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Molecular dynamics (MD) was used to simulate the effect of TiC particles distribution on the tribological behavior of the reinforced composites. The mechanical properties, friction coefficient, number of wear atoms, stress and temperature, and microscopic deformation behavior of TiC/Ni composites during nano-friction were systematically investigated by MD to reveal the effect of TiC distribution on the friction removal mechanism of the material. It was found that the larger the radius of the TiC particles, or the shallower the depth of the TiC particles, the easier it was to generate stress concentrations around the TiC particles, forming a high dislocation density region and promoting the nucleation of dislocations. This leads to severe friction hardening, reducing the atomic number of abrasive chips and reducing the friction coefficient by approximately 6% for every 1 nm reduction in depth, thus improving the anti-wear capacity. However, when the radius of the TiC particles increases and the thickness from the surface deepens, the elastic recovery in material deformation is weakened. We also found that the presence of the TiC particles during the friction process changes the stress state inside the workpiece, putting the TiC particles and the surrounding nickel atoms into a high-temperature state and increasing the concentrated temperature by 30 K for every 1 nm increase in depth. Nevertheless, the workpiece atoms below the TiC particles invariably exist in a low-temperature state, which has a great insulation effect and improves the high-temperature performance of the material. The insight into the wear characteristics of TiC particles distribution provides the basis for a wide range of TiC/Ni applications. [ABSTRACT FROM AUTHOR]

In this innovative work, Inconel 718 alloy turning simulation models under dry and cryogenic machining (Cryo) conditions are developed. The machinability characteristics of the aforementioned alloy were assessed with relation to cutting temperature ( T c t ) and cutting force ( F c f ). The comparison of the T c t and F c f results from simulation with those obtained under the identical experimental conditions served as additional evidence of the effectiveness of the suggested simulation model. By varying the cutting speed, the reduction in T c t under Cryo conditions was 9.36% to 11.98% compared to dry cutting. Regarding the force comparison under experiment and simulation, the average difference between the simulation and experimental values for the main cutting force ( F c ) was 13.73%, whereas the average deviation for the feed force ( F f ) was 14.63%. Response surface methodology (RSM) was employed to build the forecasting models for T c t and F c f in cryogenic settings. These mathematical models showed excellent predictive performance and were able to estimate the T c t and F c f under machining operations settings, according to the present research. When compared to dry cutting, Cryo reduced the cutting temperature, which had a positive impact on the alloy's machinability. [ABSTRACT FROM AUTHOR]

High entropy alloys (HEAs) of the type CrCuFeNiTi-Alx were processed through mechanical alloying. The aluminum concentration was varied in the alloy, to determine its effect on the HEAs' microstructure, phase formation, and chemical behavior. X-ray diffraction studies performed on the pressureless sintered samples revealed the presence of structures composed of face centered cubic (FCC) and body centered cubic (BCC) solid-solution phases. Since the valences of the elements that form the alloy are different, a nearly stoichiometric compound was obtained, increasing the final entropy of the alloy. The aluminum was partly responsible for this situation, which also favored transforming part of the FCC phase into BCC phase on the sintered bodies. X-ray diffraction also indicated the formation of different compounds with the alloy's metals. Bulk samples exhibited microstructures with different phases. The presence of these phases and the results of the chemical analyses revealed the formation of alloying elements that, in turn, formed a solid solution and, consequently, had a high entropy. From the corrosion tests, it could be concluded that the samples with a lower aluminum content were the most resistant to corrosion. [ABSTRACT FROM AUTHOR]

Sugarcane is the major sugar-producing crop worldwide, and hybrid F1 populations are the primary populations used in breeding. Challenged by the sugarcane genome's complexity and the sucrose yield's quantitative nature, phenotypic selection is still the most commonly used approach for high-sucrose yield sugarcane breeding. In this study, a hybrid F1 population containing 135 hybrids was constructed and evaluated for 11 traits (sucrose yield (SY) and its related traits) in a randomized complete-block design during two consecutive growing seasons. The results revealed that all the traits exhibited distinct variation, with the coefficient of variation (CV) ranging from 0.09 to 0.35, the Shannon-Wiener diversity index (H′) ranging between 2.64 and 2.98, and the broad-sense heritability ranging from 0.75 to 0.84. Correlation analysis revealed complex correlations between the traits, with 30 trait pairs being significantly correlated. Eight traits, including stalk number (SN), stalk diameter (SD), internode length (IL), stalk height (SH), stalk weight (SW), Brix (B), sucrose content (SC), and yield (Y), were significantly positively correlated with sucrose yield (SY). Cluster analysis based on the 11 traits divided the 135 F1 hybrids into three groups, with 55 hybrids in Group I, 69 hybrids in Group II, and 11 hybrids in Group III. The principal component analysis indicated that the values of the first four major components' vectors were greater than 1 and the cumulative contribution rate reached 80.93%. Based on the main component values of all samples, 24 F1 genotypes had greater values than the high-yielding parent 'ROC22' and were selected for the next breeding stage. A rapid sucrose yield estimation equation was established using four easily measured sucrose yield-related traits through multivariable linear stepwise regression. The model was subsequently confirmed using 26 sugarcane cultivars and 24 F1 hybrids. This study concludes that the sugarcane F1 population holds great genetic diversity in sucrose yield-related traits. The sucrose yield estimation model, y S Y = 2.01 x S N + 8.32 x S D + 0.79 x B + 3.44 x S H − 47.64 , can aid to breed sugarcane varieties with high sucrose yield. [ABSTRACT FROM AUTHOR]

The 26S proteasome is an ATP-dependent proteolytic complex in eukaryotes, which is mainly responsible for the degradation of damaged and misfolded proteins and some regulatory proteins in cells, and it is essential to maintain the balance of protein levels in the cell. The ubiquitin–26S proteasome pathway, which targets a wide range of protein substrates in plants, is an important post-translational regulatory mechanism involved in various stages of plant growth and development and in the maturation process of fleshy fruits. Fleshy fruit ripening is a complex biological process, which is the sum of a series of physiological and biochemical reactions, including the biosynthesis and signal transduction of ripening related hormones, pigment metabolism, fruit texture changes and the formation of nutritional quality. This paper reviews the structure of the 26S proteasome and the mechanism of the ubiquitin–26S proteasome pathway, and it summarizes the function of this pathway in the ripening process of fleshy fruits. [ABSTRACT FROM AUTHOR]

In women, ovary cancer is already the fifth leading cause of mortality worldwide. The use of cancer therapies, such as surgery, radiotherapy, and chemotherapy, may be a powerful anti-cancer therapeutic strategy; however, these therapies still have many problems, including resistance, toxicity, and side effects. Therefore, natural herbal medicine has the potential to be used for cancer therapy because of its low toxicity, fewer side effects, and high success. This study aimed to investigate the anti-cancer effect of 6-shogaol in ovarian cancer cells. 6-shogaol induces ER stress and cell death via the reduction in cell viability, the increase in LDH cytotoxicity, caspase-3 activity, and Ca2+ release, and the upregulation of GRP78, p-PERK, p-eIF2α, ATF-4, CHOP, and DR5. Moreover, 6-shogaol treatment medicates endoplasmic reticulum (ER) stress and cell death by upregulating Nox4 and releasing ROS. The knockdown of Nox4 in ovarian cancer cells inhibits ER stress and cell death by blocking the reduction in cell viability and the enhancement of LDH cytotoxicity, caspase-3 activity, Ca2+, and ROS release. In gefitinib-resistant ovarian cancer cells, A2780R and OVCAR-3R, 6-shogaol/gefitinib overcomes gefitinib resistance by inhibiting EMT phenomena such as the reduction in E-cadherin, and the increase in N-cadherin, vimentin, Slug, and Snail. Therefore, our results suggest that 6-shogaol exerts a potential anti-cancer effect in ovarian cancer and combination treatment with 6-shogaol and gefitinib may provide a novel anti-tumor therapeutic strategy in gefitinib-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]

