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BaZr1-xYxO3-δ (x = 0, 0.04, 0.08, 0.12) crucibles with doping different contents of Y2O3ript> were prepared by the pressureless sintering method, and the interfacial reaction behaviors in TiAl alloy melt was investigated using vacuum induction melting. The results revealed that the BaZrO3 ceramics contained a small amount of monoclinic ZrO2 and Ba-rich areas. With increasing Y2O3 doping content, yttrium-rich cubic ZrO2 instead of monoclinic ZrO2 generated and the average grain size decreased significantly. The results after melting showed that the thickness of the reaction layer of the BaZr1-xYxO3-δ decreased from hundreds of microns to tens of microns with the increase of the Y2O3 content. Moreover, the zirconium content in the alloy decreased. Overall, the BaZr0.96Y0.04O3-δ ceramic crucible had a small thickness of the reaction layer and slight oxygen contamination in the alloys. This study offers new insights for the further development of Y2O3-doped BaZrO3 ceramics used in melting TiAl alloys. [ABSTRACT FROM AUTHOR] more...

Conducting research on the dynamic behavior of root–soil systems is crucial for accurately assessing the seismic response of ecological slopes, thereby providing a scientific foundation for the development of appropriate seismic design measures. Documentation of the improvement of soil dynamics through vegetation root systems is insufficient in the current research. This study utilizes resonance column tests to explore how root systems influence the dynamic properties of clayey soil and to uncover the mechanisms behind this enhancement. The results indicate that both root distribution and mass density have a significant impact on the soil's dynamic shear modulus and damping ratio. When roots are distributed in the upper part of the soil, the dynamic shear modulus and damping ratio of the soil are higher than in cases of even distribution or concentration in the lower part. The dynamic shear modulus initially increases and then decreases with the increase in root mass density, reaching its peak at a root mass density of 1.5% g·cm−3. The damping ratio is influenced by both root mass density and confining pressure, with different critical root mass densities observed under varying confining pressures. The maximum enhancement in dynamic shear modulus is 27.6%, achieved at a 3% root mass density, with a peak damping ratio of 5.39%. Variations in both dynamic shear modulus and damping ratio with shear strain follow the Hardin–Drnevich hyperbolic curve. [ABSTRACT FROM AUTHOR] more...

Copyright of Immunology Quarterly / Immunológiai Szemle is the property of Medicina Konyvkiado Zrt. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...

This paper investigates the automation of hydraulic fracturing within the context of Industry 4.0, defining intelligent fracturing systems through three components: surface equipment, downhole sensing, and software control systems. The study addresses major advancements such as real-time optimization of fracturing parameters, intelligent allocation of fracturing fluids and materials, risk early warning systems, and fracture monitoring. It identifies four technical challenges: integrating heterogeneous data, developing intelligent decision-making algorithms, adaptive surface equipment adjustments, and multi-machine collaborative control. The paper reviews technological progress, foresees future benchmarks, and predicts the potential for unmanned fracturing operations, including site reconnaissance, autonomous fracturing unit driving, intelligent wellsite layout, fluid mixing, and operation execution. This comprehensive review delineates the developmental framework of intelligent fracturing, outlines key challenges, and forecasts future trends, marking a significant contribution to the field. [ABSTRACT FROM AUTHOR] more...

Caffeic acid (CA) is a polyphenolic acid compound widely distributed in plant seeds. As natural compounds with high research interest, caffeic acid and its derivatives show good activity in the treatment of tumors and inflammation and have antibacterial properties. In recent years, caffeic acid derivatives have been studied extensively, and these derivatives fall roughly into three categories: (1) caffeic acid ester derivatives, (2) caffeic acid amide derivatives, (3) caffeic acid hybrids. These caffeic acid analogues exert mainly antibacterial and antioxidant activities. Among the caffeic acid analogues summarized in this paper, compounds 1g and CAP10 have good activity against Candida albicans, and their MIC50 is 32 µg/mL and 13 μM, respectively. In a DPPH assay, compounds 3k, 5a, CS2, Phellinsin A and 8j showed strong antioxidant activity, and their IC50 values are 18.6 μM, 67.85 μM, 40.29 μM, 0.29 ± 0.004 mM, 4774.37 ± 137.20 μM, respectively. Overall, compound CAP10 had the best antibacterial activity and compound 3k had the best antioxidant activity. This paper mainly summarizes and discusses some representative caffeic acid analogs, hoping to provide better drug design strategies for the subsequent development of caffeic acid analogs. [ABSTRACT FROM AUTHOR] more...

Background: Intervention studies examining meditative movement (MM) often demonstrate benefits on physiological and psychological health. A potential mechanism associated with these outcomes is heart rate variability (HRV), an important neurophysiological biomarker of optimal and resilient health and functioning. Objective: We aimed to synthesize existing literature on the effects of two related forms of MM, Tai Chi (TC) and Qigong (QG) on HRV parameters in adult populations. Methods: Following PRISMA guidelines and Cochrane Collaboration recommendations, four databases (MEDLINE, Google Scholar, Academic Search Premier, and PubMed) were searched for articles (through December 15, 2023) that included TC and/or movement-based QG intervention versus any control condition (active or inactive) and reported at least one HRV outcome. Two reviewers independently completed study selection, data extraction, and risk-of-bias assessment. Results: We identified 148 for potential inclusion. After removing 61 duplicates, 87 full-text reviews yielded 23 articles, and 16 qualified for meta-analysis based on common HRV outcomes. Meta-analyses indicated a significant overall effect of TC/QG interventions on high-frequency power and standard deviation of the beat-to-beat intervals (SDNN), two critical HRV parameters, compared with control conditions: for HF power, standardized mean difference (SMD) = 0.29, P = 0.003, 95% Confidence interval (CI) [0.10, 0.48]; heterogeneity: I 2 = 46%, χ2 (8) = 14.89, P = 0.06; and for SDNN: SMD = 0.83, P = 0.02, 95% CI [0.16, 1.51]; heterogeneity: I 2 = 90%, χ2 (7) = 71.62, P < 0.001. Other HRV parameters did not demonstrate significant changes upon meta-analyses, but overall effect sizes showed a trend toward the expected direction. Conclusion: Based on the strength of the evidence, we conclude TC/QG interventions may shift HRV parameters toward improved health status and resilience. In addition, we offer suggestions to improve the design and measurement of future TC/QG research interventions exploring HRV. [ABSTRACT FROM AUTHOR] more...

