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Background: Recent clinical trials of anti-Aβ monoclonal antibodies (mAbs) in the treatment of early Alzheimer's disease (AD) have produced encouraging cognitive and clinical results. The purpose of this network meta-analysis (NMA) was to compare and rank mAb drugs according to their efficacy and safety. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for randomized controlled trials testing various mAbs for the treatment of cognitive decline in patients with AD, up to March 31, 2023. R software (version 4.2.3) along with JAGS and STATA software (version 15.0) were used for statistical analysis. Odds ratio (OR) for binary variables, mean difference (MD) for continuous variables, and their 95% confidence intervals (CI) were utilized to estimate treatment effects and rank probabilities for each mAb in terms of safety and efficacy outcomes. We calculated the surface under the cumulative ranking area (SUCRA) to evaluate each mAb, with higher SUCRA values indicating better efficacy or lower likelihood of adverse events. Results: Thirty-three randomized controlled trials with a total of 21,087 patients were included in the current NMA, involving eight different mAbs. SUCRA values showed that aducanumab (87.01% and 99.37%, respectively) was the most likely to achieve the best therapeutic effect based on the changes of Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale Sum of Boxes (CDR-SB) scores. Donanemab (88.50% and 99.00%, respectively) performed better than other therapies for Alzheimer's Disease Assessment Scale–cognitive subscale (ADAS-cog) and Positron Emission Tomography-Standardized Uptake Value ratio (PET-SUVr). Lecanemab (87.24%) may be the most promising way to slow down the decrease of Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS-ADL) score. In the analysis of the incidence of adverse events (subjects with any treatment-emergent adverse event), gantenerumab (89.12%) had the least potential for adverse events, while lecanemab (0.79%) may cause more adverse events. Solanezumab (95.75% and 80.38%, respectively) had the lowest incidence of amyloid-related imaging abnormalities characterized by edema and effusion (ARIA-E) and by cerebral microhemorrhages (ARIA-H) of the included immunotherapies. While SUCRA values provided a comprehensive measure of treatment efficacy, the inherent statistical uncertainty required careful analysis in clinical application. Conclusion: Despite immunotherapies significantly increasing the risks of adverse events and ARIA, the data suggest that mAbs can effectively improve the cognitive function of patients with mild and moderate AD. According to the NMA, aducanumab was the most likely to achieve significant improvements in different cognitive and clinical assessments (statistically improved MMSE and CDR-SB), followed by donanemab (statistically improved ADAS-Cog, and PET-SUVr) and lecanemab (statistically improved ADCS-ADL). [ABSTRACT FROM AUTHOR]

This document provides a detailed account of the synthesis and characterization of several chemical compounds, specifically focusing on the synthesis of an epoxy-lactone fragment commonly found in heteroatom-containing organic compounds. The authors explore different strategies for synthesizing this fragment and provide experimental data on reaction conditions and yields. The document also includes information on the physical properties and spectroscopic data of each compound synthesized. This information can be valuable for researchers studying these compounds and their properties. [Extracted from the article]

By numerically solving the time-dependent Schrödinger equation, we study high-order harmonic generation from the asymmetric diatomic molecule HeH2+ in a corotating two-color circularly polarized laser field. Our results reveal a strong correlation between the molecule orientation and the harmonic yield. The harmonics in the plateau region can achieve an intensity modulation of one to two orders of magnitude with the change in the orientation angle. Through the time-dependent evolution of ionized electron wave packets combined with the analysis of the transition dipole moment between the continuum and bound states, the modulation of the harmonic strength may be attributed to the difference in the recollision angle of ionized electron wave packets relative to the molecules. In addition, the harmonic ellipticity is also affected by the molecular orientation. Notably, we found that the harmonic with greater ellipticity and higher intensity can be obtained with an orientation angle of 147°. These findings open up new avenues for achieving enhanced efficiency, the near-circular polarization of harmonics, and precise control over harmonic polarization states. [ABSTRACT FROM AUTHOR]

• ApoE mimic peptide COG1410 effectively improved performance in spatial learning and memory of APP/PS1 mice. • ApoE mimic peptide COG1410 reduced Aβ deposition in APP/PS1 mice. • ApoE mimic peptide COG1410 reverted the ratio of A1/A2 reactive astrocytes in APP/PS1 mice. • ApoE mimic peptide COG1410 regulated BDNF/TrkB signaling pathway in the hippocampus of APP/PS1 mice. The main clinical manifestation of Alzheimer's disease is progressive cognitive decline, and its pathological features are β-amyloid (Aβ) deposition, neurofibrillary tangles, synaptic dysfunction and neuron death. Neuroinflammation is an important reason for the occurrence and development of AD, which is mainly manifested by the accumulation of activated microglia and reactive astrocytes. Apolipoprotein E (ApoE) is one of the most important apolipoprotein in the brain, which is related to metabolism, aggregation and toxicity of Aβ. However, the underlying mechanism needs to be further explored. In this study, we studied the effect of ApoE mimetic peptide COG1410 on spatial learning and memory functions, deposition of Aβ in the dentate gyrus (DG) of APP/PS1 transgenic mice, and the different effects of A1 and A2 subtypes of reactive astrocytes. Administration of COG1410 effectively improved performance in spatial learning and memory of APP/PS1 mice, reduced Aβ deposition and significantly reverted the ratio of A1/A2 reactive astrocytes, which could be associated with BDNF/TrkB signaling pathway. On the whole, the present findings suggest new possibility of using apolipoprotein E mimetic peptide to treat AD with potential effectiveness. [ABSTRACT FROM AUTHOR]

Objective To investigate the correlation and causation between age at menarche (AAM) and risk of heart failure (HF) with genetic correlation analysis and Mendelian randomization (MR). Methods Based on genome - wide association study (GWAS) data on age at menarche and heart failure, genetic correlation was assessed using linkage disequilibrium regression (LDSC) and Genomic structural equation models (Genomic SEM). Univariate MR and multivariate MR were used to explore the total and direct effects of age at menarche on heart failure risk respectively. Results There was a negative genetic correlation between AAM and HF (rg = -0. 271, P = 1. 94 X 10-9). After additionally adjusting for confounders, genomic SEM analysis revealed a negative partial correlation between AAM and HF. Univariable MR results showed that genetically predicated AAM and HF risk had a negative causal effect (IVW: OR =0.884; 95% CI: 0.854 -0.916, P < 0. 001), and multivariable MR results showed that the negative causal association remained after adjusting for confounders. Conclusion This study suggests that genetically predicted early age at menarche increases the risk of heart failure. [ABSTRACT FROM AUTHOR]

Background: Pyroptosis is crucial for controlling various immune cells. However, the role of allergen-induced CD11c + dendritic cell (DC) pyroptosis in allergic rhinitis (AR) remains unclear. Methods: Mice were grouped into the control group, AR group and necrosulfonamide-treated AR group (AR + NSA group). The allergic symptom scores, OVA-sIgE titres, serum IL-1β/IL-18 levels, histopathological characteristics and T-helper cell-related cytokines were evaluated. CD11c/GSDMD-N-positive cells were examined by immunofluorescence analysis. Murine CD11c + bone marrow-derived DCs (BMDCs) were induced in vitro, stimulated with OVA/HDM, treated with necrosulfonamide (NSA), and further cocultured with lymphocytes to assess BMDC function. An adoptive transfer murine model was used to study the role of BMDC pyroptosis in allergic rhinitis. Results: Inhibiting GSDMD-N-mediated pyroptosis markedly protected against Th1/Th2/Th17 imbalance and alleviated inflammatory responses in the AR model. GSDMD-N was mainly coexpressed with CD11c (a DC marker) in AR mice. In vitro, OVA/HDM stimulation increased pyroptotic morphological abnormalities and increased the expression of pyroptosis-related proteins in a dose-dependent manner; moreover, inhibiting pyroptosis significantly decreased pyroptotic morphology and NLRP3, C-Caspase1 and GSDMD-N expression. In addition, OVA-induced BMDC pyroptosis affected CD4 + T-cell differentiation and related cytokine levels, leading to Th1/Th2/Th17 cell imbalance. However, the Th1/Th2/Th17 cell immune imbalance was significantly reversed by NSA. Adoptive transfer of OVA-loaded BMDCs promoted allergic inflammation, while the administration of NSA to OVA-loaded BMDCs significantly reduced AR inflammation. Conclusion: Allergen-induced dendritic cell pyroptosis promotes the development of allergic rhinitis through GSDMD-N-mediated pyroptosis, which provides a clue to allergic disease interventions. AVnLpCxbGNVGDf4VdBhsuL Video Abstract [ABSTRACT FROM AUTHOR]

