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Studies have found that feature estimates are systematically compressed towards the distribution center, showing a central tendency. Additionally, the estimate of current features is affected by the previously seen feature, showing serial dependence or adaptation effect. However, these all remain unclear in the speed estimation. To address this question, we asked participants to estimate the speed of moving Gabor patches. In Experiment 1, speeds were selected from three uniform distributions with different lower and upper boundaries (i.e., slow, moderate, and fast ranges). In Experiment 2, speeds were arranged in an increasing, uniform, or decreasing distribution. The boundaries of three distributions were the same. The results found that speed estimates were systematically compressed towards the center of the uniform distribution center, showing a central tendency, and its size increased with the range boundaries. However, in the decreasing and increasing distributions, aside from central tendency, the speed estimates were also showed a bias away from the heavy tail of the distributions. Moreover, there was an attractive serial dependence that was not affected by the speed range. In summary, the current study, along with previous studies that reveal a slow-speed bias, comprehensively reveals various estimation biases in speed perception. [ABSTRACT FROM AUTHOR]

Background: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. Methods: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. Results: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). Conclusions: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients. [ABSTRACT FROM AUTHOR]

Background: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. Methods: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. Results: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). Conclusions: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients. [ABSTRACT FROM AUTHOR]

Objective: Gastric cancer is a malignant tumor with high morbidity and mortality all around the world. Because of its poor prognosis and low survival rate, the treatment of gastric cancer has received extensive attention. Cinnamaldehyde (CA) is the main single active component of the Chinese herbal medicine cinnamon, which has a variety of pharmacological effects. The inhibitory effect of CA on the growth of some tumor cells has been proven, but its therapeutic effect on gastric cancer has rarely been reported. Methods: Through network pharmacology, bioinformatics methods, and molecular docking technology, we predicted the interaction targets of CA and gastric cancer. Moreover, we found that apoptosis is an important mode of action of CA on gastric cancer cells. Subsequently, we validated it in gastric cancer cell lines cultured in vitro. Results: The results showed that in the presence of CA, the Jak2/Stat3 pathway was inhibited, the ratio of Bcl-2/Bax decreased, and the apoptosis of gastric cancer cells was promoted in a concentration-dependent. Conclusion: In conclusion, CA can promote the apoptosis of gastric cancer cells by inhibiting the activity of the Jak2/Stat3 pathway, which may achieve the effect of treating gastric cancer. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra‐performance liquid chromatography‐tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ‐glutamylcysteine; cysteinyl‐glycine; n‐acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ‐glutamylcysteine, cysteinyl‐glycine, n‐acetylcysteine, cysteine, and homocysteine were derivatized by n‐ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2 > 0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from ‐3.42 to 10.92), stability (RSD% < 5.68, RE% range from ‐2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle. [ABSTRACT FROM AUTHOR]

Background and Purpose: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR‐1 and CEMR‐2 behaved as potent μ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR‐1 and CEMR‐2 following intrathecal (i.t.) administration. Furthermore, their antinociceptive tolerance and opioid‐like side effects were also determined. Experimental Approach: The spinal antinociceptive effects of CEMR‐1 and CEMR‐2 were determined in a series of pain models, including acute radiant heat paw withdrawal test, spared nerve injury‐induced neuropathic pain, complete Freund's adjuvant‐induced inflammatory pain, visceral pain and formalin pain. Antinociceptive tolerance was evaluated in radiant heat paw withdrawal test. Key Results: Spinal administration of CEMR‐1 and CEMR‐2 produced potent and prolonged antinociceptive effects in acute pain. CEMR‐1 and CEMR‐2 may produce their antinociception through distinct μ receptor subtypes. These two analogues also exhibited significant analgesic activities in neuropathic, inflammatory, visceral and formalin pain at the spinal level. It is noteworthy that CEMR‐1 showed non‐tolerance‐forming analgesic properties, while CEMR‐2 exhibited substantially reduced antinociceptive tolerance. Furthermore, both analogues displayed no or reduced side effects on conditioned place preference response, physical dependence, locomotor activity and gastrointestinal transit. Conclusions and Implications: The present investigation demonstrated that CEMR‐1 and CEMR‐2 displayed potent and long‐lasting antinociception with a favourable side effect profile at the spinal level. Therefore, CEMR‐1 and CEMR‐2 might serve as promising analgesic compounds with minimal opioid‐like side effects. [ABSTRACT FROM AUTHOR]

Background: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. Methods: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. Results: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). Conclusions: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients. [ABSTRACT FROM AUTHOR]

New exact solutions to large constrained torsion of highly elastic soft tubes are obtained from a new hyper‐elastic constitutive model. This new model is established with a new form of the multiaxial elastic potential toward simultaneously matching multiple data sets for three benchmark modes, including the uniaxial extension of a bar, the equi‐biaxial extension of a thin plate and the plane‐strain extension of a plate strip. With the new model, exact closed‐form solutions to the stress responses for these benchmark modes are first derived and shown to be of decoupled nature, and, then, an accurate analysis for the converse Poynting effect of twisted highly elastic tubes with fixed ends is presented with a new technique in treating nonlinear coupling complexities. The main novelties are incorporated as follows. First, multiple data sets for three benchmark modes can be accurately and automatically matched with no need to identify any unknown parameters; next, the nonlinear coupled system of the governing equations for four variables in a twisted tube, including the averaged radius and the wall‐thickness as well as the axial constrained stress and the shear stress, can be reduced to treating a single nonlinear equation; and, accordingly, the nonlinear coupling complexities can be worked out and exact results are obtainable. [ABSTRACT FROM AUTHOR]

