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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.

Predicting brain invasion preoperatively should help to guide surgical decision-making and aid the prediction of meningioma grading and prognosis. However, only a few imaging features have been identified to aid prediction. This study aimed to develop and validate an MRI-based nomogram to predict brain invasion by meningioma. In this retrospective study, 658 patients were examined via routine MRI before undergoing surgery and were diagnosed with meningioma by histopathology. Least absolute shrinkage and selection operator (LASSO) regularization was used to determine the optimal combination of clinical characteristics and MRI features for predicting brain invasion by meningiomas. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to determine the discriminatory ability. Furthermore, a nomogram was constructed using the optimal MRI features, and decision curve analysis was used to validate the clinical usefulness of the nomogram. Eighty-one patients with brain invasion and 577 patients without invasion were enrolled. According to LASSO regularization, tumour shape, tumour boundary, peritumoral oedema, and maximum diameter were independent predictors of brain invasion. The model showed good discriminatory ability for predicting brain invasion in meningiomas, with an AUC of 0.905 (95% CI, 0.871–0.940) vs 0.898 (95% CI, 0.849–0.947) and sensitivity of 93.0% vs 92.6% in the training vs validation cohorts. Our predictive model based on MRI features showed good performance and high sensitivity for predicting the risk of brain invasion in meningiomas and can be applied in the clinical setting.

Lignocellulosic biomass is considered the most abundant and renewable feedstock for biobased butyric acid production. However, the furan derivatives (FAs, mainly furfural and 5-hydroxymethylfurfural) generated from the pretreatment of lignocellulose severely inhibit the growth of Clostridium tyrobutyricum, which is the best strain for producing butyric acid. The tolerance mechanism of C. tyrobutyricum to FAs has not been investigated thus far. Here, the response of C. tyrobutyricum ATCC 25755 to FA challenge was first evaluated by using comprehensive transcriptional analysis. The results indicated that the genes related to membrane transport, heat shock proteins, and transcriptional regulation were upregulated under FA stress. However, the expression of almost all genes encoding reductases was not changed, and only the ad gene CTK_RS02625 and the bud gene CTK_RS07810 showed a significant increase of ~ 1.05-fold. Then, the enzyme activity assays indicated that BUD could catalyze the reduction of FAs with relatively low activity and that AD could not participate in the conversion of FAs, indicating that the inability to rapidly convert FAs to their low-toxicity alcohols may be the main reason for the low FA tolerance of C. tyrobutyricum. This research provides insights into the development of FA-tolerant strains, thereby enhancing the bioconversion of lignocellulosic biomass to butyric acid. KEY POINTS: • The response of C. tyrobutyricum to FAs was evaluated for the first time. • Genes encoding membrane transporters and heat shock proteins were triggered by FAs. • A lack of effective FA reductases leads to low FA tolerance in C. tyrobutyricum.

Ni-based superalloys are widely used to manufacture the critical hot-end components of aviation jet engines and various industrial gas turbines. The analysis of Ni-based superalloys microstructures is an important research task during the design and development of superalloys. The material microstructure information can only be understood by experts in the long history. Image segmentation and recognition are developing techniques for accelerating the microstructure analysis automatically. Although deep learning techniques have achieved satisfactory performance, they usually suffer from generalization, i.e., performing worse on a new dataset. In this paper, a deep transfer learning method which just needs a small number of labeled images is proposed to perform the microstructure recognition on γ′ phase. To evaluate the effectiveness, we homely prepare two Ni-based superalloys at temperatures 900 °C and 1000 °C, and manually annotate two datasets named as W-900 and W-1000. Experimental results demonstrate that the proposed method only needs 3 and 5 labeled images to achieve state-of-the-art segmentation accuracy during the transfer from W-900 to W-1000 and the transfer from W-1000 to W-900, while enjoying the advantage of fast convergence. In addition, a simple and effective software for the Ni-based superalloys microstructure recognition on γ′ phase is developed to improve the efficiency of materials experts, which will greatly facilitate the design of new Ni-base superalloys and even other multicomponent alloys.