Jacket structures play an ever-increasing role in meeting the world's burgeoning energy demand by providing support structure for exploiting offshore wind energy and oil and gas resources. Many of these structures are past their design lifetimes, and thus may have suffered significant degradation, highlighting the importance of investigating their earthquake response in seismically active regions. This study investigates the seismic performance of a typical offshore jacket platform, denoted as baseline structure, as well as four versions with two longer (25% and 50% larger) and two shorter (25% and 50% smaller) natural vibration periods accounting for two levels of degradation and retrofit effects on structural performance. For each case, eleven ensembles of ground motions compatible with the site's seismic hazard are selected using the generalized conditional intensity measure methodology. The loading uncertainty is incorporated in the performance assessment procedure via probabilistic seismic demand analysis and the demand hazard is quantified. The results provide valuable information regarding reliability of these structures both at design stage and during service life, which can aid decision-making around rehabilitation of older platforms, the suitability of reusing obsolete platforms beyond service lifetime, and risk-based design of new platforms. [ABSTRACT FROM AUTHOR] more...

Naringenin is a plant polyphenol, widely explored due to its interesting biological activities, namely anticancer, antioxidant, and anti-inflammatory. Due to its potential applications and attempt to overcome the industrial demand, there has been an increased interest in its heterologous production. The microbial biosynthetic pathway to produce naringenin is composed of tyrosine ammonia-lyase (TAL), 4-coumarate-CoA ligase (4CL), chalcone synthase (CHS), and chalcone isomerase (CHI). Herein, we targeted the efficient de novo production of naringenin in Escherichia coli by performing a step-by-step validation and optimization of the pathway. For that purpose, we first started by expressing two TAL genes from different sources in three different E. coli strains. The highest p-coumaric acid production (2.54 g/L) was obtained in the tyrosine-overproducing M-PAR-121 strain carrying TAL from Flavobacterium johnsoniae (FjTAL). Afterwards, this platform strain was used to express different combinations of 4CL and CHS genes from different sources. The highest naringenin chalcone production (560.2 mg/L) was achieved by expressing FjTAL combined with 4CL from Arabidopsis thaliana (At4CL) and CHS from Cucurbita maxima (CmCHS). Finally, different CHIs were tested and validated, and 765.9 mg/L of naringenin was produced by expressing CHI from Medicago sativa (MsCHI) combined with the other previously chosen genes. To our knowledge, this titer corresponds to the highest de novo production of naringenin reported so far in E. coli. Key points: • Best enzyme and strain combination were selected for de novo naringenin production. • After genetic and operational optimizations, 765.9 mg/L of naringenin was produced. • This de novo production is the highest reported so far in E. coli. [ABSTRACT FROM AUTHOR] more...

Background: Prostate cancer is the second most common cancer in males worldwide, and its incidence is rising. Early detection is crucial for improving the outcomes, but the current screening methods have limitations. While prostate-specific antigen (PSA) testing is the most widely used screening tool, it has poor specificity, leading to a high rate of false positives and unnecessary biopsies. The existing biopsy techniques are invasive and are associated with complications. The liquid biopsy methods that analyze the biomarkers in blood or other bodily fluids offer a non-invasive and more accurate alternative for detecting and characterizing prostate tumors. Methods: Here, we present a novel liquid biopsy method for prostate cancer based on the identification of specific proteins in the extracellular vesicles isolated from the blood of patients with prostate cancer. Results: We observed that a specific combination of sEV proteins is a sensitive indicator of prostate cancer. Indeed, we found that the number of clusters expressed by specific combinations of either intra-vesicular (STAT3 and CyclinD1) or surface proteins (ERBB3, ALK, and CD81) allowed us to significantly discriminate the patients with prostate cancer from the individuals with hyperplasia. Conclusion: This new liquid biopsy method has the potential to improve prostate cancer screening by providing a non-invasive and more accurate diagnostic tool. [ABSTRACT FROM AUTHOR] more...

In relation to its rapid infrastructure expansion, exemplified by projects like the Najran Valley Dam or the rehabilitation of agricultural terraces, Saudi Arabia stands out among the Arabian Gulf nations. To mitigate the earthquake-related risks effectively, it is imperative to conduct an exhaustive analysis of its natural hazards. The southwesternmost region of Saudi Arabia is the main subject area of this study for the probabilistic seismic hazard assessment (PSHA), which aims to identify the peak ground acceleration (PGA) and spectral acceleration (SA) values. The investigation encompasses a 10% and 5% probability of occurrence over a 50-year exposure time for both B/C and C NEHRP soils. In order to take into account the earthquake activity that takes place in the vicinity of the Red Sea Rift, which in fact may have an impact on the seismic hazard in this active tectonic region, different seismic source zones were especially designed for this evaluation. Various characteristics such as the uncertainties related to the b-value, the expected maximum magnitude, and different ground motion prediction equations (GMPEs) were integrated using a logic tree scheme. Additionally, regression relationships between the computed ground motion values were established, and a novel design response spectrum was developed and recommended for several cities. Regarding the key findings, it is significant to highlight that the seismic hazard decreases towards the northeast, when moving away from the Red Sea Rift, confirming anticipated trends where proximity to the rift corresponds to increased seismic hazard. Notably, cities such as Farasan Island, Jazan, Al Qunfundhah, Al Lith and Al Birk present the highest observed hazard values among all the cities analyzed. For these cities, the obtained maximum SA values for both 475 and 975 years under B/C site conditions are as follows: 0.268 g and 0.412 g, 0.121 g and 0.167 g, 0.099 g and 0.150 g, 0.083 g and 0.135 g, and 0.066 g and 0.118 g, respectively. These results emphasize the crucial necessity of adequately evaluating and thoroughly updating the seismic hazard inherent to these particular areas to enhance the risk reduction and disaster readiness initiatives. [ABSTRACT FROM AUTHOR] more...

Chemerin is a newly described adipokine with significant effects on obesity, metabolic disorders, and immune trafficking. Recently, chemerin has gained prominence for its potential roles in cancer and tumorigenesis with pro‐ or antitumor effects. To date, most referenced multifunctions of chemerin are attributed to the chemokine‐like receptor 1 (CMKLR1), distributing broadly in many tissues. This study investigates the in vitro roles of chemerin treatment on migration and invasion of ovarian carcinoma cells (OVCAR‐3 and SK‐OV‐3) and potential underlying mechanisms. Herein, exogenous chemerin treatment promotes growth and invasion of SK‐OV‐3 cells but has no significant effects on OVCAR‐3 cells. SK‐OV‐3 cells undergo morphological elongation characterized by epithelial‐to‐mesenchymal transition (EMT) and Ras homologous genome members A (RhoA)/Rho protein‐related curl spiral kinase‐1 (ROCK1) activation. Furthermore, chemerin‐enhanced invasion and EMT of SK‐OV‐3 cells are effectively blocked by C3 transferase (C3T) and Y27632 and RhoA and ROCK1 inhibitor, respectively. More importantly, RhoA/ROCK1‐EMT‐mediated SK‐OV‐3 cell invasion is orchestrated by CMKLR1 upregulation after chemerin treatment (50 ng/mL). The silencing of CMKLR1 significantly (P < 0.0001) reverses the chemerin‐enhanced invasion, EMT, and RhoA/ROCK1 activation of SK‐OV‐3 cells. Our study indicates that chemerin promotes invasion of OC cells via CMKLR1‐RhoA/ROCK1‐mediated EMT, offering a novel potential target for metastasis of OC. [ABSTRACT FROM AUTHOR] more...