Argonautes (AGOs) interact with microRNAs (miRNAs) to form the RNA-induced silencing complex (RISC), which can posttranscriptionally regulate the expression of targeted genes. To date, however, the AGOs and their miRNA triggers remain elusive in rapeseed (Brassica napus). Here, we systematically performed a phylogenetic analysis and examined the collinear relationships of the AGOs among four Brassicaceae species. Their physicochemical properties, gene structures, and expression patterns among 81 tissues from multiple materials and developmental stages were further analyzed. Additionally, their posttranscriptional regulation was analyzed using psRNATarget prediction, miRNA-/mRNA-Seq analyses, and a qRT-PCR verification. We finally identified 10 AtAGOs, 13 BolAGOs, 11 BraAGOs, and 24 BnaAGOs. An expression analysis of the BnaAGOs in the B. napus cultivar ZS11, as well as genotypes with extreme phenotypes in various yield-related traits, revealed the conservation and diversity of these genes. Furthermore, we speculated the posttranscriptional regulation of the B. napus miR168a–AGO1s and miR403–AGO2s modules. Combining miRNA-Seq and mRNA-Seq analyses, we found that the B. napus miR168a–AGO1s module may play an essential role in negatively regulating yield traits, whereas the miR403–AGO2s module positively impacts yield. This is the first attempt to comprehensively analyze the AGOs and their miRNA triggers in B. napus and provides a theoretical basis for breeding high-yielding varieties through the manipulation of the miRNA–AGOs modules. [ABSTRACT FROM AUTHOR]

Fecal calprotectin (FC) levels correlate with the disease activity of inflammatory bowel diseases (IBD); however, the utility of FC in predicting IBD relapse remains to be determined. We aim to evaluate the efficacy of fecal calprotectin in predicting the relapse of inflammatory bowel disease. We searched Pubmed (MEDLINE), Embase, Web of Science, and the Cochrane library databases up to 7 July 2021. Our study estimated the pooled sensitivity and specificity, summary receiver operating characteristic (SROC) curve, and the optimal cut-off value for predicting IBD relapse using a multiple threshold model. A total of 24 prospective studies were included in the meta-analysis. The optimal FC cut-off value was 152 μg/g. The pooled sensitivity and specificity of FC was 0.720 (0.528 to 0.856) and 0.740 (0.618 to 0.834), respectively. FC is a useful, non-invasive, and inexpensive biomarker for the early prediction of IBD relapse. An FC value of 152 μg/g is an ideal threshold to identify patients with a high relapse probability. [ABSTRACT FROM AUTHOR]

Simple Summary: DNA damage response (DDR)-related proteins contribute to tumorigenesis, tumor progression, and drug resistance. Pharmacological inhibition of DDR-related proteins, such as checkpoint kinase 1 (Chk1), exerts antitumor effects but has serious side effects. Therefore, we attempted to specifically kill cancer cells with low concentrations of drugs by simultaneously inhibiting two DDR-related proteins. In this study, we demonstrated that the combined treatment with ataxia telangiectasia-mutated serine/threonine kinase (ATM) inhibitor (ATMi) and Chk1 inhibitor (Chk1i) exerts synergistic antitumor effects and induces cancer-specific synthetic lethality at low doses. The ATMi and Chk1i combination synergistically promotes CDK1 activation, resulting in the induction of apoptosis with enhanced cell cycle progression in cancer cells. Considering that the combined treatment exerts antitumor effects at one-tenth the concentrations described in previous reports, with high antitumor efficacy and few side effects it could be an effective treatment approach. Genetic abnormalities induce the DNA damage response (DDR), which enables DNA repair at cell cycle checkpoints. Although the DDR is thought to function in preventing the onset and progression of cancer, DDR-related proteins are also thought to contribute to tumorigenesis, tumor progression, and drug resistance by preventing irreparable genomic abnormalities from inducing cell death. In the present study, the combination of ataxia telangiectasia-mutated serine/threonine kinase (ATM) and checkpoint kinase 1 (Chk1) inhibition exhibited synergistic antitumor effects and induced synergistic lethality in colorectal cancer cells at a low dose. The ATM and Chk1 inhibitors synergistically promoted the activation of cyclin-dependent kinase 1 by decreasing the phosphorylation levels of T14 and Y15. Furthermore, the combined treatment increased the number of sub-G1-stage cells, phospho-histone H2A.X-positive cells, and TdT-mediated dUTP nick-end labeling-positive cells among colon cancer cells, suggesting that the therapy induces apoptosis. Finally, the combined treatment exhibited a robust antitumor activity in syngeneic tumor model mice. These findings should contribute to the development of new treatments for colorectal cancer that directly exploit the genomic instability of cancer cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) ranks as one of the most life-threatening malignancies worldwide, and over one billion new cases and 783,000 deaths were reported last year. The incidence of GC is exceptionally high in Asian countries. Multiple oncogenic signaling pathways are aberrantly activated and implicated in gastric carcinogenesis, leading to the malignant phenotype acquisition. G-protein-coupled receptor (GPCR) signaling is one of them, and the aberrant activation of GPCRs and G proteins promotes GC progression. The activated GPCRs/G proteins might serve as useful biomarkers for early diagnosis, prognostic prediction, and even clinically therapeutic targets. This review summarized the recent research progress of GPCRs and highlighted their mechanisms in tumorigenesis, especially in GC initiation and progression. G-protein-coupled receptors (GPCRs) belong to a cell surface receptor superfamily responding to a wide range of external signals. The binding of extracellular ligands to GPCRs activates a heterotrimeric G protein and triggers the production of numerous secondary messengers, which transduce the extracellular signals into cellular responses. GPCR signaling is crucial and imperative for maintaining normal tissue homeostasis. High-throughput sequencing analyses revealed the occurrence of the genetic aberrations of GPCRs and G proteins in multiple malignancies. The altered GPCRs/G proteins serve as valuable biomarkers for early diagnosis, prognostic prediction, and pharmacological targets. Furthermore, the dysregulation of GPCR signaling contributes to tumor initiation and development. In this review, we have summarized the research progress of GPCRs and highlighted their mechanisms in gastric cancer (GC). The aberrant activation of GPCRs promotes GC cell proliferation and metastasis, remodels the tumor microenvironment, and boosts immune escape. Through deep investigation, novel therapeutic strategies for targeting GPCR activation have been developed, and the final aim is to eliminate GPCR-driven gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Building vertical greenery has become an effective measure to solve the contradiction between the shortage of urban greenery and the increasing demand for greenery. However, the lack of direct economic benefits dampens motivation for its development. As a vital development mode for high-density cities worldwide, commercial complexes are the most appropriate buildings to support greenery because of economic agglomeration and resource integration. An important reason for whether or not commercial complex greenery is constructed is the need for an evaluation system. To bridge this research gap, we propose a holistic evaluation guideline for commercial complex greenery. First, a list of related sustainable rating systems from the academic literature and official websites was compiled and reviewed to identify and compare their referential features. Second, the limitations of these evaluation systems in assessing the greenery of commercial complexes were explored using a case study. Third, the features of commercial complex greenery were introduced through field research and interviews. Finally, a holistic evaluation guideline for vertical greenery systems in commercial complexes was proposed, including logical thinking for the evaluation system of the dimension–indicator–quantitative method, the creation of innovative evaluation indicators, the establishment of a database, the assignment of weights to different dimensions and indicators, and the construction of an evaluation mechanism for the whole life cycle. This research demonstrates the significance of an evaluation process for commercial complex greenery systems, proposes a refined guideline for its development, and rationally grasps the development direction from a macro perspective. [ABSTRACT FROM AUTHOR]

One mononuclear Mn(III) complex [MnIIIL(H2O)(MeCN)](ClO4) (1) and one hetero-binuclear complex [(CuIILMnII(H2O)3)(CuIIL)2](ClO4)2·CH3OH (2) have been synthesized with the Schiff base ligand (H2L = N,N′-bis(3-methoxysalicylidene)-1,2-phenylenediamine). Single crystal X-ray structural analysis manifests that the Mn(III) ion in 1 has an octahedral coordination structure, whereas the Mn(II) ion in 2 possesses a trigonal bipyramidal configuration and the Cu(II) ion in 2 is four-coordinated with a square-planar geometry. Electrochimerical catalytic investigation demonstrates that the two complexes can electrochemically catalyze water oxidation and CO2 reduction simultaneously. The coordination environments of the Mn(III), Mn(II), and Cu(II) ions in 1 and 2 were provided by the Schiff base ligand (L) and labile solvent molecules. The coordinately unsaturated environment of the Cu(II) center in 2 can perfectly facilitate the catalytic performance of 2. Complexes 1 and 2 display that the over potentials for water oxidation are 728 mV and 216 mV, faradaic efficiencies (FEs) are 88% and 92%, respectively, as well as the turnover frequency (TOF) values for the catalytic reduction of CO2 to CO are 0.38 s−1 at −1.65 V and 15.97 s−1 at −1.60 V, respectively. Complex 2 shows much better catalytic performance for both water oxidation and CO2 reduction than that of complex 1, which could be owing to a structural reason which is attributed to the synergistic catalytic action of the neighboring Mn(III) and Cu(II) active sites in 2. Complexes 1 and 2 are the first two compounds coordinated with Schiff base ligand for both water oxidation and CO2 reduction. The finding in this work can offer significant inspiration for the future development of electrocatalysis in this area. [ABSTRACT FROM AUTHOR]