Recent studies have found that the estimates of motion directions are biased toward the previous form orientations, showing serial dependence, and the serial dependence does not involve cognitive abilities. In the current study, we conducted two experiments to investigate whether and how attention—a cognitive ability—affected the serial dependence. The results showed that serial dependence was present in the current study, reproducing the previous findings. Importantly, when the attentional load reduced the reliability (i.e., estimation accuracy and precision) of previous form orientations (Experiment 1), the serial dependence decreased, meaning that the biases of motion direction estimates toward previous form orientations were reduced; in contrast, when the attentional load reduced the reliability of current motion directions (Experiment 2), the serial dependence increased, meaning that the biases of motion direction estimates toward previous form orientations were increased. These trends were well consistent with the prediction of the Bayesian inference theory. Therefore, the current study revealed the involvement of attention in the serial dependence of current motion direction estimation on the previous form orientation, demonstrating that the serial dependence was cognitive and the attentional effect can be a Bayesian inference process, initially revealing its computational mechanism. [ABSTRACT FROM AUTHOR]

A new and explicit form of the multi-axial elastic potential for elastic soft materials is constructed by means of two invariants of the Hencky strain. The new elasticity model with this form can bypass coupling complexities and uncertainties usually involved in parameter identification. Namely, exact closed-form solutions of decoupled nature are obtainable for stress responses under multiple benchmark modes. Unlike usual solutions with numerous coupled parameters, such new solutions are independent of one another and, as such, data sets for multiple benchmark modes can be separately matched with mutually independent single-variable functions. A comparative study is presented between a few well-known models and the new model. Results show that predictions from the former agree well with uniaxial and biaxial data, as known in the literature, but would be at variance with data for the constrained stress response in the plane-strain extension. In contrast, predictions from the new model agree accurately with all data sets. Furthermore, exact solutions for the Poynting effect of freely twisted elastic thin-walled tube are obtained from the new model. [ABSTRACT FROM AUTHOR]

A new and unified approach is proposed toward accurately analyzing overall elastoplastic responses of axially loaded bars and finite bending beams until failure. Results are presented for various constituent materials such as metals, reinforced concretes and reinforced composites, etc. Novelties in three respects are incorporated: (a) new uniaxial stress–strain functions are first presented in explicit forms for the purpose of accurately characterizing non-symmetric tensile and compressive behaviors of axially loaded bars from hardening to softening; (b) explicit solutions to both the varying neutral axis and the flexural moment of finite bending beams are then obtained directly in terms of these two uniaxial functions; and, hence, (c) the complex bending problem of various beams until failure is in a unified manner reduced to a simple issue of fitting two uniaxial functions to tension and compression data from uniaxial testing, thus bypassing the analytical and numerical complexity of various existing approaches. Numerical examples of model predictions are provided for typical constituent materials, including aluminium, meso-scopic heterogeneous concrete and ultra-high performance fiber-reinforced concrete with reinforcing rebars. Good agreement is achieved simultaneously with all experimental data for bars and beams made of these materials. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to present a direct analysis to demonstrate why markedly different tensile and compressive behaviors of concretes could not be simulated with the Drucker–Prager yield criterion. Design/methodology/approach: This study proposed an extended form of the latter for establishing a new elastoplasticity model with evolving yield strengths. Findings: Explicit closed-form solutions to non-symmetric tensile and compressive responses of uniaxial specimens at finite strain are for the first time obtained from hardening to softening. Originality/value: With such exact solutions, the yield strengths in tension and compression can be explicitly prescribed by uniaxial tensile and compressive stress-strain functions. Then, the latter two are further provided in explicit forms toward accurately simulating tensile and compressive behaviors. Numerical examples are supplied for meso-scale heterogeneous concrete (MSHC) and high-performance concrete (HPC), etc. Model predictions are in good agreement with test data. [ABSTRACT FROM AUTHOR]

Catalytic hydrolysis of ammonia borane for dehydrogenation is a promising way for generation and storage of hydrogen energy. Catalysts with reduced utilization of costly noble metals while high activity and stability are highly desired. Herein we show that the catalytic activity of the prototypical Pt/SiO2 catalysts towards ammonia borane hydrolysis could be significantly improved by the presence of a layer of Co(OH)2 beneath the supported Pt nanoparticles. By changing the Pt:Co molar ratio in the Pt-Co(OH)2/SiO2 catalysts, the hydrogen generation rates from ammonia borane hydrolysis show a volcano-type curve, with the maximum catalytic activity at the Pt:Co molar ratio of 1:11. The highest turnover frequency value of 829 molH2·molPt−1·min−1 at room temperature outperforms most of the reported Pt-based catalysts, and the apparent activation energy is drastically decreased to 36.2 kJ/mol from 61.6 kJ/mol for Pt/SiO2. The enhanced catalytic performance of Pt-Co(OH)2/SiO2 is attributed to the electrons donation from Co atoms on Co(OH)2 to Pt occurring at the metal-hydroxide interface, which is beneficial for optimizing the oxidation cleavage of the O–H bond of attacked H2O. [ABSTRACT FROM AUTHOR]

