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The increasing number of DC loads, such as electric vehicles (EVs), has resulted in micro-grid undergoing difficulty in satisfying the various demands of such loads. The study develops a multi-objective capacity optimization allocation model for hybrid micro-grid on the bases of users’ satisfaction and the orderly charging/discharging of EVs. The proposed model aims to reduce the cost of the capacity allocation of AC/DC hybrid micro-grid and improve users’ satisfaction. Particle swarm optimization algorithm is used to address the capacity optimization of hybrid micro-grid in EVs across scenarios. This study verified the rationality and effectiveness of the proposed capacity optimization model by comparing and analyzing the influence of capacity optimization on the orderly/disorderly charging/discharging of EVs and users’ satisfaction.

The electrocatalytic nitrogen (N2) reduction reaction (NRR) relies on the development of highly efficient electrocatalysts and electrocatalysis systems. Herein, we report a non-loading electrocatalysis system, where the electrocatalysts are dispersed in aqueous solution rather than loading them on electrode substrates. The system consists of aqueous Ag nanodots (AgNDs) as the catalyst and metallic titanium (Ti) mesh as the current collector for electrocatalytic NRR. The as-synthesized AgNDs, homogeneously dispersed in 0.1 M Na2SO4 solution (pH = 10.5), can achieve an NH3 yield rate of 600.4 ± 23.0 μg h−1 mgAg−1 with a faradaic efficiency (FE) of 10.1 ± 0.7% at −0.25 V (vs. RHE). The FE can be further improved to be 20.1 ± 0.9% at the same potential by using Ti mesh modified with oxygen vacancy-rich TiO2 nanosheets as the current collector. Utilizing the aqueous AgNDs catalyst, a Ti plate based two-electrode configured flow-type electrochemical reactor was developed to achieve an NH3 yield rate of 804.5 ± 30.6 μg h−1 mgAg−1 with a FE of 8.2 ± 0.5% at a voltage of −1.8 V. The designed non-loading electrocatalysis system takes full advantage of the AgNDs’ active sites for N2 adsorption and activation, following an alternative hydrogenation mechanism revealed by theoretical calculations.

Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer. New antimicrobial agents, both broad-spectrum and selective, that do not induce AMR are urgently required. Antimicrobial peptides (AMPs) are a novel class of alternatives that possess potent activity against a wide range of Gram-negative and positive bacteria with little or no capacity to induce AMR. This has stimulated substantial chemical development of novel peptide-based antibiotics possessing improved therapeutic index. This review summarises recent synthetic efforts and their impact on analogue design as well as their various applications in AMP development. It includes modifications that have been reported to enhance antimicrobial activity including lipidation, glycosylation and multimerization through to the broad application of novel bio-orthogonal chemistry, as well as perspectives on the direction of future research. The subject area is primarily the development of next-generation antimicrobial agents through selective, rational chemical modification of AMPs. The review further serves as a guide toward the most promising directions in this field to stimulate broad scientific attention, and will lead to new, effective and selective solutions for the several biomedical challenges to which antimicrobial peptidomimetics are being applied.

In this report, we introduce a novel building block for Fmoc/tBu solid phase peptide synthesis (SPPS) of β-linked O-GlcNAcylated peptides. This building block carries acid labile silyl ether protecting groups, which are fully removed under TFA-mediated peptide cleavage conditions from the resin, thus requiring fewer synthetic steps and no intermediate purification as compared to other acid or base labile protecting group strategies.

Recently, with the broad applications of deep learning technology in image denoising, many deep neural networks based on the residual block (ResBlock) have been proposed to improve the performance. This paper presents DC-ResBlock, a ResBlock with an extra dilated convolution, to replace standard ResBlock for image denoising. Our study shows that the deep neural network with DC-ResBlocks, named DRNet, can achieve a very competitive result. We experiment with other residual blocks by adding Rectified Linear Unit, batch normalization, and Dilated Convolution to the standard ResBlock in several different ways. Ablation study shows that DC-Resblock has the best denoising performance. To evaluate the robustness of proposed DRNet, we make a statistical measure using many different random seeds instead of just a single seed, as used by many previous studies. DRNet performs well in denoising gray and color images with additive white Gaussian noise. Furthermore, because of its good performance on the Smartphone Image Denoising Dataset, DRNet is hopeful to be applied in practical tasks. The code of DRNet is accessible at https://github.com/JiaHongZ/DRNet.

Currently, nitrogenous electrocatalysts (particularly, nitrogen (N)-doped carbon materials) have attracted extensive attention owing to their superior electrochemical nitrogen reduction reaction (NRR) performances. Unfortunately, doped nitrogen atoms could directly contribute to the formation of ammonia via dissociation and hydrogenation. Significantly, the type of N atoms (pyrrolic-N, pyridinic-N, or graphitic-N) in N-doped carbon donated to NH3 formation still needs to be verified. Here, using chitosan-derived N-doped porous carbon as an NRR electrocatalyst, we demonstrated that pyrrolic-N and pyridinic-N could disaggregate and hydrogenate to form NH3, leading to the increase in the yield of ammonia. To remedy this issue, metal–N bonds as an efficient and universal strategy were proposed to anchor doped N in porous carbon for NRR. Specifically, Co (Mo) atoms coordinated with N atoms could not only effectively inhibit the disaggregation of doped N atoms but also successfully promote the electrocatalytic NRR activity, thus yielding a boosted NRR performance.