Dense planting effectively increases maize yield while increasing stalk lodging risk. Appropriate row spacing can improve the maize population structure and stalk lodging resistance, but its physiological ecological mechanisms and interaction with planting density are unclear. Here, a two-year field experiment to determine the joint effects of row spacing and planting density on maize stem characteristics and the quantitative relationship of the light condition within a maize population with stalk lodging resistance indicated that the stalk mechanical strength showed a quadratic function relationship with photosynthetically active radiation (PAR), whereas the lodging rate showed an exponential function relationship with basal light transmittance (LT). Further, the basal LT was significantly positively correlated with basal internode thickness, dry weight per unit stem length (DWUL), mechanical and cortical tissue thickness, and lignin and cellulose contents. Increasing the planting density decreased the basal LT and PAR; correspondingly decreased the basal internode thickness, DWUL, mechanical and cortical tissue thickness, lignin and cellulose contents, and stalk mechanical strength; and increased the lodging rate, while increasing row spacing did the opposite. Thus, optimizing the row spacing enhanced the lodging resistance through LT and PAR improvement of the lower part of the population and further increased the grain yield by optimizing the yield components. The appropriate row spacing varied with the planting density. The proper strategy for high stalk lodging resistance and grain yielding under this experimental condition was 67,500 plants ha−1 density with 60 + 60 cm equal row spacing. [ABSTRACT FROM AUTHOR]

In recent years, due to the global energy crisis, increasingly more countries have recognized the importance of developing clean energy. Offshore wind energy, as a basic form of clean energy, has become one of the current research priorities. In the future, offshore wind farms will be developed in deep and distant sea areas. In these areas, there is a new trend of floating offshore wind platforms replacing fixed wind power platforms, due to their low cost, ease of installation, and independence from the water depth. However, the stability of offshore floating platforms is poor and their power fluctuations are significant; furthermore, they are more prone to failure because of sea wind, waves, and currents. This paper summarizes and analyzes the current research progress and critical technical issues of offshore floating wind power generation, such as stability control technology, integrated wind storage technology, wind power energy management, and long-distance transmission of electricity for floating wind power generation at sea. Finally, future research directions for key offshore wind power technologies are presented. [ABSTRACT FROM AUTHOR]

Improving bonding and mechanical strengths is important for the application of bond coats used in the construction of steel deck bridges. Graphene nanoplatelets (GNPs) are attractive nanofillers for polymer modification because of their low cost, ultra-high aspect ratio, and extraordinary thermal and mechanical performance. In this paper, GNPs were used to reinforce the epoxy asphalt bond coat (EABC). The morphology, viscosity–time behavior, contact angle, dynamic mechanical properties, and mechanical and bonding strengths of GNP-reinforced EABCs were investigated using laser confocal microscopy, a Brookfield rotational viscometer, a contact angle meter, dynamic mechanical analysis, a universal test machine, and single-lap shear and pull-off adhesion tests. GNP dispersed non-uniformly in the asphalt phase of EABC. The viscosity of the neat EABC was lowered with the inclusion of GNPs and thus the allowable construction time was extended. The existence of GNPs enhances the hydrophobicity of the neat EABC. When adding more than 0.2% GNP, the storage modulus, crosslinking density and glass transition temperatures of both asphalt and epoxy of the neat EABC increased. The mechanical and bonding properties of the neat EABC were greatly enhanced with the incorporation of GNPs. Furthermore, the mechanical and bonding strengths of the modified EABCs increased with the GNP content. GNP-reinforced EABCs can be utilized in the pavement of long-span steel bridges with long durability. [ABSTRACT FROM AUTHOR]

(1) Background: Scopoletin and scoparone, two naturally occurring coumarins, have garnered considerable attention and have been introduced to the market in China due to their high insecticidal efficacy and low toxicity. To investigate the structure–activity relationship of these coumarins, a series of scopoletin derivatives with aryl sulfate at C7 and different substitutes at C3 were designed and synthesized, and their insecticidal activity was studied. (2) Methods: A total of 28 new scopoletin derivatives were designed and synthesized. Most target compounds exhibited moderate insecticidal activity against the phytophagous mite Tetranychus cinnabarinus and the brine shrimp Artemia salina. (3) Results: Among these compounds, compounds 5a and 5j possessed the best insecticidal activities against T. cinnabarinus, with LC50 values of 57.0 and 20.0 μg/mL, respectively, whereas that of the control drug was 15.0 μg/mL. Compound 4j exhibited selective insecticidal activities against A. salina, with an LC50 value of 9.36 μg/mL, whereas its LC50 value against T. cinnabarinus was 93.0 μg/mL. The enzymatic inhibitory activity on acetylcholinesterase (AChE) showed a consistent tendency with the insecticidal activity. Further molecular docking analyses predicted the binding conformations of these compounds, which showed a good correlation between the insecticidal activity and the binding scores. (4) Conclusions: In general, a decreased electron cloud density of the Δ3,4 olefinic bond is beneficial for improving the insecticidal activity against both T. cinnabarinus and A. salina. In addition, naphthyl or benzene groups with a sulfate ester at the C7 position could further improve the insecticidal activity against A. salina. AChE was implied to be a site of action for potential insecticidal activity. The results provide insight into the rational design of a new generation of effective coumarin insecticides. [ABSTRACT FROM AUTHOR]

In this paper, a control method of a novel tilt-rotor UAV with a blended wing body layout is studied. The novel UAV is capable of vertical take-off and landing and has strong stealth capabilities that can be applied to carrier-borne reconnaissance aircraft. However, the high aspect ratio of blended wing body UAVs leads to a wingtip or oar-tip touchdown problem when adopting the conventional position-attitude control (CPAC) scheme with a large crosswind disturbance. Moreover, when the UAV is subject to interference during reconnaissance, aerial photography, and landing missions, the conventional scheme cannot provide both attitude stability and track accuracy. First, a direct thrust vectoring control (DTVC) scheme is proposed. The control authority of the rotor tilt mechanism was added to enable the decoupling of the attitude and trajectory and to improve the response rate and response bandwidth of the flight trajectory. Second, considering the problems of strong couplings and parameter uncertainties and the nonlinear features and mismatched perturbations that are inevitable in the tilt-rotor, we designed a robust UAV controller based on the backstepping sliding mode control method and determined the stability of the control system through the Lyapunov function. Finally, in the case of crosswire interference during vertical takeoff and landing and the aerial photography missions of the UAV, the numerical simulation of the CPAC scheme and the DTVC scheme was carried out, respectively, and the Monte Carlo random test method was introduced to conduct the statistical test of the landing accuracy. The simulation results show that the DTVC scheme improves the landing accuracy and speed compared to the CAPC scheme and decouples the position control loop from the attitude control loop, finally enabling the UAV to complete the flight control in the VTOL phase. [ABSTRACT FROM AUTHOR]

Digital images have unique features that include being both easily transmittable over the Internet and being easy to tamper. With the advancement of digital processing techniques and an increasing number of valuable digital images being transmitted via the Internet, image authentication has been made more crucial than ever. In this paper, we present an image authentication scheme with tamper localization and self-recovery using fragile watermarking. We embed the fragile watermarks consisting of the authentication code and the recovery information onto the image to verify its integrity. The proposed fragile watermarking scheme can authenticate the image without accessing the original image, localizing the modifications as well as verifying the integrity, and even reconstructing the tampered regions. We use an AMBTC compressed code as the authentication code to minimize the distortion introduced by embedding. To reduce the blocking effect that occurs in the reconstructed image, a VQ compressed code is applied instead of the average intensity as the recovery information. Several representative test images and 200 different test images were randomly selected from BOWS to examine the performance of the proposed scheme. Experimental results confirm that the proposed scheme can effectively resist a cutting attack and a copy-paste attack while retaining the high accuracy of tamper localization. The average TPR and average FTP rate were around 97% and 0.12%, respectively, while maintaining the image quality of the watermarked image and restoring the image at up to 48 dB and 39.28 dB, respectively. [ABSTRACT FROM AUTHOR]

