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The T cell response is an important detection index in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine development. The present study was undertaken to determine the T cell epitopes in the spike (S) protein of SARS-CoV-2 that dominate the T cell responses in SARS-CoV-2–infected patients. PBMCs from rhesus macaques vaccinated with a DNA vaccine encoding the full-length S protein were isolated, and an ELISPOT assay was used to identify the recognized T cell epitopes among a total of 158 18-mer and 10-aa-overlapping peptides spanning the full-length S protein. Six multipeptide-based epitopes located in the S1 region, with four of the six located in the receptor-binding domain, were defined as the most frequently recognized epitopes in macaques. The conservation of the epitopes across species was also verified, and peptide mixtures for T cell response detection were established. Six newly defined T cell epitopes were found in the current study, which may provide a novel potential target for T cell response detection and the diagnosis and vaccine design of SARS-CoV-2 based on multipeptide subunit-based epitopes.

Immune checkpoint inhibitors exhibit limited response rates in patients with triple-negative breast cancer (TNBC), suggesting that additional immune escape mechanisms may exist. Here, we performed two-step customized in vivo CRISPR screens targeting disease-related immune genes using different mouse models with multidimensional immune-deficiency characteristics. In vivo screens characterized gene functions in the different tumor microenvironments and recovered canonical immunotherapy targets such as Ido1 . In addition, functional screening and transcriptomic analysis identified Lgals2 as a candidate regulator in TNBC involving immune escape. Mechanistic studies demonstrated that tumor cell–intrinsic Lgals2 induced the increased number of tumor-associated macrophages, as well as the M2-like polarization and proliferation of macrophages through the CSF1/CSF1R axis, which resulted in the immunosuppressive nature of the TNBC microenvironment. Blockade of LGALS2 using an inhibitory antibody successfully arrested tumor growth and reversed the immune suppression. Collectively, our results provide a theoretical basis for LGALS2 as a potential immunotherapy target in TNBC.

The combination of solution IR spectroscopy measurement, fast cooling crystallization experiments, conformational search, and molecular computation was investigated in detail in this study to explo...

Anion redox chemistry is an essential component of many high energy density electrode materials, while accompanying with voltage hysteresis and fade, which currently hinders its widespread use. Here we demonstrate cation-synergy stabilizing anion redox of Chevrel phase Mo6S8 in aluminum ion battery. EELS and XAS reveal that S is fully reduced, and Mo6 cluster is firstly oxidized and then reduced with Al3+ ions insertion, which originates from the contraction and elongation of Mo-Mo bond in Mo6 cluster verified by atomic-resolved imaging. DFT calculations uncover that the energy level of [Mo-Mo]* antibonding orbitals is lifted and fell by Mo-Mo bond evolution, resulting in the synergetic cationic and anionic redox, which contributes to the stable structure upon cycling. Our work figures out the electrochemical redox mechanism of Mo6S8 in aluminum ion batteries and provides implications generally for the design of materials employing anion redox chemistry.

Summary Memristive devices offer desirable voltage-regulated conductance switching and promise to address zettabyte storage challenges in the big-data era. Generally, most of these reported devices use amorphous solids, where the structural and compositional inhomogeneity is regarded as the origin of stochastic variability. Self-assembling peptide crystals with solution-processed fabrication, controllable morphologies, and structural stability are therefore a promising candidate to address the reliability issues. Here we report a planar diffusive memristor that possesses reliable switching characteristics based on a quasi-one-dimensional crystallized material: diphenylalanine (FF) microrod (MR). This element offers a preferential ion migration path, confining conductive filaments in a defined crystalline surface and therefore reducing programming stochasticity. Ion transport confinement along FF MR was observed via in situ electrostatic force microscopy technique. Additionally, FF MR memristor with high switching uniformity and reproducible relaxation dynamic provides an ideal hardware platform for reliable nociceptor emulation and hardware identification of four-bit decimal numbers.

The functionality of functional materials originates from field and local symmetry. The local symmetry in matter science is described by four degrees of freedom: Lattice, charge, orbit and spin. To understand and use the rich physical properties brought by the structural distortion of atomic nearest neighbors and second nearest neighbors under symmetry breaking, we need to grasp the fine structure of matter at the picometer scale. This paper reviews the exploration of the origin of functional materials by picometer scale electron microscopy in the three cases in the lattice degree of freedom, the expansion and contraction of the polyhedron, the tilt and rotation of the polyhedron and the cation displacement. In the expansion and contraction of the polyhedron degree of freedom, we use picometer scale scanning transmission electron microscopy (STEM) studies of lithium ion battery materials, which can be classified as the unit cell breathing model and Jahn-Teller effect, to illustrate the relationship between functionalities and structural origins. In the tilt and rotation of the polyhedron degree of freedom, we mainly focus on the heterointerface among functional oxides. The emergent phenomena arising from this heterointerface form most of the topics of modern condensed matter physics, such as high temperature superconductivity, magnetoresistance, antiferromagnetic, multiferroics, etc. Lattice mismatch caused polyhedron tilt and rotation alter the local symmetry of the oxides, and hence various functionalities are created. In terms of cation displacement degree of freedom, ferroelectricity is the typical example to show the structure-property relationship. The most exciting future of ferroelectric material is the potential to be the next generation memory material because of its topological property. With the help of aberration corrected (AC)-STEM, flux closure type and vortex type ferroelectric domain were directly observed at picometer accuracy. Furthermore, through in-situ mechanical and electric force studies, reverse transition from topological and normal ferroelectric state was observed, which paves the way of the application of the ferroelectric material as future memory material system. At the electronic structure level, the charge structure under the picometer-scale lattice structure is reviewed. Through the simultaneously recorded EELS data, we can know the valence state and content fluctuation of certain element. For example, in lithium ion battery materials, atomic and electronic structure changes all the time during the whole working duration. It is crucial to know the local valence state of the transition metal elements. AC-STEM and electron energy loss spectroscopy (EELS) can help us to solve this problem under one time acquisition. And future perspectives of the electron microscopy research on the orbit and spin structure with high spacial resolution are discussed, such as monochromatic EELS, electron-energy-loss magnetic circular dichroism (EMCD), electron-energy-loss magnetic linear dichroism (EMLD) and convergent beam electron diffraction (CBED). CBED is considered to be the best way to discover the orbit structure with high spacial resolution. In terms of spin structure, EMCD and EMLD are not the direct methods to detect the electron spin, which limits the resolution and signal to noise ratio of acquired results. In the future, spin polarized electron source is considered as the proper way to discover the spin structure with high spacial resolution. Nowadays, spacial resolution is not the limit of the TEM. The ability of accessing more kinds of materials, powerful in-situ method and acquiring orbit and spin structure with picometer resolution are goals for us.