We report a fluidized electrocatalysis system, composed of metallic titanium (Ti) mesh as the current collector and aqueous ultrafine Co3O4 nanoparticles (NPs) catalyst fabricated by the laser ablation in liquid (LAL) technique, for the efficiently electrocatalytic nitrogen reduction reaction (NRR) to ammonia (NH3). The results indicated that utilizing this fluidized electrocatalysis system, the LAL-fabricated ultrafine Co3O4 NPs highly dispersed in 0.1 M Na2SO4 solution (pH=10.5) exhibit high NRR activity, affording an NH3 yield rate of 235.0 μg h-1 mgcat.-1 and a faradaic efficiency (FE) of 16.3% at -0.30 V (vs. RHE). The superior NRR performance can be ascribed to the fluidized electrocatalysis approach to take full advantage of the exposed oxygen vacancies active sites of Co3O4 NPs for N2 adsorption and activation.

As a toughening agent, LaPO4 has been used to improve several properties of ceramics. In such applications, its compatibility with the matrix material should be considered first. In this study, the compatibility of LaPO4 and magnesium lanthanum hexa-aluminate (LaMgAl11O19, LMA) was elucidated at temperatures ranging from room temperature to 1600 °C. The compositions, thermal stabilities, thermal conductivities and microstructures of the above-mentioned materials were analysed using X-ray diffraction, thermogravimetry-differential scanning calorimetry, thermal conductivity tester and scanning electron microscopy. The results indicated that the two materials maintained a good compatibility at temperatures lower than 1600 °C. At 1600 °C, the diffusion of La was observed to alter the chemical composition of LaPO4 and accelerate its reaction with LMA, leading to the formation of LaAlO3 and magnesium lanthanum aluminium oxide, resulting in the increase of thermal conductivity.

The in-situ measurements for r-tables have attracted special attention owing to their advantages, including increased speed, simplicity of use, and nondestructive road effects. This study presents ...

Amine elimination of Ln[N(SiMe3)2]3(μ-Cl)Li(THF)3 with aminophenol H[ON] {H[ON] = 2-(CH2NC5H10)-4,6-tBu2-C6H3OH} in 1:2 molar ratio in THF gave the monometallic rare-earth metal amide complexes [ON]2LnN(SiMe3)2 (Ln = Yb (1), Y (2), Gd (3), Sm (4), Nd (5)) in 57%—73% isolated yields. All these complexes were characterized by elemental analysis. The molecular structures of complexes 1–4 were determined by single crystal X-ray diffraction. These complexes are highly active for l -lactide polymerization to give high molecular weight polymers with unimodal molecular weight distributions. In addition, these complexes can also initiate rac-lactide polymerization with high activity to afford heterotactic-rich polylactides.

During CFRP hole-making, exit damages such as burrs and delamination frequently occur. To adequately eliminate the influence of the axial force on the damages, a new combined drill-milling process was proposed. But the details of the cutting forces and the undeformed chip geometry in the helical milling phase for special drill-milling tool have not yet been comprehensively described and analyzed. Theoretical and experimental analyses of the drill-milling cutting forces and the performance of the novel drill-milling tool are investigated. The results indicate that the helical milling parameters significantly affect the undeformed chip transverse areas as well as the cutting forces. During the drilling phase, the exit tears and delamination can be observed, but few exit burrs can be left. During the helical milling phase, the drilling-induced damages can be further reduced even removed completely. The cutting forces Fx and Fy increase up to 15.9% and 22.6%, respectively, when ng increases from 60 to 180 rpm. When e increases from 0.1 to 1.3 mm, Fx and Fy increase up to 69.9% and 44.4%, respectively. Fx and Fy increase up to 40.3% and 35.2% respectively, when vf increases from 6 to 24 mm/min. But Fx and Fy decrease up to 18.0% and 10.4% respectively, when nz increases from 2000 to 5000 rpm.

Process-induced damages, such as burrs and delamination, frequently occur and are the critical hole quality issues for CFRPs. These damages are strongly influenced by the axial cutting force. By employing the novel drill-milling process, the influence of the axial cutting force may be completely eliminated, and the process-induced damages can be remarkably removed. The drill-milling tools with a better performance are very critical to the drill-milling process. In this paper, according to the drill structure with V-shaped cutting edges and the mill structure with double-crossed helix flutes, two different new drill-milling tools are designed, and a series of tests are conducted on CFRPs. The result indicates that the influences of the cutting forces on the damages can be remarkably reduced during the helical milling phase by employing the drill-milling process. Under the same cutting conditions, the cutting forces of T2 are significant less than that of T1. The re-trimming effect of T2 is superior significant than that of T1 during the helical milling phase. The damages can be significantly reduced by using these two tools, especially by using T2 tool.

