Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases.

Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases often characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro-inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils, and other types of FcεRI-bearing cells and may play a role in promoting autoantibody production and other pro-inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.

Autoimmune chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a debilitating mast cell-driven disease characterized by recurrent wheals and/or angioedema. Substantial progress has been made in dissecting the 2 main autoimmune mechanisms that drive the pathogenesis of CSU. Type I autoimmune (autoallergic) CSU is associated with IgE antibodies against autoantigens, for example, thyroid peroxidase and IL-24. Type IIb autoimmune CSU is mediated by autoantibodies that activate mast cells, for example, via IgE and FcεRI, and is present in less than 10% of patients with CSU when strict criteria are used, that is, triple positivity of autologous serum skin test, immunoassays for IgG autoantibodies, and basophil activation tests. A subpopulation of patients with CSU has both types. Type IIb autoimmune CSU is characterized by higher disease severity, concomitant autoimmune diseases, low levels of total IgE, elevated levels of IgG-anti-thyroid peroxidase, basopenia, eosinopenia, poor response to antihistamines and to omalizumab, and a good response to cyclosporine. Novel targeted therapies for CSU are under development such as ligelizumab, an anti-IgE, fenebrutinib and remibrutinib, Bruton's tyrosine kinase inhibitors, and dupilumab, an anti-IL-4Rα. Further studies should investigate the overlap between autoallergic and type IIb autoimmune CSU, optimize the diagnosis of both autoimmune endotypes using easy-to-perform, noninvasive, and inexpensive markers, and assess differences in response to therapy.

Simultaneous partial nitrification, denitrification, and phosphorus removal in sequencing batch reactors via controlled reduced aeration and short-term sludge retention time decrease.

Simultaneous bio-treatment processes of organic carbon (C)-, nitrogen (N)-, and phosphorus (P)-containing wastewater are challenged by insufficient carbon sources in the effluent. In the present study, two parallel anaerobic/aerobic sequencing batch reactors (R-1 and R-2) treating low C/N (≤4) wastewater were employed using different partial nitrification start-up strategies, controlled reduced aeration, and decreased sludge retention time. Advanced removal efficiencies for NH4+-N (≥96%), total nitrogen (TN, ≥86%), PO43--P (≥95%), and CODintra (≥91%) were realized, with TN and PO43--P effluent concentrations of 10.0 ± 3.5 and 0.11 ± 0.3 mg/L in R-1 and 9.28 ± 4.0 and 0.11 ± 0.1 mg/L in R-2, respectively. Higher nitrite accumulation rate (nearly 100%) and TN (121.1 ± 0.7 mg TN/g VSS·d) and P (12.5 ± 0.6 mg PO43--P/g VSS·d) removal loadings were obtained in R-2 by a thorough elimination of nitrite-oxidizing bacteria. Moreover, different microbial structures and nutrient removal pathways were identified. Denitrifying glycogen-accumulating organisms (Candidatus Competibacter) and phosphorus-accumulating organisms (PAOs) (Tetrasphaera) removed N and P with partial nitrification-endogenous denitrification pathways and aerobic P removal in R-1. In R-2, aerobic denitrifying bacteria (Psychrobacter) and PAOs ensured N and P removal through the partial nitrification-aerobic denitrification and aerobic P removal pathways. Compared to R-1, R-2 offers greater efficiency, convenience, and scope to further reduce carbon-source demand.

Appeal of word of mouth: Influences of public opinions and sentiment on ports in corporate choice of import and export trade in the post-COVID-19 era.

With the advent of the post-COVID-19 era, corporate managers of import and export trade are now more sensitive in their daily work, and their decisions are more likely to be influenced by the emotional bias of public opinions, especially regarding cooperation with trade ports of frequent circulation. Therefore, how to manage public opinion and sentiment in the post-COVID-19 era will be a new opportunity and challenge for the marketing management of ports. For the above considerations, through the same frequency verification between public opinions and sentiment on ports and corporate choice of import and export trade, and through analysis of the influence mechanism, the present study demonstrates the positive effects of public opinions and sentiment on ports in corporate choice of import and export trade in the post-COVID-19 era, verifies the significance of shaping word of mouth in port management, puts forward the great role of public opinions and sentiment in the cognitive and emotional empathy in the choice of import and export trade, and provides theoretical guidance for port managers' strategic choices in the post-COVID-19 era.

Effect of the interface on femtosecond laser damage of a metal-dielectric low dispersion mirror.