In this work, a new quantitative analysis method of multi-components analysis via a single marker strategy coupled with high-performance liquid chromatography (HPLC) analysis, was proposed to analyze nine nucleosides (cytidine, uridine, 2'-deoxyuridine, inosine, guanosine, 2'-deoxyguanosine, thymidine, adenosine, and 2'-deoxyadenosine) as quality control markers in Rhizoma Paridis. Guanosine was set as the internal reference substance, whose content in Rhizoma Paridis was determined using conventional external standard method. Then, relative correction factors between guanosine and the other eight nucleosides were measured respectively. The amounts of the other eight components were calculated according to the relative correction factors by the quantitative analysis of multi-components via a single marker method. Finally, the result of vector angle cosine analysis showed that there was no significant difference of the contents between the external standard method and the quantitative analysis of multi-components via a single marker method, indicating that the quantitative analysis of multi-components via a single marker method can be applied for the quality control of Rhizoma Paridis. As far as we know, this is also the first report to analyze nucleosides by the quantitative analysis of multi-components via a single marker method, providing an efficient and promising quality assessment method for other traditional Chinese medicine containing nucleosides.

Piper crocatum Ruiz & Pav. (P. crocatum), a traditional medicinal plant, has been shown to possess various pharmacological activities, including anticancer activity, antioxidant activity, antibacterial activity, anti-hyperglycemic activity, anti-allergic inflammatory activity and others. To identify the potential anti-allergic inflammatory effective constituents of P. crocatum, 13 single compounds were isolated from the methanol extract of P. crocatum leaves, and their structures were identified by contrasting their NMR spectroscopic data and previously published papers. First, the anti-allergic inflammatory activities of these single compounds were examined by accessing immune function related biomarkers such as nitric oxide (NO) and β-hexosaminidase. We found that the methanol extract and catechaldehyde (compound 1) potently suppressed NO production. Additionally, Western blot analysis showed that P. crocatum methanol extract and compound 1 suppressed the production of NO by reducing inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these observations, P. crocatum methanol extract and compound 1 remarkably decreased β-hexosaminidase release from RBL-2H3 cells stimulated with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA)-specific immunoglobulin E (IgE) antibodies. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicated that P. crocatum methanol extract and compound 1 exhibited no cytotoxicity to RAW264.7 and RBL-2H3 cells. Based on these findings, compound 1 is suggested as an active anti-allergic inflammatory component of P. crocatum.

Exsolution of catalytic nanoparticles (NPs) from perovskites has arisen as a flexible method to develop high-performance functional materials with enhanced durability for energy conversion and catalytic synthesis applications. Here, we unravel the interface structure of the in situ exsolved alloy nanoparticles from the double perovskite substrate on the atomic scale. The results show that the Co-Fe alloy NPs exsolved topologically from the {100} facets terminations of the Sr2FeMo0.65Co0.35O6-δ (SFMC) double perovskite along ⟨100⟩ directions exhibiting the same orientation and identical crystal structure. The lattice planes of these two phases align and insert into each other at the interface, forming a smooth and continuous coherent connection. The presence of moire patterns at the interface confirms the topological exsolution mechanism. The coherent interface can significantly reduce the interfacial energy and therefore stabilize the exsolved nanoparticles. Therefore, excellent and stable electrochemical performance of the NP-decorated SFMC perovskite is observed as the anode for solid oxide fuel cells. Our contribution promotes a fundamental understanding of the interface structure of the in situ exsolved alloy nanoparticles from perovskite substrate.