Objective: We performed a systematic review and meta-analysis of the efficacy and safety of nusinersen and risdiplam in the treatment of spinal muscular disease (SMA). Methods: We screened the literature published in Pubmed, Web of Science, Embase, and Cochrane before July 2023 to conduct randomized controlled trials to test the treatment of SMA patients with nusinersen and risdiplam. The data were analyzed using Review Manager 5.4 software and Stata version 15.0 software. Results: A total of six randomized controlled trials were included, involving 728 SMA patients, to synthesize evidence. It is reported that nusinersen treatment was beneficial for increasing the score of the Hammersmith Functional Motor Scale—Expanded (HFMSE) (WMD: 4.90; 95% CI: 3.17, 6.63; p < 0.00001), Revised Upper Limb Module (RULM) (WMD: 3.70; 95% CI: 3.30, 4.10; p < 0.00001), and Hammersmith Infant Neurological Evaluation Section 2 (HINE-2) (WMD: 5.21; 95% CI: 4.83, 5.60; p < 0.00001). In addition, the risdiplam treatment group also showed statistically significant improvements in the HFMSE score (WMD:0.87; 95% CI: 0.05, 1.68; p = 0.04), the 32-item Motor Function Measure (MFM32) (WMD:1.48; 95% CI: 0.58, 2.38; p = 0.001), and (WMD: 1.29; 95% CI: 0.57, 2.01; p = 0.0005). Nusinersen and risdiplam did not cause a statistically significant increase in the RULM score for adverse events (OR: 0.93; 95% CI: 0.51, 1.7; p = 0.82) and for severe adverse events (OR: 0.77; 95% CI: 0.47, 1.27; p = 0.31). Conclusion: Our analysis found that nusinersen and risdiplam treatment showed clinically meaningful improvement in motor function and a similar incidence rate of adverse events compared with the placebo. Further research should be carried out to provide a direct comparison between the two drugs in terms of safety and efficacy. [ABSTRACT FROM AUTHOR]

Purpose: Arthroscopic superior capsule reconstruction (SCR) with the long head of the biceps (LHBT) was performed to restore structural stability, force couple balance, and shoulder joint function. This study aimed to evaluate the functional outcomes of SCR using the LHBT over at least 24 months of follow-up. Method: This retrospective study included 89 patients with massive rotator cuff tears who underwent SCR using the LHBT, met the inclusion criteria and underwent follow up for at least 24 months. The preoperative and postoperative shoulder range of motion (forward flexion, external rotation, and abduction), acromiohumeral interval (AHI), visual analog scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score and Constant–Murley score were obtained, and the tear size, and Goutallier and Hamada grades were also investigated. Results: Compared with those measured preoperatively, the range of motion, AHI, and VAS, Constant–Murley, and ASES scores were significantly improved immediately postoperatively (P < 0.001) and at the 6-month, 12-month, and final follow-ups (P < 0.001). At the last follow-up, the postoperative ASES score and Constant-Murley score increased from 42.8 ± 7.6 to 87.4 ± 6.1, and 42.3 ± 8.9 to 84.9 ± 10.7, respectively; with improvements of 51 ± 21.7 in forward flexion, 21.0 ± 8.1 in external rotation, and 58.5 ± 22.5 in abduction. The AHI increased 2.1 ± 0.8 mm and the VAS score significantly changed from 6.0 (5.0, 7.0) to 1.0 (0.0, 1.0), at the final follow-up. Eleven of the 89 patients experienced retears, and one patient needed reoperation. Conclusion: In this study with at least 24-months of follow-up, SCR using the LHBT for massive rotator cuff tears could effectively relieve shoulder pain, restore shoulder function and increase shoulder mobility to some extent. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Objective: The goal of this research was to review the literature from randomized controlled trials (RCTs) on the impacts of moxibustion on cancer-related fatigue (CRF) as well as provide credible evidence to guide clinical practice. Methods: Three English electronic medical databases (PubMed, Embase, and the Cochrane Library) and two Chinese databases (China National Knowledge Infrastructure and Wanfang) were searched. Only randomized controlled trials on the effect of moxibustion on CRF were included in this systematic review. Study selection, data extraction, and validation were all carried out independently by two reviewers. The revised Cochrane Risk of Bias tool was used to assess the quality of the RCTs (RoB 2.0). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was applied to assess effect sizes in individual RCTs and pooled effect sizes in meta-analyses. Data were meta-analyzed using Stata (version 14.0). Results: In a random-effects meta-analysis of 24 RCTs with 1894 participants, the aggregated standardized mean difference (SMD) revealed a statistically significant association between moxibustion and alleviation from cancer-related fatigue (SMD = − 1.66, 95% CI = − 2.05, − 1.28, p = 0.000). Pooled results, however, show significant heterogeneity (I2 = 92.5%), and the evidence is insufficient to determine whether this association varies systematically by measuring tools and moxibustion modalities. Furthermore, evidence ranging from very low to low showed that moxibustion had an immediate positive effect on patients with CRF. Conclusion: Moxibustion may have a therapeutic effect on cancer-related fatigue. However, further large-scale, multicenter, high-quality RCTs on moxibustion for fatigue relief and safety are still needed because of the handful of studies included and the low methodological quality. [ABSTRACT FROM AUTHOR]

In the process of intense laser–matter interactions, the transition dipole moment is a basic physical quantity at the core, which is directly related to the internal structure of the solid and dominates the optical properties of the solid in the intense laser field. Therefore, the reconstruction of the transition dipole moment between solid energy bands is extremely important for clarifying the ultrafast dynamics of carriers in the strong and ultrashort laser pulse. In this review, we introduce recent works of reconstructing transition dipole moment in a solid, and the advantages and drawbacks of different works are discussed. [ABSTRACT FROM AUTHOR]

Purpose: To review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2O) abuse, and analyze the factors that affect outcomes. Methods: Patients with N2O abuse treated in the Department of Neurology between January 2018 and December 2020 were included. The clinical data of these patients were collected, and follow‐up was conducted to determine the outcomes. Results: The average age of the 110 patients with N2O abuse was 21.4 ± 4.2 years (range: 14–33 years). Clinical presentation primarily included neurological symptoms, such as limb numbness and/or weakness (97%), psychiatric symptoms, changes in appetite, and skin hyperpigmentation. Laboratory test results were characterized by vitamin B12 deficiency (60%, 34 out of 57 cases) and high homocysteine level (69%, 31 out of 45 cases). Electromyography indicated mixed axonal and demyelination injury (92%, 80 out of 87 cases). Motor and sensory nerves were simultaneously involved, and injury primarily involved the lower limbs. One hundred and seven (97%) patients were clinically diagnosed with peripheral neuropathy, of whom 26 (24%) exhibited spinal abnormalities on magnetic resonance imaging, supporting a diagnosis of subacute combined degeneration. Treatment included N2O withdrawal and vitamin B12 supplementation. Reexamination of six patients indicated that treatment was effective. Follow‐up was completed for 51 patients. Thirty‐four patients (67%) recovered completely, 17 patients (33%) had residual limb numbness, and only one patient experienced relapse. Sex was an independent prognostic factor; the outcomes of female patients were better than that of male patients. Conclusion: The recreational use of N2O has largely expanded among youth in recent decades, which has become a growing public health concern in China. It highlights the importance of the recognition of various clinical symptoms, particularly limb numbness and/or weakness related to the cases of N2O abuse. The therapeutic administration of vitamin B12 supplementation and N2O withdrawal can make the overall prognosis good, especially for female patients. [ABSTRACT FROM AUTHOR]