Membrane remodeling is a fundamental cellular process that is crucial for physiological functions such as signaling, membrane fusion and cell migration. Tetraspanins (TSPANs) are transmembrane proteins of central importance to membrane remodeling events. During these events, TSPANs are known to interact with themselves and other proteins and lipids; however, their mechanism of action in controlling membrane dynamics is not fully understood. Since these proteins span the membrane, membrane properties such as rigidity, curvature and tension can influence their behavior. In this Review, we summarize recent studies that explore the roles of TSPANs in membrane remodeling processes and highlight the unique structural features of TSPANs that mediate their interactions and localization. Further, we emphasize the influence of membrane curvature on TSPAN distribution and membrane domain formation and describe how these behaviors affect cellular functions. This Review provides a comprehensive perspective on the multifaceted function of TSPANs in membrane remodeling processes and can help readers to understand the intricate molecular mechanisms that govern cellular membrane dynamics. [ABSTRACT FROM AUTHOR] more...

Fast-scan cyclic voltammetry (FSCV) is an electrochemical sensing technique that can be used for neurochemical sensing with high spatiotemporal resolution. Carbon fiber microelectrodes (CFMEs) are traditionally used as FSCV sensors. However, CFMEs are prone to electrochemical fouling caused by oxidative byproducts of repeated serotonin (5-HT) exposure, which makes them less suitable as chronic 5-HT sensors. Our team is developing a boron-doped diamond microelectrode (BDDME) that has previously been shown to be relatively resistant to fouling caused by protein adsorption (biofouling). We sought to determine if this BDDME exhibits resistance to electrochemical fouling, which we explored on electrodes fabricated with either femtosecond laser cutting or physical cleaving. We recorded the oxidation current response after 25 repeated injections of 5-HT in a flow-injection cell and compared the current drop from the first with the last injection. The 5-HT responses were compared with dopamine (DA), a neurochemical that is known to produce minimal fouling oxidative byproducts and has a stable repeated response. Physical cleaving of the BDDME yielded a reduction in fouling due to 5-HT compared with the CFME and the femtosecond laser cut BDDME. However, the femtosecond laser cut BDDME exhibited a large increase in sensitivity over the cleaved BDDME. An extended stability analysis was conducted for all device types following 5-HT fouling tests. This analysis demonstrated an improvement in the long-term stability of boron-doped diamond over CFMEs, as well as a diminishing sensitivity of the laser-cut BDDME over time. This work reports the electrochemical fouling performance of the BDDME when it is repeatedly exposed to DA or 5-HT, which informs the development of a chronic, diamond-based electrochemical sensor for long-term neurotransmitter measurements in vivo. [ABSTRACT FROM AUTHOR] more...

Importance: There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN., Objective: To present the long-term efficacy and safety of patisiran in adults with hATTR-PN., Design, Setting, and Participants: This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE., Intervention: Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years., Main Outcomes and Measures: Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life-Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed., Results: At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and -3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival., Conclusions and Relevance: In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine., Trial Registration: ClinicalTrials.gov Identifier: NCT02510261. more...

Phellinus linteus (PL) is a medicinal fungus known for producing hispolon, a bioactive compound with antioxidant, anti-inflammatory, and anticancer properties. However, the natural scarcity of PL and the unsuccessful cultivation of its fruiting bodies have led to the exploration of alternative methods for enhancing its bioactive compound production. In this study, static fermentation was employed, and Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), was added to the culture medium to induce epigenetic modifications and enhance hispolon production. After 30 days of fermentation, the hispolon concentration was analyzed using high-performance liquid chromatography (HPLC), mycelial dry weight was measured, and the expression of hispolon synthesis-related enzymes was quantified using quantitative PCR (qPCR). Additionally, the anticancer potential of the fermented media was assessed in human breast adenocarcinoma HTB-26 cells using assays for cytotoxicity, reactive oxygen species (ROS) formation, apoptosis, antioxidant activity, and autophagy markers. The results revealed that the addition of 400 µM VPA increased hispolon production by 120% and mycelial dry weight by 41%, likely due to enhanced transcriptional accessibility. Furthermore, the PL fermentation media significantly inhibited HTB-26 cell growth through the induction of ROS formation, autophagy, and apoptosis. These findings suggest that VPA-enhanced static fermentation of PL offers a promising strategy for optimizing hispolon production and developing effective anticancer therapeutics., Competing Interests: Declarations. Conflict of interest: The authors declare that there are no conflicts of interest., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.) more...

The phosphoenol pyruvate–oxaloacetate–pyruvate-derived amino acids (POP-AAs) comprise native intermediates in cellular metabolism, within which the phosphoenol pyruvate–oxaloacetate–pyruvate (POP) node is the switch point among the major metabolic pathways existing in most living organisms. POP-AAs have widespread applications in the nutrition, food, and pharmaceutical industries. These amino acids have been predominantly produced in Escherichia coli and Corynebacterium glutamicum through microbial fermentation. With the rapid increase in market requirements, along with the global food shortage situation, the industrial production capacity of these two bacteria has encountered two bottlenecks: low product conversion efficiency and high cost of raw materials. Aiming to push forward the update and upgrade of engineered strains with higher yield and productivity, this paper presents a comprehensive summarization of the fundamental strategy of metabolic engineering techniques around phosphoenol pyruvate–oxaloacetate–pyruvate node for POP-AA production, including L-tryptophan, L-tyrosine, L-phenylalanine, L-valine, L-lysine, L-threonine, and L-isoleucine. Novel heterologous routes and regulation methods regarding the carbon flux redistribution in the POP node and the formation of amino acids should be taken into consideration to improve POP-AA production to approach maximum theoretical values. Furthermore, an outlook for future strategies of low-cost feedstock and energy utilization for developing amino acid overproducers is proposed. [ABSTRACT FROM AUTHOR] more...