Background: Atopic dermatitis (AD) is a widely acquired, relapsing inflammatory skin disease. Biologics are now widely used in patients with moderate-to-severe AD. Objective: This work aims to summarize both label and off-label biologics on AD treatment in phase II and phase III stages, and compile evidence on the efficacy of the most-studied biologics. Methods: We conducted a comprehensive literature search through PubMed, EMBASE, and ClinicalTrials.gov to identify all documented biological therapies for AD. The criteria were further refined to focus on those treatments with the highest evidence level for AD with at least one randomized clinical trial supporting their use. Only studies or articles published in English were enrolled in this study. Findings: Primary searches identified 525 relevant articles and 27 trials. Duplicated articles and papers without a full text were excluded. Only completed trials were enrolled. We included 28 randomized controlled trials, 4 unpublished trials, 2 observational studies, and 1 meta-analysis. Eight kinds of biologics, including IL-4/IL-13 inhibitors, JAK inhibitors, anti-IL-13 antibodies, anti-IL-22 antibodies, anti-IL-33 antibodies, thymic stromal lymphopoietin inhibitor (TSLP), OX40 antibodies, and H4R-antagonists were included in this work. Dupliumab, as the most widely used and investigated biologic, was reported in 1 meta-analysis and 4 trials exploring its long-term use and application in both adults and pediatric patients. Besides dupilumab, four other IL-4/IL-13 inhibitors recruited were all randomized, clinical trials at phase 2–3 stage. Six different kinds of JAK inhibitors were summarized with strong evidence revealing their significant therapeutic effects on AD. There were 3 trials for nemolizumab, an anti-IL-13 antibody, all of which were in the phase 2 clinical trial stage. Results showed nemolizumab could be another alternative therapy for moderate-to-severe AD with long-term efficiency and safety. Conclusion: The biological therapies with the most robust evidence on efficacy and long-term safety for AD treatment include dupilumab, barcitinib, abrocitinib, and delgocitinib. Most of the biologics mentioned in this review were still at the exploratory stage. This review will help practitioners advise patients seeking suitable biological therapies and offer experimental study directions for treatment.

Resistive random access memory (RRAM) based on hybrid organic–inorganic halide perovskite (HOIP) materials has recently gained significant interest due to its low activation energy of ion migration. HOIP RRAM has been reported to exhibit outstanding performance, but they still suffer from issues of high operating voltage and poor uniformity. Here, we provide an efficient method for improving the resistive switching characteristics of HOIP RRAM by integrating an Au tip in the bottom electrode to regulate the growth of conductive filaments (CFs). The Ag/polymethylmethacrylate/CH3NH3PbI3/Au tip/indium tin oxide RRAM exhibits a lower set voltage of −0.11 V, a larger ON/OFF ratio of 108, excellent durability (up to 4 × 103 times), low power consumption, and good non-volatility. Moreover, the time-dependent resistive switching characteristics were investigated by a statistical analysis of the data on the turn-on time based on the Weibull distribution. Tests using transmission electron microscopy, electron energy depletion spectroscopy, and energy dispersive spectroscopy have demonstrated that the formation and rupture of CFs occur mainly in the CH3NH3PbI3 layer and that the CFs should be composed of Ag atoms and I vacancies. Our research offers a strategy for enhancing the stability of perovskite devices and promoting the application of low-power, high-density non-volatile memory devices.

Organic pigments are important in a range of fields, from printing ink to industrial coatings. Azo pigments are some of the most common pigments in use today, but they typically have poor solvent solubility and tend to agglomerate. Consequently, the size and crystal structure of the pigment particles has a crucial effect on their optical and physical properties, such as color strength and solvent resistance, respectively. Several technologies, such as microreactors, have been developed to control pigment particle size, but an in-depth study of the effects of modification conditions on pigment properties (color, flowability, and solvent resistance) has not been reported to date. Therefore, in this paper, we report the surface modification of C.I. Pigment Red 146 particles using anionic (Igepon T) and non-ionic surfactants (Peregal O-25) and additives (DB-60 as the second diazo component and graphene oxide) on the pigment properties. In addition, we examined the effect of hydrothermal treatment at different temperatures on the same properties. The various modifications resulted in an increase in the solvent resistance, a reduction in the particle size (from 30.581 to 12.252 μm), a narrowing of the particle size distribution, and an increase in hydrophilicity. In addition, the color brightness and brilliance were significantly improved, and the maximum color strength reached 112.6%. These findings have applications for the development of pigments having enhanced color properties, solvent resistance, and processability.

Background: Metastasis is the main death reason for triple-negative breast cancer (TNBC). Thus, identifying the driving genes associated with metastasis of TNBC is an urgent need. CRISPR screens have dramatically enhanced genome editing and made it possible to identify those genes associated with tumor metastasis. Methods: Here, we performed customized in vivo CRISPR screens targeting metastasis-related genes obtained from transcriptome analysis. By applying Cox proportional hazard regression models, we developed and verified a three-gene signature (RhoV, TSNARE1 and C19orf33) to predict the disease-free survival in TNBC. Next, immunoprecipitation and LC-MS/MS were conducted to explore the metastasis mechanism of RhoV.Results: The three-gene signature successfully predicts the disease-free survival in TNBC. Furthermore, our data demonstrated RhoV as a key gene involving in tumor metastasis, which was frequently upregulated in TNBC and correlated with poor survival. Knockdown of RhoV significantly suppressed cell invasion, migration and metastasis both in vitro and in vivo. In addition, we explored the physically association between RhoV and activated EGFR and verified the association was dependent on GRB2 through a specific proline-rich motif in N-terminus of RhoV. Conclusions: Taken together, our research firstly reveals that RhoV serves as an EGFR-mediated metastasis mechanism activator and thus provides a mechanistic basis for TNBC metastasis and may be a valuable therapeutic target.

With the development of artificial intelligence and Internet of Things, hand gesture recognition techniques have attracted great attention owing to their excellent applications in developing human-machine interaction (HMI). Here, the authors propose a non-contact hand gesture recognition method based on intelligent metasurface. Owing to the advantage of dynamically controlling the electromagnetic (EM) focusing in the wavefront engineering, a transmissive programmable metasurface is presented to illuminate the forearm with more focusing spots and obtain comprehensive echo data, which can be processed under the machine learning technology to reach the non-contact gesture recognition with high accuracy. Compared with the traditional passive antennas, unique variations of echo coefficients resulted from near fields perturbed by finger and wrist agonist muscles can be aquired through the programmable metasurface by switching the positions of EM focusing. The authors realize the gesture recognition using support vector machine algorithm based on five individual focusing spots data and all-five-spot data. The influences of the focusing spots on the gesture recognition are analyzed through linear discriminant analysis algorithm and Fisher score. Experimental verifications prove that the proposed metasurface-based non-contact wireless design can realize the classification of hand gesture recognition with higher accuracy than traditional passive antennas, and give an HMI solution.