The North Qaidam Orogenic Belt (NQOB) is characterized by widespread Palaeozoic magmatism and high to ultrahigh-pressure metamorphism that provides important information regarding the continental crust growth and tectonic evolution in the North Qaidam. Our work focuses on the geology, geochronology, whole-rock geochemistry, and Sr–Nd isotopy of granitoids in the Tanjianshan area in the northern NQOB. The results indicate that the 486–469 Ma adakitic and TTG-like granitoids originated from the partial melting of Middle–Late Mesoproterozoic lower crustal materials with the addition of juvenile mafic lower crust at high pressures under an active continental margin setting. The 396–392 Ma I-type granitoids originated from the partial melting of juvenile crustal materials with the addition of ancient crustal component in a post-collisional setting. Geochronological studies show that there are significant regional differences in magmatism between the northern and rest parts of the NQOB. In the northern part, extensive and prolonged magmatism was widespread during oceanic subduction (~526–460 Ma) and post-collisional extension (~420–350 Ma) but magmatism in the stage of orogenic collision was absent. The Early Palaeozoic adakitic magmatism suggest a significant continental crustal reworking in a subduction zone during 486–469 Ma along the NQOB. The initial oceanic subduction may have occurred prior to ca. 526 Ma. An intense and multiple-stage extension developed at ~420–350 Ma in the northern part of the NQOB following the orogenic collapse. Lithospheric delamination and subsequent mafic magma underplating may be the main geodynamic mechanism resulting in the uprooting of the continental crust and ore mineralization in response. [ABSTRACT FROM AUTHOR]

Obesity has emerged as a major public health concern with a staggering 39% worldwide prevalence as of 2021. Given the magnitude of the problem and considering its association with chronic low-grade systemic inflammation, it does not come as a surprise that obesity is now considered one of the major risk factors for the development of several chronic diseases, such as diabetes, cardiovascular problems, and cancer. Adipose tissue dysfunction in obesity has taken center stage in understanding how changes in its components, particularly adipocytes and macrophages, participate in such processes. In this review, we will initially focus on how changes in adipose tissue upon excess fat accumulation generate endocrine signals that promote cancer development. Moreover, the tumor microenvironment or stroma, which is also critical in cancer development, contains macrophages and adipocytes, which, in reciprocal paracrine communication with cancer cells, generate relevant signals. We will discuss how paracrine signaling in the tumor microenvironment between cancer cells, macrophages, and adipocytes favors cancer development and progression. Finally, as reactive oxygen species participate in many of these signaling pathways, we will summarize the information available on how antioxidants can limit the effects of endocrine and paracrine signaling due to dysfunctional adipose tissue components in obesity. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer is a major cause of death worldwide. The major challenges associated with the conventionally used treatment modalities include the recurrence of the cancer and the adverse effects of the chemotherapeutic drugs. Natural products play a very important role in drug discovery and have potential effects against various cancers in general and oral cancer in particular. The major problem with natural products is their poor bioavailability, which limits their therapeutic application. Therefore, an attempt is made to comprehensively utilize various formulation strategies that can help in improving the bioavailability of various anticancer natural compounds. In this work, we have presented recent advancements in novel strategies for natural product delivery that lead to the significant enhancement of bioavailability, in vivo activity, and fewer adverse events for the prevention and treatment of oral cancer. Oral cancer is emerging as a major cause of mortality globally. Oral cancer occupies a significant proportion of the head and neck, including the cheeks, tongue, and oral cavity. Conventional methods in the treatment of cancer involve surgery, radiotherapy, and immunotherapy, and these have not proven to completely eradicate cancerous cells, may lead to the reoccurrence of oral cancer, and possess numerous adverse side effects. Advancements in novel drug delivery approaches have gained popularity in cancer management with an increase in the number of cases associated with oral cancer. Natural products are potent sources for drug discovery, especially for anticancer drugs. Natural product delivery has major challenges due to its low solubility, poor absorption, inappropriate size, instability, poor permeation, and first-pass metabolism. Therefore, it is of prime importance to investigate novel treatment approaches for the delivery of bioactive natural products. Nanotechnology is an advanced method of delivering cancer therapy with minimal damage to normal cells while targeting cancer cells. Therefore, the present review elaborates on the advancements in novel strategies for natural product delivery that lead to the significant enhancement of bioavailability, in vivo activity, and fewer adverse events for the prevention and treatment of oral cancer. Various approaches to accomplish the desired results involve size reduction, surface property modification, and polymer attachment, which collectively result in the higher stability of the formulation. [ABSTRACT FROM AUTHOR]

Under corrosive environments, concrete material properties can deteriorate significantly, which can seriously affect structural safety. Therefore, it has important engineering applications to improve the durability performance at a lower economic cost. This paper proposes a new, highly durable concrete using inexpensive construction materials such as basalt fiber, sodium methyl silicate, and inorganic aluminum salt waterproofing agent. With the massive application of sewage treatment projects, the problem of concrete durability degradation is becoming more and more serious. In this paper, five types of concrete are developed for the sewage environment, and the apparent morphology and fine structure of the specimens after corrosion in sewage were analyzed. The density, water absorption, and compressive strength were measured to investigate the deterioration pattern of concrete properties. It was found that ordinary concrete was subject to significant corrosion, generating large deposits of algae on the surface and accompanied by sanding. The new concrete showed superior corrosion resistance compared to conventional concrete. Among other factors, the inorganic aluminum salt waterproofing agent effect was the most prominent. The study found that the strength of ordinary concrete decreased by about 15% in the test environment, while the new concrete had a slight increase. Comprehensive evaluation showed that the combination of basalt fiber and inorganic aluminum salt waterproofing agent had the best effect. Its use is recommended. [ABSTRACT FROM AUTHOR]

Snf5 (sucrose nonfermenting) is a core component of the SWI/SNF complexes and regulates diverse cellular processes in model eukaryotes. In plant pathogenic fungi, its biological function and underlying mechanisms remain unexplored. In this study, we investigated the biological roles of MoSnf5 in plant infection and fungal development in the rice blast pathogen Magnaporthe oryzae. The gene deletion mutants of MoSNF5 exhibited slower vegetative hyphal growth, severe defects in conidiogenesis, and impaired virulence and galactose utilization capacities. Domain dissection assays showed that the Snf5 domain and the N- and C-termini of MoSnf5 were all required for its full functions. Co-immunoprecipitation and yeast two-hybrid assays showed that MoSnf5 physically interacts with four proteins, including a transcription initiation factor MoTaf14. Interestingly, the ∆MoTaf14 mutants showed similar phenotypes as the ∆Mosnf5 mutants on fungal virulence and development. Moreover, assays on GFP-MoAtg8 expression and localization showed that both the ∆Mosnf5 and ∆MoTaf14 mutants were defective in autophagy. Taken together, MoSnf5 regulates fungal virulence, growth, and conidiation, possibly through regulating galactose utilization and autophagy in M. oryzae. [ABSTRACT FROM AUTHOR]

The properties and oxidation wear patterns in the composite nanostructured coating of Zr-ZrN-(Zr,Mo,Al)N were studied during the turning of Inconel 718 alloy at the cutting speeds of vc = 125 and 200 m/min. The hardness of the coating, its elastic modulus, and critical fracture load during the scratch testing were determined. The study focused on the tribological properties of the Zr-ZrN-(Zr,Mo,Al)N coating at temperatures of 400–900 °C paired with an insert made of Inconel 718, which exhibited a certain advantage over the reference coatings of Zr-ZrN and Ti-TiN-(Ti,Cr,Al)N of similar thickness. The coating of Zr-ZrN-(Zr,Mo,Al)N provided for the longest tool life at the cutting speed of vc = 125 m/min (the tool life was four times longer in comparison with that of the uncoated tool and 15% longer in comparison with that of the Ti-TiN-(Ti,Cr,Al)N-coated tool) and at the cutting speed of vc = 200 m/min (the tool life was 2.5 times longer in comparison with that of the uncoated tool and 75% longer in comparison with that of the Ti-TiN-(Ti,Cr,Al)N-coated tool). While at the cutting speed of vc = 125 m/min, the surface coating layers exhibit only partial oxidation of the external layers (to a depth not exceeding 250 nm), with mostly preserved cubic nitride phases, and then the cutting speed of vc = 200 m/min leads to almost complete oxidation (to the depth of at least 500 nm), however, with a partially preserved nanolayered structure of the coating. [ABSTRACT FROM AUTHOR]

