The authors report observations of a dense and inhomogeneous ring at a surprisingly large distance from the trans-Neptunian body Quaoar.

Abstract To investigate effects of agomelatine and mirtazapine on sleep disturbances in patients with major depressive disorder. A total of 30 depressed patients with sleep disturbances, 27 of which completed the study, took agomelatine or mirtazapine for 8 weeks. Subjective scales were administered, and polysomnography was performed at baseline and at the end of week 1 and 8. Functional magnetic resonance imaging was performed at baseline and at the end of week 8. Compared with baseline, scores on the Hamilton Depression Scale, Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Sleep Dysfunction Rating Scale, and Insomnia Severity Index after 8 weeks of treatment significantly decreased in both groups, with no significant differences between groups, accompanied by significant increases in total sleep time, sleep efficiency, and rapid eye movement (REM) sleep and significant decrease in wake after sleep onset. Mirtazapine treatment increased N3 sleep at week 1 compared with agomelatine treatment, but this difference disappeared at week 8. The increases in the percentage and duration of N3 sleep were positively correlated with increases in connectivity between right dorsal lateral prefrontal cortex (dlPFC) and right precuneus and between left posterior cingulate cortex and right precuneus in both groups, respectively. Functional connectivity (FC) between right dlPFC and left precuneus in mirtazapine group was higher compared with agomelatine group after 8 weeks of treatment. These findings indicated that both agomelatine and mirtazapine improved sleep in depressed patients, and the effect of mirtazapine was greater than agomelatine with regard to rapidly increasing N3 sleep and gradually improving FC in the brain.

Arm movement kinematics may provide a more sensitive way to assess neurorehabilitation outcomes than existing metrics. However, measuring arm kinematics in people with stroke can be challenging for traditional optical tracking systems due to non-ideal environments, expense, and difficulty performing required calibration. Here, we present two open-source methods, one using inertial measurement units (IMUs) and another using virtual reality (Vive) sensors, for accurate measurements of wrist position with respect to the shoulder during reaching movements in people with stroke. We assessed the accuracy of each method during a 3D reaching task. We also demonstrated each method’s ability to track two metrics derived from kinematics-sweep area and smoothness-in people with chronic stroke. We computed correlation coefficients between the kinematics estimated by each method when appropriate. Compared to a traditional optical tracking system, both methods accurately tracked the wrist during reaching, with mean signed errors of 0.09 ± 1.81 cm and 0.48 ± 1.58 cm for the IMUs and Vive, respectively. Furthermore, both methods’ estimated kinematics were highly correlated with each other (p < 0.01). By using relatively inexpensive wearable sensors, these methods may be useful for developing kinematic metrics to evaluate stroke rehabilitation outcomes in both laboratory and clinical environments.

Bragg scattering of nonlinear surface waves over a wavy bottom is studied using two-dimensional fully nonlinear numerical wave tanks (NWTs). In particular, we consider cases of high nonlinearity which lead to complex wave generation and transformations, hence possible multiple Bragg resonances. The performance of the NWTs is well verified by benchmarking experiments. Classic Bragg resonances associated with second-order triad interactions among two surface (linear incident and reflected waves) and one bottom wave components (class I), and third-order quartet interactions among three surface (linear incident and reflected waves, and second-order reflected/transmitted waves) and one bottom wave components (class III) are observed. In addition, class I Bragg resonance occurring for the second-order (rather than linear) transmitted waves, and Bragg resonance arising from quintet interactions among three surface and two bottom wave components, are newly captured. The latter is denoted class IV Bragg resonance which magnifies bottom nonlinearity. It is also found that wave reflection and transmission at class III Bragg resonance have a quadratic rather than a linear relation with the bottom slope if the bottom size increases to a certain level. The surface wave and bottom nonlinearities are found to play opposite roles in shifting the Bragg resonance conditions. Finally, the results indicate that Bragg resonances are responsible for the phenomena of beating and parasitic beating, leading to a significantly large local free surface motion in front of the depth transition.

China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2–3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma. This randomised, open-label, phase 2–3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab–bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes. Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab–bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8–46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5–11·7) in the sintilimab–bevacizumab biosimilar group and 10·0 months (8·4–11·7) in the sorafenib group. Patients in the sintilimab–bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1–5·7]) than did patients in the sorafenib group (2·8 months [2·7–3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46–0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab–bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached–not reached] vs 10·4 months [8·5–not reached]; HR 0·57, 95% CI 0·43–0·75; p<0·0001). The most common grade 3–4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab–bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab–bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab–bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause). Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients. Innovent Biologics. For the Chinese translation of the abstract see Supplementary Materials section.