Industrial development is an essential foundation of the national economy, but the industry is also the largest source of air pollution, of which power plants, iron and steel, building materials, and other industries emit large amounts of pollutants. Therefore, the Chinese government has promulgated a series of stringent emission regulations, and it is against this backdrop that research into air pollution control technologies for key industrial sectors is in full swing. In particular, during the 13th Five-Year Plan, breakthroughs have been made in pollution control technology for key industrial sectors. A multi-pollutant treatment technology system of desulfurization, denitrification, and dust collection, which applies to key industries such as power plants, steel, and building materials, has been developed. High-performance materials for the treatment of different pollutants, such as denitrification catalysts and desulfurization absorbers, were developed. At the same time, multi-pollutant synergistic removal technologies for flue gas in various industries have also become a hot research topic, with important breakthroughs in the synergistic removal of NO

Objective: The value of frozen section in the intraoperative diagnosis of breast cancer that failed to be diagnosed by previous core needle biopsy (CNB) is indeterminate. To evaluate and improve the clinical utility of frozen section on this kind of breast cancer, we conducted a retrospective data analysis and constructed a prediction model.Method: We reviewed data of breast cancer patients that failed to be diagnosed by previous CNB (CNB-undiagnosable) in Fudan University Shanghai Cancer Center (FUSCC) from May 1, 2006 to December 31, 2019. Clinical characteristics of patients were collected. the correlation between clinical features and false negative rate (FNR) of frozen sections was explored with logistic regression analysis, after which a nomogram was constructed to predict the probability of false negative.Result: The diagnostic sensitivity of frozen section on CNB-undiagnosable breast cancer was 67.18%, and the FNR was 32.82%. In multivariate analysis, papillary lesion (OR, 4.251; 95% CI, 2.804-6.492; PConclusion: Frozen sections are valuable in the intraoperative diagnoses of CNB-undiagnosable breast cancers. It is recommended to implement the intraoperative frozen sections for high-risk breast lesions with a low probability of false negative indicated by prediction, so as to minimize the occurrence of unnecessary second operation.

Cyclina sinensis is an edible clam widely distributed along the coastal waters of Asia. In the present study, a polysaccharide (CSP-1) isolated from C. sinensis was purified by a DEAE-Sepharose Fast Flow column, and it had an average molecular weight of 3.8 × 105 Da and a prevalent component monosaccharide of Glc. The results of methylation analysis and 1D/2D NMR indicated that CSP-1 was a glycogen constructed with α-1,4-Glc and branched at C-6 every 9 Glc residues. In addition, Cong red test suggests CSP-1 was not a helical conformation, and irregular and spherical lumps were observed by AFM. Moreover, CSP-1 was found to possess potent immunostimulatory activity on the basis of its significant abilities to enhance NO production and cytokines (TNF-α, IL-1β and IL-6) secretion in RAW 264.7 macrophages.

Since 2008, the Chinese state has been developing new public housing programs, which are widely used to distribute public housing among talent workers. This paper examines public housing allocation...

C-reactive protein (CRP) is an important biomarker for acute inflammation and infection and widely used clinically for the assessment of various diseases and the monitoring of patients’ conditions. At present, the clinical test methods for CRP mainly include immunoturbidimetry, enzyme-linked immunosorbent assays, and lateral flow assays. In recent years, developments in analysis theory and improvements in materials science have resulted in the continual emergence of analytical methods and techniques, such as biosensor technology and microfluidics. In this paper, we summarized the development and application of CRP analytical methods and focus on the developments during the last five years. In addition, we predicted the research directions for novel CRP assays and provide new ideas for the development of CRP analytical methods with high sensitivity and specificity that can meet clinical needs.

Catalytic hydrogenation is one of the backbones of the chemical industry. Controlling the reaction behaviour of the activated hydrogen species over oxide-supported metal catalysts is essential. Aside from the expected addition to substrates, the activated hydrogen species would also destroy the active structures. Here we show that, with the assistance of alkali cations, the atomically dispersed Ru(iii) on Al2O3 exhibits enhanced performance in the hydrogenation of a broad range of substrates. The alkali cations facilitate the hydrogenation mediated by heterolytic hydrogen species, which not only restrain the hydride species from migrating to interfacial oxygen, thus suppressing the reduction and aggregation of ruthenium, but also stabilize the negatively charged transition states and intermediates through enhanced Columbic attraction. Distinctively, an inverse H/D isotope effect related to H2 splitting as the rate-determining step over the atomically dispersed ruthenium-catalysed hydrogenation is predicted and confirmed. Alkali metals have been traditionally used to promote heterogeneous catalysts, albeit their mode of action remains controversial. Now, the authors demonstrate the multifaceted role of sodium ions in promoting atomically dispersed Ru(iii) on Al2O3, resulting in a superior hydrogenation catalyst.