Purpose: Our previous study has shown that AVE 0991, a nonpeptide analogue of Ang-(1-7), ameliorates cognitive decline and inhibits NLRP3 inflammasome of astrocytes in Alzheimer's disease model mice. Additionally, several studies have suggested that activation of autophagy appears to effectively inhibit the progression of neuroinflammation. However, it is unclear whether AVE 0991 can modulate astrocyte autophagy to suppress neuroinflammation in Alzheimer's disease. Materials and Methods: APP/PS1 mice and Aβ-treated primary astrocytes were used as the research objects in vivo and in vitro, respectively. Water maze test was used to evaluate cognitive function of mice, Nissl staining and immunofluorescence staining was used to assess neuronal damage. ELISA kits were used to detect the levels of Ang-(1-7) and Aβ in the cortex, and qRT-PCR was used to detect the expression of cortical inflammation-related mediators. The expression of autophagy-related proteins in cortex were detected by Western blot. The upstream molecular responses involved in inflammation inhibition by AVE 0991 were validated by means of using the Mas1 antagonist and autophagy inhibitor. Results: We found that 30 days of intraperitoneal administration of AVE 0991 improved. Aβ deposition, neuronal death, and cognitive deficits in APP/PS1 Alzheimer's disease model mice. Moreover, AVE 0991 treatment greatly suppressed astrocyte-mediated inflammation and up-regulated the expression of autophagy. Furthermore, the inhibitory effect of AVE 0991 on the expression of inflammatory factors was reversed by 3-MA, an autophagy inhibitor. Conclusion: These findings suggest that regulation of autophagy is critical for inhibiting astrocyte neuroinflammatory responses and demonstrate a potential neuroprotective mechanism by which AVE 0991 could suppress neuroinflammatory responses by enhancing autophagy. [ABSTRACT FROM AUTHOR]

An efficient and simple procedure for the preparation of 2‐pyridinone is reported. The obtained products contained various bicyclic 2‐pyridinones and multi‐substituted 6‐amino‐2‐pyridinones. This approach employed 3‐hydroxy‐2‐aryl acrylate and nitro ketene aminal as substrates, and the corresponding 2‐pyridinones were obtained in good to excellent yields. This method may be used for the synthesis of bicyclic 2‐pyridinones, as well as multi‐substituted complex 2‐pyridinones. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a widespread and frequently reported multifactorial ocular disease that not only causes ocular discomfort but also damages the cornea and conjunctiva. At present, topical administration is the most common treatment modality for DED. Due to the existence of multiple biological barriers, instilled drugs generally exhibit short action times and poor penetration on the ocular surface. To resolve these issues, several advanced drug delivery systems have been proposed. This review discusses new dosage forms of drugs for the treatment of DED in terms of their characteristics and advantages. Innovative formulations that are currently available in the market and under clinical investigation are elaborated. Meanwhile, their deficiencies are discussed. It is envisioned that the flourishing of advanced drug delivery systems will lead to improved management of DED in the near future. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor DNA (ctDNA) has emerged as a noninvasive biomarker for dynamically monitoring tumors. However, published data on perioperative ctDNA in patients with operable non-small cell lung cancer (NSCLC) are currently limited.Methods: This prospective study recruited 123 patients with resectable stage I to IIIA NSCLC. Preoperative and postoperative plasma samples and tumor tissue samples were subjected to next-generation sequencing with a panel of 425 cancer-related genes. Peripheral blood samples were collected before surgery, postoperatively within 1 month, and every 3 to 6 months for up to 3 years.Results: After 4 exclusions, 119 eligible patients were enrolled from June 2016 to February 2019. Presurgical ctDNA was detectable in 29 of 117 patients (24.8%) and was associated with inferior recurrence-free survival (RFS; hazard ratio [HR], 2.42; 95% CI, 1.11-5.27; P = .022) and inferior overall survival (OS; HR, 5.54; 95% CI, 1.01-30.35; P = .026). Similarly, ctDNA was detected in 12 of 116 first postsurgical samples (10.3%) and was associated with shorter RFS (HR, 3.04; 95% CI, 1.22-7.58; P = .012). During surveillance after surgery, longitudinal ctDNA-positive patients (37 of 119; 31.1%) had significantly shorter RFS (HR, 3.46; 95% CI, 1.59-7.55; P < .001) and significantly shorter OS (HR, 9.99; 95% CI, 1.17-85.78; P = .010) in comparison with longitudinal ctDNA-negative patients. Serial ctDNA detection preceded radiologic disease recurrence by a median lead time of 8.71 months.Conclusions: These results suggest that perioperative ctDNA analyses can predict recurrence and survival, and serial ctDNA analyses can identify disease recurrence/metastasis earlier than routine radiologic imaging in patients with resectable NSCLC.Lay Summary: The utility of serial circulating tumor DNA (ctDNA) monitoring for predicting disease recurrence and survival for early-stage non-small cell lung cancer (NSCLC) has not been well characterized. The detection of ctDNA before and after surgery is associated with the identification of a high risk of disease recurrence and long-term patient outcomes for resectable NSCLC. Perioperative ctDNA analyses identify disease recurrence earlier than routine radiologic imaging. ctDNA analyses can detect minimal residual disease for resectable NSCLC and thus can facilitate early intervention. [ABSTRACT FROM AUTHOR]