Identifying distributed strain sensing (DSS) patterns (or signatures), particularly those arising from different hydraulic fracture geometries, has gained significant attention and research effort. Recent works have generated a catalogue of signatures for planar hydraulic fractures in an elastic rock formation. Yet, in numerous cases (e.g., fault motion and some geothermal reservoir stimulation), the main mode of deformation is a shear on a fracture or a network of natural fractures (particularly during low pressure injection/circulation). However, the specific fiber signatures that result from such shear deformation have not been studied. In this study, we use a three-dimensional poroelastic hydraulic fracture simulator to capture the strain signatures resulting from the shear deformation of fractures in various orientations with respect to the monitoring well. Five key cases are examined: one where the fracture strike is perpendicular to the fiber, another with the strike running parallel to the fiber, a third case where the fracture strike is at 45 degrees to the fiber, a fourth case with a strike slip fault perpendicular to the fiber, and a fifth case where fiber is intersecting the fracture. Theoretically and physically meaningful results were obtained in all five cases, which completely differ from the heart-shaped signature of tensile fracture propagation. It was discovered that the strain pattern changes with the shear deformation direction with respect to the fiber. The model is then used to simulate the response of a fracture network at Utah FORGE to injection to assess whether a signature might be expected in response to the planned injection and circulation rates, and, if so, what strain pattern might be expected. The simulation confirms that a strain response can indeed be observed. More importantly, the fiber response that would be detected in the monitoring well would be a combination of strain signatures from dilation and shear deformation of differently oriented natural fractures. The results in this study provide useful insights on the application of fiber to other stimulation and/or circulation scenarios where shear deformation of a fracture or fracture network plays a major role. [ABSTRACT FROM AUTHOR] more...

Caffeic acid (CA) is a phenolic acid compound widely used in pharmaceutical and food applications. However, the efficient synthesis of CA is usually limited by the resources of individual microbial platforms. Here, a cross-kingdom microbial consortium was developed to synthesize CA from sugarcane bagasse hydrolysate using Escherichia coli and Candida glycerinogenes as chassis. In the upstream E. coli module, shikimate accumulation was improved by intensifying the shikimate synthesis pathway and blocking shikimate metabolism to provide precursors for the downstream CA synthesis module. In the downstream C. glycerinogenes module, conversion of p-coumaric acid to CA was improved by increasing the supply of the cytoplasmic cofactor FAD(H2). Further, overexpression of ABC transporter-related genes promoted efflux of CA and enhanced strain resistance to CA, significantly increasing CA titer from 103.8 mg/L to 346.5 mg/L. Subsequently, optimization of the inoculation ratio of strains SA-Ec4 and CACg27 in this cross-kingdom microbial consortium resulted in an increase in CA titer to 871.9 mg/L, which was 151.6% higher compared to the monoculture strain CA-Cg27. Ultimately, 2311.6 and 1943.2 mg/L of CA were obtained by optimization of the co-culture system in a 5 L bioreactor using mixed sugar and sugarcane bagasse hydrolysate, respectively, with 17.2-fold and 14.6-fold enhancement compared to the starting strain. The cross-kingdom microbial consortium developed in this study provides a reference for the production of other aromatic compounds from inexpensive raw materials. [ABSTRACT FROM AUTHOR] more...

Food is one of the factors with the highest impact on human health. Today, attention is paid not only to food properties such as energy provision and palatability but also to functional aspects including phytochemical, antioxidant properties, etc. Massaman and spicy basil leaf curries are famous Thai food dishes with a good harmony of flavor and taste, derived from multiple herbs and spices, including galangal rhizomes, chili pods, garlic bulbs, peppers, shallots, and coriander seeds, that provide an array of health benefits. The characterization of phytochemicals detected by LC-ESI-QTOF-MS/MS identified 99 components (Masaman) and 62 components (spicy basil leaf curry) such as quininic acid, hydroxycinnamic acid, luteolin, kaempferol, catechin, eugenol, betulinic acid, and gingerol. The cynaroside and luteolin-7-O-glucoside found in spicy basil leaf curry play a key role in antioxidant activities and were found at a significantly higher concentration than in Massaman curry. Phenolic and flavonoid compounds generally exhibit a bitter and astringent taste, but all the panelists scored both curries higher than 7 out of 9, confirming their acceptable flavor. Results suggest that the Massaman and spicy basil leaves contain various phytochemicals at different levels and may be further used as functional ingredients and nutraceutical products. [ABSTRACT FROM AUTHOR] more...

The engineering properties of rigid–soft mixtures (i.e., sand-tire chip mixtures) under static loading conditions have been extensively studied; however, the corresponding properties under repetitive loading have not been adequately examined. This study investigates the evolution of the maximum shear modulus (Gmax) and compression index (Cc) of rigid–soft mixtures subjected to static and repetitive loading up to the number of cycles = 104. A floating ring oedometer cell equipped with bender elements and an automatic control system was designed to investigate the impact of the size ratio (SR) and tire chip fraction (TF) on Gmax and Cc during repetitive loading. During the initial static loading, the Gmax of tested mixtures increase with increasing SR or decreasing TF because SR and TF determine the connectivity between rigid sand particles. A huge increase in Gmax of rigid–soft mixtures during the repetitive loadings compared to pure sand and pure tire chip indicates the transition of sand-to-rubber contacts to sand-to-sand contacts caused by the repetitive loadings. The increased rate of coordination number between sand particles caused by repetitive loading is a function of SR and TF, resulting in the highest increase in Gmax caused by repetitive loadings for the mixture with SR = 0.44 at TF = 20%, reflecting an opposite effect of SR on Gmax compared to static loading. In addition, the lower impact of SR on Cc after repetitive loadings was observed. [ABSTRACT FROM AUTHOR] more...

Background: We previously showed that total tumor resection enhances metastatic growth in a syngeneic metastatic mouse model of neuroblastoma. In this study, we further investigated which surgical factors contributed most to metastatic growth. Methods: Tumor cells derived from MYCN transgenic mice were subcutaneously injected into wild-type mice. Mice were randomly assigned to receive partial resection (PR group), subcutaneous implantation of a sponge (Sp group), or observation (Obs group). The lymph node metastasis volume and the frequency of lung metastasis were compared 14 days after assignment by measuring C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Results: The lymph node metastasis volume in the Sp group was larger than in the Obs group (148.4 [standard deviation {SD}: 209.5] vs. 10.2 [SD 12.8] mm3). The frequency of lung metastasis was greater in the Sp group than in the PR group (11.9 [SD 12.2] vs. 6.6 [SD 4.0] counts/slide). The CRP level in the Sp group was higher than in the PR group (2.3 [SD 0.5] vs. 1.5 [SD 0.4] μg/mL), and the IL-6 level in the Sp group was higher than in the PR or Obs groups (28.4 [SD 34.5] vs. 12.4 [SD 19.0] vs. 5.4 [SD 8.1] pg/mL). Conclusion: Metastatic growth may be enhanced by systemic inflammation. [ABSTRACT FROM AUTHOR] more...