Background: This study aims to identify the underlying genetic defects of β‐crystallin (CRYB) genes responsible for congenital cataracts in a group of Chinese families. Methods: Detailed family history and clinical data of six Chinese families with autosomal dominant congenital cataracts were recorded. Targeted exome sequencing was applied to detect the underlying genetic defects for the families. Generated variants were confirmed by PCR and sanger sequencing. Afterward, bioinformatic analysis through several computational predictive programs was performed to assess impacts of mutations on protein structure and function. Results: A total of 53 participants (23 affected and 30 unaffected) from six unrelated Chinese families were recruited. Cataract phenotypes covered nuclear, total, posterior polar, pulverulent, snowflake‐like, and zonular. Through targeted exome sequencing, six mutations in four β‐crystallin genes were revealed which included five missense mutations CRYBB1 p.Q70P, CRYBB2 p.E23Q, CRYBB2 p.A49V, CRYBB2 R188C, CRYBA4 p.M14K and one splice mutation CRYBB3 c.75+1 G>A. In silico results predicted pathogenic for all four missense variants except variant CRYBB2‐p.A49V yielded results as tolerant. The CRYBB3 c.75+1 G>A splice site mutation was predicted to be deleterious by leading to a broken splice site, a premature stop codon, and subsequently resulting in a short peptide of 113 amino acids, which may affect protein features. Conclusion: The obtained results expanded mutational and phenotype spectrum of β‐crystallin genes and offer clues for pathogenesis of congenital cataracts. The data also demonstrated that targeted exome sequencing is valuable for providing molecular diagnostic information for congenital cataract patients. [ABSTRACT FROM AUTHOR]

Marine carbon sink is one of the important methods to solve the problem of carbon emission in China. Under the dual constraints of economic development demand and ecological capacity, more policy means need to be explored to achieve carbon emission peak and carbon neutrality in China. There is great potential for the construction of marine carbon sink in China. Hence it is of great significance to build an integrated carbon sink system by combining marine carbon sink with land carbon sink. In the path to achieve marine carbon sequestration increase based on marine ecological improvement, marine breeding, coastal wetland protection and pollution emission will provide the possibility for the increase of marine carbon sequestration. On the basis of the original carbon trading market, through the design of reasonable carbon trading rules, we can guide more resources into the field of marine carbon sink construction by means of market, and achieve the goal of enhancing China's carbon strength. [ABSTRACT FROM AUTHOR]

• Specific knockout of Notch2 in Treg cells can result in a marked spontaneous inflammatory response. • Specific knockout of Notch2 in Treg cells can lead to disturbance of the subpopulation of CD4 + T cells. To investigate the long-term alterations in immune function and spontaneous inflammation in mice following specific knockout of Notch2 (Notch2KO) in Treg cells. A Treg cell-specific Notch2 knockout mouse model was constructed, and the mice were named Notch2KO mice. The pathological changes and inflammatory cell infiltration in the lungs, skin, and liver of the mice at 2, 6, 9, and 12 months of age were evaluated by HE staining. The expression of Th1/Th2/Th17/Treg transcription factors was detected by Western blotting. The proportion of CD4 + T-cell subsets was determined by flow cytometry. The levels of Th1/Th2/Th17/Treg cytokines were measured by enzyme-linked immunosorbent assays (ELISAs). The expression level of Notch2 in Treg cells from the Notch2KO mice was significantly decreased compared with that in Treg cells from the control mice (P < 0.05). HE staining showed that compared with the control mice, the Notch2KO mice displayed spontaneous inflammation and had a large amount of inflammatory cell infiltration in the lungs and skin (P < 0.05). The number of Treg cells, the expression level of Foxp3, and the level of IL-10 were reduced in the Notch2KO mice compared with the control mice (P < 0.05), and these metrics further decreased with increasing age (P < 0.05). In contrast, the number of Th1/Th2 cells, the expression level of T-bet/GATA3, and the levels of Th1 cytokines (IFN-γ)/Th2 cytokines (IL-4, IL-5, and IL-13) were significantly increased in the Notch2KO mice (P < 0.05), and these metrics further increased with increasing age (P < 0.05). There was no significant change in the number of Th17 cells, the expression of RORγt, or the level of IL-17. Further analysis showed that the balance of Th1/Th2 and Treg/Th17 cells in the Notch2KO mice was shifted, and the ratio showed a downward trend over time (P < 0.05). The number and function of Treg cells can be severely inhibited by a specific knockout of Notch2 in Treg cells, leading to immune disorders that gradually worsen over time. [ABSTRACT FROM AUTHOR]

Trehalose is a non-reducing disaccharide with a wide range of applications in food, cosmetic, and pharmaceutical industries. Cyanobacteria are promising cell factories to produce biochemicals by using solar energy and CO 2. Trehalose is biosynthesized at low intracellular concentrations as a salt-inducible compatible solute in some cyanobacteria. In the current study, we demonstrated the efficient trehalose production without salt induction in cyanobacteria by metabolic engineering. The trehalose transporter 1 (TRET1) from an anhydrobiotic insect (Polypedilum vanderplanki) was successfully expressed in the engineered strains and the intracellular trehalose was efficiently secreted to the medium. As the results, the engineered strain co-expressing maltooligosyl trehalose synthase (MTS), maltooligosyl trehalose trehalohydrolase (MTH) and TRET1 secreted 97% of trehalose to the medium, and the titer was up to 2.7 g/L in 15 days. In addition, 5.7 g/L trehalose was produced by semi-continuous cultivation in 34 days. Taken together, this work demonstrates cyanobacteria can be applied as cell factories for direct sunlight-driven conversion of CO 2 into excreted trehalose. • Efficient trehalose production from CO 2 was achieved in cyanobacteria. • The trehalose production in cyanobacteria was independent of salt stress. • A trehalose transporter from an insect improved trehalose production and secretion. • Over 97% of the produced trehalose was secreted to the medium. [ABSTRACT FROM AUTHOR]

The demand to repair areas contaminated with hydrocarbon products has led to the development of new technologies for the treatment of contaminants in an unconventional method, that is, no physical or chemical methods are used. Biosurfactants are amphiphilic biomolecules produced by microorganisms that can be used in environments contaminated by petroleum products due to their unexceptionable tensile properties. Petroleum degrading strain Rhodococcus erythropolis HX-2 was found to be an effective producer of biosurfactants. The resulting biosurfactant (named NK) exhibits high physicochemical properties in terms of surface activity. It is capable of reducing surface tension from 54.99 to 28.89 mN/m and critical micelle concentration (CMC) is 100 mg/L. NK was found to be a substitute for chemically synthesized surfactants because of its higher solubilization efficiency for petroleum and polycyclic aromatic hydrocarbons, superior to SDS, Tween 80, Triton X-100 and Rhamnolipid (a wide used biosurfactant). In addition, it exhibits favorable emulsion stability over a wide range of pH (3–10), temperature (20–100 °C) and salinity ranges (5–20 g/L). It was found that the addition of biosurfactant can improve the efficiency of petroleum degradation, therefore it has potential applications in bioremediation. Rhodococcus erythropolis HX-2 is an effective petroleum degrading strain. HX-2 is a potential source of biosurfactant production. The biosurfactant NK reduces surface tension and exhibits high emulsification activity. The biosurfactant NK is effective over a wide range of temperatures, pH and salinity. The biosurfactant NK shows high solubilization efficiency for petroleum as well as polycyclic aromatic hydrocarbons. [ABSTRACT FROM AUTHOR]