Background Abnormally expressed in diverse cancers, circZFR has been correlated with clinical outcomes of cancer patients. Aim of this meta-analysis was to elucidate the prognostic role of circZFR in multiple human malignancies. Methods Literature retrieval was conducted by systematically searching on Pubmed, Web of Science, and the Cochrane Library up to December 2nd, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). The reliability of the pooled results was assessed through sensitivity analysis and the publication bias was measured by Begg’s and Egger’s test. Results A total of seventeen studies comprising 1098 Chinese patients were enrolled in this meta-analysis. Results demonstrated that high circZFR expression was correlated with an unfavorable OS (HR = 2.14, 95% CI 1.74, 2.64). High circZFR expression predicted larger tumor size (OR = 2.79, 95% CI 1.52, 5.12), advanced clinical stage (OR = 3.38, 95% CI 1.49, 7.65), tendentiousness of lymph node metastasis (LNM) (OR = 3.08, 95% CI 2.01, 4.71), and malignant grade (OR = 3.18, 95% CI 1.09, 9.30), but not related to age, gender, and distant metastasis (DM). Conclusions High circZFR expression was associated with unfavorable OS and clinicopathologic parameters including tumor size, clinical stage, LNM, and histology grade, implicating a promising prognostic factor in cancers.

BackgroundLong-standing inflammatory bowel disease predisposes to the development of colorectal cancer (CRC). Interleukin (IL) -6, a pivotal link between chronic inflammation and tumor progression, has recently been recognized as a potential target. The effect of IL-6 on proliferation and metastasis of CRC by activating STAT3 pathway has been widely demonstrated in recent years, but few on mediating tumor immune evasion has been reported. MethodsIn this study, we analyzed IL-6 gene expression in human CRC tissues and carried out survival probability in CRC patients with TCGA Data portal and GEO Database. We studied CRC tumorigenesis in vivo by inoculating MC38 tumors and induced-CRC model via AOM/DSS （azoxymethan / dextran sulfate sodium）in (IL-6 deficient) IL-6-/- and (wild type) WT mice. We measured tumor growth and detected CD8+ T cells via immunofluorescence, we validated the function of IL-6 in tumorigenesis and tumor immune evasion in subcutaneous transplantation models. Using endoscopy monitoring and immunofluorescence, we validated the function of IL-6 in tumor immune evasion in AOM/DSS models. We conducted colitis model with DSS reveal the relationship of IL-6 and MHC-1 molecules by qRT-PCR and bioinformatics analysis. Organoid and CRC cells culture, western blot analysis, and qRT-PCR were used to investigate the expression and significance of MHC-1 molecules in vitro without IL-6 stimulation. MHC-1 molecules levels were also detected in tumors of IL-6-/- and WT mice from MC38-bearing tumor models and AOM/DSS models. Subcutaneous MC38 implantation models in C57BL/6 J mice were established to investigate anti-IL-6 therapy on CRC tumorigenesis. In vivo efficacy were conducted using antibodies blocking IL-6 and PD-1 in mice subcutaneous-bearing different types of tumors. Results Bio-information analysis and results of our center founded that IL-6 was remarkably overexpressed in CRC and its elevation was associated with poor prognosis. We observed that IL-6-/- mice were less susceptible to develop tumors, compared to (wild type) WT mice. Interestingly, infiltrated CD8+ T cells were found to exhibit high expression in tumor of IL-6-/- mice. High level of IL-6 was found in colitis model, with down-regulation of MHC-1molecules. Moreover, in vitro experiments, we found that IL-6 may act as a negative regulator in IFNγ-STAT1-MHC-1 signaling. In addition, vivo trials also confirmed that MHC-1 mRNA levels are negatively related to the existence of IL-6. Furthermore, blockade of IL-6 also activated CD8+ T-cell accumulation and led to the high PDL-1 expression in CRC, which can sensitize animals to anti-PD-1 therapy. Importantly, compared to treatment with anti-IL-6 alone and single treatment of anti-PD-1, combined IL-6 and PD-1 blockade greatly improved the therapeutic effect, not only in CRC but also melanoma and breast cancer.Conclusions Our study demonstrated that IL-6 act as a negative regulator in immunological surveillance to promote tumor immune evasion by inhibiting the response of cell to IFNγ. Blocking IL-6 enhanced tumor response to anti-PD-1 therapy via infiltration of CD8+ T cell and high expression of PDL-1. Based on the findings of our study, IL-6 is a novel target to improve the efficacy of immunotherapy.