A pair of enantiomeric ligands, (2R,3R)‐dibenzyl‐2,3‐bis(isonicotinoyloxy)succinate ((R,R)‐L) and (2S,3S)‐dibenzyl‐2,3‐bis(isonicotinoyloxy)succinate ((S,S)‐L), are designed and synthesized. Seven copper (II) coordination polymers {[Cu((R,R)‐L)Br2(THF)] ⋅ CH3CN} n (1 a) and {[Cu((S,S)‐L)Br2(THF)] ⋅ CH3CN}n (1 b), {[Cu((R,R)‐L)Cl2(THF)] ⋅ CH3CN}n (2 a) and {[Cu((S,S)‐L)Cl2(THF)] ⋅ CH3CN}n (2 b), {[Cu((R,R)‐L)(NO3)2(CH3CN)]}n (3 a) and {[Cu((S,S)‐L)(NO3)2(CH3CN)]}n (3 b), {[Cu((R,R)‐L)2(CH3CN)2](ClO4)2 ⋅ 3CH3CN}n (4) were obtained through the assemblies with CuBr2, CuCl2 ⋅ 2H2O, Cu(NO3)2 ⋅ 3H2O, Cu(ClO4)2 ⋅ 6H2O, respectively. Single‐crystal X‐ray diffraction and circular dichroism analysis demonstrate that 1 a–3 a, 1 b–3 b have a mono chiral one‐dimensional (1D) chain‐like spiral structure, while 4 have 1D chain‐like structure whose metal centers have chiral propeller coordination environment. Ligand structure, anions and solvent systems have a regulatory effect on the formation of chiral helical structure. Further investigation has proved that 1 a can be used as circular dichroism spectrum probe for monitoring L‐/D‐cysteine and L‐/D‐penicillamine configuration and concentration in aqueous media based on ligand interchange mechanism. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to show how gradual strength degradation of metal beams under cyclic bending up to fatigue failure is simulated based on a new elastoplasticity model free of any yield criterion. Design/methodology/approach: A new approach is proposed toward accurately and explicitly prescribing evolution of non-uniform stress distribution on beam cross-section under cyclic bending and, as such, gradual degradation of the bending strength can be directly determined. Findings: Explicit results for the bending response in a whole cyclic process up to fatigue failure are obtained and the fatigue characteristic curve is for the first time simulated directly between the curvature amplitude and the cycle number to failure. Originality/value: First, explicit and accurate determination of the non-uniform stress distribution on beam cross-section is achieved with asymptotic softening effects. Second, degradation of the bending strength can be directly deduced cycle by cycle. Finally, the relationship between the bending moment and the curvature is calculated using new and efficient numerical algorithms, thus bypassing usual time-consuming calculations with finite element procedures. Numerical results are presented and in good agreement with experimental data. [ABSTRACT FROM AUTHOR]

Toward directly simulating pseudo-elastic effects of shape memory alloys, new elastoplastic equations of von Mises type are proposed by correlating the yield surface radius with the yield surface center, thus establishing a new elastoplasticity model characterized by three coupled quantities for isotropic and anisotropic hardening. Within the framework of conventional macroscopic elastoplasticity, it is demonstrated that the new model can exactly reproduce pseudo-elastic hysteresis effects of shape memory alloys, with no need to characterize any microstructural features of solid–solid phase transitions. To this end, explicit expressions for the three hardening quantities introduced are presented in terms of two single-variable functions. Then, exact closed-form solutions are obtained for the uniaxial stress–strain responses in a loading and a subsequent unloading process, and such responses are shown to give rise to a hysteresis loop shaped just by the foregoing two single-variable functions. As such, hysteresis loops of arbitrary shapes can be simulated in a straightforward and accurate manner simply prescribing two single-variable functions shaping such loops. For the first time, cumbersome and time-consuming procedures both for conducting statistical averaging schemes and for identifying numerous unknown parameters may be bypassed with broad applicability. [ABSTRACT FROM AUTHOR]

The application of hepatitis B virus (HBV)–T‐cell receptor (TCR) T‐cell immunotherapy in patients with HBV‐related hepatocellular carcinoma (HBV‐HCC) has been apathetic, as the expression of HBV antigens by both normal HBV‐infected hepatocytes and HCC cells with HBV‐DNA integration increases the risk of on‐target off‐tumor severe liver inflammatory events. To increase the safety of this immunotherapeutic approach, we developed messenger RNA (mRNA) HBV‐TCR‐redirected T cells that—due to the transient nature of mRNA—are functionally short lived and can be infused in escalating doses. The safety of this approach and its clinical potential against primary HBV‐HCC have never been analyzed in human trials; thus, we studied the clinical and immunological parameters of 8 patients with chronic HBV infection and diffuse nonoperable HBV‐HCC treated at weekly intervals with escalating doses (1 × 104, 1 × 105, 1 × 106, and 5 × 106 TCR+ T cells/kg body weight) of T cells modified with HBV‐TCR encoding mRNA. The treatment was well tolerated with no severe systemic inflammatory events, cytokine storm, or neurotoxicity observed in any of these patients throughout treatment. Instead, we observed a destruction of the tumor lesion or a prolonged stable disease in 3 of 8 patients. Importantly, the patients without clinically relevant reductions of HCC did not display any detectable peripheral blood immunological alterations. In contrast, signs of transient localized liver inflammation, activation of the T‐cell compartment, and/or elevations of serum chemokine (C‐X‐C motif) ligand (CXCL) 9 and CXCL10 levels were detected in patients with long‐term clinical benefit. Conclusion: We show that despite the reduced in vivo half‐life (3‐4 days), adoptive transfer of mRNA HBV‐TCR T cells into patients with HBV‐HCC show long‐term clinical benefit that was associated with transient immunological alterations. [ABSTRACT FROM AUTHOR]