Metal-dielectric low dispersion mirrors (MLDM) have a promising application prospect in petawatt (PW) laser systems. We studied the damage characteristics of MLDM and found that the damage source of MLDM (Ag + Al2O3+SiO2) is located at the metal-dielectric interface. We present the effect of the interface on the femtosecond laser damage of MLDM. Finite element analysis shows that thermal stress is distributed at the interface, causing stress damage which is consistent with the damage morphology. After enhancing the interface adhesion and reducing the residual stress, the damage source transfers from the interface to a surface SiO2 layer, and the damage threshold can be increased from 0.60 J/cm2 to 0.73 J/cm2. This work contributes to the search for new techniques to improve the damage threshold of MLDM used in PW laser systems.

Low-dispersion mirror with a broad bandwidth and high laser damage resistance.

A low-dispersion mirror (LDM), an important component in ultrafast laser systems, requires both a broad low-dispersion laser-induced damage threshold (LIDT). It is difficult for a traditional quarter-wavelength-based dielectric LDM to achieve these characteristics at the same time. We propose a novel, to the best of our knowledge, low-dispersion mirror (NLDM) that combines periodic chirped layers at the top and alternating quarter-wavelength layers at the bottom. Low dispersion is achieved by introducing a large same group delay (GD) for different wavelengths, so the bandwidth is broadened greatly. In addition, owing to the staggered electric field intensity peak effect in the structure, the NLDM shows the potential for high laser damage resistance. The experiments demonstrated that the NLDM doubles the low-dispersion bandwidth, while the LIDT is also increased compared with the LDM. This novel concept results in improved performance and paves the way toward a new generation of the LDM for ultrafast bandwidth and a high laser applications.

Clinicopathological Analysis and Prognostic Assessment of Transcobalamin I (TCN1) in Patients with Colorectal Tumors.

BACKGROUND Colorectal cancer (CRC) is one of the most common malignancies worldwide. Overall survival (OS) of patients is largely dependent on disease stage at diagnosis and/or surgical resection. TCN1 mainly encodes the vitamin B12 transporter, transcobalamin. Early studies show that TCN1 is a marker of CRC progression, but the impact of TCN1 on survival is unclear. MATERIAL AND METHODS We reviewed and analyzed colorectal tumor records, summarized the clinicopathological data, performed immunohistochemical detection of TCN1 again, and semi-quantitatively analyzed protein expression in tumor tissue, non-tumor tissue, and lymph nodes. We followed up patients for 5-year survival. RESULTS Of 123 patients, 60 (48.7%) had a strong TCN1 immunohistochemical reaction, 36 (29.3%) had a moderate immune response, and 27 (22.0%) had weak expression. The level of immunohistochemical reactivity of TCN1 was correlated with the degree of histological differentiation (H (2.92)=4.976; P=0.083). Survival analysis showed that OS in patients with low TCN1 expression was significantly longer than that in the medium and high TCN1 expression groups (P=0.045). Five-year OS in patients with low, medium, and high TCN1 expression was 88.9%, 50.0%, and 40.0%, respectively. In univariate analysis, TCN1 immune expression was significantly correlated with the 5-year survival rate. CONCLUSIONS Although independent risk factors affecting survival of patients with CRC are age, serum CA125, CA19-9, lymph node metastasis, and nerve invasion, negative factors affecting overall 5-year survival in TCN1 should not be ignored, because its high expression suggests a worse clinical prognosis.

Angle-adjustment-based tunable chirped mirrors with continuous dispersion compensation.

We report the feasibility of continuously tunable dispersion control with chirped mirrors (CMs). The concept of tunable second-order and higher-order dispersion is also proposed. Our prototype dispersion-tunable CM makes it possible to provide continuous dispersion support, advancing the CM technique to a new level by overcoming the drawback of the discrete dispersion compensation nature of traditional CMs. This brings extreme convenience and flexibility to the compensation of the dispersion and ensures tailored dispersion compensation in ultrafast laser systems. In our proof-of-concept study, continuously tunable group delay dispersion (GDD) is achieved by altering the angles of incidence on the mirrors. Moreover, continuous duration tunable laser pulses are demonstrated by applying our GDD-tunable CMs in an ultrafast laser system.

[Developing traditional Chinese medicine injection is the need for curing sickness to save patients].