PurposeTo develop and validate three radiomics nomograms for preoperative prediction of pathological and progression diagnosis in non-small cell lung cancer (NSCLC) as well as circulating tumor cells (CTCs).Patients and methodsA total of 224 and 134 patients diagnosed with NSCLC were respectively gathered in 2018 and 2019 in this study. There were totally 1,197 radiomics features that were extracted and quantified from the images produced by computed tomography (CT). Then we selected the radiomics features with predictive value by LASSO and combined them into radiomics signature. Logistic regression models were built using radiomics signature as the only predictor, which were then converted to nomograms for individualized predictions. Finally, the performance of the nomograms was assessed on both two cohorts.ResultsAs for discrimination, the AUC of pathological diagnosis nomogram and progression diagnosis nomogram in NSCLC were both higher than 90% in the training cohort and higher than 80% in the validation cohort. The performance of the CTC-diagnosis nomogram was somehow unexpected where the AUC were range from 60% to 70% in both two cohorts. As for calibration, nonsignificant statistics (p>0.05) yielded by Hosmer-Lemeshow tests suggested no departure between model prediction and perfect fit. Additionally, decision curve analyses demonstrated the clinically usefulness of the nomograms.ConclusionWe developed radiomics-based nomograms for pathological, progression and CTC diagnosis prediction in NSCLC, respectively. Nomograms for pathological and progression diagnosis were demonstrated well performed to facilitate the preoperative individualized prediction, while the nomogram for CTC-diagnosis prediction needed improvement.

Ca2+ signals regulate the function of many immune cells and promote immune responses to infection, cancer, and autoantigens. Ca2+ influx in immune cells is mediated by store-operated Ca2+ entry (SOCE) that results from the opening of Ca2+ release-activated Ca2+ (CRAC) channels. The CRAC channel is formed by three plasma membrane proteins, ORAI1, ORAI2, and ORAI3. Of these, ORAI1 is the best studied and plays important roles in immune function. By contrast, the physiological role of ORAI3 in immune cells remains elusive. We show here that ORAI3 is expressed in many immune cells including macrophages, B cells, and T cells. To investigate ORAI3 function in immune cells, we generated Orai3−/− mice. The development of lymphoid and myeloid cells in the thymus and bone marrow was normal in Orai3−/− mice, as was the composition of immune cells in secondary lymphoid organs. Deletion of Orai3 did not affect SOCE in B cells and T cells but moderately enhanced SOCE in macrophages. Orai3-deficient macrophages, B cells, and T cells had normal effector functions in vitro. Immune responses in vivo, including humoral immunity (T cell dependent or independent) and antitumor immunity, were normal in Orai3−/− mice. Moreover, Orai3−/− mice showed no differences in susceptibility to septic shock, experimental autoimmune encephalomyelitis, or collagen-induced arthritis. We conclude that despite its expression in myeloid and lymphoid cells, ORAI3 appears to be dispensable or redundant for physiological and pathological immune responses mediated by these cells.

Extended experience with meaningful pitch information has been shown to benefit music perception as well as speech perception where pitch cues are important, such as segregation of competing speech and tonal language perception. Interestingly, pitch perception has been shown to be similar between non-musicians who speak a tonal language and musicians who speak a non-tonal language, both of which outperform non-musicians who speak a non-tonal language. However, it is unknown whether extensive music training can further benefit pitch perception in tonal language speakers. In this study, melodic contour identification, spectro-temporal pattern perception, and masked speech recognition was measured in 16 adult normal-hearing musicians and 16 non-musicians; all were Chinese native speakers of Mandarin. Melodic contour identification, spectro-temporal pattern perception, and masked speech recognition all were significantly better for musicians than for non-musicians. Compared to non-musicians, musicians better utilized talker sex cues to segregate competing speech; utilization of talker sex cues by musicians was associated with the onset and extent of music training. Across all participants, spectro-temporal pattern perception was associated with better masked speech understanding. The data suggest that early and extensive music training may further benefit tonal language speakers’ perception and utilization of pitch cues.

In order to solve the difficult problem of deep learning-based robot vision tracking algorithm research and implementation, a deep learning-based target tracking algorithm and a classical tracking algorithm were proposed. It mainly uses the combination of traditional TLD algorithm and GOTURN algorithm to benefit from a large number of offline training data and updates the learner online, so that the whole system has better performance in real-time and accuracy. The results show that the performance of the TLD algorithm is poor regardless of the accuracy curve or the accuracy curve, and the performance of GOTURN-LD is significantly improved when the illumination changes. In the face of occlusion problem, the TLD algorithm shows strong robustness. Although GOTURN-LD is not very stable, its performance is better than GOTURN on the whole.