High‐efficiency algorithms are proposed for numerically integrating elasto‐plastic rate equations for the purpose of simulating metal failure effects under repeated loading conditions. Results are obtained with a newly established elasto‐plasticity model which can automatically simulate both low and high cycle fatigue failure effects, with reference to neither damage‐like variables nor ad hoc failure criteria. Novelties are incorporated in a few respects. First, multiaxial loading processes with arbitrarily changing principal stresses and axes can be treated in a broad sense beyond usually treated proportional loading cases. Second, by means of the commonly used J2‐invariant of the deviatoric stress, multiaxial loading cases can be directly treated just as in the uniaxial loading case. Third, high cost in time consumption can be considerably reduced in evaluating both low and high cycle failure effects. Numerical examples are presented for simulating uniaxial and multiaxial fatigue failure effects and simulation results are in good agreement with experimental data. Results show that the computation speed with the new algorithms exceeds 600 times faster than usual integration algorithms. [ABSTRACT FROM AUTHOR]

We report an efficient and environment‐friendly approach for the synthesis of multisubstituted 7‐oxo‐7H‐chromeno[3,2‐c]quinolin‐5‐ium salts using ambient air as a green sole oxidant. The chromeno[3,2‐c]quinolin‐5‐ium salts were prepared through metal‐free cascade intermolecular cycloaddition/oxidation reaction of 3‐formylchromones and N‐substituted anilines using HClO4 as the reagent and promoter under concise one‐pot conditions. In the applied research, the resulting quinolinium salts could serve as synthons and could be further transformed to diverse synthetically useful 3‐(2‐hydroxy‐benzoyl)quinolin‐4‐ones in water. This protocol offers a simple cascade strategy to synthesize a wide variety of natural‐like chromeno[3,2‐c]quinolin‐5‐ium salts and quinolin‐4‐ones, and shows some academic research potential as well as industrial applications. [ABSTRACT FROM AUTHOR]

Coprinus comatus, widely known as "Jituigu", is an important commodity and food in China. The yield of C. comatus, however, is substantially reduced by the autolysis of the fruiting bodies after harvest. To gain insight into the molecular mechanism underlying this autolysis, we divided the growth of C. comatus fruiting bodies into four stages: infant stage (I), mature stage (M), discolored stage (D), and autolysis stage (A). We then subjected these stages to de novo transcriptomic analysis using high-throughput Illumina sequencing. A total of 12,946 unigenes were annotated and analyzed with the Gene Ontology (GO), Clusters of Orthologous Groups of proteins (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG). We analyzed the differentially expressed genes (DEGs) between stages I and M, M and D, and D and A. Because the changes from M to D are thought to be related to autolysis, we focused on the DEGs between these two stages. We found that the pathways related to metabolic activity began to vary in the transition from M to D, including pathways named as autophagy—yeast, peroxisome, and starch and sucrose metabolism. This study also speculates the possible process of the autolysis of Coprinus comatus. In addition, 20 genes of interest were analyzed by quantitative real-time PCR to verify their expression profiles at the four developmental stages. This study, which is the first to describe the transcriptome of C. comatus, provides a foundation for future studies concerning the molecular basis of the autolysis of its fruiting bodies. [ABSTRACT FROM AUTHOR]

Purpose: A new and explicit form of the elastic strain-energy function for modeling large strain elastic responses of soft solids is constructed based on Hencky's logarithmic strain tensor. Design/methodology/approach: Well-designed invariants of the Hencky strain are introduced for characterizing deformation modes and, furthermore, a new interpolating technique is proposed for combining piecewise splines into a single smooth function. Findings: With this new form and this new technique, objectives in three respects may be achieved for the first time. Originality/value: First, no adjustable parameters need to be treated. Second, large strain responses for three benchmark modes are derivable in a decoupled sense without involving strongly nonlinear coupling effects. Finally, large strain data may be automatically and accurately matched for three benchmark modes, including uniaxial, equi-biaxial and plane-strain extension. Numerical examples are presented and compared with usual approaches. [ABSTRACT FROM AUTHOR]

In summary, this study suggested that Ang-(1-7) analogue AVE0991 inhibited astrocyte-mediated neuroinflammation via SNHG14/miR-223-3p/NLRP3 pathway and offered neuroprotection in APP/PS1 mice. Astrocytes from AVE0991-treated APP/PS1 mice exhibited a significant reduction in NLRP3 protein levels (Figure 3A and B), indicating a suppression of NLRP3 inflammasome in astrocytes following AVE0991 treatment. This finding was consistent with previous observations that NLRP3 is a direct target of miR-223-3p.[45],[46] Lastly, we revealed that miR-223-3p levels in the astrocytes were upregulated by AVE0991 while miR-223-3p inhibitor reversed the AVE0991-induced suppression of NLRP3 inflammasome. [Extracted from the article]