According to different working environments and functional requirements, radial magnetic bearings (RMBs) have various design methods. Some methods' lack of effectiveness or accuracy is likely to cause significant differences in the structural performance of magnetic bearings, which will cause serious problems such as limited bearing capacity and complex control. This paper analyzes the structure topology of a magnetic bearing according to the application scenario of RMBs, then proposes a general design example of an 8-pole magnetic bearing based on magnetic circuit analysis and reveals the linearity between electromagnetic force and current as well as air gap through finite element analysis and the influence of magnetic saturation on the load capacity of the magnetic bearing structure. After completing the preliminary design, we further optimize the structure, take the genetic algorithm as an example to iterate the influence coefficient, and summarize and prospect. The design scheme and optimization method proposed in this paper only provide a valuable reference for researchers and factories when devising RMB devices. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells commonly escape cell death and proliferate endlessly. We review the molecular mechanisms that are fundamental to this process and suggest that these changes also lead to instability in the genetic make-up (genes and chromosomes) of putative cancer cells. In this way, cells in the very early stages of cancer development acquire unlimited growth potential and also develop cellular diversity, which may facilitate more aggressive cell behaviour and the development of overt cancer. These observations have important clinical implications. We highlight a recent sensitive technique to detect chromosome instability in cells that are shed into the saliva, which can be used for the detection of the early stages of cancer of the mouth. In addition, we discuss new drug developments that are designed to target chromosome instability and, therefore, eliminate potentially dangerous cells before cancer development. An escape from cellular senescence through the development of unlimited growth potential is one of the hallmarks of cancer, which is thought to be an early event in carcinogenesis. In this review, we propose that the molecular effectors of senescence, particularly the inactivation of TP53 and CDKN2A, together with telomere attrition and telomerase activation, all lead to aneuploidy in the keratinocytes from oral potentially malignant disorders (OPMD). Premalignant keratinocytes, therefore, not only become immortal but also develop genotypic and phenotypic cellular diversity. As a result of these changes, certain clonal cell populations likely gain the capacity to invade the underlying connective tissue. We review the clinical implications of these changes and highlight a new PCR-based assay to identify aneuploid cell in fluids such as saliva, a technique that is extremely sensitive and could facilitate the regular monitoring of OPMD without the need for surgical biopsies and may avoid potential biopsy sampling errors. We also draw attention to recent studies designed to eliminate aneuploid tumour cell populations that, potentially, is a new therapeutic approach to prevent malignant transformations in OPMD. [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) is a powerful tool that post-transcriptionally silences target genes in eukaryotic cells. However, silencing efficacy varies greatly among different insect species. Recently, we met with little success when attempting to knock down genes in the mirid bug Apolygus lucorum via dsRNA injection. The disappearance of double-stranded RNA (dsRNA) could be a potential factor that restricts RNAi efficiency. Here, we found that dsRNA can be degraded in midgut fluids, and a dsRNase of A. lucorum (AldsRNase) was identified and characterized. Sequence alignment indicated that its 6 key amino acid residues and the Mg 2+ -binding site were similar to those of other insects' dsRNases. The signal peptide and endonuclease non-specific domain shared high sequence identity with the brown-winged green stinkbug Plautia stali dsRNase. AldsRNase showed high salivary gland and midgut expression and was continuously expressed through the whole life cycle, with peaks at the 4th instar ecdysis in the whole body. The purified AldsRNase protein obtained by heterologously expressed can rapidly degrade dsRNA. When comparing the substrate specificity of AldsRNase, 3 specific substrates (dsRNA, small interfering RNA, and dsDNA) were all degraded, and the most efficient degradation is dsRNA. Subsequently, immunofluorescence revealed that AldsRNase was expressed in the cytoplasm of midgut cells. Through cloning and functional study of AldsRNase, the enzyme activity and substrate specificity of the recombinant protein, as well as the subcellular localization of nuclease, the reason for the disappearance of dsRNA was explained, which was useful in improving RNAi efficiency in A. lucorum and related species., (© 2023 Institute of Zoology, Chinese Academy of Sciences.)

RNA interference (RNAi) is a form of gene silencing triggered by double-stranded RNA (dsRNA) that operates in all eukaryotic cells. RNAi has been widely investigated in insects to determine the underlying molecular mechanism, to investigate its role in systemic antiviral defense, and to develop strategies for pest control. When insect cells are infected by viruses, viral dsRNA signatures trigger a local RNAi response to block viral replication and generate virus-derived DNA that confers systemic immunity. RNAi-based insect pest control involves the application of exogenous dsRNA targeting genes essential for insect development or survival, but the efficacy of this approach has limited potency in many pests through a combination of rapid dsRNA degradation, inefficient dsRNA uptake/processing, and ineffective RNAi machinery. This could be addressed by dsRNA screening and evaluation, focusing on dsRNA design and off-target management, as well as dsRNA production and delivery. This review summarizes recent progress to determine the role of RNAi in antiviral defense and as a pest control strategy in insects, addressing gaps between our fundamental understanding of the RNAi mechanism and the exploitation of RNAi-based pest control strategies., (© 2023 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.)

Marine fungi can metabolize structurally diverse active components, and have become an important source of drug lead molecules. In the present study, the chemical investigation on the EtOAc extract of the fermentation broth of the marine-derived fungus Trametes sp. ZYX-Z-16 led to the isolation of eight meroterpenoids (1–8), including two undescribed ones, together with ten ergostane steroid analogues (9–18). The structures of two new spiromeroterpenoids, asnovolin H (1) and asnovolin I (2), were determined based on 1D, 2D NMR, and HRESIMS spectroscopic data along with ECD spectra calculations. All compounds were tested for antibacterial and α-glucosidase inhibitory activity. Among them, compound 12 showed definite antibacterial activities against Staphylococcus aureus ATCC 6538 (MIC 32 μg/mL) and Bacillus subtilis ATCC 6633 (MIC 16 μg/mL). In addition, compounds 9 and 10 showed superior inhibitory activity, with IC50 values of 104.1 and 111.3 μM, respectively, to the positive control acarbose (304.6 μM). [ABSTRACT FROM AUTHOR]

Inconel 718 is a well-known nickel-based superalloy used for high-temperature applications. The aim of the present study was to formulate a constitutive equation (CE) that can be used to account for the deformation behavior of Inconel 718. Compression tests were performed using Gleeble 3800, a thermomechanical simulator, at temperatures ranging from 900 to 1200 °C, at strain rates varying from 0.1 to 10/s. Before compression tests, each specimen was rapidly heated to the desired test temperature while the initial contact pressure was kept relatively low. Thus, compression was performed while the temperature of the entire system, including the specimen and the die, was not uniform. Before conducting an upsetting finite element analysis to determine CE parameters, the heating conditions applied in the Gleeble tests were first subjected to a Joule heating analysis, to simulate the temperature distribution in each specimen prior to the compression process. The spatial temperature distribution of the specimen and the die were determined using a Joule heating analysis, and these results were used as input data for the subsequent finite element analysis of the compression process. From this, the parameters in the obtained Hansel–Spittel equation were estimated for each temperature condition, by employing the regression optimization method, which was used to minimize the deviation between experimental and simulated load values. To validate this optimization process, the experimentally measured flow stresses with respect to the strain rate for each temperature condition were compared with the forming load, determined by the finite element analysis of the compression process using the optimized CE obtained in the present study. It was confirmed that when the optimization process was applied, there was a decrease in the root mean square error. The major findings confirmed the validity of the CE optimization method combined with Joule heating analysis for determining the CE's parameters for high-temperature applications. [ABSTRACT FROM AUTHOR]