Safety issues of traditional Chinese medicine injections has been heated debate. There are two diametrically opposed views: it should be used reasonable and developed healthily or be forbidden to use. Some people have many misunderstandings and prejudices about the safety of traditional Chinese medicine injections. Compared with western medicine,traditional Chinese medicine has its own particularity. Traditional Chinese medicine has complex components. Its research and clinical application is different from western medicine. Adverse reactions of traditional Chinese medicine injections are related to many factors,such as a large number of irrational use,blind use of traditional Chinese medicine injections and western medicine injections,counterfeit and substandard drugs,incorrect methods of intravenous infusion,toxicity of supplementary materials,drug ingredients. Developing traditional Chinese medicine injection is the need for curing sickness to save patients. The purposeful, targeted, organized and planned systematic research of traditional Chinese medicine injections should be strengthened,especially the safety of traditional Chinese medicine. Strengthen supervision and control of rational drug use.Strengthen the examination and approval,supervision and management of all aspects to ensure the safety of patients.

Improving laser damage resistance of 355 nm high-reflective coatings by co-evaporated interfaces.

355 nm high-reflective multilayer coatings with or without coevaporated interfaces (CEIs) were prepared by electron beam evaporation under the same deposition condition. Their transmission spectra, surface roughness, and mechanical stress properties were evaluated. Elemental composition analysis of the multilayer interfaces was performed using x-ray photoelectron spectroscopy, and laser-induced damage thresholds were obtained in both 1-on-1 and 300-on-1 testing modes. The coatings with CEIs reveal a lower mechanical stress and a higher laser damage resistance when irradiated with high laser fluence, and the corresponding damage modeling indicates that CEIs can significantly decrease defect density. The resulting damage morphologies show that CEI coatings can significantly suppress coating delamination and exhibit a "bulk-like" damage behavior, demonstrating better damage performance against high-power lasers.

Suppression of nano-absorbing precursors and damage mechanism in optical coatings for 3ω mirrors.

Damage precursors in the 3ω (351 nm) mirror for a high-power laser system are investigated as well as the relevant damage mechanisms. The precursors are classified into two ensembles according to the different laser resistance and damage features. The former is nano-absorbing precursors, which are sensitive to the standing wave electric field and vulnerable to the laser irradiation. The latter is submicrometer nodular defects, which have higher laser resistance and are sensitive to the adhesion strength between the fluoride coatings and oxide coatings. The damage due to nano-absorbing precursors is efficiently suppressed with the double stack design that screens the electric field in the oxides. Currently, the nodular seed is major originating from the Al2O3/SiO2 stack. Even for the same defect type and mirror, the final damage features are dependent on the local mechanical properties at the irradiation location. The investigations of the damage mechanisms provide a direction to further improve the laser-induced damage threshold of the 3ω mirror.

CdTe/ZnS quantum dots as fluorescent probes for ammonium determination.

Novel CdTe/ZnS quantum dot (QD) probes based on the quenching effect were proposed for the simple, rapid, and specific determination of ammonium in aqueous solutions. The QDs were modified using 3-mercaptopropionic acid, and the fluorescence responses of the CdTe/ZnS QD probes to ammonium were detected through regularity quenching. The quenching levels of the CdTe/ZnS QDs and ammonium concentration showed a good linear relationship between 4.0 × 10(-6) and 5.0 × 10(-4) mol/L; the detection limit was 3.0 × 10(-7) mol/L. Ammonium contents in synthetic explosion soil samples were measured to determine the practical applications of the QD probes and a probable quenching mechanism was described. Copyright © 2015 John Wiley & Sons, Ltd.

[Effect of allicin on myocardial fibrosis after myocardial infarction in rats and its relationship with TGFß/Smads signal transduction].

Allicin is the internationally accepted active substance of garlic, and has cardiovascular protective effect. This research was designed to investigate the effect of allicin on myocardial fibrosis after myocardial infarction and explore the relationship between the effect and TGFß1/Smads signaling pathway. The rat myocardial infarction model were made by ligating the left anterior desending coronary artery. The drugs were administered intraperitoneally 24 h after the operation. After 21 days, the rats were sacrificed and myocardial collagen fibres were observed by Masson staining. The protein expression of Ⅰ, Ⅲ collagen and TGFß1, Smad3, Smad7 in the myocardium was measured by the immunohistochemistry. The results showed that myocardial fibrosis was serious and the expression of Ⅰ, Ⅲ collagen was increased in model group. After treatment with allicin, the myocardial fibrosis could be relieved markedly, and the expression of collagen was down-regulated. Meanwhile, TGFß1 and Smad3 in heart tissue could be down-regulated and Smad7 could be up-regulated in allicin groups. So allicin may exhibit anti-myocardial fibrosis effect on rats, and the mechanism of this is related to TGFß/Smads signal transduction.