• Specific knockout of Notch2 gene in Treg cells can significantly inhibit the growth of HNSCC. • Specific knockout of Notch2 in Treg cells can significantly inhibit the function of Tregs and enhance the anti-HNSCC effect. • The tumor tissues had significant pyroptosis in Treg cell-specific Notch2-knockout mice. To investigate the effect of Notch2 gene knockout in Treg cells on head and neck squamous cell carcinoma (HNSCC) in mice. A mouse model of HNSCC was constructed. Flow cytometry and immunofluorescence were used to examine the numbers of related immune cells and programmed cell death in tumor cells in the spleen and tumor microenvironment of mice. Western blotting was used to measure the expression of related proteins in tumor tissues. The tumor volume of regulatory T (Treg) cell-specific Notch2-knockout mice (experimental group) was significantly smaller than that of control mice (control group) (P < 0.05). Compared with those in the control group, the number of Treg cells and the expression of Ki67 in Treg cells in the spleen and tumor tissue were significantly decreased in the experimental group, while the numbers of CD45+ hematopoietic cells, CD4+ T cells, CD8+ T cells, T helper 1 (Th1) cells, CD11b+ cells (macrophages), and CD11b+CD11c+ cells (dendritic cells) and the expression of Ki67 in CD4+ T cells and CD8+ T cells were significantly increased (P < 0.05). There was no significant difference in the number of Th2 cells between the two groups (P > 0.05). Immunofluorescence analysis showed that the numbers of CD4+ T cells and CD8+ T cells in the tumor tissue in the experimental group were significantly higher than those in the control group (P < 0.05). Compared with that in the control group, programmed cell death in the experimental group was significantly increased (P < 0.05). Moreover, the expression levels of NLRP3, Caspase-1 and GSDMD in the tumor tissues of the experimental group were higher than those in the control group (P < 0.01), while the expression levels of BCL2, Bax, ATG5, LC3 and p62 were not significantly different (P > 0.05). Specific knockout of the Notch2 gene in Treg cells significantly decreases the function of Treg cells, inhibits the growth of HNSCC and improves the immune microenvironment in mice, thus effectively treating HNSCC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Improving the wettability of PPENK for BF by synergistic action. • Enhancing the interfacial properties by organic/inorganic hybrid strategy. • Constructing modulus transitional interface by combining rigid & soft phases. • Introducing an idea of "micro-composite" for the tensile behavior of modified BFs. Basalt fiber reinforced high-performance thermoplastic (BFRHTP) composites are promising materials for application in military, aerospace, chemical, automobile, and other high-tech industries. However, their mechanical properties are still largely limited by poor interfacial properties because of the smooth, inert, and low-energy surface of BF. In this study, an organic/inorganic hybrid sizing agent was used for BF surface modification to construct an appropriate modulus transition layer for the interface with a combination of soft and rigid phases. Organic poly(ether nitrile) (PEN) and inorganic carboxylic multi-walled carbon nanotubes (MWCNT-COOH) in hybrid sizing agents (PEN/CNT) were respectively used as soft and rigid phases to design the interfacial structure. The tensile strength, flexural strength, interlaminar and interfacial shear strength of the basalt fiber reinforced poly(phthalazinone ether nitrile ketone) composites were increased by 60, 33, 62, and 144%, respectively. This approach provides a simple, green, and promising strategy for enhancing the interfacial properties of BFRHTP composites. [ABSTRACT FROM AUTHOR]

This paper presents a global optimization method for structural design optimization, which integrates subset simulation optimization (SSO) and the dynamic augmented Lagrangian multiplier method (DALMM). The proposed method formulates the structural design optimization as a series of unconstrained optimization sub-problems using DALMM and makes use of SSO to find the global optimum. The combined strategy guarantees that the proposed method can automatically detect active constraints and provide global optimal solutions with finite penalty parameters. The accuracy and robustness of the proposed method are demonstrated by four classical truss sizing problems. The results are compared with those reported in the literature, and show a remarkable statistical performance based on 30 independent runs. [ABSTRACT FROM AUTHOR]

We study the conformation of an amphiphilic comb-like copolymer in a selective solvent by using Brownian dynamics simulations. Our results demonstrate that, there is an optimal total degree of polymerization to form spherical micelles. Only when the total degree of polymerization is less than the optimal total degree of polymerization, a unimolecular spherical micelle can be formed, otherwise, the spherical micelle will be transformed into a cylindrical micelle. When the total degree of polymerization is less than the optimal total degree of polymerization, the radius of gyration and the stretching factor meet an exponential relationship, where the power exponent decreases with the increase of the length of hydrophilic side chains. The fundamental principles uncovered here afford insights for the optimization of molecular design of amphiphilic comb-like copolymers in various applications. [ABSTRACT FROM AUTHOR]

Wireless power transfer (WPT) working at megahertz (MHz) is widely considered a promising technology for midrange and low-power applications. A Class $ E^2$ dc–dc converter is composed of a Class E power amplifier (PA) and a Class E rectifier. It is attractive for applications in MHz WPT due to the soft-switching properties of both the PA and the rectifier. Using the existing design, the Class $E^2$ dc–dc converter can only achieve optimal performance such as a high efficiency under a fixed operating condition. Meanwhile, in real applications variations in the coil relative position and the final load are common. The purpose of this paper is to analyze and develop a general design methodology for a robust Class $E^2$ dc–dc converter in MHz WPT applications. Component and system efficiencies are analytically derived, which serve as the basis for the determination of the design parameters. The classical matching network of the Class E PA is also improved that provides the required impedance compression capability. Then, a robust parameter design procedure is developed. Both the experimental and calculated results show that proposed design approach can significantly improve the robustness of the efficiency of the Class $E^2$ dc–dc converter against variations in coil relative position and final load. Finally, the experiments show that the range of variation of the system efficiency is narrowed from 47.5%–85.0% to 73.3%–83.7% using the proposed robust design. [ABSTRACT FROM AUTHOR]

Demulsification of steam-assisted gravity drainage (SAGD)–produced liquid from the Xinjiang oil field was investigated in this study. The heavy crude oil in the produced liquid presents a high density, high viscosity, high resin and asphaltene contents, and high acid value. Thus, this liquid is difficult to separate. The effect of cationic deoiling agents on the separation of the SAGD-produced liquid was tested. W590 showed the highest separation efficiency among the deoiling agents surveyed. Zeta-potential experiments revealed that cationic deoiling agents could neutralize negative charges on the oil droplet surface and significantly reduce the oil content in the separated water. After the produced liquid was settled with 220 mg/L W590 at 90 °C for 1 h, the oil content in the water could be rapidly decreased to 198.0 mg/L and the water content in the produced liquid could be reduced from 86.2% to 22% to obtain a W/O emulsion. In the second process of separation, the demulsifier FC20 was applied. Under an electric field, the water content in the emulsion to which 30% diesel oil had been added could be reduced to 1.0% with 300 mg/L FC20, a 750 V/cm electric field for 20 min, and a settling time at 90 °C for 4 h. [ABSTRACT FROM AUTHOR]

• Treg cell frequency is positively associated with the effects of AIT. • AIT can reduce the proportions of PU-1+ Treg subtypes in AR patients. • PU-1+ Treg cell numbers can potentially be used as an indicator to monitor the therapeutic effect of AIT on AR. To investigate the role of Tregs and their subtypes in the treatment of allergic rhinitis with allergen immunotherapy (AIT) as well as the underlying mechanism. 1. Thirty-one healthy controls, 29 Allergic rhinitis (AR) patients and 16 AR patients treated with AIT were recruited. The total nasal symptom scores (TNSSs) were calculated. The serum levels of IgE, IL-2, TNF-α, IFN-γ, IL-4, IL-5, IL-6, IL-10 and IL-17 were measured. 2. Changes in the proportions of CD4+ T cells, Treg cells, Treg subtypes and Th1/Th2/Th9/Th17/Tfh cells in the peripheral blood of the subjects in the three groups were measured. 3. The correlations of Treg cells, Treg subtypes and TNSS with the levels of various cytokines in the AR group and AIT group were analysed. 1. Compared with the control group, the TNSS and IgE, IL-5 and IL-6 levels in the AR group were significantly increased, while the IL-2, IFN-γ and IL-10 levels were significantly decreased (P < 0.05). Compared with the AR group, the TNSS and IgE, IL-5 and IL-6 levels in the AIT group were significantly decreased, while the IL-2, IFN-γ and IL-10 levels were significantly increased (P < 0.05). 2. Compared with the control group, the proportions of Tregs, GATA3+ Tregs and Th1 cells in the AR group were significantly reduced, while the proportions of PU-1+ Tregs, T-bet+ Tregs and Th2 cells were significantly increased (P < 0.05). Compared with the AR group, the proportions of Tregs and Th1 cells in the AIT group were significantly increased, while the proportions of PU-1+ Tregs and Th2 cells were decreased (P < 0.05). 3. Correlation analysis showed that Treg cell proportions were negatively correlated with the TNSS, sIgE levels, IL-5 levels and IL-6 levels but positively correlated with the IL-2 and IL-10 levels (P < 0.05). PU-1+ Treg cell proportions were positively correlated with the TNSS, sIgE levels, IL-5 levels and IL-6 levels but negatively correlated with the Treg cell proportions, IL-2 levels and IL-10 levels (P < 0.05). AIT can reduce the proportions of PU-1+ Treg subtypes in AR patients. PU-1+ Treg cell numbers can potentially be used as an indicator to monitor the therapeutic effect of AIT on AR. [ABSTRACT FROM AUTHOR]