The World Health Organisation has deemed several multi-drug resistant (MDR) nosocomial bacterial pathogens to be of significant threat to human health. A stark increase in morbidity, mortality and the burden to healthcare systems around the world can be attributed to the development of resistance in these bacteria. Accordingly, alternative antimicrobial agents have been sought as an attractive means to combat MDR pathogens, with one such example being antimicrobial peptides (AMPs). Given the reported activity of AMPs, including Pardaxin, MSI-78, dermaseptin-PC (DMPC) and Cecropin B, it is important to understand their activities and modes of action against bacteria for further AMP design. In this study, we compared these AMPs against a panel of nosocomial bacterial pathogens, followed by detailed mechanistic studies. It was found that Pardaxin (1-22) and MSI-78 (4-20) displayed the most pronounced antimicrobial activity against the tested bacteria. The mechanistic studies by membrane permeability and molecular dynamics simulation further confirmed the strong membrane interaction and structure of Pardaxin (1-22) and MSI-78 (4-20), which contributed to their potent activity. This study demonstrated a structure and activity guidance for further design of Pardaxin (1-22) and MSI-78 (4-20) as therapeutics against MDR pathogens. The different effects of DMPC (1-19) and Cecropin B (1-21) on membrane integrity and phospholipid membrane interactions provided critical information for the rational design of next-generation analogues with specificity against either Gram-negative or Gram-positive bacteria.

The growing epidemic of diabetes means that there is a need for therapies that are more efficacious, safe, and convenient. Here, we report the efficient synthesis of a novel disulfide dimer of human insulin tethered at the N-terminus of its B-chain through placement of a cysteine residue. The resulting peptide was shown to bind to both the insulin receptor isoform B and insulin-like growth factor-1 receptor with comparable affinity to native insulin. In in vivo insulin tolerance tests, the dimer was equipotent to Actrapid insulin and possessed a sustained duration of action greater than that of Actrapid and Glargine. While the secondary structure of our dimeric insulin was similar to that of insulin, it was more resistant to proteolysis. More importantly, our analogue was produced in quantitative yield from a monomeric thiol insulin scaffold. Our results suggest that this dimer has significant potential to address the clinical needs in the treatment of diabetes.

Background Recreational N2O abuse is an important etiology of neurological impairment in young patients, which may easily be ignored clinically. Few current studies have investigated the characteristics or the effects experienced by its users. We aimed to explore any correlation between the clinical severity and biomarkers and spinal magnetic resonance imaging (MRI) abnormalities, identify independent factors associated with spinal MRI abnormalities, and ascertain factors affecting depression/anxiety in patients with N2O‐related neurological disorders. Methods Patients with N2O‐related neurological disorders were enrolled retrospectively between February 2017 and July 2020. Their demographic, clinical, laboratory, neuroimaging, electrophysiological, and neuropsychological findings were analyzed. Correlation analyses were conducted using Spearman's or Pearson's correlation and linear regression analysis. Independent factors associated with spinal MRI abnormalities were identified using univariate and multivariate analyses. Results The principal clinical manifestations of N2O‐related neurological disorders (n = 63; 38 men, 25 women; mean age ± SD: 22.60 ± 4.46 years) were sensory disturbance, followed by gait disturbance and pyramidal tract damage. A significant negative correlation existed between serum vitamin B12 levels and clinical severity (r = −0.309, p = .014), which disappeared after linear regression. An interval of less than 6 months between initial N2O abuse and hospitalization was independently associated with spinal MRI abnormalities (39.47% vs. 72.00%, respectively; χ 2 = 6.40, p = .01). Thirty‐eight (60.32%) and 40 (63.49%) patients experienced anxiety and depression, respectively. Moreover, the higher the clinical scores/serum homocysteine levels, the greater the severity of anxiety/depression (r = 0.442, p, We develop a research to explore any correlation between clinical severity and biomarkers and spinal magnetic resonance imaging (MRI) abnormalities, identify independent factors associated with spinal‐MRI abnormalities, and ascertain factors affecting depression/anxiety in patients with N2O‐related neurological disorders.

Refractory intercostal neuralgia is a troublesome disease with long treatment cycle and short-term therapeutic effects. No treatment modality has given effective pain relief. The authors present here a safe and effective endoscopic surgical option for refractory intercostal neuralgia.To introduce the surgical techniques of percutaneous endoscopic intercostal neurectomy used for refractory intercostal neuralgia and to evaluate its safety and efficacy.A retrospective study.The Department of Orthopedics at the Hebei General Hospital in China.Thirteen patients with refractory intercostal neuralgia were treated with percutaneous endoscopic intercostal neurectomy. Patients were followed up to 12 months postoperatively. The pain was measured by the Visual Analog Scale (VAS) score. Complications, such as aspiration, dysfunction, infection, and local hematoma were analyzed.Pain was relieved in all 13 patients, with only 1 patient reporting burning sensation along the intercostal nerve distribution area after operation. No other complications were found. All patients had significant improvement, with significantly lower VAS scores recorded postoperatively. No recurrence was reported during the follow-up period.The retrospective nature of this study is a limitation, as well as the small sample size and short observation time.Endoscopic intercostal neurotomy is an effective and safe minimally invasive surgical treatment for refractory intercostal neuralgia.