Ewing sarcoma (EwS) is a malignant sarcoma which occurs in bone and soft tissues commonly happening in children with poor survival rates. Changes in cell metabolism, such as glycolysis, may provide the environment for the transformation and progression of tumors. We aimed to build a model to predict prognosis of EwS patients based on glycolysis and metabolism genes. Candidate genes were obtained by differential gene expression analysis based on GSE17679, GSE17674 and ICGC datasets. We performed GO and KEGG pathway enrichment analysis on candidate genes. Univariate Cox and LASSO Cox regression analyses were conducted to construct a model to calculate the Risk Score. GSEA was done between high-risk and low-risk groups. CIBERSORT was applied to analyze the immune landscape. We got 295 candidate glycolysis-metabolism-related genes which were enriched in 620 GO terms and 18 KEGG pathways. 12 Genes were selected by univariate Cox model and 5 of them were determined by LASSO Cox regression analysis to be used in the construction of the Risk Score model. The Risk Score could be considered as an independent prognosis factor. The immune landscape and immune checkpoints' expression significantly differed between high- and low-risk groups. Our research constructed a new glycolysis-metabolism-related genes (FABP5, EMILIN1, GLCE, PHF11 and PALM3) based prognostic signature for EwS patients and assisted in gaining insight into prognosis to improve therapies further., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...

This study answers four research questions by contextualising the background to Japan's "carbon neutrality and net-zero" (CNN) policy, which was announced in October 2020, and identifying important changes in Japanese climate policy between 1990 and 2020. What is the link between the problem of fairness under the Kyoto targets and the Japanese government's initial reluctance towards ambitious carbon emission reductions? Why did the Japanese business sector initially resist the possibility of ambitious carbon emission reductions? How has the term "climate crisis" contributed to the need for CNN policy? Why did the Japanese government change its reluctant stance and announce the CNN policy in October 2020? Four main findings were extracted from a narrative technique-based analysis of Japan's policy documents related to CNN. The following are the findings: [i] the framing of climate change as a "climate crisis" by influential Japanese climate stakeholders was a key motivation for Japan to formally announce its CNN policy in October 2020; [ii] pressure from the international community and the political leadership of the Yoshihide Suga administration are essential factors that led the Japanese government to change its stance and announced this policy; [iii] it is possible that the policy could have been announced sooner, but concern among Japanese climate stakeholders about the problem of fairness in the Kyoto Protocol's emission reduction targets likely impeded such an announcement; and [iv] this concern underpinned Keidanren's (or the business sector's) consistent opposition to the introduction of regulatory schemes. These results emerge for the first time in a study of Japan's carbon neutrality, particularly in terms of the broader context of climate politics. Finally, we offer a possible explanation for Suga's deliberate announcement of the CNN policy. This opens up space for future research to complement our study by providing important indicators on the trajectory of this important policy. [ABSTRACT FROM AUTHOR] more...

L-Tyrosine, an aromatic non-essential amino acid, is the raw material for many important chemical products, including levodopa, resveratrol, and hydroxytyrosol. It is widely used in the food, drug, and chemical industries. There are many studies on the synthesis of L-tyrosine by microorganisms, however, the low titer of L-tyrosine limited the industrial large-scale production. In order to enhance L-tyrosine production in Escherichia coli, the expression of key enzymes in the shikimate pathway was up- or down-regulated. The L-tyrosine transport system and the acetic acid biosynthesis pathway were modified to further enhance L-tyrosine production. In addition, the phosphoketolase pathway was introduced in combination with cofactor engineering to redirect carbon flux to the shikimate pathway. Finally, after adaptive laboratory evolution to low pH an optimal strain was obtained. The strain can produce 92.5 g/L of L-tyrosine in a 5-L fermenter in 62 h, with a yield of 0.266 g/g glucose. [ABSTRACT FROM AUTHOR] more...

The present study aimed to investigate the mechanism of TiAl formation through molecular dynamics simulation (MDS) and spark plasma sintering (SPS) methods. The results of the MDS method suggested that TiAl3 is the first intermetallic compound formed by the diffusion of Ti(s) and Al(l) atoms into their interface at 1340 K, followed by the formation of the Ti3Al compound on the interface of Ti/TiAl3. Afterward, by the diffusion of Al(l) atoms into the layers, Ti2Al5 and then TiAl2 compounds were formed on the interfaces of Ti3Al/TiAl3 and Ti3Al/Ti2Al5, respectively. Finally, the TiAl compound formed on TiAl2/Ti3Al interface by a similar procedure. Indeed, the formation mechanisms of TiAl were controlled by the diffusion mechanism to the different interfaces formed during the process. Moreover, the SPS process was employed to validate the MDS results through Rietveld's analysis of the XRD patterns and microscopic structure investigations by SEM and FESEM, in addition to EDX spectroscopy, for the samples at various times. Comparing the results obtained by the MDS and SPS methods revealed that, despite the limitations of the MDS method, this atomic scale method can effectively predict the formation mechanisms of the intermetallic compounds. [ABSTRACT FROM AUTHOR] more...

For a searchable version of these abstracts, please visit www.acrabstracts.org. [ABSTRACT FROM AUTHOR]

Assessing the dynamic response of soft and compressible soils is a prerequisite for many earthquake geotechnical engineering applications. Dynamic characterization is represented in terms of strain-dependent dynamic soil properties (Gmax, G/Gmax, and damping ratio-D variation with shear strain-γ) and liquefaction potential. The current study aims to investigate the dynamic response of two soft-natured cohesive soils sampled from one of the most active seismic regions of India (Assam). Four advanced dynamic characterization techniques have been employed for strain-dependent dynamic soil characterization. Bender element tests are adopted for low-strain testing, resonant column tests for intermediate-strain range, dynamic simple shear tests for high-strain testing, and cyclic triaxial apparatus for assessing the liquefaction potential of the chosen soil specimens. The obtained results are discussed in terms of shear modulus degradation and damping ratio variation with γ as influencing parameter. The independent equipment-specific results are combined to form a set of comprehensive dynamic soil properties over a wide strain range (0.001 to 5%) which can be readily adopted for earthquake geotechnical applications for similar soils from northeastern India. Easy-to-use analytical expressions have been developed utilizing the experimental results and nonlinear regression analyses. Further, a case study of nonlinear effective stress–based ground response analysis has been conducted to demonstrate the applicability of established dynamic soil characteristics. It has been realized from the case study that the soft soil deposits in northeastern India are prone to seismic wave amplification for low seismic motions and attenuation for high-intensity seismic motions. The wide range of results presented in this article will prove advantageous in carrying out nonlinear effective stress analysis and developing constitutive models for numerical simulations of foundations and soils in northeastern India. [ABSTRACT FROM AUTHOR] more...