Adjusting the focal length by changing the liquid interface of the liquid lens has become a potential method. In this paper, the lattice-Boltzmann-electrodynamic (LB-ED) method is used to numerically investigate the zooming process of a movable and focus-tunable electrowetting-on-dielectrics (EWOD) liquid lens by combining the LBM chemical potential model and the electrodynamic model. The LB method is used to solve the Navier–Stokes equation, and the Poisson–Boltzmann (PB) equation is introduced to solve the electric field distribution. The experimental results are consistent with the theoretical results of the Lippmann–Young equation. Through the simulation of a liquid lens zoom driven by EWOD, it is found that the lens changes from a convex lens to a concave lens with the voltage increases. The focal length change rate in the convex lens stage gradually increases with voltage. In the concave lens stage, the focal length change rate is opposite to that in the convex lens stage. During the zooming process, the low-viscosity liquid exhibits oscillation, and the high-viscosity liquid appears as overdamping. Additionally, methods were proposed to accelerate lens stabilization at low and high viscosities, achieving speed improvements of about 30% and 50%, respectively. Simulations of lens motion at different viscosities demonstrate that higher-viscosity liquids require higher voltages to achieve the same movement speed. [ABSTRACT FROM AUTHOR]

A method based on fluid–structure coupling is used in this study to calculate the response of a rocket fairing as it is falling. Some cases of vibration divergence of the fairing were found, and the influence of some specific factors was analyzed. The aerodynamic forces are calculated by using computational fluid dynamics (CFD) software and the structural responses by the modal-superposition method. The data are then subjected to modal interpolation in the CFD solver for the next cycle of calculation. The dynamic pressure, Mach number, and angle of attack are fixed in this process. Given that the fairing has a fixed attitude during falling, its rotation is ignored in calculations for the simulation. The results are then used to propose a framework for the fluid–structure coupling-based analysis of a non-streamlined structure. The mechanism of the fairing is discussed based on this method, and the effects of the settings of the solver, Mach number, dynamic pressure, and structural stiffness on it are investigated. Dangerous and safe regions are identified as the fairing falls back to the ground. Three methods are then provided based on the above analysis to prevent damage to the fairing as it falls to ground, such as increasing structure rigidity, attitude control, and opening the parachute at high altitude. A comprehensive method was used to suppress the vibration of the fairing during the descent, which was proven to be effective. [ABSTRACT FROM AUTHOR]

Both aldosterone and arginine vasopressin (AVP) are produced in the heart and may participate in cardiac fibrosis. However, their relationship remains unknown. This study aims to demonstrate the regulation and role of AVP in aldosterone synthesis in the heart. Rats were subjected to a sham operation or myocardial infarction (MI) by ligating the coronary artery. Cardiac function and fibrosis were assessed using echocardiography and immunohistochemical staining, respectively. In addition, the effects of AVP stimulation on cardiac microvascular endothelial cells (CMECs) were studied using ELISA, real-time PCR, and Western blotting. Compared with the rats having undergone a sham operation, the MI rats had an increased LVMI, type I collagen composition, and concentrations of aldosterone and AVP in the heart but decreased cardiac function. As the MI rats aged, the LVMI, type I collagen, aldosterone, and AVP increased, while the LVMI decreased. Furthermore, AVP time-dependently induced aldosterone secretion and CYP11B2 mRNA expression in CMECs. The p-CREB levels were significantly increased by AVP. Nevertheless, these effects were completely blocked by SR49059 or partially inhibited by KN93. This study demonstrated that AVP could induce the secretion of local cardiac aldosterone, which may involve CaMK and CREB phosphorylation and CYP11B2 upregulation through V1 receptor activation. [ABSTRACT FROM AUTHOR]

China has the largest sweet potato planting area worldwide, as well as the highest yield per unit area and total yield. Drought is the most frequently encountered environmental stress during the sweet potato growing season. In this study, we investigated salicylic acid (SA)-mediated defense mechanisms under drought conditions in two sweet potato varieties, Zheshu 77 and Zheshu 13. Drought stress decreased growth traits, photosynthetic pigments and relative water contents, as well as the photosynthetic capability parameters net photosynthetic rate, stomatal conductance and transpiration rate, whereas it increased reactive oxygen species production, as well as malondialdehyde and abscisic acid contents. The application of SA to drought-stressed plants reduced oxidative damage by triggering the modulation of antioxidant enzyme activities and the maintenance of optimized osmotic environments in vivo in the two sweet potato varieties. After SA solution applications, NCED-like3 expression was downregulated and the abscisic acid contents of drought-stressed plants decreased, promoting photosynthesis and plant growth. Thus, foliar spraying an appropriate dose of SA, 2.00–4.00 mg·L−1, on drought-stressed sweet potato varieties may induce resistance in field conditions, thereby increasing growth and crop yield in the face of increasingly frequent drought conditions. [ABSTRACT FROM AUTHOR]

Glymphatic dysfunction has been linked to cognitive decline in several neurodegenerative diseases. In cerebral small vessel disease (CSVD), the mechanism of white matter hyperintensities (WMH)-related cognitive impairment (CI) is still under investigation. The diffusion tensor image (DTI) analysis along the perivascular space (ALPS) method has been considered to be a reliable parameter to evaluate glymphatic function. Therefore, we applied the ALPS-index to determine the influence of glymphatic function on CI in CSVD. In total, 137 CSVD patients (normal cognitive group, mild CI group, and dementia group) and 52 normal controls were included in this study. The ALPS-index was calculated based on the DTI. Correlation analyses and mediation analysis were conducted to examine the relationship between glymphatic function and cognition. Remarkable differences in the ALPS-index were observed between subjects with and without CI. The ALPS-index was negatively correlated with age, WMH volume, and general cognitive function in all CSVD patients. In the mild CI group, the ALPS-index was independently positively related to episodic memory, and mediated the relationship between WMH volume and episodic memory. In conclusion, the ALPS-index is a potential marker for early recognition of CI in CSVD. Glymphatic dysfunction mediates the relationship between WMH and CI in CSVD. [ABSTRACT FROM AUTHOR]

Lung cancer is considered the most commonly diagnosed cancer and one of the leading causes of death globally. Despite the responses from small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients to conventional chemo- and radiotherapies, the current outcomes are not satisfactory. Recently, novel advances in DNA sequencing technologies have started to take off which have provided promising tools for studying different tumors for systematic mutation discovery. To date, a limited number of DDR inhibition trials have been conducted for the treatment of SCLC and NSCLC patients. However, strategies to test different DDR inhibitor combinations or to target multiple pathways are yet to be explored. With the various biomarkers that have either been recently discovered or are the subject of ongoing investigations, it is hoped that future trials would be designed to allow for studying targeted treatments in a biomarker-enriched population, which is defensible for the improvement of prognosis for SCLC and NSCLC patients. This review article sheds light on the different DNA repair pathways and some of the inhibitors targeting the proteins involved in the DNA damage response (DDR) machinery, such as ataxia telangiectasia and Rad3-related protein (ATR), DNA-dependent protein kinase (DNA-PK), and poly-ADP-ribose polymerase (PARP). In addition, the current status of DDR inhibitors in clinical settings and future perspectives are discussed. [ABSTRACT FROM AUTHOR]

The assessment of posture and asymmetries is common in musculoskeletal clinical practice, and correction is a frequent goal. In this setting, posture and asymmetries are usually interpreted in terms of musculoskeletal issues. This study aimed to evaluate spinal asymmetries in case studies of unilateral nephroptosis. A systematic review was performed using PubMed, CINAHL, Scopus and Web of Science. We included case reports and case series of nephroptotic patients which showed diagnostic imaging that allowed us to assess the presence of spinal asymmetries in the frontal plane. The methodological quality of the selected studies was assessed by using Case Report (CARE) checklist. Nineteen studies were included, with a total number of 78 reported patients (69 women) ranging 22 to 44 years old (mean: 29). Only one patient presented with medial nephroptosis, while the rest presented with caudal migration. Ninety-one percent of the cases affected to the right kidney. All cases but two showed homolateral flank closure (lower rib descent, iliac crest raise and/or homolateral side-bending). The correction of nephroptosis, either by supine position or surgical treatment, removed asymmetries in some cases while other cases improved only partly. Manual therapists must consider visceral implications while assessing body posture. Further, since the most common symptom of nephroptosis is loin pain, and it has been claimed that loin pain is underdiagnosed, manual therapists should consider its potential presence during clinical practice. Finally, being that nephroptosis shares several features with idiopathic lumbar scoliosis (type of patient, postural adaptation), more research is needed regarding any possible relation between them. [ABSTRACT FROM AUTHOR]