Oral dental infections are one of the most common diseases affecting humans, with caries and periodontal disease having the highest incidence. Caries and periodontal disease arise from infections caused by oral bacterial pathogens. Current misuse and overuse of antibiotic treatments have led to the development of antimicrobial resistance. However, recent studies have shown that cationic antimicrobial peptides are a promising family of antibacterial agents that are active against oral pathogenic bacteria and also possess less propensity for development of antimicrobial resistance. This timely Review has a focus on two primary subjects: (i) the oral bacterial pathogens associated with dental infections and (ii) the current development of antimicrobial peptides targeting oral pathogens.

The current commercially available glucagon formulations for the treatment of severe hypoglycemia must be reconstituted immediately prior to use, owing to the susceptibility of glucagon to fibrillation and aggregation in an aqueous solution. This results in the inconvenience of handling, misuse, and wastage of this drug. To address these issues, we synthesized a glycosylated glucagon analogue in which the 25th residue (Trp) was replaced with a cysteine (Cys) and a Br-disialyloligosaccharide was conjugated at the Cys thiol moiety. The resulting analogue, glycoglucagon, is a highly potent full agonist at the glucagon receptor. Importantly, glycoglucagon exhibits markedly reduced propensity for fibrillation and enhanced thermal and metabolic stability. This novel analogue is thus a valuable lead for producing stable liquid glucagon formulations that will improve patient compliance and minimize wastage.

BackgroundComputed tomography (CT) plays an essential role in classifying stroke, quantifying penumbra size and supporting stroke-relevant radiomics studies. However, it is difficult to acquire standard, accurate and repeatable images during follow-up. Therefore, we invented an intelligent CT to evaluate stroke during the entire follow-up.MethodsWe deployed a region proposal network (RPN) and V-Net to endow traditional CT with intelligence. Specifically, facial detection was accomplished by identifying adjacent jaw positions through training and testing an RPN on 76,382 human faces using a preinstalled 2-dimensional camera; two regions of interest (ROIs) were segmented by V-Net on another training set with 295 subjects, and the moving distance of scanning couch was calculated based on a pre-generated calibration table. Multiple cohorts including 1,124 patients were used for performance validation under three clinical scenarios.ResultsCranial Automatic Planbox Imaging Towards AmeLiorating neuroscience (CAPITAL)-CT was invented. RPN model had an error distance of 4.46 ± 0.02 pixels with a success rate of 98.7% in the training set and 100% with 2.23 ± 0.10 pixels in the testing set. V-Net-derived segmentation maintained a clinically tolerable distance error, within 3 mm on average, and all lines presented with a tolerable angle error, within 3° on average in all boundaries. Real-time, accurate, and repeatable automatic scanning was accomplished with and a lower radiation exposure dose (all P < 0.001).ConclusionsCAPITAL-CT generated standard and reproducible images that could simplify the work of radiologists, which would be of great help in the follow-up of stroke patients and in multifield research in neuroscience.

Primary anti-phospholipid antibody syndrome (pAPS) is a multi-organ autoimmune disease, and autoantibodies are involved in its pathogenesis. Follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) are critical for B cell maturation and antibody production, but their roles in pAPS remain unknown. We enrolled 32 pAPS patients and 23 healthy controls (HCs) and comprehensively analyzed circulating Tfh and Tfr, as well as their subsets, using flow cytometry. Clinical data including autoantibody levels were collected and their correlations with Tfh and Tfr subsets were analyzed. In addition, correlation analyses between B cell functional subsets and Tfh and Tfr were performed. Changes and potential effects of serum cytokines on Tfr and Tfh were further explored. We found the circulating Tfr was significantly decreased while Tfh and Tfh/Tfr ratios were increased in pAPS patients. Tfh2, inducible T cell co-stimulator (ICOS)+ programmed cell death 1 (PD-1)+ Tfh and Ki-67+ Tfh percentages were elevated, while CD45RA−forkhead box protein 3 (FoxP3)hi, Helios+, T cell immunoglobulin and ITIM (TIGIT)+ and Ki-67+ Tfr percentages were decreased in pAPS patients. New memory B cells and plasmablasts were increased and altered B cell subsets and serum autoantibodies were positively correlated with Tfh, Tfh2, ICOS+PD-1+ Tfh cells and negatively associated with Tfr, CD45RA−FoxP3hi Tfr and Helios+ Tfr cells. In addition, pAPS with LA/aCL/β2GPI autoantibodies showed lower functional Tfr subsets and higher activated Tfh subsets. Serum interleukin (IL)-4, IL-21, IL-12 and transforming growth factor (TGF)-β1 were up-regulated and associated with Tfh and Tfr subset changes. Our study demonstrates that imbalance of circulating Tfr and Tfh, as well as their functional subsets, is associated with abnormal autoantibody levels in pAPS, which may contribute to the pathogenesis of pAPS.

Electrochemical N2 reduction to NH3 has been considered as a promising sustainable and clean process to replace the conventional Haber–Bosch process. However, the development of efficient and stabl...

