The Connecting Method for the Spiral Blades of Concrete Mixer Truck

For the spiral blade of the concrete mixing tank of concrete mixer truck, in order to satisfy the stirring and discharging performance, the installation angle and helix angle of the blade should be assigned according to their segmentation function. Due to the different helix angles and the installation tilt angles, a junction gap of blade is formed at the joint, resulting in the severe silting of discharge or the uneven agitation. We put forward a more reasonable solution by using the MFG (method of fitting gradient) to solve the gap connection of spiral blades. The MFG that can reduce the discharging residual rate of the mixing material has been verified by experiments and applied to actual mass production. We also make the coupling simulation of Multi-Physics Field based on simulation software 17-STARCCM+® to visually verify the scientificity of design and study the complex stresses distribution inside the actual mixing tank. Finally, we provide an up-to-date reference for the design of spiral logarithmic blade, solving the problem of the gap at the traditional spiral-blade connection

Three dimension high definition manometry evaluated postoperative anal canal functions in children with congenital anorectal malformations

BackgroundWe aimed to evaluate the function of the reconstructed anal canal in postoperative anorectal malformations (ARMs) patients through three dimension (3D) high-definition anorectal manometry.MethodsFrom January 2015 to December 2019, 3D manometry was performed as a postoperative functional assessment of patients with ARMs divided into age subgroups based on the time of manometry. Manometric parameters, such as the length of the anorectal high-pressure zone (HPZ-length), the mean resting and squeeze pressure of HPZ (HPZ-rest and HPZ-sqze), recto-anal inhibitory reflex (RAIR), and strength distribution of the anal canal, were collected and compared with age-matched controls. Their functional outcomes were analyzed with SPSS 23.0 software for statistical analysis.Results171 manometric measurements were performed on 142 postoperative patients (3 months∼15 years). The HPZ-rest in all patients was significantly lower than in age-matched controls (p < 0.05). HPZ-sqze was notably decreased in patients older than 4 years, whereas other age groups were comparable to controls (p < 0.05). The proportions of asymmetric strength distribution and negative RAIR were higher in ARMs patients. The type of anorectal malformations and lower HPZ-rest were the impact factors affecting postoperative functional outcomes.ConclusionsThe majority of the ARMs patients had acceptable functional outcomes. 3D manometry can objectively assess the reconstructed anal canal function. The patients with fecal incontinence had a high proportion of extremely low HPZ-rest and HPZ-sqze, negative RAIR, and asymmetric strength distribution. The manometric details will help the clinicians explore the causes of defecation complications and guide further management

Increasing mass-to-flux ratio from the dense core to the protostellar envelope around the Class 0 protostar HH 211

To study transportation of magnetic flux from large to small scales in protostellar sources, we analyzed the Nobeyama 45-m N2H+ (1-0), JCMT 850 um polarization, and ALMA C18O (2-1) and 1.3 mm and 0.8 mm (polarized) continuum data of the Class 0 protostar HH 211. The magnetic field strength in the dense core on a 0.1 pc scale was estimated with the single-dish line and polarization data using the Davis-Chandrasekhar-Fermi method, and that in the protostellar envelope on a 600 au scale was estimated from the force balance between the gravity and magnetic field tension by analyzing the gas kinematics and magnetic field structures with the ALMA data. Our analysis suggests that from 0.1 pc to 600 au scales, the magnetic field strength increases from 40-107 uG to 0.3-1.2 mG with a scaling relation between the magnetic field strength and density of $B \propto \rho^{0.36\pm0.08}$, and the mass-to-flux ratio increases from 1.2-3.7 to 9.1-32.3. The increase in the mass-to-flux ratio could suggest that the magnetic field is partially decoupled from the neutral matter between 0.1 pc and 600 au scales, and hint at efficient ambipolar diffusion in the infalling protostellar envelope in HH 211, which is the dominant non-ideal magnetohydrodynamic effect considering the density on these scales. Thus, our results could support the scenario of efficient ambipolar diffusion enabling the formation of the 20 au Keplerian disk in HH 211.Comment: 27 pages, 12 figures, accepted by Ap

Rifaximin Alters Intestinal Microbiota and Prevents Progression of Ankylosing Spondylitis in Mice

