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Abstract Evidence suggested that the use of partial dopamine D2/D3 receptor agonists may be a better choice for the treatment of Parkinson's disease (PD), and the stimulation of 5-HT1A receptors (mainly via nondopaminergic mechanisms) alleviates motor and nonmotor disorders of PD, implying that the multitarget approach may provide a double bonus for the treatment of the disease. In this study, 20 novel 1-(3-((6-fluoropyridin-3-yl)oxy)propyl)piperazine derivatives were designed and synthesized using a bioisosterism approach, and their activities for D2/D3/5-HT1A receptors were further tested. The results showed that several compounds exhibited a multitarget combination of D2/5-HT1A agonism. Compounds 7b and 34c showed agonistic activities on D2/D3/5-HT1A receptor. The EC50 value of 7b for D2/D3/5-HT1A receptor were 0.9/19/2.3 nmol/L, respectively; and the EC50 value of 34c for D2/D3/5-HT1A receptor were 3.3/10/1.4 nmol/L, respectively. In addition, 34c exhibited good metabolic stability (the half-life T 1/2 = 159.7 minutes) in vitro, which is of great significance for the further exploration of multitarget anti-PD drugs.

Background: Gastric acid suppressants have a major impact on gut microbiome which in turn, may increase the risk of cholelithiasis, but epidemiological evidence remains unclear. We undertook this research to evaluate the association between regular use of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) with risk of cholelithiasis.Methods: Prospective cohort study included 477,293 UK residents aged 37–73 years from the UK Biobank. We included the participants reported PPI or H2RA use, and were free of cholelithiasis or cancer. We evaluated hazard ratios (HRs) of regular use of PPIs or H2RAs and risk of cholelithiasis adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications, and clinical indications.Results: We identified 12,870 cases of cholelithiasis over a median follow-up of 8.1 years. Regular use of PPIs (HR 1.22 95% CI 1.16–1.29) or H2RAs (HR 1.16, 95% CI 1.05–1.28) was associated with an increased risk of cholelithiasis after confounding adjustment. There were no major differences among individual PPIs/H2RAs. The absolute risk of PPI-associated cholelithiasis was increased with the baseline predicted risk evaluated by known environmental and genetic risk factors (Risk differences in the lowest vs. the highest quartile: 1.37 vs. 4.29 per 1,000 person-years).Conclusion: Regular use of PPIs and H2RAs was associated with increased risk of cholelithiasis. Future prospective studies are required to confirm whether the observed associations are casual.

Owing to the complex formation mechanism of hydrodynamic landslides and the involvement of multiple influencing factors, the accuracy of the current prediction model of hydrodynamic landslide evolution process is unsatisfactory. This limitation prevents adequate monitoring and early warning on possible landslides in an area. To improve the accuracy of prediction model of hydrodynamic landslide evolution process supported by monitoring big data, the variational mode decomposition (VMD) and support vector regression (SVR) based on deep learning were integrated in the present study. Typical hydrodynamic landslide in the Three Gorges Reservoir Area (TGRA) in China is used as a case study for landslide displacement prediction. First, the VMD was utilized to decompose the cumulative displacement into the trend, periodic, and random terms. Then, external factors were decomposed into subsequences, and those characterized by periodicity and randomness were selected as input datasets. The associated displacement terms were then predicted using the Random Search–Support Vector Regression model. Finally, the total displacement was obtained by superimposing the three predicted components, and this was used to evaluate the performance of the model. The results show that the model improves the performance and accuracy of predicting the displacement associated with a hydrodynamic landslide, and the relative error is ≤2%.

The postoperative survival time and quality of life of patients with colon adenocarcinoma (COAD) varies widely. In order to make accurate decisions after surgery, clinicians need to distinguish patients with different prognostic trends. However, we still lack effective methods to predict the prognosis of COAD patients. Accumulated evidences indicated that the inhibition of peroxisome proliferator-activated receptors (PPARs) and a portion of their target genes were associated with the development of COAD. Our study found that the expression of several PPAR pathway-related genes were linked to the prognosis of COAD patients. Therefore, we developed a scoring system (named PPAR-Riskscore) that can predict patients’ outcomes. PPAR-Riskscore was constructed by univariate Cox regression based on the expression of 4 genes (NR1D1, ILK, TNFRSF1A, and REN) in tumor tissues. Compared to typical TNM grading systems, PPAR-Riskscore has better predictive accuracy and sensitivity. The reliability of the system was tested on six external validation datasets. Furthermore, PPAR-Riskscore was able to evaluate the immune cell infiltration and chemotherapy sensitivity of each tumor sample. We also combined PPAR-Riskscore and clinical features to create a nomogram with greater clinical utility. The nomogram can help clinicians make precise treatment decisions regarding the possible long-term survival of patients after surgery.