Background & aims: Immunotherapy with hepatitis B virus (HBV)-specific TCR redirected T (HBV-TCR-T) cells in HBV-related hepatocellular carcinoma (HBV-HCC) patients after liver transplantation was reported to be safe and had potential therapeutic efficacy. We aim to investigate the safety of HBV-TCR-T-cell immunotherapy in advanced HBV-HCC patients who had not met the criteria for liver transplantation. Methods: We enrolled eight patients with advanced HBV-HCC and adoptively transferred short-lived autologous T cells expressing HBV-specific TCR to perform an open-label, phase 1 dose-escalation study (NCT03899415). The primary endpoint was to evaluate the safety of HBV-TCR-T-cell therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03) during the dose-escalation process. The secondary endpoint was to assess the efficacy of HBV-TCR-T-cell therapy by evaluating the anti-tumor responses using RECIST criteria (version 1.1) and the overall survival. Results: Adverse events were observed in two participants among the 8 patients enrolled. Only one patient experienced a Grade 3 liver-related adverse event after receiving a dose of 1 × 105 HBV-TCR-T cells/kg, then normalized without interventions with immunosuppressive agents. Among the patients, one achieved a partial response lasting for 27.7 months. Importantly, most of the patients exhibited a reduction or stabilization of circulating HBsAg and HBV DNA levels after HBV-TCR-T-cell infusion, indicating the on-target effects. Conclusions: The adoptive transfer of HBV-TCR-T cells into advanced HBV-HCC patients were generally safe and well-tolerated. Observations of clinical efficacy support the continued development and eventual application of this treatment strategy in patients with advanced HBV-related HCC. Clinical trials registration: This study was registered at ClinicalTrials.gov (NCT03899415). [ABSTRACT FROM AUTHOR]

A new criterion for predicting metal failure effects under cyclic loading conditions is derived from an innovative elastoplasticity model established most recently. As compared with usual approaches, novel results with this new criterion are presented in four respects: (i) both low and high cycle fatigue effects can be simultaneously simulated in a unified and direct manner; (ii) cumbersome trial‐and‐error procedures in identifying numerous unknown parameters can be bypassed; (iii) time‐consuming numerical procedures are not involved in treating responses in cyclic loading processes; and, for the first time, (iv) data sets for fatigue failure can be simultaneously matched for various cases of the cyclic stress ratio. Numerical examples show that model predictions are in accurate agreement with test data. [ABSTRACT FROM AUTHOR]

K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga , including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga , more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb. [ABSTRACT FROM AUTHOR]

Background and Purpose: Immunosuppressive drugs have shown great promise in treating autoimmune diseases in recent years. A series of novel oxazole derivatives were screened for their immunosuppressive activity. PO-322 [1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)] was identified as the most effective of these compounds. Here, we have investigated the mechanism(s) underlying the inhibition of T-cell proliferation in vitro by PO-322, as well as its effects on the delayed-type hypersensitivity (DTH) response and imiquimod-induced dermatitis in vivo.Experimental Approach: T-cell proliferation and apoptosis were analysed with flow cytometry. Cell viability was assessed with a CCK-8 assay. Protein kinase activity was assessed by SelectScreen Kinase Profiling Services. The phosphorylation of signal-regulated molecules was measured by Western blot. Cytokine levels were determined by elisa. The effect of PO-322 on DTH and imiquimod-induced dermatitis was evaluated in BALB/c mice.Key Results: PO-322 inhibited human T-cell proliferation with anti-CD3/anti-CD28 mAbs or alloantigen without significant cytotoxicity. Importantly, PO-322 was a selective inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1) and decreased NDRG1 phosphorylation but not p70S6K, STAT5, Akt, or ERK1/2 phosphorylation. Furthermore, PO-322 inhibited IFN-γ, IL-6, and IL-17 expression but not IL-10 expression. Finally, treatment with PO-322 was safe and effective for ameliorating the DTH response and imiquimod-induced dermatitis in mice.Conclusions and Implications: PO-322 exerted immunosuppressive activity in vitro and in vivo by selectively inhibiting SGK1 activity. PO-322 represents a potential lead compound for the design and development of new drugs for the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

New finite strain elastoplastic J 2 -flow equations with no reference to the yield condition are proposed for the purpose of simultaneously simulating low-to-ultrahigh cycle failure effects of metals. As inherent response features of such new equations, the entire responses up to eventual failure under cyclic and non-cyclic loadings of constant and variable amplitudes are automatically predicted, in a direct sense without involving any additional damage-like variables and any ad hoc failure criteria. The thermodynamic consistency is ensured by demonstrating that the intrinsic dissipation is identically non-negative. Furthermore, a high-efficiency algorithm for integrating the elastoplastic rate equations is established toward bypassing very time-consuming numerical procedures in treating cyclic responses with high and even ultrahigh cycle number. With numerical examples, model predictions are shown to be in good agreement with fatigue failure data for low, high and very high cycle numbers, and the new algorithm is shown to be much faster and far more efficient than usual integration procedures. [ABSTRACT FROM AUTHOR]