Recently, accumulating evidence has suggested that gut microbiota may be involved in the occurrence and development of ankylosing spondylitis (AS). It has been suggested that rifaximin have the ability to modulate the gut bacterial communities, prevent inflammatory response, and modulate gut barrier function. The goal of this work is to evaluate the protective effects of rifaximin in fighting AS and to elucidate the potential underlying mechanism. Rifaximin were administered to the proteoglycan (PG)-induced AS mice for 4 consecutive weeks. The disease severity was measured with the clinical and histological of arthritis and spondylitis. Intestinal histopathological, pro-inflammatory cytokine levels and the intestinal mucosal barrier were evaluated. Then, western blot was performed to explore the toll-like receptor 4 (TLR-4) signal transducer and NF-κB expression. Stool samples were collected to analyze the differences in the gut microbiota via next-generation sequencing of 16S rDNA. We found that rifaximin significantly reduced the severity of AS and resulted in down-regulation of inflammatory factors, such as TNF-α, IL-6, IL-17A, and IL-23. Meanwhile, rifaximin prevented ileum histological alterations, restored intestinal barrier function and inhibited TLR-4/NF-κB signaling pathway activation. Rifaximin also changed the gut microbiota composition with increased Bacteroidetes/Firmicutes phylum ratio, as well as selectively promoting some probiotic populations, including Lactobacillales. Our results suggest that rifaximin suppressed progression of AS and regulated gut microbiota in AS mice. Rifaximin might be useful as a novel treatment for AS

NaxD is a deacetylase required for lipid A modification and Francisella pathogenesis

Modification of specific Gram-negative bacterial cell envelope components, such as capsule, O-antigen and lipid A, are often essential for the successful establishment of infection. Francisella species express lipid A molecules with unique characteristics involved in circumventing host defences, which significantly contribute to their virulence. In this study, we show that NaxD, a member of the highly conserved YdjC superfamily, is a deacetylase required for an important modification of the outer membrane component lipid A in Francisella. Mass spectrometry analysis revealed that NaxD is essential for the modification of a lipid A phosphate with galactosamine in Francisella novicida, a model organism for the study of highly virulent Francisella tularensis. Significantly, enzymatic assays confirmed that this protein is necessary for deacetylation of its substrate. In addition, NaxD was involved in resistance to the antimicrobial peptide polymyxin B and critical for replication in macrophages and in vivo virulence. Importantly, this protein is also required for lipid A modification in F. tularensis as well as Bordetella bronchiseptica. Since NaxD homologues are conserved among many Gram-negative pathogens, this work has broad implications for our understanding of host subversion mechanisms of other virulent bacteria

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer.

peer reviewedCurrent therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Cysteine-Scanning Analysis of the Chemoreceptor-Coupling Domain of the Escherichia coli Chemotaxis Signaling Kinase CheA

The C-terminal P5 domain of the histidine kinase CheA is essential for coupling CheA autophosphorylation activity to chemoreceptor control through a binding interaction with the CheW protein. To locate P5 determinants critical for CheW binding and chemoreceptor control, we surveyed cysteine replacements at 39 residues predicted to be at or near the P5 surface in Escherichia coli CheA. Two-thirds of the Cys replacement proteins exhibited in vitro defects in CheW binding, either before or after modification with a bulky fluorescein group. The binding-defective sites were widely distributed on the P5 surface and were often interspersed with sites that caused no functional defects, implying that relatively minor structural perturbations, often far from the actual binding site, can influence its conformation or accessibility. The most likely CheW docking area included loop 2 in P5 folding subdomain 1. All but four of the binding-defective P5-Cys proteins were defective in receptor-mediated activation, suggesting that CheW binding, as measured in vitro, is necessary for assembly of ternary signaling complexes and/or subsequent CheA activation. Other Cys sites specifically affected receptor-mediated activation or deactivation of CheA, demonstrating that CheW binding is not sufficient for assembly and/or operation of receptor signaling complexes. Because P5 is quite similar to CheW, whose structure is known to be dynamic, we suggest that conformational flexibility and dynamic motions govern the signaling activities of the P5 domain. In addition, relative movements of the CheA domains may be involved in CheW binding, in ternary complex assembly, and in subsequent stimulus-induced conformational changes in receptor signaling complexes