Single-atom catalysts not only maximize metal atom efficiency, they also display properties that are considerably different to their more conventional nanoparticle equivalents, making them a promising family of materials to investigate. Herein we developed a general host–guest strategy to fabricate various metal single-atom catalysts on nitrogen-doped carbon (M1/CN, M = Pt, Ir, Pd, Ru, Mo, Ga, Cu, Ni, Mn). The iridium variant Ir1/CN electrocatalyses the formic acid oxidation reaction with a mass activity of 12.9 $${{{\rm{A}}\,{\rm{mg}}^{-1}_{{\rm{Ir}}}}}$$ whereas an Ir/C nanoparticle catalyst is almost inert (~4.8 × 10−3 $${{{\rm{A}}\,{\rm{mg}}^{-1}_{{\rm{Ir}}}}}$$). The activity of Ir1/CN is also 16 and 19 times greater than those of Pd/C and Pt/C, respectively. Furthermore, Ir1/CN displays high tolerance to CO poisoning. First-principle density functional theory reveals that the properties of Ir1/CN stem from the spatial isolation of iridium sites and from the modified electronic structure of iridium with respect to a conventional nanoparticle catalyst. Single-atom catalysts maximize metal atom efficiency and exhibit properties that can be considerably different to their nanoparticle equivalent. Now a general host–guest strategy to make various single-atom catalysts on nitrogen-doped carbon has been developed; the iridium variant electrocatalyses the formic acid oxidation reaction with high mass activity and displays high tolerance to CO poisoning.

Cenospheres are the main component of industrial waste of fly ash and taking full advantage of them has good economic and environmental values. In this paper, cenospheres sensitized emulsion explos...

Efficient, accurate and convenient foreign-gene insertion strategies are crucial for the high-throughput and rapid construction of large DNA viral vectors, but relatively inefficient and labour-intensive methods have limited the application of recombinant viruses. In this study, we applied the nonhomologous insertion (NHI) strategy, which is based on the nonhomologous end joining (NHEJ) repair pathway. Compared to the currently used homologous recombination (HR) strategy, we obtained a higher efficiency of foreign-gene insertion into the herpes simplex virus (HSV) genome that reached 45 % after optimization. By using NHI, we rapidly constructed recombinant reporter viruses using a small amount of clinical viruses, and the recombinant virus was stable for at least ten consecutive passages. The fidelity of NHI ranged from 70–100% and was related to the sequence background of the insertion site according to the sequencing results. Finally, we depict the dynamic process by which the foreign-gene donor plasmid and viral genome are rapidly cleaved by Cas9, as revealed by quantitative pulse analysis. Furthermore, the NHI strategy exerted selection pressure on the wild-type and reverse-integrated viral genomes to efficiently integrate the foreign gene in a predetermined direction. Our results indicate that the use of a rationally designed NHI strategy can allow rapid and efficient foreign gene knock-in into the HSV genome and provide useful guidance for gene insertion into large DNA viral genomes using NHI.

In this study we investigate the prediction and prognostic value of CXCL8–CXCR1/2 axis for Triple-negative breast cancer (TNBC) patients underwent neoadjuvant chemotherapy (NAC) following standard radical surgery. A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. Serum CXCL8 level was measured at baseline and at surgery via Enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to detect CXCR1 and CXCR2 expression in patients with residual tumors after NAC. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation. Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. CXCL8 level was significantly upgraded after NAC in CXCR1/2+ patients and downgraded after NAC in CXCR1/2− patients. Higher pCR rate was more likely observed in patients with lower CXCL8 level at surgery (P = 0.004, HR 0.939, 95% CI 0.900–0.980). In the multivariate survival model, CXCR1/2 expression was of an independent prognostic value for survival (CXCR1/2+, HR 2.149, 95% CI 0.933–4.949; CXCR1/2++, HR 3.466, 95% CI 1.569–7.655, CXCR1/2− was used as a reference; P = 0.003). Patients with higher level of CXCR1/2 expression were more likely to suffer unfavorable outcome. This study contributes to the clarification of the value of serum CXCL8 level to predict pCR for TNBC patients, and prognostic performance of CXCR1/2 in non-pCR responders after NAC. The CXCL8–CXCR1/2 might play an important role in tailoring and modifying the NAC strategy for advanced TNBCs; however, further confirmatory studies are needed.

Titanosilcalite-1 (TS-1) supported gold catalysts (Au/TS-1) are promising for propene oxide (PO) synthesis through gas-phase propene epoxidation with hydrogen and oxygen. Herein, we report an effic...

OBJECTIVES To investigate whether second-look endoscopy (SLE)-guided therapy could be used to prevent post-endoscopic variceal ligation (EVL) early bleeding. METHODS Consecutive cirrhotic patients with large esophageal varices (EV) receiving successful EVL for acute variceal bleeding (AVB) or secondary prophylaxis were enrolled. The patients were randomized into a SLE group and a non-SLE group (NSLE) 10 days after EVL. Additional endoscopic interventions as well as proton pump inhibitors and octreotide administration were applied based on the SLE findings. The post-EVL early rebleeding and mortality rates were compared between the two groups. RESULTS A total of 252 patients were included in the final analysis. Post-EVL early rebleeding (13.5% vs 4.8%, P = 0.016) and bleeding-caused mortality (4.8% vs 0%, P = 0.013) were more frequently observed in the NSLE group than in the SLE group. However, post-EVL early rebleeding and mortality rates were reduced by SLE in patients receiving EVL for AVB only but not in those receiving secondary prophylaxis. Patients with Child-Pugh classification B to C at randomization (hazard ratio [HR] 8.77, P = 0.034), AVB at index EVL (HR 3.62, P = 0.003), discontinuation of non-selective β-blocker after randomization (HR 4.68, P = 0.001) and non-SLE (HR 2.63, P = 0.046) were more likely to have post-EVL early rebleeding. No serious adverse events occurred during SLE. CONCLUSION SLE-guided therapy reduces post-EVL early rebleeding and mortality rates in cirrhotic patients with large EV receiving EVL for AVB.