UT-Austin's Devine Fracture Pilot Site, 50 miles southwest of San Antonio, Texas, has been targeted for a comprehensive, multidisciplinary development of fracture diagnostic techniques that are cross-validated by ground-truth data acquisition near a recently created, 175-ft-deep, horizontal hydraulic fracture (Ahmadian et al. 2018 Demonstration of proof of concept of electromagnetic geophysical methods for high resolution illumination of induced fracture networks. In Proceedings of the SPE Hydraulic Fracturing Technology Conference and Exhibition, The Woodlands, Texas, USA, 23–25 January 2018. SPE-189858-MS.). To evaluate the fracture diagnostic methods at this site, we conducted injection tests with a predefined volumetric flow-rate profile, resembling a diagnostic fracture injection test on September 2020. Subsequently, we developed hydrogeological and geomechanical models based on flow-rate and bottomhole-pressure measurements. History-matching efforts using a simplified layer-cake hydrogeological model resulted in the field-scale formation permeability of 9.87 × 10–15 m2 (10 mD) and Darcy-scale fracture permeability. The analysis of the bottomhole pressure and injection-rate history showed that (1) the newly created horizontal fracture was closed adjacent to the injection well pre-injection and (2) the initial pump-pressure increase at a nominal volumetric injection rate led to near-well fracture reopening, fluid conductivity increase, and abrupt injection-rate increase. To overcome hydrogeological-model limitations of predicting fracture reopening throughout injection, we extended the modeling to a finite-element, poroelastic analysis of horizontal-fracture growth using a cohesive-zone model. Using this fracture-reopening model, we improved the history match of the transient-pressure response during the experiment by adjusting the hydromechanical properties. Post-injection pressure transient analyses helped reduce uncertainty in the overburden-stress gradient, and the initial hydraulic-fracturing simulation verified the plausibility of achieving the surveyed propped fracture area. Highlights: We proposed a procedure for developing a hydrogeological model to improve the history matching of the bottomhole pressure during a hydraulic-fracture reopening. We compared the outcomes of this hydrogeological model with a calibrated poroelastic model, showing the advantage of the later model for fracture reopening and re-closure. We suggest using a spatiotemporally variable fracture permeability obtained from a poroelastic model in a hydrogeological model to simulate fracture reopening. We estimated an almost similar overburden-stress gradient using G-function pressure transient analysis of post-shut-in bottomhole pressure data from two short and long injection tests. [ABSTRACT FROM AUTHOR] more...

Background: Aromatic compounds derived from tyrosine are important and diverse chemicals that have industrial and commercial applications. Although these aromatic compounds can be obtained by extraction from natural producers, their growth is slow, and their content is low. To overcome these problems, many of them have been chemically synthesized from petroleum-based feedstocks. However, because of the environmental burden and depleting availability of feedstock, microbial cell factories are attracting much attention as sustainable and environmentally friendly processes. Results: To facilitate development of microbial cell factories for producing tyrosine derivatives, we developed simple and convenient tyrosine-producing Escherichia coli platforms with a bacterial phenylalanine hydroxylase, which converted phenylalanine to tyrosine with tetrahydromonapterin as a cofactor, using a synthetic biology approach. By introducing a tetrahydrobiopterin-regeneration system, the tyrosine titer of the plasmid-based engineered strain was 4.63 g/L in a medium supplemented with 5.00 g/L phenylalanine with a test tube. The strains were successfully used to produce industrially attractive compounds, such as tyrosol with a yield of 1.58 g/L by installing a tyrosol-producing module consisting of genes encoding tyrosine decarboxylase and tyramine oxidase on a plasmid. Gene integration into E. coli chromosomes has an advantage over the use of plasmids because it increases genetic stability without antibiotic feeding to the culture media and enables more flexible pathway engineering by accepting more plasmids with artificial pathway genes. Therefore, we constructed a plasmid-free tyrosine-producing platform by integrating five modules, comprising genes encoding the phenylalanine hydroxylase and tetrahydrobiopterin-regeneration system, into the chromosome. The platform strain could produce 1.04 g/L of 3,4-dihydroxyphenylalanine, a drug medicine, by installing a gene encoding tyrosine hydroxylase and the tetrahydrobiopterin-regeneration system on a plasmid. Moreover, by installing the tyrosol-producing module, tyrosol was produced with a yield of 1.28 g/L. Conclusions: We developed novel E. coli platforms for producing tyrosine from phenylalanine at multi-gram-per-liter levels in test-tube cultivation. The platforms allowed development and evaluation of microbial cell factories installing various designed tyrosine-derivative biosynthetic pathways at multi-grams-per-liter levels in test tubes. [ABSTRACT FROM AUTHOR] more...

Depressive disorders are a common and debilitating form of mental illness with significant impacts on individuals and society. Despite the high prevalence, the underlying causes and mechanisms of depressive disorders are still poorly understood. Neurochemical systems, including serotonin, norepinephrine, and dopamine, have been implicated in the development and perpetuation of depressive symptoms. Current treatments for depression target these neuromodulator systems, but there is a need for a better understanding of their role in order to develop more effective treatments. Monitoring neurochemical dynamics during depressive symptoms is crucial for gaining a better a understanding of their involvement in depressive disorders. Genetically encoded sensors have emerged recently that offer high spatial-temporal resolution and the ability to monitor neurochemical dynamics in real time. This review explores the neurochemical systems involved in depression and discusses the applications and limitations of current monitoring tools for neurochemical dynamics. It also highlights the potential of genetically encoded sensors for better characterizing neurochemical dynamics in depression-related behaviors. Furthermore, potential improvements to current sensors are discussed in order to meet the requirements of depression research., (© 2024 International Society for Neurochemistry.) more...

P-coumaric acid (p-CA), a pant metabolite with antioxidant and anti-inflammatory activity, is extensively utilized in biomedicine, food, and cosmetics industry. In this study, a synthetic pathway (PAL) for p-CA was designed, integrating three enzymes (AtPAL2, AtC4H, AtATR2) into a higher l-phenylalanine-producing strain Escherichia coli PHE05. However, the lower soluble expression and activity of AtC4H in the PAL pathway was a bottleneck for increasing p-CA titers. To overcome this limitation, the soluble expression of AtC4H was enhanced through N-terminal modifications. And an optimal mutant, AtC4H L373T/G211H , which exhibited a 4.3-fold higher k cat /K m value compared to the wild type, was developed. In addition, metabolic engineering strategies were employed to increase the intracellular NADPH pool. Overexpression of ppnk in engineered E. coli PHCA20 led to a 13.9-folds, 1.3-folds, and 29.1% in NADPH content, the NADPH/NADP + ratio and p-CA titer, respectively. These optimizations significantly enhance p-CA production, in a 5-L fermenter using fed-batch fermentation, the p-CA titer, yield and productivity of engineered strain E. coli PHCA20 were 3.09 g/L, 20.01 mg/g glucose, and 49.05 mg/L/h, respectively. The results presented here provide a novel way to efficiently produce the plant metabolites using an industrial strain., (© 2024 Wiley Periodicals LLC.) more...