In this paper, a pre-anodized inlaying ultrathin carbon paste electrode (PAIUCPE) with 316L as a matrix was constructed by a simple and fast electrochemical pretreatment. Using xanthine (Xa) and hypoxanthine (HXa) as the target compounds, the pH effects compositions of buffer solution, the accumulation times, hydrogen bond catalysis, degree of auxiliary electrode reaction on the size of peak currents ( Ip) of Xa and HXa was discussed in detail. Also, it was proposed that Xa and HXa were respectively absorbed at the surface of PAIUCPE through hydrogen bonding. The influencing mechanisms of the PAIUCEP on electrochemical oxidation of Xa and HXa were explained in detail. Moreover, the linear relationships for the Xa and HXa were obtained in the range of 6×10−8-3×10−5 mol/L and 2×10−7-7×10−5 mol/L, respectively. The detection limits for the Xa and HXa were 1.2×10−8 mol/L and 5.7×10−8 mol/L, respectively. Moreover, this proposed method could be applied to determine the Xa and HXa in human urine simultaneously with satisfactory results. [ABSTRACT FROM AUTHOR]

• The nasal mucosa of mice in the AR group showed significantly increased LC3II expression, and co-expressed with DCs markers. • The degree of autophagy in DCs increased with the increase of allergen concentration in a dose-dependent manner. • Allergen-induced DCs autophagy aggravated AR by increasing antigen-presenting function and promoting the immune imbalance. The level of autophagy in CD11c+ dendritic cell (DC) and its contribution to the subsequent immune imbalance are still unclear. The aim of this study was to investigate the role and mechanism of them in promoting the allergic inflammatory response. Nasal mucosa tissues were collected from allergic rhinitis (AR) mice and their control group to detect the expression of LC3II, P62 and ATG5 and CD11c+DC autophagy. Different concentration of OVA or the combination of OVA and autophagy inhibitor (3-MA) were used to induce the differentiation of mouse bone marrow-derived DCs (CD11c+BMDCs). Differences in LC3II, P62 and ATG5 expression and autophagosome formation were detected. BMDCs in the above groups were cocultured with spleen lymphocytes to detect the proportions of effector T cells and changes in cytokines. OVA-loaded BMDCs were injected intravenously into C57BL/6 mice to develop allergic model. The nasal mucosa of mice in the AR group showed significantly increased LC3II and ATG5 protein expression, whereas showed significantly decreased P62 protein expression. Moreover, LC3II was mainly co-expressed with CD11c+ DC markers. In vitro, OVA stimulation induced the increase of autophagosomes and the expression of autophagy-related proteins in BMDCs in a dose-dependent manner, and inhibition of autophagy showed significantly decreased LC3II and ATG5 expression and autophagosome abundance. In addition, OVA-induced BMDC autophagy can affect CD4+T cell differentiation and related cytokine levels, however, the Th1/Th2/Th9/Th17/Treg/Tfh cell immune imbalances were significantly reversed after the addition of 3-MA. Adoptive transfer of OVA-loaded BMDCs could promote the allergic inflammation, while the administration of 3-MA on OVA-loaded BMDCs could significantly reduce the AR inflammation. Overall, our findings demonstrate that allergen can induce CD11c+DC autophagy in a dose-dependent manner and promote the immune imbalance of downstream T cells towards a proinflammatory phenotype. [ABSTRACT FROM AUTHOR]

This paper discusses the assignment of generalized time constant for a non-all-pole system. The generalized time constant is found to be important because it simultaneously influences the speed of response, damping (i.e., overshoot), and robustness. For the ease of explanation, a general two-mass system is introduced as a case study, which has one pair of $j\omega$-axis zeroes. Under an ideal two-parameter control configuration, the exact lower bound of the generalized time constant is determined that results in monotonic step responses, while a moderate generalized time constant is shown to be desirable for robustness purposes. A modified-Integral–Proportional–Derivative control configuration is then adopted for the implementation of the ideal two-parameter controller. It is found that, in real applications, a specific control configuration and signal delay may also impose limits on the assignment of the generalized time constant and characteristic ratios. Due to the clear physical meaning of the polynomial method, the tradeoff relationship among the speed of response, damping, and robustness can be explicitly represented. This unique advantage leads to a straightforward controller design procedure. Finally, the theoretical analysis is validated by experimental results. [ABSTRACT FROM PUBLISHER]

Transient receptor potential vanilloid 1 (TRPV1) antagonists can inhibit the transmission of nociceptive signals from the peripheral to the central nervous system (CNS), providing a new strategy for pain relief. In this work, in order to develop potent, CNS-penetrant, and orally available TRPV1 antagonists, three series of novel molecules based on the key pharmacophore structures of classic TRPV1 ligands SB-705498 and MDR-652 were designed and synthesized. Through systematic in vitro and in vivo bioassays, (S)– N -(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide (7q) was finally identified, which had enhanced TRPV1 antagonistic activity (IC 50 (capsaicin) = 2.66 nM), excellent CNS penetration (brain/plasma ratio = 1.66), favorable mode-selectivity, good bioavailability, and no side effects of hyperthermia. Molecular docking and dynamics studies indicated that the high binding affinity of compound 7q to TRPV1 was related to multiple interactions, which resulted in significant conformational changes of TRPV1. Overall, our findings have led to a potent, mode-selective, and CNS-penetrant TRPV1 antagonist as a valuable lead for development of novel TRPV1 antagonists. In this work, in order to find a potent, mode-selective, CNS-penetrant, and orally available TRPV1 antagonist, two series of novel TRPV1 antagonists based on the key pharmacophore structures of classic TRPV1 ligands SB-705498 and MDR-652 were designed and synthesized, and their in vitro and in vivo activities were evaluated. [Display omitted] • Two series of novel TRPV1 antagonists based on the key pharmacophore structures of classic TRPV1 ligands SB-705498 and MDR-652 were designed and synthesized. • The most promising compound 7q was a mode-selective TRPV1 antagonist which could effectively block the capsaicin-activated channel (IC 50 = 2.66 nM) without increasing core body temperature. • More importantly, compound 7q demonstrated excellent CNS-penetrant, favorable ClogP, good bioavailability, and high binding affinity to TRPV1. [ABSTRACT FROM AUTHOR]

Based on the strong field approximation theory and numerical solution of Maxwell's propagation equations, the high–order harmonic is generated from a neon (Ne) atom irradiated by a high–intensity laser pulse whose central wavelength is 800 nm. In the harmonic spectrum, it is found that in addition to the odd harmonics of the driving laser, a new frequency peak appeared. By examining the time–dependent behavior of the driving laser, it is found that the symmetry of the laser field is broken. We demonstrated that these new spectrum peaks are caused by the intensity reduction and frequency blue shift of the high–intensity laser during propagation. Our results reveal that it is feasible to modulate the harmonics of the specific energy to produce high–intensity harmonic emission by changing the gas density and the position of the gas medium interacting with the laser pulse. [ABSTRACT FROM AUTHOR]

High-order harmonic generation of atoms irradiated by an ultrashort laser pulse was calculated by numerically solving the time-dependent Schrödinger equation and the Bohmian trajectory scheme. The harmonic spectra with the two schemes are quantitatively consistent. Using the wavelet behavior of the Bohmian trajectory, the spatio-temporal features of harmonic emission from different energy regions are analyzed. It is found that the spatio-temporal distribution of the harmonic well revealed the physical mechanism of harmonic generation. This method will contribute to the understanding of harmonic emission mechanisms in complex systems, which include many atoms. [ABSTRACT FROM AUTHOR]

By using the numerical solution of the time-dependent Schrödinger equation, we theoretically explored the high-order harmonic generation process under the interaction of high-intensity two-color ultrashort driving laser pulses with atoms. The symmetry of the electric field of the laser pulse will be broken. The producing electric field was controlled at the subcycle level by an IR laser and its second harmonic, which has the unique characteristic that two sequential half-cycles become distinct, rather than merely opposite in sign. Compared with the case of the atom in the fundamental laser pulse, the harmonic efficiency showed an increase of 1∼2 orders of magnitude at specific harmonic order with this combined pulse action. Through the theoretical analysis with the "three-step model", it was demonstrated that the enhancement of the harmonic intensity is due to the fast ionization of electrons at the ionization moment and the short time from ionization to recombination of ionized electrons. In addition, effects of the peak field amplitude ratio, the full width at half maximum, the phase delay of the two-color pulses, the laser intensity and ionization probability on the harmonic efficiency enhancement were also investigated. [ABSTRACT FROM AUTHOR]

Researching ultrafast dynamics and creating coherent light sources will both benefit significantly from the establishment of polarization control in high-order harmonic generation (HHG). By employing the time-dependent density functional theory method, we investigate HHG of carbonyl sulfide molecules using a combination of a linear polarized infrared (IR) laser and a weaker orthogonal Terahertz (THz) field. Our findings show that by adjusting the amplitude of the THz field, the movement scale of electrons in the THz direction can be tuned, thereby one can control the harmonic intensity in the IR laser direction. This method allows for the creation of near-circularly polarized attosecond pulses. Furthermore, the ellipticity of the attosecond pulse may be changed by modifying the carrier-envelope phase of the IR laser pulse. [ABSTRACT FROM AUTHOR]

