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Skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and melanoma, are the most common malignancies in the United States. Loss of DNA repair pathways in the skin plays a significant role in tumorigenesis. In recent years, targeting DNA repair pathways, particularly homologous recombination deficiency (HRD), has emerged as a potential therapeutic approach in cutaneous malignancies. This review provides an overview of DNA damage and repair pathways, with a focus on HRD, and discusses major advances in targeting these pathways in skin cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors have been developed to exploit HRD in cancer cells. PARP inhibitors disrupt DNA repair mechanisms by inhibiting PARP enzymatic activity, leading to the accumulation of DNA damage and cell death. The concept of synthetic lethality has been demonstrated in HR-deficient cells, such as those with BRCA1/2 mutations, which exhibit increased sensitivity to PARP inhibitors. HRD assessment methods, including genomic scars, RAD51 foci formation, functional assays, and BRCA1/2 mutation analysis, are discussed as tools for identifying patients who may benefit from PARP inhibitor therapy. Furthermore, HRD has been implicated in the response to immunotherapy, and the combination of PARP inhibitors with immunotherapy has shown promising results. The frequency of HRD in melanoma ranges from 18% to 57%, and studies investigating the use of PARP inhibitors as monotherapy in melanoma are limited. Further research is warranted to explore the potential of PARP inhibition in melanoma treatment. [ABSTRACT FROM AUTHOR]

The western Sulige gas field is a new and key reserve area for the rolling development of the Sulige gas field in China. However, due to the complex gas–water relationship and the difficulty in identifying gas and water formation, the scale and benefit deployment of the gas field are seriously restricted. In particular, almost all of the wells in the area produce water, and no water measurements have been carried out for any single well, which leads to an unclear understanding of the dynamic characteristics of the production wells, thus affecting the productivity calculations of the gas wells and the overall regional productivity evaluation. Based on the testing data for a gas well, the impacts of the reservoir property parameters on the gas and water production were analyzed by combining the production performance and static geological characteristics. It was determined that the physical parameters K, Kh, and φSg had good positive correlations with gas production but not with water production; thus, effective prediction cannot be obtained for water production in gas well testing. After the analysis of the liquid-loading law, the gas wells were classified into three types: continuous liquid-carrying production, slight liquid-loading, and liquid-loading wells. In general, up to 96% of the gas wells were liquid-loaded. According to the different production performances exhibited in the different stages of the gas wells, five types of methods for diagnosing water production wells were proposed (gas testing, pilot production, gas–liquid two-phase measurement testing, liquid level detection, and production performance analysis), as well as the diagnostic criteria and corresponding solutions. To obtain real-time water production data for each well and investigate the change in the water–gas ratio (WGR) during the whole production process, a water production splitting method for gas wells based on three-dimensional geological modeling and numerical simulation combined with the constraints of the total water production of gas gathering stations was explored and established. The splitting results can be used to evaluate the water and gas productivity of gas wells and determine the best deliquification period. The gas well productivity when water production was considered was about 10% lower than that when water production was not considered. The best deliquification period was determined to be 125 days for wells with small water production, 20 days for wells with moderate water production, and 3 days for wells with serious water production. The results of this study could provide technical support for the scientific evaluation of gas well production indicators, reduction in development costs, and improvement in oil recovery. [ABSTRACT FROM AUTHOR]

As the incidence of prostate cancer (PCa) has increased, screening based on prostate-specific antigen (PSA) has become controversial due to the low specificity of PSA. Therefore, we investigated the diagnostic performance of prostate health index (PHI) density (PHID) for the detection of PCa and clinically significant PCa (csPCa) compared to PSA, PSA density (PSAD), and PHI as a triaging test. We retrospectively reviewed 306 men who underwent prostate biopsy for PSA levels of 2.5 to 10 ng/mL between January 2020 and April 2023. Of all cohorts, 86 (28.1%) and 48 (15.7%) men were diagnosed with PCa and csPCa, respectively. In ROC analysis, the highest AUC was identified for PHID (0.812), followed by PHI (0.791), PSAD (0.650), and PSA (0.571) for PCa. A similar trend was observed for csPCa: PHID (AUC 0.826), PHI (AUC 0.796), PSAD (AUC 0.671), and PSA (0.552). When the biopsy was restricted to men with a PHID ≥ 0.56, 26.5% of unnecessary biopsies could be avoided; however, 9.3% of PCa cases and one csPCa case (2.1%) remained undiagnosed. At approximately 90% sensitivity for csPCa, at the given cut-off values of PHI ≥ 36.4, and PHID ≥ 0.91, 48.7% and 49.3% of unnecessary biopsies could be avoided. In conclusion, PHID had a small advantage over PHI, about 3.6%, for the reduction in unnecessary biopsies for PCa. The PHID and PHI showed almost the same diagnostic performance for csPCa detection. PHID can be used as a triaging test in a clinical setting to pre-select the risk of PCa and csPCa. [ABSTRACT FROM AUTHOR]