Experimental demonstration of laser damage caused by interface coupling effects of substrate surface and coating layers.

The laser damage resistance of the coatings for high-power laser systems depends greatly on the surface quality of the substrate. In our work, experimental approaches were employed to understand the interface coupling effect of the substrate surface and coatings on the laser resistance of the coatings. A 1064 nm anti-reflection (AR) coating was deposited by an e-beam coater onto fused silica with and without micro-scale pits (structural defects). The micro-scale pits were precisely fabricated by femtosecond laser processing to prevent the emergence of subsurface cracks. Different deposition temperatures were characterized in order to verify the intensity of the interface coupling effect of the substrate and coating layers. Our experimental results indicate that impurities that are introduced in the finishing process, shifted to the substrate surface, and aggregated during the heating process, play a much more crucial role than structural defects (length: ∼7 µm; width: ∼3 µm; depth: ∼0.8 µm) in the laser-induced damage process. By effectively reducing the intensity of the interface coupling effect, the e-beam AR coatings, whose laser-induced damage resistance was closed to the bare substrate, was prepared.

Impact of substrate pits on laser-induced damage performance of 1064-nm high-reflective coatings.

The laser damage resistance of coatings in high-power laser systems depends significantly on the surface quality of the substrate. In our experiment, pits were precisely fabricated on the surface of fused silica substrate using a femtosecond laser processing bench. The HfO2/SiO2 high-reflective coatings at 1064 nm were deposited by conventional e-beam evaporation onto fused silica substrates with and without pits, respectively. The internal crack that was induced by the substrate geometrical structure was first observed in our experiment. The laser-induced damage threshold test showed negative effects of the substrate pits on the laser resistance of high-reflective coatings. Simulations by the finite element method were carried out, and results demonstrated that the modulation of a high reflector multilayer geometry could lead to electrical-field amplification and reduce laser damage resistance. Combined with its poor mechanical properties, the pits on substrate could contribute to the occurrence of damages.

Beam modulation caused by the plasma scalds in the multilayer dielectric films.

The near-field phase modulation (NFPM) caused by the plasma scalds is investigated with a newly proposed mixed overcoat layer model. Based on the NFPM, the far-field intensity modulation (FFIM) is calculated and discussed with the scalar diffraction theory. The results indicate that both the NFPM and FFIM are sensitive to the scalding depth. A feature curve is developed to analyze the NFPM for arbitrary scalding depth. The modulation can be ignored when the scalding depth is less than the first feature point in the feature curve. Even though the diffraction intensity in the Fresnel region can be enhanced dozens of times, the FFIM in the Fraunhofer region can recover gradually if the scalding depth is below a critical value. The preliminary experimental results are consistent with the theoretical prediction.

Near-field enhancement of the nanostructure on the fused silica with rigorous method.

A rigorous electromagnetic method is developed to analyze the resonance effect of near field caused by nanoscale subsurface defects, which play a key role in describing absorption enhancement during laser-matter interaction for transparent dielectric materials. The total electric field calculated with this new method is consistent with the result of finite-difference time-domain simulation. The concept of mode amplitude density spectrum is developed to analyze the specific modes of the total field. A new mode parameter is proposed to demarcate the contribution of the resonance. The frequency space is divided into four parts and the resonance effect is analyzed as well as the contributions of different modes to the total field. The influence of the structure parameters on the near-field modulation and energy transference is also discussed. It is found that the enhancement mechanism of the near-field and local absorption is the resonance effect caused by the total internal reflection on the sidewall of the nanostructure. In addition, the surrounding energy is mainly guided into the structure by the root of the structure via the energy flow analysis.

[Academician Li Lianda talking about doctors doing scientific research].

At present, Chinese medical field faces with an important problem of how to correctly handle the relationship between medical and scientific research. Academician Li Lianda advocates doctors doing scientific research under the premise of putting the medical work first. He points out that there are many problems in the process of doctors doing scientific research at present such as paying more attention to scientific research than medical care, excessively promoting building scientific research hospital, only paying attention to training scientific talents, research direction be flashy without substance, the medical evaluation system should be improved and so on. Medical, scientific research and teaching are inseparable because improving medical standards depends on scientific research and personnel training. But not all doctors need to take into account of medical treatment, scientific research and teaching in the same degree while not all hospitals need to turn into three-in-one hospital, scientific research hospital or teaching hospital. It must be treated differently according to the actual situation.