Mutations in isocitrate dehydrogenase (IDH) are frequently found in low-grade gliomas, secondary glioblastoma, chondrosarcoma, acute myeloid leukemias, and intrahepatic cholangiocarcinoma. However, the molecular mechanisms of how IDH2 mutations induce carcinogenesis remain unclear. Using overlapping PCR, transfection, immunoblotting, immunoprecipitation, measurements of enzyme activity, glucose, lactic acid, ATP, and reactive oxygen species (ROS), cell viability, protein degradation assays post-inhibition of the 26S proteasome (bortezomib) or HSP90 (17-AAG), and a homology model, we demonstrated that the properties of ten cancer-associated IDH2 variants (R140G/Q/W and R172S/K/M/W/G/C/P) arising from point mutations are closely related to their structure and stability. Compared with wild-type IDH2, the R172 and R140 point mutations resulted in a decrease in IDH2 activity, ROS, and lactate levels and an increase in glucose and ATP levels under normal and hypoxic conditions, indicating that mutant IDH2 increases cell dependency on mitochondrial oxidative phosphorylation, and reduces glycolysis under hypoxia. Overexpression of most of IDH2 point mutants showed anti-proliferative effects in the 293T and BV2 cell lines by inhibition of PI3K/AKT signaling and cyclin D1 expression and/or induced the expression of TNF-α and IL-6. Furthermore, bortezomib treatment resulted in dramatic degradation of IDH2 mutants, including R140G, R140Q, R140W, R172S and R172K, whereas it had little impact on the expression of WT and other mutants (R172M, R172W, R172G, R172C and R172P). In addition, targeting HSP90 minimally affected the expression of mutated IDH2 due to a lack of interaction between HSP90 and IDH2. The homology model further revealed that changes in conformation and IDH2 protein stability appeared to be associated with these point mutations. Taken together, our findings provide information important for understanding the molecular mechanisms of IDH2 mutations in tumors. [ABSTRACT FROM AUTHOR]

Phthalonitrile resin is a potential high-performance composite matrix, its brittleness and weak interaction with fiber are the main obstacles to its wide application. High-performance thermoplastic poly(phthalazinone ether nitrile)s (PPEN) and poly(phthalazinone ether nitrile ketone)s (PPENK) have been used to toughen basalt fiber (BF) reinforced 4,4′-bis(3,4-dicyanophenoxy)biphenyl (BPh) composite. The curing kinetics for the BPh/PPEN and BPh/PPENK blends have been investigated using DSC. The structures and thermal properties of the cured BPh blends have been studied in detail. The effects of PPEN and PPENK on the mechanical properties of the modified BF/BPh composite have been assessed. The non-notched impact strength of BF/BPh/PPENK laminate can be up to 107.7 kJ/m2, which is 64.2% higher than that of the BF/BPh laminate. And the interlaminar shear strength of BF/BPh/PPEN laminate can reach 42.5 MPa, 134.8% higher than that of the BF/BPh laminate. Simultaneously, the fracture surface of the laminate showed that the thermoplastic PPEN and PPENK can significantly inhibit the delamination between the layers and the fiber pullout and debonding. [Display omitted] • The mechanical properties of BF/BPh were significantly improved by the introduction of PPEN(K) with pendant cyano groups. • The properties of modified BF/BPh composites can be tuned by the pendant cyano content on thermoplastic resin. • The introducing of high-performance thermoplastic PPEN(K) remains the excellent thermal properties of BF/BPh composites. [ABSTRACT FROM AUTHOR]

Sambucus adnata Wall. belongs to Caprifoliaceae family. Phytochemical investigation on the aerial parts of S. adnata led to the isolation and identification of 17 known compounds (1 – 17) including triterpenoids and sterols. Compounds 1 and 8 are isolated from Sambucus adnata for the first time, and it is the first report that compounds 2, 5–6, 9–10, 12–15, and 17 are isolated from the plants of genus Sambucus. Importantly, three types of abundant components: (3 β)-urs-12-en-3-yl stearate (0.33 g/kg, ursane type), (3 β)-olean-12-en-3-yl stearate (0.17 g/kg, oleanane type), and lupenyl palmitate (0.52 g/kg, lupinane type) could be used as potential chemotaxonomic markers to distinguish among species of Sambucus. [Display omitted] • Sambucus adnata Wall. was investigated on its chemical components. • 17 compounds including triterpenoids and sterols were isolated. • Compounds 6 , 10 , and 14 could be used as potential chemotaxonomic markers to distinguish among species of Sambucus. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) are associated with a high mortality rate. Mutations in the V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) proto-oncogene GTPase (KRAS) are frequently observed in these cancers. Owing to its structural attributes, KRAS has traditionally been regarded as an "undruggable" target. However, recent advances have identified a novel mutational regulatory site, KRASG12C switch II, leading to the development of two KRASG12C inhibitors (adagrasib and sotorasib) that are FDA-approved. This groundbreaking discovery has revolutionized our understanding of the KRAS locus and offers treatment options for patients with NSCLC harboring KRAS mutations. Due to the presence of alternative resistance pathways, the use of KRASG12C inhibitors as a standalone treatment for patients with CRC is not considered optimal. However, the combination of KRASG12C inhibitors with other targeted drugs has demonstrated greater efficacy in CRC patients harboring KRAS mutations. Furthermore, NSCLC and CRC patients harboring KRASG12C mutations inevitably develop primary or acquired resistance to drug therapy. By gaining a comprehensive understanding of resistance mechanisms, such as secondary mutations of KRAS, mutations of downstream intermediates, co-mutations with KRAS, receptor tyrosine kinase (RTK) activation, Epithelial-Mesenchymal Transitions (EMTs), and tumor remodeling, the implementation of KRASG12C inhibitor-based combination therapy holds promise as a viable solution. Furthermore, the emergence of protein hydrolysis-targeted chimeras and molecular glue technologies has been facilitated by collaborative efforts in structural science and pharmacology. This paper aims to provide a comprehensive review of the recent advancements in various aspects related to the KRAS gene, including the KRAS signaling pathway, tumor immunity, and immune microenvironment crosstalk, as well as the latest developments in KRASG12C inhibitors and mechanisms of resistance. In addition, this study discusses the strategies used to address drug resistance in light of the crosstalk between these factors. In the coming years, there will likely be advancements in the development of more efficacious pharmaceuticals and targeted therapeutic approaches for treating NSCLC and CRC. Consequently, individuals with KRAS-mutant NSCLC may experience a prolonged response duration and improved treatment outcomes. [ABSTRACT FROM AUTHOR]

The interfacial modification of basalt-fiber-reinforced polymer (BFRP) composites is an essential research field and many techniques have been developed to improve the adhesion between basalt fiber (BF) and the matrix. However, most studies were based on the matrixes of general plastics and epoxy resins. In this work, five different chain structures of thermoplastic sizing agents were used to improve the interfacial properties of unidirectional BF-reinforced soluble and high-temperature-resistant poly(phthalazinone ether nitrile ketone) (BF/PPENK) composites. DMA results showed that the poly(ether nitrile) (PEN)-sized BF/PPENK (BF-PEN/PPENK) composite exhibited the optimal interfacial performance, with a storage modulus (E′) and glass transition temperature (Tg) up to 50 GPa and 288 °C, respectively. Moreover, the tensile strength, compressive strength, flexural strength, and interlaminar shear strength of the BF-PEN/PPENK composite reached 778 MPa, 600 MPa, 1115 MPa and 57 MPa, respectively, and increased by 42%, 49%, 20% and 30% compared with the desized BF/PPENK composite. This study provides some suggestions for the design of sizing agents to modify the interface of BF and high-performance thermoplastic resin. [ABSTRACT FROM AUTHOR]