Purpose: A new approach is proposed toward accurately matching any given realistic hardening and softening data from uniaxial tensile test up to failure and moreover, toward bypassing usual tedious implicit trial-and-error iterative procedures in identifying numerous unknown parameters. Design/methodology/approach: Finite strain response features of metals with realistic hardening-to-softening transition effects up to eventual failure are studied for the first time based on the self-consistent elastoplastic J2-flow model with the logarithmic stress rate. As contrasted with usual approximate and incomplete treatments merely considering certain particular types of hardening effects such as power type hardening, here a novel and explicit approach is proposed to obtain a complete form of the plastic-work-dependent yield strength over the whole hardening and softening range. Findings: A new multi-axial evolution equation for both hardening and softening effects is established in an explicit form. Complete results for the purpose of model validation and prediction are presented for the finite strain responses of monotonic uniaxial stretching up to failure. Originality/value: New finite strain elastoplastic equations are established with a new history-dependent variable equivalently in place of the usual plastic work. With these equations, a unified and accurate simulation of both gardening and softening effects up to failure is achieved for the first time in an explicit sense without involving usual tedious implicit trial-and-error iterative procedures. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-based chemotherapy was previously considered as the standard adjuvant therapy for improved overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. However, the benefit was limited due to high risks of recurrence and adverse events. In the present study, the efficacy of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutant patients after surgery was investigated using the latest updated data. Methods: This meta-analysis included a comprehensive range of relevant studies identified from database searches. Disease-free survival (DFS) and OS with hazard ratios (HRs) were calculated using random-effect or fixed-effect models. Subgroup analysis was also performed. Results: A total of seven randomized clinical trials were included in the meta-analysis and involved 1,283 NSCLC patients harboring EGFR mutations. In resected EGFR-mutant NSCLC patients, adjuvant EGFR-TKIs were significantly better than chemotherapy in terms of DFS (HR: 0.41; 95%CI: 0.24–0.70, P = 0.001), without showing any benefit in OS (HR: 0.72; 95%CI: 0.37–1.41, P = 0.336). No significant difference in DFS was observed between patients with EGFR exon 19 deletion and those with L858R mutation. Resected EGFR-mutant NSCLC patients treated with osimertinib experienced improved DFS and a lower risk of brain recurrence than those treated with gefitinib or erlotinib. Adjuvant EGFR-TKIs reduced the risk of bone and lung relapse, without decreasing the risk of local recurrence and liver relapse. Conclusion: This meta-analysis shows that adjuvant EGFR-TKI therapy could significantly prolong DFS in patients with resected EGFR-mutant NSCLC. Treatment with osimertinib showed improved DFS with a lower risk of brain recurrence than treatment with gefitinib or erlotinib for resected disease. [ABSTRACT FROM AUTHOR]

Background: Although adjuvant chemotherapy is established for patients with non-small-cell lung cancer (NSCLC), the long-term survival remains to be improved. Postsurgical circulating tumor DNA (ctDNA) analysis of resectable NSCLC may identify patients at high risk of recurrence after adjuvant chemotherapy and facilitate personalized therapy. Methods: This analysis included 38 patients who underwent curative-intent resection and received adjuvant chemotherapy for NSCLC. ctDNA analyses of tumor tissue, and pre- and post-operative plasma samples were performed with next-generation sequencing targeting 425 cancer-relevant genes. We define a ctDNA positive event as at least one shared mutation identified simultaneously in the plasma and tumor specimens. The primary endpoint was recurrence-free survival (RFS). Results: At least one somatic mutation was identified in the tumor tissue of all 38 patients. Tumor tissue-specific mutated ctDNA was detected in the preoperative plasma samples of 19 (50%) patients. ctDNA in preoperative plasma was in good accordance with that in tissue. ctDNA was detectable in the first post-operative pre-chemotherapy samples of 8 of 35 (22.9%) patients and was associated with inferior RFS (HR, 3.69; P = 0.033). ctDNA was detected in the first post-chemotherapy samples of 8 of 36 (22.2%) patients and was also associated with inferior RFS (HR, 8.76; P < 0.001). Conclusions: Postoperative and post-chemotherapy ctDNA is a promising prognostic marker for resected NSCLC. ctDNA analyses may define a subgroup that remains at high risk of relapse despite standard adjuvant chemotherapy, and may help to inform intensified therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: To date, breast cancer remains the most common malignant tumor in women. In recent years, a growing number of studies on polycomb proteins have been conducted. The Ring finger protein1 (RING1), an essential component of the polycomb family of proteins, plays vital roles in the tumorigenesis of various cancer types. However, further research is required in determining RING1 expression and prognostic value in breast cancer. Method: RING1 expression level in multiple cancer types was evaluated using the XENA and UALCAN databases. Real-time quantitative PCR (real-time qPCR) and immunohistochemistry (IHC) were used to confirm this expression. The prognostic value was analyzed using our follow-up data and the Kaplan–Meier plotter website. RING1 co-expressed genes and its promoter methylation level were calculated using the cBioPortal and UALCAN online tools. The gene ontology (GO) and the Kyoto encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed using the DAVID online analysis tool. Result: RING1 expression was upregulated in CHOL (Bile Duct Cancer), ESCA (Esophageal Cancer), LIHC (Liver Cancer), and PCPG (Pheochromocytoma & Paraganglioma). However, its expression level was decreased in COAD (Colon Cancer), KICH (Kidney Chromophobe), KIRP (kidney papillary cell carcinoma), THCA (Thyroid Cancer), and BRCA (Breast carcinoma). RING1 low expression is an unfavorable prognostic factor in many cancer patients, especially in breast cancer patients. For breast cancer, the IHC result showed that RING1 protein expression significantly and negatively correlates with tumor size (P = 0.029), LNM (P = 0.017), TNM stage (P = 0.016), ER (P = 0.005), Ki67 (P = 0.015), and p53 status (P = 0.034). Moreover, the multivariate Cox regression model indicated that RING1 (P = 0.038) and ER (P = 0.029) expressions were independent prognostic markers for breast cancer. RING1 co-expressed genes were selected and included HDAC10, PIN1, CDK3, BAX, and BAD. GO analysis and KEGG pathway analyses revealed that RING1 related genes, were mainly enriched in "regulation of transcription", "apoptotic process", "protein transport", "protein binding", "Notch signaling pathway", and "Homologous recombination". Conclusion: RING1 expression was downregulated in breast cancer, and its low expression was associated with worse disease outcomes. RING1 may act as a new prognostic biomarker for breast cancer. [ABSTRACT FROM AUTHOR]