During the measurement of spectral luminous efficiency function $$V\left( \lambda \right)$$, monochromatic visual stimuli of higher luminance can be obtained by narrow band optical filters with broad band light sources, compared to monochromators. However, the distortion of $$V\left( \lambda \right)$$ is inevitably caused due to the bandwidth of the optical filters. In this paper, the effect of optical filters and light source spectra on the spectral luminous efficiency function $$V\left( \lambda \right)$$ measurement is studied. Filters with different spectral transmittances and light sources with different spectral power distributions are considered in the model to simulate visual sensitivity experiment. Compared with real $$V\left( \lambda \right)$$, the distortion of the simulated $$V\left( \lambda \right)$$ caused by the bandwidth of filters is quantitatively evaluated with the aid of a quality indicator, mismatch error $$f'$$. Results and conclusions in this paper can be used as a guide to optimize the design of the visual sensitivity experiments for $$V\left( \lambda \right)$$ measurement.

Most of the existing simultaneous localization and mapping (SLAM) methods are based on the static environment assumption. The presence of moving objects in the scene will lead to much uncertainty in SLAM results, which also hinders the loop-closure detection (LCD). Although moving object tracking (MOT) is necessary for planning and decisions, it is often accomplished separately. To jointly solve SLAM and MOT for complex urban driving scenarios, this paper presents a high performance method named 4D-SLAM based on the fusion of LiDAR and IMU. The integration of SLAM and MOT is formulated as a joint posterior probability problem based on a dynamic Bayesian network (DBN) and is implemented with the following four sequential stages: preprocessing, moving object detection and tracking, odometry estimation and mapping. In the preprocessing stage, the motion distortion uncertainty caused by LiDAR scanning is first compensated for, and the initial LiDAR motion is estimated. In the moving object detection and tracking stage, we exploit a CNN-based segmentation network to detect the potential moving objects first, then the states of the potential moving objects are optimized by an unscented Kalman filter (UKF). In the odometry estimation stage, the distinctive planar and edge features extracted from a static background point cloud are used for the odometry estimation, and a two-step Levenberg-Marquardt optimization method is adopted to solve the 6DOF pose across consecutive scans. In the mapping stage, the mapping based on the pose estimation result and LCD are realized, and graph-based global optimization is exploited to further improve the map consistency for large scale environment. The comprehensive experiments with the open source dataset KITTI and the data collected by us show that the presented method not only outperforms the SOTA SLAM methods in terms of trajectory and mapping accuracy but can also detect and track moving objects efficiently.

The uncertainty of worn parts is a challenge for the remanufacturing process. Therefore, an integrated optimization decision method for remanufacturing process based on conditional evidence theory under uncertainty is proposed. On the basis of production history data of remanufacturing enterprises, prior information of the remanufacturing process is generated, and the prior evidence is constructed. Then, depending on the relationship between the parameters and the processing technology, the information of detection and evaluation of parts' characteristic parameters is transformed into evidence. The prior evidence and the evidence are fused corresponding to the parameter value. Then, the influence law among production data, characteristics of worn parts and technological process in remanufacturing is revealed. The fusion result has a one-to-one correspondence with the processing technology of worn parts. According to the decision rules, the optimal processing technology of worn parts can be obtained by judging the fusion results. The statistical data of remanufacturing worn crankshafts shows that the quality improved by 2.5%, the production cost reduced by 5.6%, and the time saved by 7.3%. This study provides theoretical and methodological support for the optimization of remanufacturing production.

This work reports the synthesis of core-shell structured Au@C composite through a simple one-step laser ablation technique. The results demonstrate that the Au@C with a mean nanosphere size of ∼8.0 nm is composed of a spherical shaped Au core and 1-2 layered graphitic carbon shell with abundant defects. As a nitrogen reduction reaction (NRR) electrocatalyst, the Au@C gives a large NH

The chemical oxygen demand (COD) of waste water from bamboo heat treatment is mainly organic macromolecule compound which degraded from hemicellulos, lignin and extractives. COD is toxic to aquatic organism and human body and very difficult to degrade. The paper studied the possibility of pre-treating the bamboo heat treated waste water (BHTWW) by combination of iron-carbon micro electrolysis and Fenton method. Orthogonal experiment was designed with 3 factors: the initial pH value, retention time and H2O2 dosage, and carried out with a dynamic sampling device with 2:1 iron carbon ratio. Results showed that the iron-carbon micro electrolysis and Fenton were proved to be a potential method in pre-treating BHTWW, and the optimum parameter should be pH 3.0, 40 min residence time and 0.5 % H2O2. After pre-treating, the removal rate of COD was 60.29 %, and B/C (biochemical oxygen demand after 5 days (BOD5)/COD increased from 0.037 to 0.32, the biodegradability was significantly improved. During the pretreatment, the nutrients in BHTWW had been oxidized, the double bound, conjugated double bond in guaiac lignin were opened or broken and degraded into more small molecular, nutrients such as TOC (total organic carbon) content, total nitrogen and total sugar content all decreased which all contributed for the increase of B/C. The microstructure of activated carbon appeared broken and collapses after pretreatment which indicated that they were eroded or involved during the micro electrolysis reaction.