This study investigated a new predictive model of the shear modulus reduction ( G G max − Log (γ c)) and damping ratio (ξ − Log (γc)) curves for sensitive eastern Canada clays. The model was established based on experimental measurements of G G max and ξ performed on 69 sensitive clay specimens from eastern Canada. The compiled database was first analyzed to qualitatively assess the influences of different soil parameters on the measurements. Next, statistical analyses using regression analysis and the modified hyperbolic model were performed. It was found that the G G max and ξ values of sensitive eastern Canada clays were influenced mainly by the plasticity index (Ip), mean effective stress (σ m ′) , and structure, which was quantified by the liquidity index (IL). Based on the statistical analysis performed, new equations for G G max and ξ were proposed. The newly proposed model was compared with previously published models. The comparison clearly showed that the proposed model was more representative of sensitive eastern Canada clays. Consequently, it is suggested that the proposed model is more appropriate for use in the dynamic analysis of sensitive eastern Canada clay deposits as well as other similar soils. [ABSTRACT FROM AUTHOR] more...

Featured Application: The proposed computer-aided algorithm aims to introduce an approach to implement the performance and expand the capability of the downhole method in defining the shear wave velocity and the elastic damping ratio profiles. This contribution introduces a computerized semi-automated procedure coupled with a dedicated algorithm to improve shear wave velocity assessment and the on-site elastic damping ratio estimation of ground materials. The standard equipment of the downhole method is integrated with a horizontal geophone (guardian) placed on the field surface. Mask tapering and band multi-filter functions improve first arrival, recognizing and isolating SH-wave trains to estimate damping ratio profiles. These are computed by treating signals using a frequency–time combined approach (frequency–time packets method). The signals are corrected to consider the different source pulse amplitude, the effects of the propagation path, and scattering. The damping ratio profile is statistically computed in terms of the local drift of trend on the amplitude ratio series that would otherwise have a normal distribution centered on zero. These profiles intercept the lithology changes in the test sites and meet the damping values stemming from previous field tests and the laboratory experimental tests available in the literature regarding materials such as the ones investigated here. [ABSTRACT FROM AUTHOR] more...

Objective. Patients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL, among patients with systemic lupus erythematosus (SLE). Methods. This was a cross-sectional study using baseline data from the Trust Measurement for Physicians and Patients with SLE (TRUMP2-SLE) study, an ongoing multicenter cohort study conducted at 5 academic centers. The 14-item Functional, Communicative, and Critical Health Literacy Scale assessed the 3 dimensions of HL; each item of the scale was scored on a 4-point Likert scale, ranging from 1 to 4. Outcomes were trust in one’s physician and trust in physicians in general using the 5-item Wake Forest Physician Trust Scale, which ranged from 0 to 100 points. General linear models were fit. Results. A total of 362 patients with SLE were included. Trust in one’s physician increased with higher functional and communicative HL (per 1-point increase: mean difference 3.39, 95% CI 0.39-6.39, and mean difference 5.88, 95% CI 2.04-9.71, respectively). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-point increase: mean difference 7.09, 95% CI 2.34-11.83, and mean difference –6.88, 95% CI –11.72 to –2.04, respectively). Longer internet use was associated with both higher communicative and critical HL. Conclusion. The findings suggest that rheumatologists need to improve their communication to match each patient’s HL, which may foster trust and lead to improved self-management and outcomes in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust. [ABSTRACT FROM AUTHOR] more...

In current seismic performance-based assessment approaches, nonlinear dynamic analysis of structures generally relies on ground motions selected based on their pseudo-spectral accelerations, with little or no consideration for ground-motion duration. Part I of this study, presented in this article, attempts to comprehensively quantify the impact of ground-motion duration on the nonlinear structural performance of case-study inelastic single-degree-of-freedom systems for shallow-crustal seismicity conditions. The effect of duration is decoupled from that of ground-motion amplitude and spectral shape by assembling sets of spectrally equivalent long- and short-duration records. Such sets are employed in incremental dynamic analyses of a wide range of computational models incorporating in-cycle and cyclic strength and stiffness deterioration. The structural response is quantified in terms of peak- and cumulative-based engineering demand parameters. Formal hypothesis testing is used to assess the statistical significance of duration's impact on the median structural capacity of the considered structural systems. Furthermore, the derivation of duration-dependent fragility and vulnerability relationships demonstrates that ground-motion duration effectively impacts the nonlinear structural performance of various systems, and it should be accounted for in current practice. The fragility median values for highly deteriorating structural systems under long-duration ground motions are found to be up to 21% or 34.0% smaller than the short-duration counterpart if a peak- or cumulative-based engineering demand parameter is adopted, respectively. [ABSTRACT FROM AUTHOR] more...

The properties of LaMO 3 (M: 3d transition metal) perovskite crystals are significantly dependent on point defects, whether introduced accidentally or intentionally. The most studied defects in La-based perovskites are the oxygen vacancies and doping impurities on the La and M sites. Here, we identify that intrinsic antisite defects, the replacement of La by the transition metal, M, can be formed under M-rich and O-poor growth conditions, based on results of an accurate many-body ab initio approach. Our fixed-node diffusion Monte Carlo (FNDMC) calculations of LaMO 3 ( M = Mn , Fe, and Co) find that such antisite defects can have low formation energies and are magnetized. Complementary density functional theory (DFT)-based calculations show that Mn antisite defects in LaMnO 3 may cause the p-type electronic conductivity. These features could affect spintronics, redox catalysis, and other broad applications. Our bulk validation studies establish that FNDMC reproduces the antiferromagnetic state of LaMnO 3 , whereas DFT with PBE (Perdew–Burke–Ernzerhof), SCAN (strongly constrained and appropriately normed), and the LDA+U (local density approximation with Coulomb U) functionals all favor ferromagnetic states, at variance with experiment. [ABSTRACT FROM AUTHOR] more...