Bismaleimide resin has poor toughness, limiting its wide application potential. High-performance thermoplastic amino-terminated poly(phthalazinone ether nitrile sulfone)s (PPENS-DA) with different cyano group content, have been prepared and used to toughen blends of 4,4′-bismaleimidodiphenyl-methane (BDM)/diallyl bisphenol A (DABPA). The rheological properties and curing kinetics for the PPENS-DA/BDM/DABPA blends have been investigated using rotational rheometry and DSC. The mechanical and thermal properties of the cured BMI blends have been studied in detail. The effects of level of loading and the cyano group content of PPENS-DA on the mechanical properties of cured blends have been assessed. The notched impact strength of PPENS-DA/BDM/DABPA blends can be up to 3.98 MPa, which is 65.15% higher than that of the pristine BDM/DABPA blend. Simultaneously, the thermal properties of blends have been improved with T g increasing from 237 °C to 265 °C. Furthermore, an isothermal rheological model was established, and the model curve was verified to be consistent with the experimental value. Image 1 • The amino-terminated poly(phthalazinone ether nitrile sulfone)s (PPENS-DA) was introduced into the BDM/DABPA blend system. • The impact toughness of BDM was significantly improved by the participating of PPENS-DA in the crosslinking reaction. • The introduction of high-performance thermoplastic PPENS-DA improved the glass transition temperature of BDM/DABPA blend. • The isothermal rheological model of PPENS-DA/BDM/DABPA blends was established. [ABSTRACT FROM AUTHOR]

Wu, J.; Qiao, Y.; Xu, Y.; Xiao, M., and Feng, H., 2020. Analysis and optimization of factors influencing marine tourism economic development of Beibu Gulf. In: Gong, D.; Zhang, M., and Liu, R. (eds.), Advances in Coastal Research: Engineering, Industry, Economy, and Sustainable Development. Journal of Coastal Research, Special Issue No. 106, pp. 73–76. Coconut Creek (Florida), ISSN 0749-0208. With the steady growth of China's economy, people's living standards have improved. In 2018, there were 5.54 billion domestic tourists, an increase of 10.8% over 2017. Domestic tourism revenue reached 5127.8 billion yuan, an increase of 12.3%. Therefore, tourism has become the main way for people to relax and enjoy their surroundings. Beibu Gulf depends on marine tourism to develop its economy. Beibu Gulf Economic Zone is rich in marine tourism resources. Through integration with regional cultural characteristics, Beibu Gulf marine tourism has become the main pillar industry of local economic development. The planning of Beibu Gulf clearly indicates that Beibu Gulf needs to take advantage of its unique features based on tourism needs. By relying on China's excellent tourism cities, Beibu Gulf Economic Zone will become a regional and international tourism destination. This paper first analyzes the factors influencing Beibu Gulf marine tourism. Marine tourism is a huge grey system, which can be used to analyze the factors influencing economic development. This paper mainly analyzes the factors influencing the Beibu Gulf marine tourism economy, and then analyzes the data from the Beibu Gulf marine economy in 2004–17 through the grey correlation method. [ABSTRACT FROM AUTHOR]

Chronic infections, caused by multidrug-resistant (MDR) bacteria, constitute a serious problem yet often underappreciated in clinical practice. The in situ monitoring of the bacteria-infected disease is also necessary to track and verify the therapeutic effect. Herein we present a facile approach to overcome the above challenges through a Raman tag 3,3′-diethylthiatricarbocyanine iodide (DTTC)-conjugated gold-silver nanoshells (AuAgNSs). With a strong responsive of the near-infrared laser due to surface plasmon resonance (SPR) from hybrid metallic nanoshell structure, AuAgNSs exhibits an efficient photothermal effect, and it simultaneously releases silver ions during laser irradiation to bacterial eradicate. Herein, two MDR bacteria strain, methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum β-lactamase Escherichia coli , are chosen as models and studied both in vitro and in vivo. As a result, the AuAgNSs-DTTC substrates enable surface-enhanced Raman scattering imaging to provide a non-invasive and extremely high sensitive detection (down to 300 CFU mL−1 for MRSA) and prolonged tracking (at least 8 days) of residual bacteria. In a chronic MRSA-infected wound mouse model, the AuAgNSs gel-mediated photothermal therapy/silver-release leads to a synergistic would healing with negligible toxicity or collateral damage to vital organs. These results suggest that AuAgNSs-DTTC is a promising anti-bacterial tool for clinical translation. 3,3′-diethylthiatricarbocyanine iodide (DTTC)-conjugated gold-silver nanoshell (AuAg) nanosystems are fabricated to enable surface-enhanced Raman scattering imaging and photothermal eradication to multidrug-resistant bacteria. Remarkably, the designed nanostructures provide a non-invasive and highly sensitive detection (down to 300 CFU mL−1 for MRSA) and prolonged tracking (at least 8 days) of residual bacteria during wound healing. Image 1 [ABSTRACT FROM AUTHOR]

Glycinebetaine (GB) is an osmoprotectant found in plants under environmental stresses that incorporates drought and is associated with drought tolerance in several plants, such as the woody pear. However, how GB improves drought tolerance in pears remains unclear. In the current study, we explored the mechanism by which GB enhances drought tolerance of whole pear plants (Pyrus bretschneideri Redh. cv. Suli) supplied with exogenous GB. The results showed that on the sixth day after withholding water, levels of O2·−, H2O2, malonaldehyde (MDA) and electrolyte leakage in the leaves were substantially increased by 143%, 38%, 134% and 155%, respectively. Exogenous GB treatment was substantially reduced O2·−, H2O2, MDA and electrolyte leakage (38%, 24%, 38% and 36%, respectively) in drought-stressed leaves. Furthermore, exogenous GB induced considerably higher antioxidant enzyme activity in dry-stressed leaves than drought-stressed treatment alone on the sixth day after withholding water, such as superoxide dismutase (SOD) (201%) and peroxidase (POD) (127%). In addition, these GB-induced phenomena led to increased endogenous GB levels in the leaves of the GB 100 + drought and GB 500 + drought treatment groups by 30% and 78%, respectively, compared to drought treatment alone. The findings obtained were confirmed by the results of the disconnected leaf tests, in which GB contributed to a substantial increase in SOD activity and parallel dose- and time-based decreases in MDA levels. These results demonstrate that GB-conferred drought resistance in pears may be due in part to minimizing symptoms of oxidative harm incurred in response to drought by the activities of antioxidants and by reducing the build-up of ROS and lipid peroxidation. [ABSTRACT FROM AUTHOR]

Background: The present study aims to identify the underlying genetic defects in a Chinese family with autosomal dominant congenital cataracts (ADCC). Methods: Detailed family histories and clinical data were recorded. Targeted exome sequencing of 54 known cataract-associated genes combined with high-throughput next-generation sequencing was conducted followed by Sanger sequencing and bioinformatic analysis to identify the causative gene lesion for the family. Results: A four-generation Chinese family with posterior pole type cataract were enrolled. Enrichment of targeted genes revealed a new heterozygous p.X176Y mutation in the stop codon of αB-crystallin (CRYAB) gene, which resulted in the loss of the stop codon and prolongation of the mutant protein by 19 amino acid residues (p.X176Yfs19*). Sanger sequencing showed complete co-segregation with the disease. The elongated mutant protein was predicted to be pathogenic by forming new α-helix and random-coil in the secondary structure as well as producing an extended strand in the tertiary structure, potentially leading to increased hydrophobicity and reduced protein stability. Conclusions: Our report added a new mutation in the spectrum of congenital cataracts. The data suggested that X176 residue in the COOH-terminal is of crucial importance for the αB-crystallin protein function which was valuable for further study of the pathogenesis of congenital cataracts. Abbreviations:CRYAB: αB-crystallin; DNA: deoxyribonucleic acid; PCR: polymerase chain reaction; TES: targeted exome sequencing; ACD: αB-crystallin domain. [ABSTRACT FROM AUTHOR]

Land surface temperature (LST) inversion using remote sensing is a crucial tool to study the land surface thermal environment. To improve the resolution of the inverted LST, a downscaling method is used but it often reduces the accuracy. Here, a difference mean distribution (DMD) method was developed to post-process the downscaled LST. Landsat 8 and Sentinel 2 images were used to test and Field measured LSTs in Tianjin, China were used to verify the method. Results show DMD method reduces MAE and RMSE by 1.36°C and 1.50°C, respectively indicating that it can improve the accuracy of the downscaled LST. [ABSTRACT FROM AUTHOR]