Selenium (Se) and fish oil (FO) exert anti-epidermal growth factor receptor (EGFR) action on tumors. This study aimed to compare the anti-cancer efficacy of EGFR inhibitors (gefitinib and erlotinib) alone and in combination with nutritional supplements of Se/FO in treating lung cancer. Lewis LLC1 tumor-bearing mice were treated with a vehicle or Se/FO, gefitinib or gefitinib plus Se/FO, and erlotinib or erlotinib plus Se/FO. The tumors were assessed for mRNA and protein expressions of relevant signaling molecules. Untreated tumor-bearing mice had the lowest body weight and highest tumor weight and volume of all the mice. Mice receiving the combination treatment with Se/FO and gefitinib or erlotinib had a lower tumor volume and weight and fewer metastases than did those treated with gefitinib or erlotinib alone. The combination treatment exhibited greater alterations in receptor signaling molecules (lower EGFR/TGF-β/TβR/AXL/Wnt3a/Wnt5a/FZD7/β-catenin; higher GSK-3β) and immune checkpoint molecules (lower PD-1/PD-L1/CD80/CTLA-4/IL-6; higher NKp46/CD16/CD28/IL-2). These mouse tumors also had lower angiogenesis, cancer stemness, epithelial to mesenchymal transitions, metastases, and proliferation of Ki-67, as well as higher cell cycle arrest and apoptosis. These preliminary results showed the Se/FO treatment enhanced the therapeutic efficacies of gefitinib and erlotinib via modulating multiple signaling pathways in an LLC1-bearing mouse model. [ABSTRACT FROM AUTHOR]

Acer L. species are well known as ornamental trees due to their colourful leaves in autumn season. Acer pictum subsp. mono (Maxim.) H. Ohashi (APM) and Acer tataricum subsp. ginnala (Maximowicz) Wesmael (ATG) form leaves with completely different colours in autumn, yellow and red, respectively. In response to this phenomenon, we investigated the metabolic regulation of APM and ATG in different seasons by combining metabolomics, ionomics, the antioxidant system and pigment content. The results showed that the process of senescence and discolouration exists in leaves of different Acer species, and the regulatory strategy shows species specificity. Compared with green leaves, the accumulation of primary metabolites in autumn leaves of APM was extensively depleted, chlorophyll content was decreased, and antioxidant enzymes and C6C3C6 type phenolic compounds synergistically enhanced the antioxidant capacity of plants to cope with senescence. Carotenoid content was raised, which together with phenolic compounds (chlorogenic acid, rutin) provides the leaves with a yellow colour. The response of chlorophyll and the antioxidant system in autumn leaves of ATG is consistent with that of APM, while sugar content increases. The increased anthocyanin content in autumn leaves of ATG explains the transition of leaves from green to the red colour, which may be accompanied by the combined effect of elements (Fe, Zn, Mn) and isoflavones. This study provides a reference for the study of colouration mechanism and seasonal adaptation in Acer L. species. [ABSTRACT FROM AUTHOR]

Simple Summary: The study was the first to screen seven genes and identify the set of genes using twelve machine learning algorithms that predict the progression from oral leukoplakia to oral squamous cell carcinoma. We verified these genes by RT-qPCR experiments and speculated on the possible molecular mechanisms through the results. These genes could be used as biomarkers for early diagnosis and predicting patients with a high risk of malignant transformation. This will aid in early intervention, improve the patient prognosis, and reduce the incidences of oral squamous cell carcinoma. The aim of the study is to identify key genes during the progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC) and predict effective diagnoses. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were performed to identify seven genes associated with the progression from OL to OSCC. Twelve machine learning algorithms including k-nearest neighbor (KNN), neural network (NNet), and extreme gradient boosting (XGBoost) were used to construct multi-gene models, which revealed that each model had good diagnostic efficacy. The functional mechanism or the pathways associated with these genes were evaluated using enrichment analysis, subtype clustering, and immune infiltration analysis. The enrichment analysis revealed that the genes enriched were associated with the cell cycle, cell division, and intracellular energy metabolism. The immunoassay results revealed that the genes primarily affected the infiltration of proliferating T cells and macrophage polarization. Finally, a nomogram and Kaplan–Meier survival analysis were used to predict the prognostic efficacy of key genes in OSCC patients. The results showed that genes could predict the prognosis of the patients, and patients in the high-risk group had a poor prognosis. Our study identified that the seven key genes, including DHX9, BCL2L12, RAD51, MELK, CDC6, ANLN, and KIF4A, were associated with the progression from OL to OSCC. These genes had good diagnostic efficacy and could be used as potential biomarkers for the prognosis of OSCC patients. [ABSTRACT FROM AUTHOR]

This article discusses the specific application features of end mills with Ti-TiN-(Ti,Cr,Al)N, Zr-ZrN-(Zr,Mo,Al)N, and ZrHf-(Zr,Hf)N-(Zr,Hf,Cr,Mo,Al)N multilayer nanocomposite coatings during the machining of the Inconel 718 nickel–chromium alloy. The hardness, fracture resistance during scratch testing, structure, and phase composition of the coatings were studied. The tribological properties of the samples were compared at temperatures of 400–900 °C. Tests were conducted to study the wear resistance of the coated end mills during the milling of the Inconel 718 alloy. The wear mechanism of the end mills was studied. It was found that in comparison with the other coatings, the Zr-ZrN-(Zr,Mo,Al)N coating had the highest hardness and the lowest value of the adhesion component of the coefficient of friction at high temperatures. However, the Zr-ZrN-(Zr,Mo,Al)N coating exhibited good resistance to cracking and oxidation during the milling of the Inconel 718 alloy. Based on the above, the Zr-ZrN-(Zr,Mo,Al)N coating can be considered a good choice as a wear-resistant coating for the end milling of the Inconel 718 alloy. [ABSTRACT FROM AUTHOR]

Secretory phospholipase A2s (sPLA2s) are found in a wide range of organisms from bacteria to higher plants and animals and are involved in varied and cellular processes. However, roles of these enzymes in microbial pathogens remain unclear. Here, an sPLA2 (BbPLA2) was characterized in the filamentous insect pathogenic fungus, Beauveria bassiana. BbPLA2 was exclusively expressed in insect hemolymph‐derived cells (hyphal bodies), and its expression was induced by insect‐derived nutrients and lipids, and nutrient starvation. High levels of secretion of BbPLA2 were observed as well as its distribution in hyphal body lipid drops (LDs). Overexpression of BbPLA2 increased the ability of B. bassiana to utilize insect‐derived nutrients and lipids, and promoted LD accumulation, indicating functions for BbPLA2 in mediating LD homeostasis and assimilation of insect‐derived lipids. Strains overexpressing BbPLA2 showed moderately increased virulence, including more efficient penetration of the insect cuticle and evasion of host immune responses as compared to the wild type strain. In addition, B. bassiana‐activated host immune genes were downregulated in the BbPLA2 overexpression strain, but upregulated by infections with a ΔBbPLA2 strain. These data demonstrate that BbPLA2 contributes to LD homeostasis, assimilation of insect‐derived lipids, and repression of host immune responses. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade targeting PDCD1 (PD-1) or CD274 (PD-L1) has demonstrated efficacy and interest across multiple cancers. However, the exact determinants of the response and cancer-specific molecular features remain unclear. A recent pan-cancer study identified a PDCD1/CD274-related immunotherapy network of 40 genes that had differential patient survival associations across multiple cancers. However, the survival relevance of this network in mesothelioma could not be assessed due to a lack of available survival data for the mesothelioma study included. Mesothelioma, a rare cancer that most commonly arises in the pleural membranes around the lung, does have immune checkpoint blockade as an approved treatment strategy, yet questions over its efficacy remain. RNA-seq data from 87 pleural mesothelioma patients were interrogated on cBioPortal to assess the role of the PDCD1/CD274 network identified in a previous study, in addition to identifying repurposed drugs that may have therapeutic efficacy. Extensive literature searches were conducted to identify known information from the literature around the genes shown to impact patient survival (CCR5, GATD3A/GATD3, CXCR6, GZMA, and TBC1D10C). The same literature validation was performed for putative repurposed drugs that were identified as potential immunotherapeutic adjuvants in the context of mesothelioma (disulfiram, terfenadine, maraviroc, clioquinol, chloroxine, and oxyphenbutazone). Only disulfiram returned a specifically focused research article based on the literature search. This article demonstrated cytotoxicity in a panel of five human MPM cell lines of mixed histology (epithelioid, biphasic, and sarcomatoid). There was little information on the remaining five drugs, yet the clear preclinical efficacy of disulfiram validates the methodology used herein and prompts further exploration of the remaining drugs in mesothelioma. This study ultimately sheds light on novel preclinical information of genes related to PDCD1/CD274 in mesothelioma, as well as identifying putative drugs that may have therapeutic efficacy either independently or as an immunotherapeutic adjuvant. [ABSTRACT FROM AUTHOR]