Simple Summary: Novel therapeutic targets are needed to improve treatments of aggressive cancers and viral diseases. Tetraspanins represent an emerging class of anticancer targets, notably the transmembrane protein CD81 which has been structurally well characterized. CD81 plays key roles in tumor growth and dissemination, and serves as a co-receptor for a number of viruses. The protein interacts with a variety of protein partners involved in different signaling pathways. Here, we provide an overview of the complementary approaches used to target CD81, with monoclonal antibodies and small molecules, including both natural products and synthetic compounds. Drug design approaches are discussed, as well as the limitations associated with the targeting of this ubiquitous protein. CD81 is considered as a promising anticancer and antiviral target. Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target. [ABSTRACT FROM AUTHOR] more...

Earth–rock dams are typical soil–rock mixtures with high heterogeneity. Mastering the effect of dam heterogeneity on seismic wavefields is the premise of accurately detecting hidden risks in dams. In this paper, based on the soil–rock mixture characteristics of actual dams, a soil–rock mixture model that can reflect the heterogeneity of dams is established through local segmentation and reassignment of random disturbances. The influence of local area size on model heterogeneity is described. The seismic wavefield in a soil–rock mixture dam is numerically simulated through a staggered-grid finite-difference algorithm with second-order accuracy in time and sixth-order accuracy in space. Then, the effect of dam heterogeneity on effective wavefields is analyzed. The results show that the heterogeneity of the earth–rock dam can lead to scattered waves in the seismic wavefield, and the scattered waves are mainly generated by Rayleigh surface waves. In the seismic record, scattered waves with strong energy appear in the region below the surface waves. The scattered wave energy is weak and close to that in the homogeneous media in the region above the surface waves. As the rock content in the dam increases, the scattering of seismic wavefields and the energy of scattered waves weaken gradually. The scattered waves generated by the heterogeneity of the dam significantly impact the reflected longitudinal wave and converted wave but, affect the reflected shear wave less. The numerical simulation results are consistent with the acquired seismic wavefield from the field test, proving the effectiveness of the numerical simulation for the seismic wavefield propagation characteristics of the earth–rock dam. [ABSTRACT FROM AUTHOR] more...

Background: Homeobox transcription factor encoding genes, genomic screen homeobox 1 and 2 (gsx1 and gsx2), are expressed during neurodevelopment in multiple vertebrates. However, we have limited knowledge of the dynamic expression of these genes through developmental time and the gene networks that they regulate in zebrafish. Results: We confirmed that gsx1 is expressed initially in the hindbrain and diencephalon and later in the optic tectum, pretectum, and cerebellar plate. gsx2 is expressed in the early telencephalon and later in the pallium and olfactory bulb. gsx1 and gsx2 are co‐expressed in the hypothalamus, preoptic area, and hindbrain, however, rarely co‐localize in the same cells. gsx1 and gsx2 mutant zebrafish were made with TALENs. gsx1 mutants exhibit stunted growth, however, they survive to adulthood and are fertile. gsx2 mutants experience swim bladder inflation failure that prevents survival. We also observed significantly reduced expression of multiple forebrain patterning distal‐less homeobox genes in mutants, and expression of foxp2 was not significantly affected. Conclusions: This work provides novel tools with which other target genes and functions of Gsx1 and Gsx2 can be characterized across the central nervous system to better understand the unique and overlapping roles of these highly conserved transcription factors. Key Findings: gsx1 and gsx2 expression is dynamic during embryonic and larval stages of neurodevelopment in zebrafish, and gsx1 expression appears to be in differentiating neurons based on their morphology and position.gsx1 and gsx2 are expressed together in several developing brain regions, however, they rarely colocalize in the same cells.Early forebrain patterning in gsx1 mutants appears normal, and Gsx1 might partially compensate for loss of Gsx2 function as more severe forebrain gene expression loss is observed in gsx1 and gsx2 mutants compared to gsx2 mutants in some instances.Complementation testing between different gsx1 or gsx2 mutant alleles shows that mutant phenotypes arise from altered gsx1 or gsx2 function. [ABSTRACT FROM AUTHOR] more...

Chromosome‐based engineering is a superior approach for gene integration generating a stable and robust chassis. Therefore, an effective amplifier, T7 RNA polymerase (T7RNAP) from bacteriophage, has been incorporated into Escherichia coli W3110 by site‐specific integration. Herein, we performed the 5‐aminolevulinic acid (5‐ALA) production in four T7RNAP‐equipped W3110 strains using recombinant 5‐aminolevulinic synthase and further explored the metabolic difference in best strain. The fastest glucose consumption resulted in the highest biomass and the 5‐ALA production reached to 5.5 g/L; thus, the least by‐product of acetate was shown in RH strain in which T7RNAP was inserted at HK022 phage attack site. Overexpression of phosphoenolpyruvate (PEP) carboxylase would pull PEP to oxaloacetic acid in tricarboxylic acid cycle, leading to energy conservation and even no acetate production, thus, 6.53 g/L of 5‐ALA was achieved. Amino acid utilization in RH deciphered the major metabolic flux in α‐ketoglutaric acid dominating 5‐ALA production. Finally, the ribulose‐1,5‐bisphosphate carboxylase/oxygenase (RuBisCO) and phosphoribulokinase were expressed for carbon dioxide recycling; a robust and efficient chassis toward low‐carbon assimilation and high‐level of 5‐ALA production up to 11.2 g/L in fed‐batch fermentation was established. [ABSTRACT FROM AUTHOR] more...

BACKGROUND: Probiotic lactic acid bacterium Lactiplantibacillus plantarum is widely used in the dairy and other fermented food industries. L. plantarum AR113 harbors a C30 carotenoid operon crtNM based on genomic analysis, but the yield of C30 carotenoid is only 8.1 μg g‐1 DCW. RESULTS: To improve the productivity of C30 carotenoid, crtNM from L. plantarum AR113 was cloned and reconstructed in Escherichia coli BL21(DE3). The proteins crtN and crtM were successfully expressed based on a sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE) analysis, and the carotenoid was detected using high‐performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LC–MS). In comparison with the constitutive promoter P44, the use of the inducible T7 promoter significantly increased the carotenoid content in E. coli. The fermentation conditions were also optimized with induction by 0.5 mmol/L IPTG at 20 °C for 7 h. The yield of C30 carotenoid reached 154.5 μg g‐1 DCW, which was 18‐fold higher than that of L. plantarum AR113. The 2,2‐diphenyl‐1‐picryl (DPPH) and 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6sulfonic acid (ABTS) radical scavenging capacity of C30 carotenoids synthesized by heterologous expression in E. coli was also higher than that of the antioxidant food additive butylated hydroxytoluene. CONCLUSIONS: Our findings suggest that E. coli has strong potential as a basic chassis for the production of C30 carotenoids from Lactiplantibacillus with high antioxidant activity. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR] more...