Background: Breast cancer is a common diagnosed malignancy and the leading cause of cancer-related death worldwide. Data on burden and changing trends of breast cancer are of value for policymaking. We therefore aimed to determine the pattern of breast cancer incidence, mortality, and disability-adjusted life-years (DALYs), as well as temporal trends, from 1990 to 2017. Methods: We collected detailed information on breast cancer between 1990 and 2017 using the results of the Global Burden of Disease study in 2017. The number of incident cases, deaths and DALYs attributable to breast cancer are reported as well as age standardized rates. Estimated annual percentage changes (EAPCs) in breast cancer age standardized rate were calculated to quantify the temporal trends. Moreover, attributable burden to breast cancer risk factors were also estimated using the comparative risk assessment framework of the GBD study. Results: There were 878,686 incident cases and 349,581 deaths of breast cancer globally in 2017, contributing to 17,708,600 DALYs. The age standardized incidence rate increased between 1990 and 2017, while the age standardized mortality rate and DALY rate decreased. The corresponding EAPCs were 0.41 (95% CI: 0.35 to 0.47), -0.62 (95% CI: -0.68 to -0.55), -0.56 (95% CI: -0.63 to -0.48), respectively. These trends were heterogeneous across regions and countries. The increase in the age standardized incidence rate was more prominent in countries with a low socio-demographic index and the decrease in the age standardized mortality rate and DALY rate was more prominent in countries with a high socio-demographic index. Percentage of breast cancer deaths due to alcohol use (12.94% to 9.64%) and tobacco (7.15% to 5.14%) was decreasing while deaths due to high body-mass index (4.03% to 6.54%) and high fasting plasma glucose (5.94% to 7.26%) was increasing. Conclusion: Breast cancer remains a major public health concern globally. The trends of incidence, mortality, and DALYs were heterogeneous across regions and countries, suggesting that the allocation of appropriate health care resources for breast cancer prevention, screening and treatment should be considered. Citation Format: Yue Gong, Peng Ji, Xin Hu, Zhi-Ming Shao. The burden and trends of breast cancer from 1990 to 2017 at the global, regional, and national level: Results from the global burden of disease study 2017 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-16.

Background Metastatic regional lymph nodes (LN) is a strong predictor of worse long-term outcome. Therefore, different LN staging systems have been proposed in recent years. In this study, we proposed a modified lymph node ratio (mLNR) as a new lymph node staging system and then compared the prognostic performance of mLNR with American Joint Committee on Cancer N stage, lymph node ratio (LNR) and log odds of metastatic lymph nodes in breast cancer patients. Methods Breast cancer patients who underwent surgery between 2004 and 2012 were identified from the Surveillance, Epidemiology, and End Results database. Restricted cubic spline functions were calculated to characterize the association between variables and the risk of death. The Cox proportional hazards models were constructed to assess the predictive ability of different lymph node staging systems using the Akaike’s Information Criterion (AIC) and Harrell’s concordance index (C-index). Results A total of 264,096 breast cancer patients were enrolled and 187,785 (71.1%) patients had a limited number of LNs harvested. In the limited LN harvest cohort, the prognostic performance of LNR decreased and mLNR could greatly solve this problem. In addition, among the entire cohort, mLNR modeled as a continuous value had the best predictive ability (AIC: 922021.9 and C-index: 0.727) than other lymph node staging systems. Conclusions The predictive ability of LNR is restricted by a limited LN harvest. However, mLNR shows superiority to LNR and other lymph node staging systems especially in a limited LN harvest cohort, making mLNR the most powerful lymph node staging systems., Highlights • We selected 264,096 patients, which is enough to support our conclusion. • We used two indexes to fully verify the fit of different lymph staging systems. • The mLNR improved the prognostic predictive ability best.

The rational design and synthesis of multimetallic nanostructures (NSs) with rich defects are of significant importance for their diverse applications, including their promising usage as high-effic...

Background The associations between socioeconomic statuses and survival outcomes of breast cancer remain unclear. No model has included both histological and socioeconomic factors to predict the survival of breast cancer. This study was designed to develop nomograms to predict breast cancer–specific survival (BCSS) and overall survival (OS) with consideration of socioeconomic factors for breast cancer patients. Materials and methods We included a total of 207 749 female patients, diagnosed with malignant breast cancer between 2007 and 2012 from the Surveillance, Epidemiology, and End Results database. BCSS and OS were evaluated with Gray's test and log‐rank tests, respectively. Marital statuses, insurance statuses, residence, median household income, poverty rate, unemployment rate, and education level were included as socioeconomic factors in univariate and multivariate Cox regression analyses. Clinicopathological factors and socioeconomic factors were integrated to construct nomograms. Calibration plots and concordance indexes (C‐indexes) were used to evaluate the accuracy and discrimination of the models. Results Four and three socioeconomic factors were involved in constructing the nomograms for 3‐, 5‐, and 7‐year BCSS and OS, respectively. The C‐indexes of the final nomograms were higher than those of the TNM staging system for predicting BCSS (0.835 vs 0.782; P, The findings from this population‐based study identify important socioeconomic factors at diagnosis, namely insurance status, marital status, median household income, educational level, and residence, which are closely associated with the survival of breast cancer. A survival prediction model for breast cancer patients was developed and validated based on nomograms, and for convenience of the users, we transferred models into a user‐friendly online tool. Both doctors and patients can use this online tool for free to predict survival from perspectives of pathology and socioeconomics, which is more accurate than traditional TNM staging.