A finite strain J2‐flow model of von Mises type for elastoplastic behaviors of metals is proposed with a new characterization of the evolving yield strength. It is intended for providing solutions to a few unresolved issues concerning a simultaneous simulation of realistic hardening and softening effects for metals up to failure. Such issues are concerned with three respects, namely, how to ensure that the simulation is accurate in the sense that sufficient uniaxial experimental data for both hardening and softening effects can be matched with no errors, how to ensure that the simulation is explicit in the sense that any implicit trial‐and‐error iterative procedures in identifying numerous parameters can be bypassed, and how to ensure that the simulation is of broad applicability in the sense that any given uniaxial data for metals can be automatically matched. With the new model proposed, solutions to such issues are obtained by presenting an accurate and explicit form of the yield strength function that automatically matches any given test data. Numerical examples with realistic hardening‐to‐softening transition effects are presented for the first time for the finite strain responses of both uniaxial stretching and simple shearing up to the eventual failure. [ABSTRACT FROM AUTHOR]

Objective Long noncoding RNAs (lncRNAs) are widely involved in the carcinogenesis and development of cancers. We conducted a meta-analysis to evaluate the diagnostic performance of lncRNAs in hepatocellular carcinoma (HCC). Methods After the inclusion and exclusion process, relevant information was extracted. Heterogeneity between studies was evaluated, and data synthesis was conducted by employing a bivariate random-effects model. Results In total, 20 eligible studies were enrolled. The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.80–0.90) and 0.88 (95% CI, 0.82–0.92), respectively. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 7.1 (95% CI, 4.9–10.2), 0.16 (95% CI, 0.11–0.23), and 44 (95% CI, 25–79), respectively. The results of the linear regression method and visual inspection of the Deeks funnel plot did not indicate significant publication bias. Conclusion Our meta-analysis suggested that lncRNAs have high diagnostic performance for HCC and have the potential for clinical application. [ABSTRACT FROM AUTHOR]

Background: Limited treatment strategies are available for squamous-cell lung cancer (SQLC) patients. Few studies have addressed whether immune-related genes (IRGs) or the tumor immune microenvironment can predict the prognosis for SQLC patients. Our study aimed to construct a signature predict prognosis for SQLC patients based on IRGs. Methods: We constructed and validated a signature from SQLC patients in The Cancer Genome Atlas (TCGA) using bioinformatics analysis. The underlying mechanisms of the signature were also explored with immune cells and mutation profiles. Results: A total of 464 eligible SQLC patients from TCGA dataset were enrolled and were randomly divided into the training cohort (n = 232) and the testing cohort (n = 232). Eight differentially expressed IRGs were identified and applied to construct the immune signature in the training cohort. The signature showed a significant difference in overall survival (OS) between low-risk and high-risk cohorts (P < 0.001), with an area under the curve of 0.76. The predictive capability was verified with the testing and total cohorts. Multivariate analysis revealed that the 8-IRG signature served as an independent prognostic factor for OS in SQLC patients. Naive B cells, resting memory CD4 T cells, follicular helper T cells, and M2 macrophages were found to significantly associate with OS. There was no statistical difference in terms of tumor mutational burden between the high-risk and low-risk cohorts. Conclusion: Our study constructed and validated an 8-IRG signature prognostic model that predicts clinical outcomes for SQLC patients. However, this signature model needs further validation with a larger number of patients. [ABSTRACT FROM AUTHOR]

Late-onset Alzheimer's disease (AD) accounts for most of all AD casesand is currently considered a complex disorder caused by a combination of environmental and genetic factors. As an important family member of triggering receptor expressed on myeloid cells (TREM), TREM-like transcript 2 gene (TREML2) locates on human chromosome 6p21.1, a newly-identified hot zone for AD susceptibility, and encodes atransmembrane immune receptor. Emerging evidence implied a potential role of TREML2 in the susceptibility and pathogenesis of AD. Here, we review the recent literature about the association of TREML2 variants with AD risk and disease endophenotypes. Moreover, we summarize the latest findings regarding cellular localization and biological functions of TREML2 and speculate its possible role in AD pathogenesis. In addition, we discuss future research directions of TREML2 and AD. [ABSTRACT FROM AUTHOR]

COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients. Immunophenotyping of patients with COVID-19 is ongoing, but much remains to be learned. Here the authors analyze 41 hospitalized patients with COVID-19 and show a higher degree of lymphopenia in various immune cell subsets as well as cytotoxicity and T cell inhibitory marker expression in severe cases compared with mild. [ABSTRACT FROM AUTHOR]