A triphenylamine-based "turn-on" fluorescent chemosensor, (E)-3-(benzyloxy)-N′-{[4′-(diphenyl-amino)-4-hydroxy[1,1′-biphenyl]-3-yl]methylidene}benzohydrazide (BDHBMB), containing a 3-benzyloxy-benzo-hydrazide moiety was successfully synthesized. It showed high selectivity, excellent anti-interference performance, and remarkable sensitivity for Al3+ ions in methanol solution. After the addition of Al3+, BDHBMB exhibited strong fluorescence emission (18 times enhancement) at λ 573 nm due to the formation of a rigid conjugate structure based on chelation-enhanced fluorescence (CHEF) mechanism. A great linearity with a correlation coefficient R2 of 0.99 was observed in the concentration range 0–60 μM. The binding constant and the limit of detection (LOD) for Al3+ were calculated to be 1.48×103 M–1 and 8.94×10–8 M, respectively. The "turn-on" fluorescent probe was successfully applied to visual detection of Al3+ in test paper. [ABSTRACT FROM AUTHOR]

Actinomycetes (a group of filamentous bacteria) are the dominant microbial order in the Daqu (DQ) fermentation starter and in the pit mud (PM) of the Baijiu fermentation microbiome. Actinomycetes produce many of the key enzymes and flavor components, and supply important precursors, which have a major influence on its characteristic aroma components, to other microorganisms during fermentation. This paper reviews the current progress on actinomycete research related to Baijiu fermentation, including the isolation and identification, distribution, interspecies interactions, systems biology, and main metabolites. The main metabolites and applications of the actinomycetes during Baijiu fermentation are also discussed. [ABSTRACT FROM AUTHOR]

Several recent studies have pointed out that arc GTPase activating protein 1 (RACGAP1) is a putative oncogene in many human tumors. However, to date, no pan-cancer analysis has been performed to study the different aspects of this gene expression and behavior in tumor tissues. Here, we applied several bioinformatics tools to perform a comprehensive analysis for RACGAP1. First, we assessed the expression of RACGAP1 in several types of human tumors and tried to correlate that with the stage of the tumors analyzed. We then performed a survival analysis to study the correlation between RACGAP1 upregulation in tumors and the clinical outcome. Additionally, we investigated the mutation forms, the correlation with several immune cell infiltration, the phosphorylation status of the interested protein in normal and tumor tissues, and the potential molecular mechanisms of RACGAP1 in cancerous tissue. The results demonstrated that RACGAP1, a highly expressed gene across several types of tumors, correlated with a poor prognosis in several types of human cancers. Moreover, it was found that RACGAP1 affects the tumor immune microenvironment by influencing the infiltration level of several immune cells. Collectively, the current study provides a comprehensive overview of the oncogenic roles of RACGAP1, where our results nominate it as a potential prognostic biomarker and a target for antitumor therapy development. [ABSTRACT FROM AUTHOR]

Spring cold stress (SCS) compromises the reproductive growth of wheat, being a major constraint in achieving high grain yield and quality in winter wheat. To sustain wheat productivity in SCS conditions, breeding cultivars conferring cold tolerance is key. In this review, we examine how grain setting and quality traits are affected by SCS, which may occur at the pre-anthesis stage. We have investigated the physiological and molecular mechanisms involved in floret and spikelet SCS tolerance. It includes the protective enzymes scavenging reactive oxygen species (ROS), hormonal adjustment, and carbohydrate metabolism. Lastly, we explored quantitative trait loci (QTLs) that regulate SCS for identifying candidate genes for breeding. The existing cultivars for SCS tolerance were primarily bred on agronomic and morphophysiological traits and lacked in molecular investigations. Therefore, breeding novel wheat cultivars based on QTLs and associated genes underlying the fundamental resistance mechanism is urgently needed to sustain grain setting and quality under SCS. [ABSTRACT FROM AUTHOR]

Simple Summary: This review aims at analyzing an emergent topic regarding the possible combined use of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), anticancer drugs approved to treat tumors with defective repair of DNA damage, and immunostimulating agents, like Immune Checkpoint Inhibitors (ICIs), that represent the current treatment of a variety of malignancies. Preclinical investigation shows how PARPi, by positively impacting anti-tumor immune response through DNA damage-related mechanisms, might render cancer cells more responsive to immunotherapies, especially in the setting of genomic instability. In addition to well-recognized mechanisms that may be elicited by PARPi, recent experimental evidence is summarized further supporting the potential synergistic effects of PARPi and ICIs. We believe that an in-depth analysis of the tumor genome as well as of the characteristics of the tumor microenvironment at a single-patient level, along with an implementation of clinical trials that are presently at an early-stage, can contribute to identify more effective and individually-tailored treatments. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induce cytotoxic effects as single agents in tumors characterized by defective repair of DNA double-strand breaks deriving from BRCA1/2 mutations or other abnormalities in genes associated with homologous recombination. Preclinical studies have shown that PARPi-induced DNA damage may affect the tumor immune microenvironment and immune-mediated anti-tumor response through several mechanisms. In particular, increased DNA damage has been shown to induce the activation of type I interferon pathway and up-regulation of PD-L1 expression in cancer cells, which can both enhance sensitivity to Immune Checkpoint Inhibitors (ICIs). Despite the recent approval of ICIs for a number of advanced cancer types based on their ability to reinvigorate T-cell-mediated antitumor immune responses, a consistent percentage of treated patients fail to respond, strongly encouraging the identification of combination therapies to overcome resistance. In the present review, we analyzed both established and unexplored mechanisms that may be elicited by PARPi, supporting immune reactivation and their potential synergism with currently used ICIs. This analysis may indicate novel and possibly patient-specific immune features that might represent new pharmacological targets of PARPi, potentially leading to the identification of predictive biomarkers of response to their combination with ICIs. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study is to discover and characterize novel small cell lung cancer (SCLC) subtypes and further identify their relationship with existing SCLC subtypes. We identified SCLC-M (mesenchymal) tumors as SCLC subtypes that are distinctive of SCLC-I (inflamed) tumors. SCLC-M tumors showed elevated epithelial-to-mesenchymal transformation (EMT) activity but a low level of anticancer immune activity also with unfavorable clinical outcomes. Gene expression- and immunohistochemistry-based prediction suggests that SCLC-M tumors comprise approximately 5% of primary SCLC tumors. Given these unique molecular and clinical features, SCLC-M tumors should be taken into account in the clinical settings of SCLC management. While molecular subtypes of small cell lung cancers (SCLC) based on neuroendocrine (NE) and non-NE transcriptional regulators have been established, the association between these molecular subtypes and recently recognized SCLC-inflamed (SCLC-I) tumors is less understood. In this study, we used gene expression profiles of SCLC primary tumors and cell lines to discover and characterize SCLC-M (mesenchymal) tumors distinct from SCLC-I tumors for molecular features, clinical outcomes, and cross-species developmental trajectories. SCLC-M tumors show elevated epithelial-to-mesenchymal transformation (EMT) and YAP1 activity but a low level of anticancer immune activity and worse clinical outcomes than SCLC-I tumors. The prevalence of SCLC-M tumors was 3.2–7.4% in primary SCLC cohorts, which was further confirmed by immunohistochemistry in an independent cohort. Deconvoluted gene expression of tumor epithelial cells showed that EMT and increased immune function are tumor-intrinsic characteristics of SCLC-M and SCLC-I subtypes, respectively. Cross-species analysis revealed that human primary SCLC tumors recapitulate the NE-to-non-NE progression murine model providing insight into the developmental relationships among SCLC subtypes, e.g., early NE (SCLC-A and -N)- vs. late non-NE tumors (SCLC-M and -P). Newly identified SCLC-M tumors are biologically and clinically distinct from SCLC-I tumors which should be taken into account for the diagnosis and treatment of the disease. [ABSTRACT FROM AUTHOR]