Objective. This study aimed to evaluate whether the site of C7 neurotomy affects spinal cord glial cell activation and pain-related behavior on the paralyzed side in a rat stroke model. Methods. After middle cerebral artery occlusion (MCAO) was induced in male Sprague-Dawley rats, they underwent C7 neurotomy 0, 2, and 4 mm distal to the intervertebral foramen on the paralyzed side. Pain-related behavior and immunofluorescence examination of spinal cord glial cell activation in the ipsilateral C7 dorsal horn were evaluated. Results. Mechanical paw withdrawal threshold (MPWT) was lower, and the number of microglia and astrocytes (/mm2) was higher as the distance between the site of C7 neurotomy and the intervertebral foramen decreased from 4 mm to 0. Conclusion. The site of C7 neurotomy affects MPWT and spinal cord glial proliferation in rats with MCAO. Nerve division closer to intervertebral foramen resulted in lower MPWT and higher degree of glial proliferation in the spinal cord.

Real-time crop harvest data acquisition from harvesters during harvesting operations is an important way to understand the distribution of crop harvest in the field. Most real-time monitoring systems for grain yield using sensors are vulnerable to factors such as low accuracy and low real-time performance. To address this phenomenon, a real-time grain yield monitoring system was designed in this study. The real-time monitoring of yield was accomplished by adding three pairs of photoelectric sensors to the elevator of the corn kernel harvester. The system mainly consists of a signal acquisition and processing module, a positioning module and a visualization terminal; the signal acquisition frequency was set to 1 kHz and the response time was 2 ms. When the system operated, the signal acquisition and processing module detected the sensor signal duration of grain blocking the scrapers of the grain elevator in real-time and used the low-potential signal-based corn grain yield calculation model constructed in this study to complete the real-time yield measurement. The results of the bench tests, conducted under several different operating conditions with the simulated elevator test bench built, showed that the error of the system measurement was less than 5%. Field tests were conducted on a Zoomlion 4YZL-5BZH combined corn kernel harvester and the results showed that the average error of measured yield was 3.72%. Compared to the yield measurement method using the weighing method, the average error of the bench test yield measurement was 7.6% and the average error of yield measurement in field trials with a mass flow sensor yield measurement system was 16.38%. It was verified that the system designed in this study has high yield measurement accuracy and real-time yield measurement, and can provide reference for precision agriculture and high yield management.

Abstract A total of 20 novel aryl piperazine derivatives were designed and synthesized, and their structures were confirmed by mass spectrometry and nuclear magnetic resonance analyses. Their 5-HT1A and sigma-1 receptor affinities were determined, and six of them showed high affinities (K i

Landslide scale measurement and hazard risk assessment are crucial, especially since landslide deposits often have an expansion effect, and can lead to more serious secondary hazard events. In this study, we obtained substantial high-resolution terrain and orthophoto data through multiple UAV photography and field surveys. Based on GIS spatial analysis and landslide geometric models, sliding and deposit data for 42 loess landslides in the Heifangtai tableland were calculated. The results show that sliding volume and sliding area have the highest correlation with the power-law distribution ($V_e = 1.204A^{1.1360}$ V e = 1.204 A 1.1360 ). The ratio of $H_{max}/L_{max}$ H max / L max increases with the increase of sliding volume and deposit volume of the landslides, with an average value of 0.306. The ratio of H/L has a higher correlation with deposit volume, and the fitting expression is $H_{max}/L_{max} = 0.187V_D^{-0.123}$ H max / L max = 0.187 V D − 0.123 . The VEC of 42 loess landslides ranged from 1.05 to 2.53, while the AVEC was about 1.503. The correlation analysis show that the VEC is positively correlated with AEC, Hmov, Hmov/Lmax and Lmov/Lmax but negatively correlated with Dave. The essence of the volume expansion effect is that landslide fluidity increases, resulting in looser deposit distribution, larger pore scale in the deposit and lower overall compaction. Loess collapse in the Heifangtai tableland lack protection from the liquefaction of the sliding mass basement, resulting in large VEC values. The semi-ellipsoid model is a valuable approach for landslide volume assessment in the Chinese Loess Plateau, yielding an average error rate of restoring the sliding volume of landslides of 13.55%. This study provides a useful reference for accurate evaluations at the landslide scale. [ABSTRACT FROM AUTHOR]