Maize (Zea mays L.) is one of the most important crops in China. Since 2020, a new leaf spot disease has occurred in southwest China in areas such as Yunnan, Sichuan and Hubei provinces. Typical symptoms appeared after tasseling. The spots are scattered on the leaf surface, round to oval in shape with diameter range 3-20 mm. Spots are initially water-soaked, gradually turning yellow or white. In 2021, diseased leaf samples with typical white spot were collected for pathogen isolation and identification in Qujing, Yunnan province. Four small pieces of leaf tissue (about 0.25 cm2 in area) were excised from the edge of the necrotic lesion of each plant, surface sterilized with 75% ethanol for 1 min, rinsed three times with sterile distilled water, and soaked in sterile distilled water for 5 min. The solution was plated on Luria Broth medium (LB) plate (Shin et al. 2022) . After incubation at 28°C for 24 h, round, smooth-edged yellow colonies appeared in the LB plate. The bacterium isolated was gram-negative, negative for oxidase, positive for peroxidase, indole, citrate (Wells et al. 1987). Three strains (PA21QJ01, PA21QJ02 and PA21QJ03) showed identical colony morphology. PA21QJ01 was used for further molecular analyses. DNA was extracted from fresh colonies cultured in LB(Shin et al. 2022), and the fragments at the 16S rDNA, gyrB and rpoB loci were amplified using primers 27F/1492R (Galkiewicz and Kellogg 2008), UP-1/UP-2r (Yamamoto and Harayama 1995) and rpoBCM81-F/rpoBCM32b-R (Brady et al. 2008), respectively. The sequences of fragments of 16S rDNA, gyrB and rpoB from isolate PA21QJ01 were was deposited in GenBank (accession number: OM184301.1, OM302500, OM302499). A search for homologous sequences using BLAST resulted in 99.9, 99.6 and 99.8% identity of 16S rDNA, gyrB and rpoB, respectively, with sequences from the NN08200 of Pantoea ananatis (GenBank accession numbers: MK415050.1 for 16S rDNA, CP035034.1 for gyrB and CP035034.1.1 for rpoB). Above molecular results indicated that PA21QJ01 isolated from maize white spot is P. ananatis. Pathogenicity tests were performed on tasseled plants of the suscptible maize variety Wugu1790. After culture in LB medium plate at 30°C for 12 h, the bacterial solution was used for inoculation at a concentration of 1 × 108 CFU ml-1. After 7 days of inoculation, the leaves of the plants appeared water-soaked. After 10 days, white spot developed with brown margin. In contrast, the control plants remained healthy and symptomless. The same P. ananatis was reisolated in the inoculated maize plants, fulfilled Koch's law. In the last decade, P. ananatis has been reported to cause maize white spot in South Africa, Mexico, Poland, Argentina, Brazil (Sauer et al. 2015), and Ecuador (Toaza et al.2021). It has caused crop diseases with other crops, such as onion, rice, pineapple, melon, and sorghum, and others (Sauer et al. 2015). It caused leaf blight and leaf steak in rice in China (Yu et al. 2021). This is the first report of maize white spot caused by P. ananatis in China. However, to our knowledge, this is the first report of maize white spot disease in China. Attentions should be paid to screening for disease-resistant resources and breeding disease-resistant hybrids. Reference: Wells, J. M. et al. 1987. Int. J. Syst. Bacteriol. 37:136-143. Shin, G. Y. et al. 2022. Plant Dis. Doi: 10.1094/PDIS-08-21-1810-SC. Brady, C., et al. 2008. Syst. Appl. Microbiol. 31:447. Galkiewicz, J. P., and Kellogg, C. A. 2008. APPL ENVIRON MICROB, 74.24: 7828-7831. Toaza, A. et al. 2021. Plant Dis. Doi:10.1094/PDIS-02-21-0298-PDN Yamamoto, S., and Harayama, S. 1995. APPL ENVIRON MICROB, 61:1104.L. Sauer, A. V. et al. 2015. Agronomy Science and Biotechnology. Doi:10.33158/ASB.2015v1i1p21 Yu et al. 2021. Plant Dis. Doi:10.1094/PDIS-05-21-0988-PDN.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Background Highly expressed STOML2 has been reported in a variety of cancers, yet few have detailed its function and regulatory mechanism. This research aims to reveal regulatory mechanism of STOML2 and to provide evidence for clinical therapeutics, via exploration of its role in colorectal cancer, and identification of its interacting protein. Methods Expression level of STOML2 in normal colon and CRC tissue from biobank in Nanfang Hospital was detected by pathologic methods. The malignant proliferation of CRC induced by STOML2 was validated via gain-of-function and loss-of-function experiments, with novel techniques applied, such as organoid culture, orthotopic model and endoscopy monitoring. Yeast two-hybrid assay screened interacting proteins of STOML2, followed by bioinformatics analysis to predict biological function and signaling pathway of candidate proteins. Target protein with most functional similarity to STOML2 was validated with co-immunoprecipitation, and immunofluorescence were conducted to co-localize STOML2 and PHB. Pathway regulated by STOML2 was detected with immunoblotting, and subsequent experimental therapy was conducted with RAF inhibitor Sorafenib. Results STOML2 was significantly overexpressed in colorectal cancer and its elevation was associated with unfavorable prognosis. Knockdown of STOML2 suppressed proliferation of colorectal cancer, thus attenuated subcutaneous and orthotopic tumor growth, while overexpressed STOML2 promoted proliferation in cell lines and organoids. A list of 13 interacting proteins was screened out by yeast two-hybrid assay. DTYMK and PHB were identified to be most similar to STOML2 according to bioinformatics in terms of biological process and signaling pathways; however, co-immunoprecipitation confirmed interaction between STOML2 and PHB, rather than DTYMK, despite its highest rank in previous analysis. Co-localization between STOML2 and PHB was confirmed in cell lines and tissue level. Furthermore, knockdown of STOML2 downregulated phosphorylation of RAF1, MEK1/2, and ERK1/2 on the MAPK signaling pathway, indicating common pathway activated by STOML2 and PHB in colorectal cancer proliferation. Conclusions This study demonstrated that in colorectal cancer, STOML2 expression is elevated and interacts with PHB through activating MAPK signaling pathway, to promote proliferation both in vitro and in vivo. In addition, combination of screening assay and bioinformatics marks great significance in methodology to explore regulatory mechanism of protein of interest.

Improving resource efficiency and reducing waste discharge are the inevitable trend of the development of sustainable machining system. Therefore, a data-driven sustainability evaluation method of machining system is proposed. The input (energy, materials, equipment, R&D and services), and output (wastes and products) data of machining system are collected. These dimensional data are processed by emergy. The emergy flow calculation model of the machining process is established for data modeling, and the sustainability evaluation index of machining system is constructed for data analysis. Finally, an engine base machining process is taken as case study for innovative practice; and the targeted process optimization is adopted based on its sustainability evaluation for innovative practice. The feasibility and effectiveness of the method are verified. This study provides theoretical and methodological support for promoting the sustainability of the manufacturing industry.