In this work, we report the synthesis of TiO2 nanotube arrays with Au nanocrystals (Au@TiO2) via magnetron sputtering and thermal annealing at 450 °C. The prepared TiO2 nanotube arrays are characterized by field emission scanning electron microscopy, X-ray diffraction and transmission electron microscopy. The annealing leads to the formation of a layer of Au nanocrystals on the surface of TiO2 nanotubes and the dewetting of Au nanofilms on the top of TiO2 nanotube arrays. Using the Au@TiO2 nanotube arrays as anode material, we prepare lithium-ion half cells, and study the electrochemical performance of the lithium-ion half cells. The experimental results show that the lithium-ion half cells with the Au@TiO2 nanotube arrays prepared with the thickest Au film of 160 nm have the smallest charge-transfer resistance and the lithium-ion half cells with TiO2 nanotube arrays have the largest charge-transfer resistance. The specific capacity of the lithium-ion half cells with the Au@TiO2 nanotube arrays prepared with Au nanofilm of 120 nm is ~185 mAh·g−1, about twice of those with TiO2 nanotube arrays after 200 cycles. The Au nanocrystals in TiO2 nanotube arrays improve the cycle stability of the lithium-ion half cells with the Au@TiO2 nanotube arrays as anode material.

Nanoscale field-effect transistors (FETs) represent a unique platform for real time, label-free transduction of biochemical signals with unprecedented sensitivity and spatiotemporal resolution, yet their translation toward practical biomedical applications remains challenging. Herein, we demonstrate the potential to overcome several key limitations of traditional FET sensors by exploiting bioactive hydrogels as the gate material. Spatially defined photopolymerization is utilized to achieve selective patterning of polyethylene glycol on top of individual graphene FET devices, through which multiple biospecific receptors can be independently encapsulated into the hydrogel gate. The hydrogel-mediated integration of penicillinase was demonstrated to effectively catalyze enzymatic reaction in the confined microenvironment, enabling real time, label-free detection of penicillin down to 0.2 mM. Multiplexed functionalization with penicillinase and acetylcholinesterase has been demonstrated to achieve highly specific sensing. In addition, the microenvironment created by the hydrogel gate has been shown to significantly reduce the nonspecific binding of nontarget molecules to graphene channels as well as preserve the encapsulated enzyme activity for at least one week, in comparison to free enzymes showing significant signal loss within one day. This general approach presents a new biointegration strategy and facilitates multiplex detection of bioanalytes on the same platform, which could underwrite new advances in healthcare research.

Narrowing high-temperature superconducting (HTS) tapes can effectively enhance the ability of antielectromagnetic interference. In addition, different structures of HTS wires are necessary for HTS applications. Thereby, a kind of soldered-stacked-square (3S) HTS Wires has been proposed. This paper presents a process of fabricating several 3S HTS wires. A normal second-generation (2G) HTS tape having 4-mm width was narrowed into four 1-mm-width narrow HTS tapes. The main propose of this paper is to study different effects of mechanical force on the critical current of 3S HTS wires. Therefore, we measured the critical current variation of these wires from the torsion, bending, and tension effects points of view, respectively. Compared with their initial critical current values, if the reduction of the influenced critical current is smaller than 5%, it can be considered that these 3S HTS wires are workable. Based on the results of the experiment, the limitations of mechanical force for these wire applications are: minimal twisting pitch of 64 mm, minimal bending diameter of 54 mm, and maximum tensile force of 374 N.

Angular dependence of second generation (2G) high-temperature superconducting (HTS) tape is a crucial parameter for its industrial applications. Known as soldered-stacked-square (3S) HTS wire, a novel structure of HTS wire has been proposed in our previous research. In this paper, angular dependence of 1 mm HTS tape, 4 mm tape, 1 mm 3S HTS wire, and 1 mm 3S HTS twisted wire were measured in liquid nitrogen bath, respectively. It can be found that the 3S HTS wire would not enhance the critical current density under external magnetic field, while an isotropic angular dependence is obtained when 3S HTS wire is twisted. The test results obtained in this paper provides useful information for the future applications of 3S HTS wire.

Electroadhesive grippers can be used to pick up a wide range of materials, and those with variable stiffness functionality can increase load capacity and strength. This paper proposes an electroadhesive gripper (VSEAF) with variable stiffness function and a simple construction based on low melting point alloys (LMPAs) with active form adaptation through pneumatic driving. Resistance wires provide active changing stiffness. For a case study, a three-fingered gripper was designed with three electroadhesive fingers of varied stiffness. It is envisaged that these electroadhesive grippers with variable stiffness would extend the preparation process and boost the use of electroadhesion in soft robot applications.