CoMnOx catalysts were prepared using a microwave (MW)/ultrasonic (US)-assisted method. Amorphous/crystalline regions in CoMnOx (MW = 250 W US = 300 W) increased the oxygen vacancy content and CoMnOx exhibited excellent activity for methane oxidation (T90 = 330 °C). A new approach is provided here to improve the activity of transition metal catalysts. [ABSTRACT FROM AUTHOR]

By strong oxygen plasma treatment on monolayer MoS2, we observe the disappearance of the Raman modes of MoS2. We propose the hypothesis that the state of MoS2 translates from crystal to amorphous after strong oxygen plasma treatment. The evidences of no MoO3 formation shown by Raman spectra and the appearance of the Mo6+ peak and decreased O concentration shown by X-ray photoelectron spectroscopy support our hypothesis. The amorphization of monolayer MoS2 is further confirmed by the quenching of photoluminescence (PL) and the disappearance of two absorption peaks related to A, B exciton which demonstrates the disordered bandgap. Finally, we found that the amorphous MoS2 can improve the absorption fraction at the visible light (500~ 750 nm) which is potential for future visible light photocatalysis.

Ten-eleven translocation (TET) methylcytosine dioxygenases catalyze the oxidative reactions of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC), which are intermediate steps during DNA demethylation. It is reported that somatic mutations of TET2 gene are identified in a variety of human tumors, especially in hematological malignancies. The tendency and mechanism of cellular differentiation in different systems are affected by TET2 via regulation of associated gene expression or maintenance of demethylated state. TET2 acts as a critical driver of tumorigenesis through the conversion of 5-mC to 5-hmC and successive oxidation products. Sometimes, it requires special interactions and cofactors. Here, we reviewed recent advances in understanding the function of TET2 proteins in regulating cell differentiation, and its role in various tumors focusing on several digestive cancers. Keywords: Demethylation, Ten-eleven translocation-2, Differentiation, Digestive tumors

Depression and transient ischaemic attacks are tightly regulated but the neural circuits underlying depression-modulated ischaemic injury are not known. Here, the authors show that the locus coeruleus-CA1 pathway is involved in depression-associated ischaemia susceptibility.

Abstract Background Three-dimensional (3D) reconstruction of human peripheral nerves, as a useful tool to understand the nerve internal information and functional basis, has become an important area of research in the peripheral nerve field. Methods In this study, we proposed a two-dimensional (2D) Karnovsky–Roots toluidine blue ponceau 2R (K-B-2R) staining method based upon conventional Karnovsky–Roots staining. It significantly improved the ability to display nerve fascicles, motor and sensory nerve fiber textures. In this method, Karnovsky–Roots staining was carried out, followed by toluidine blue counterstain and ponceau 2R counterstain. Results Comparisons were conducted between the three methods in staining of median nerve sections, which showed similar distribution characters in acetylcholinesterase-positive sites. The additional counterstaining did not change the basis of Karnovsky–Roots staining. However, the resulting images from this new method significantly facilitated the subsequent 3D nerve reconstruction and 3D printing. Conclusions These results show that the new staining method significantly enhanced the display qualities of nerve fascicle edges and fiber textures of motor and sensory nerves and facilitated 3D nerve reconstruction.

Abstract This study reported an asymmetric synthesis of 1,2-limonene epoxides. The absolute stereochemistry was controlled by a Jacobsen epoxidation of cis-1,2-limonene epoxide (with diastereomeric excess of 98%) and trans-1,2-limonene epoxide (with diastereomeric excess of 94%), which could be used as important raw materials for the preparation of related cannabinoid drugs.