Lithium-rich layered oxides (LLOs) are considered promising cathode materials for lithium-ion batteries because of their high reversible capacity, which is attributed to the exploitation of the novel anionic redox in addition to the conventional cationic redox process. Transition metal (TM) migration, which is known to be the main cause of the voltage decay in LLOs, is now understood to also be the critical factor triggering anionic redox, although this origin is still under debate. A better understanding of the specific TM migration behavior and its effect during charge/discharge would thus enable further development of this class of materials. Herein, we demonstrate that the unique TM migration during charge/discharge significantly alters the lithium diffusion mechanism/kinetics of LLO cathodes. We present clear evidence of the much more sluggish lithium diffusion occurring during discharge (lithiation) than during charge (de-lithiation), which contrasts with the traditional lithium diffusion model based on simple topotactic lithium intercalation/deintercalation in the layered framework. The reversible but asymmetric TM migration in the structure, which originates from the non-equivalent local environments around the TM during the charge and discharge processes, is shown to affect the lithium mobility. This correlation between TM migration and lithium mobility led us to propose a new lithium diffusion model for layered structures and suggests the importance of considering TM migration in designing new LLO cathode materials.

Non-noble metal isolated single atom site (ISAS) catalysts have attracted much attention due to their low cost, ultimate atom efficiency and outstanding catalytic performance. Herein, atomically dispersed Fe atoms are prepared by a covalent organic framework (COF)-absorption–pyrolysis strategy. The obtained Fe ISASs anchored on COF-derived N-doped carbon nanospheres (Fe-ISAS/CN) served as a multi-functional catalyst in electro-catalysis and organic catalysis, exhibiting better catalytic performance than commercial Pt/C for the ORR with good stability and methanol tolerance. Besides electro-catalysis, the Fe-ISAS/CN also showed outstanding catalytic performance in organic reactions, such as the selective oxidation of ethylbenzene to acetophenone and dehydrogenation of 1,2,3,4-tetrahydroquinoline with excellent reactivity, selectivity, stability and recyclability. Co and Ni ISAS materials can also be prepared by this method, suggesting that it is a general strategy to obtain metal ISAS catalysts. This work will provide new insight into the design of COF-derived metal ISAS multi-functional catalysts for electro-catalysis and organic reactions using rationally designed synthetic routes and the optimized structure of substrates., Fe isolated single-atom sites anchored on COF-derived N-doped carbon nanospheres as efficient multi-functional catalysts.

A novel rhodium/copper-cocatalyzed coupling–cyclization reaction of o-alkenyl arylisocyanides with vinyl azides has been developed for the first time. In this transformation, the reactive vinyl carbodiimides generated in situ from the coupling reaction of o-alkenyl arylisocyanides with vinyl azides undergo intramolecular [4 + 2] cycloaddition and provide a new and efficient strategy for the synthesis of polysubstituted α-carbolines by the formation of two C–C bonds, one C–N bond and two aromatic rings in a single step from readily available acyclic starting materials.

Natural biomaterials are potential candidates for the next generation of green electronics due to their biocompatibility and biodegradability. On the other hand, the application of biocomposite systems in information storage, photoelectrochemical sensing, and biomedicine has further promoted the progress of environmentally benign bioelectronics. Here, we mainly review recent progress in the development of biocomposites in data storage, focusing on the application of biocomposites in resistive random-access memory (RRAM) and field effect transistors (FET) with their device structure, working mechanism, flexibility, transient characteristics. Specifically, we discuss the application of biocomposite-based non-volatile memories for simulating biological synapse. Finally, the application prospect and development potential of biocomposites are presented., Graphical abstract

Antibiotic treatment, as an important therapeutic intervention, can cause damage to the host microbiome and the intestinal mucosal barrier. In order to find a way to alleviate the side effects of antibiotics, the present study investigated the effects of fucoidan (ANP) isolated from Ascophyllum nodosum on gut microbiota dysbiosis and colonic inflammation induced by ciprofloxacin-metronidazole (CiMe) in C57BL/6J mice. Our results showed that dietary ANP prevented colon shortening, alleviated the colonic tissue damages, and partially reversed the alteration of gut microbiota by increasing the abundance of potentially beneficial bacteria, e.g., Ruminococcaceae_UCG_014 and Akkermansia and decreasing the abundance of harmful bacteria, e.g., Proteus and Enterococcus. ANP also suppressed the overproduction of TNF-α, IL-1β, and IL-6 and promoted the expression of IL-10. In addition, ANP reversed the decreased production of short-chain fatty acids in CiMe-treated mice. Furthermore, correlation analysis indicated the presence of critical gut microbiota, which played important roles in reducing the inflammation-related indices. Thus, the present study suggests that fucoidan isolated from Ascophyllum nodosum is effective in providing protection against the negative effects of antibiotics on gut microbiota and colonic health.

Memristor devices have been of great interest over the past decade for the implementation of brain-inspired memory and computing owing to their inherent multistage memory, exquisite structure and higher integration. Herein, a CsPbBr3 QD-based protocol was constructed to exhibit analog memristive characteristics. The field-driven charge trapping/detrapping process was accelerated in the highlighted asymmetric electrode configuration to enable persistent dual direction current modulation, which serves as a basis for synaptic weight variation in the human brain. Significantly, the synaptic functions of long-term potentiation (LTP), long-term depression (LTD) and spike-timing-dependent plasticity (STDP) have been emulated on the device level. Furthermore, light signal-facilitated paired-pulse facilitation (PPF) behavior was validated with in situ atomic force microscopy (AFM) based on electrical techniques. These results may pave a new way to produce memristive devices with advanced implications for future neuromorphic computing.