Introduction: Effective communication is of paramount importance in delivering patient-centred care. Effective communication between the healthcare personnel and the patient leads to better compliance, better health outcomes, decreased litigation, and higher satisfaction for both doctors and patients. Objective: The objective of the study was to evaluate the effectiveness of a comprehensive blended communication program to improve the communication skills and the confidence level of all staff of a department of emergency medicine in Singapore in dealing with challenging communication situations. Methods: All doctors and nurses working in the selected Children's Emergency Department (ED) attended blended teaching to improve communication skills. Qualitative feedback was gathered from participants via feedback forms and focus group interviews. Communication-related negative feedback in the ED was monitored over a period of 18 months, from 1st July 2017 to 31st December 2018. Results: Immediately after the course, 95% of the participants felt that they were able to better frame their communications. Focus group interviews revealed four main themes: (A) Increased empowerment of staff; (B) Improved focus of communication with parents; (C) Reduced feeling of incompetence when dealing with difficult parents and; (D) Increased understanding of main issues and parental needs. There was 81.8% reduction in communication-related negative feedback received in the ED monthly after the workshop had been carried out (95% confidence interval 0.523, 0.8182). Conclusion: A comprehensive blended communication workshop resulted in a perceived improvement of communication skills among the healthcare personnel and significantly decreased the communication-related negative feedback in a pediatric ED. [ABSTRACT FROM AUTHOR]

In the present study, an exopolysaccharide (EPS) producer Rhodococcus erythropolis HX-2 was isolated from Xinjiang oil field, China. The HX-2 EPS (name HPS) production reached 8.957 g/L by RSM in MSM medium. The HPS was purified by ethanol precipitation and fractionation by DEAE-Cellulose and Sepharose column, the yield of HPS was 3.736 g/L. HPS composed by glucose, galactose, fucose, mannose and glucuronic acid. FT-IR spectroscopy indicated the presence of a large amount of hydroxyl groups. NMR spectroscopy indicated the existence of both α and β-configuration for sugar moieties present in HPS. The degradation temperature (255.4 °C) of the HPS was determined by thermogravimetric analysis (TGA). A reticular structure of HPS was observed by SEM and the AFM analysis of the HPS revealed straight chains line. Meanwhile, the WSI and WHC of HPS were 92.15 ± 3.05% and 189.45 ± 5.65%, respectively. Finally, In vitro anticancer activity purified EPS was evaluated on L929 normal cells, A549 cancer cells, SMMC-7721 liver cancer cells and Hela cervical cancer cell. HPS inhibited the growth of cancer cells in a certain concentration without damage to normal cells. These characteristics indicate that its potential application value in food, industry and pharmaceutical application. Unlabelled Image • The purified EPS fractions (HPS) were obtained from Rhodococcus erythropolis HX-2. • The HPS production reached 8.957 g/L in MSM medium through response surface method (RSM). • HPS is a heteropolysaccharide and a reticular structure was observed by SEM. • This is the first report of exopolysaccharide showed the higher viscosity and anticancer activity by Rhodococcus sp. [ABSTRACT FROM AUTHOR]

Background: Congenital cataract is a significant cause of visual impairment and blindness. The present study examined the disease-causing mutations in three Chinese families with autosomal dominant congenital cataract (ADCC) to provide the preliminary evidence of the mechanisms underlying congenital cataract formation. Methods: Three pedigrees affected with ADCC were recruited. All participants underwent detailed ophthalmic examinations. Leucocyte DNA was extracted from venous blood for direct sequencing of candidate genes. In silico bioinformatics analysis was conducted to verify the functional impacts of the mutant proteins. Distribution patterns of connexin proteins were assessed through fluorescence microscopy using an enhanced green fluorescent protein (EGFP)-labeled expression vector in stably transfected Hek293 cells. Results: We identified three Chinese pedigrees with ADCC. Family 1 and family 2 presented with pulverized cataract and family 3 with an unknown phenotype. Direct sequencing of family 1 and family 2 revealed a missense mutation of c.64G>A encoding for G22S of connexin46 (Cx46), while a similar c.64G>A encoding for G22S of connexin50 (Cx50) was found in family 3; both mutations co-segregated well within all affected individuals in their families and were absent from 100 unrelated controls. Bioinformatics analysis revealed with high confidence that both mutations were deleterious. Confocal microscopy revealed the accumulation of both mutant connexins in the cytoplasm with punctate staining and a failure of gap junction formation between adjacent cells. Conclusions: Two novel G22S mutations of Cx46 and Cx50 were identified, and preliminary functional analysis revealed a potential deleterious effect of these mutations due to the malfunction of connexins. Abbreviations: ADCC: autosomal dominant congenital cataract; Cx26: connexin26; Cx32: connexin32; Cx46: connexin46; Cx46WT: wild-type connexin46; Cx50: Connexin50; Cx50WT: wild-type connexin50; DAPI: 4ʹ,6-diamidino-2-phenylindole; EGFP: enhanced green fluorescent protein; FBS: fetal bovine serum; GJA-:gap junction alpha-; PCR: polymerase chain reaction; PolyPhen: polymorphism phenotyping; PSIC: position-specific independent count; RPMI: Roswell Park Memorial Institute; TM1: first transmembrane. [ABSTRACT FROM AUTHOR]

Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole as A-region and triazole as B-region. The SAR analysis indicated that 2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed better potency compared to the corresponding dihydroindole analogues. Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1 H -1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole (6g), a potent TRPV1 antagonist. In vitro , using cells expressing recombinant human TRPV1 channels, 6g displayed potent antagonism activated by capsaicin (IC 50 = 0.075 μM) and only partially blocked acid activation of TRPV1. In vivo , 6g exhibited good efficacy in capsaicin-induced and heat-induced pain models and had almost no hyperthermia side-effect. Furthermore, pharmacokinetic studies revealed that compound 6g had a superior oral exposure after oral administration in rats. To understand its binding interactions with the receptor, the docking study of 6g was performed in rTRPV1 model and showed an excellent fit to the binding site. On the basis of its superior profiles, 6g could be considered as the lead candidate for the further development of antinociceptive drugs. Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole as A-region and triazole as B-region. Image 1 • Design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists which constructed on 2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole as A-region and triazole as B-region. • Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1 H -1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1 H -pyrido[3,4- b ]indole (6g), a potent TRPV1 antagonist. • 6g exhibited potent antagonism activated by capsaicin (IC 50 = 0.075 μM) and only partially blocked acid activation of TRPV1, and demonstrated good efficacy in different pain models and did not elevate core body temperature. [ABSTRACT FROM AUTHOR]

Abstract The vast distribution, abundant reserves, and high combustion utilization rate of natural gas hydrate make it an appealing alternative energy source. Nevertheless, the special physical and mechanical properties of the hydrate production test area in the South China Sea have led to frequent geological disasters, requiring monitoring and early warning of potential geohazards. To facilitate this process, a model was established to determine the relationship between sediment resistivity and physical properties in this area. However, there is currently no suitable sediment resistivity inversion model for this region. We obtained an 8 m-long core sediment sample from the hydrate production test area in the South China Sea using a core sediment sampler aboard the research vessel “Marine Geology 6”. Indoor geotechnical tests were conducted to determine the vertical variation characteristics of the sediment, and indoor resistivity tests were performed to obtain its resistivity vertical variation. Using empirical power function formulae, we established a relationship model between resistivity and physical properties, which we then compared with relevant data from nearby sea areas. This model lays the foundation for using in situ resistivity to invert the dynamic changes of sediment physical properties and promote the development of deep-sea engineering geology. [ABSTRACT FROM AUTHOR]

Ovarian tissue cryopreservation is an effective fertility protective strategy for preadolescent female cancer patients, whose tumor treatment cannot be delayed. In the present study, the effects of sericin, as an antioxidant, on mice ovarian tissue freezing and thawing were investigated. Mice ovarian tissues were cryopreserved and thawed in medium containing 0.5% or 1%sericin (w/v), and 0.1 mM melatonin. Then, the follicular morphology was observed. The levels of antioxidant enzymes were determined, including glutathione (GSH), glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) and catalase (CAT). Moreover, the levels of nitric oxide (NO), malondialdehyde (MDA) and lactate dehydrogenase (LDH) were also tested. Besides, apoptosis-related proteins Bcl-2 and Bax were determined. Our results showed that 1% sericin maintained follicular morphology, inhibited apoptosis, decreased MDA and NO levels, and boosted endogenous antioxidant enzyme levels, while had no significant effect on LDH levels. Furthermore, these effects may be related with the activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of Rapamycin (mTOR) signaling pathway, as demonstrated by increased PI3K, p -AKT and mTOR levels. These findings demonstrate that 1% sericin may reduce oxidative stress and protect ovarian tissues during freezing and thawing via PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]