Enterocytozoon hepatopenaei (EHP) and Vibrio parahaemolyticus acute hepatopancreatic necrosis disease (VPAHPND) are two of the diseases that have frequently infected farmed shrimp in recent years, causing great economic losses to the shrimp industry worldwide. In this study, we established a sensitive and accurate duplex droplet digital PCR (ddPCR) method that can simultaneously detect and quantify the two pathogens simultaneously. The results showed that the ddPCR methods could detect EHP and VPAHPND specifically. The sensitivity levels of ddPCR for EHP and VPAHPND were 2.3 copies/μl and 4.6 copies/μl, respectively, which were 10-fold higher than the sensitivity of the qPCR assay and showed good reproducibility. Twenty-six suspected diseased shrimp samples were used for practical determination. For EHP, the detection rates of ddPCR and qPCR were 53.84% and 42.31%, respectively; for VPAHPND, the detection rates of ddPCR and qPCR were both 23.08%. The results indicated that the ddPCR method shows superiority for detection in samples with low viral loads, which will facilitate monitoring of the source and transmission of EHP and VPAHPND and will help control shrimp epidemic disease.

Studying the deformation and failure mechanism of the Tanziyan landslide in Yesanguan Town, Badong County, and designing the controlling measures are of great significance to ensure the sustainable development of urban planning and construction. In this paper, stability of Tanziyan landslide is analyzed using the calculation method of complex plane slip surface. After consideration of the essential characteristics of the disaster body,the deformation and failure mechanism of the landslide is studied, and the corresponding landslide treatment measures are presented. Results show stability state of the landslide is understable to unstable as a whole, and the development process can be roughly divided into three stages: sliding, bending and the cracks are connected. Finally, it is proposed to cut and reshape the slope from the crack groove on the slope top to the national highway, and thenlattice beams and anchor cables are presented to protect the reshaped slope surface. Ecological bags are used to stack and regreen between the lattice structures. A retaining wall is built on the inner side of the national highway at the bottom of the slope cutting area, an active protective net is laid on the east side of the crack groove, and monitoring works are set for potential deformation areas. In short, experiences of engineering practice in this landslidecan provide reference for similar projects.

Metabolic reprogramming is a hallmark of cancer. However, systematic characterizations of metabolites in triple-negative breast cancer (TNBC) are still lacking. Our study profiled the polar metabolome and lipidome in 330 TNBC samples and 149 paired normal breast tissues to construct a large metabolomic atlas of TNBC. Combining with previously established transcriptomic and genomic data of the same cohort, we conducted a comprehensive analysis linking TNBC metabolome to genomics. Our study classified TNBCs into three distinct metabolomic subgroups: C1, characterized by the enrichment of ceramides and fatty acids; C2, featured with the upregulation of metabolites related to oxidation reaction and glycosyl transfer; and C3, having the lowest level of metabolic dysregulation. Based on this newly developed metabolomic dataset, we refined previous TNBC transcriptomic subtypes and identified some crucial subtype-specific metabolites as potential therapeutic targets. The transcriptomic luminal androgen receptor (LAR) subtype overlapped with metabolomic C1 subtype. Experiments on patient-derived organoid and xenograft models indicate that targeting sphingosine-1-phosphate (S1P), an intermediate of the ceramide pathway, is a promising therapy for LAR tumors. Moreover, the transcriptomic basal-like immune-suppressed (BLIS) subtype contained two prognostic metabolomic subgroups (C2 and C3), which could be distinguished through machine-learning methods. We show that N-acetyl-aspartyl-glutamate is a crucial tumor-promoting metabolite and potential therapeutic target for high-risk BLIS tumors. Together, our study reveals the clinical significance of TNBC metabolomics, which can not only optimize the transcriptomic subtyping system, but also suggest novel therapeutic targets. This metabolomic dataset can serve as a useful public resource to promote precision treatment of TNBC.

Rapid urbanization has had an important impact on the pattern and function of rural land use. To better understand the key drivers of the landscape pattern evolution in southern Henan in China from 1980 to 2020, we used techniques of GIS(Geographic Information System) technology and the geodetector model in the research area of landscape pattern evolution characteristics. The research results show that the land use transformation in the rural areas of southern Henan has been characterized by the conversion of production land to living land and ecological land, with the highest conversion rate and continuous growth of construction land, a decreasing trend of cropland, and continuous and stable growth of land for forest and water body in the past 40 years. Land use conversion in the rural areas of southern Henan is mainly concentrated in the northern, central, and southern areas, and the spatial conversion has shifted from mountainous areas to the plains. The center of gravity of forest, cropland, and water body has most obviously shifted, and human interference and ecological environment destruction are the main influencing factors. The overall landscape pattern in the rural areas of southern Henan has increased in fragmentation and landscape heterogeneity, evenness has decreased, irregular patches have increased, and landscape connectivity has decreased. The combined effect of the six dimensions of elevation, slope, night lighting, average annual precipitation, average annual temperature, and population density in the rural areas of southern Henan has led to the transformation of land use and changes in landscape pattern. Physical geographic factors are the main drivers of rural landscape pattern changes in southern Henan, while population density changes and urbanization are secondary drivers. The results of the study have important guiding significance for the further optimization of rural landscape patterns and the sustainable development of rural areas.