As a violation of moral integrity, corporate financial irregularities not only cause losses to investors and other stakeholders, but the enterprise itself is also punished by the relevant regulatory authorities. However, to realize their own interests, some enterprises still violate laws and participate in financial irregularities. Good environmental, social, and governance (ESG) performance can reduce corporate risks, improve financial status, and constrain financial irregularities. This study empirically clarifies the impact of ESG performance on financial irregularities in Chinese listed companies. Furthermore, we examine the moderating role of stakeholder attention—that is, the public, media, and institutional investors. Based on 1050 observations of non-financial and non-real estate companies listed on the Shanghai and Shenzhen Stock exchanges from 2011 to 2020, this study examines the impact of ESG performance on financial irregularities using a fixed-effects model. Additionally, we verify the moderating effect of public, media, and institutional investor attention to the impact of ESG on financial irregularities. The results indicate that firms with better ESG performance have fewer financial irregularities. At the same time, the greater the attention of the public, media, and investors, the stronger the inhibitory effect of ESG performance on financial irregularities. This study helps broaden the relevant corporate social responsibility (CSR) and financial management theories and provides theoretical support for enterprises to improve ESG performance and inhibit financial irregularities. [ABSTRACT FROM AUTHOR]

The sweet potato weevil (Cylas formicarius) is a critical pest producing enormous global losses in sweet potato crops. Traditional pest management approaches for sweet potato weevil, primarily using chemical pesticides, causes pollution, food safety issues, and harming natural enemies. While RNA interference (RNAi) is a promising environmentally friendly approach to pest control, its efficacy in controlling the sweet potato weevil has not been extensively studied. In this study, we selected a potential target for controlling C. formicarius, the Troponin I gene (wupA), which is essential for musculature composition and crucial for fundamental life activities. We determined that wupA is abundantly expressed throughout all developmental stages of the sweet potato weevil. We evaluated the efficiency of double-stranded RNAs in silencing the wupA gene via microinjection and oral feeding of sweet potato weevil larvae at different ages. Our findings demonstrate that both approaches significantly reduced the expression of wupA and produced high mortality. Moreover, the 1st instar larvae administered dswupA exhibited significant growth inhibition. We assessed the toxicity of dswupA on the no-target insect silkworm and assessed its safety. Our study indicates that wupA knockdown can inhibit the growth and development of C. formicarius and offer a potential target gene for environmentally friendly control., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

The efficiency of RNA interference (RNAi) has always limited the research on the phenotype innovation of Lepidoptera insects. Previous studies have found that double-stranded RNA-degrading enzyme (dsRNase) is an important factor in RNAi efficiency, but there have been no relevant reports in butterflies (Papilionoidea). Papilio xuthus is one of the important models in butterflies with an extensive experimental application value. To explore the effect of dsRNase in the RNAi efficiency on butterflies, six dsRNase genes (PxdsRNase 1-6) were identified in P. xuthus genome, and their dsRNA-degrading activities were subsequently detected by ex vivo assays. The result shows that the dsRNA-degrading ability of gut content (<1 h) was higher than hemolymph content (>12 h). We then investigated the expression patterns of these PxdsRNase genes during different tissues and developmental stages, and related RNAi experiments were carried out. Our results show that different PxdsRNase genes had different expression levels at different developmental stages and tissues. The expression of PxdsRNase2, PxdsRNase3, and PxdsRNase6 were upregulated significantly through dsGFP injection, and PxdsRNase genes can be silenced effectively by injecting their corresponding dsRNA. RNAi-of-RNAi studies with PxEbony, which acts as a reporter gene, observed that silencing PxdsRNase genes can increase RNAi efficiency significantly. These results confirm that silencing dsRNase genes can improve RNAi efficiency in P. xuthus significantly, providing a reference for the functional study of insects such as butterflies with low RNAi efficiency., (© 2024 Wiley Periodicals LLC.)

Petals in rapeseed (Brassica napus) serve multiple functions, including protection of reproductive organs, nutrient acquisition, and attraction of pollinators. However, they also cluster densely at the top, forming a thick layer that absorbs and reflects a considerable amount of photosynthetically active radiation. Breeding genotypes with large, small, or even petal-less varieties, requires knowledge of primary genes for allelic selection and manipulation. However, our current understanding of petal-size regulation is limited, and the lack of markers and pre-breeding materials hinders targeted petal-size breeding. Here, we conducted a genome-wide association study on petal size using 295 diverse accessions. We identified 20 significant single nucleotide polymorphisms and 236 genes associated with petal-size variation. Through a cross-analysis of genomic and transcriptomic data, we focused on 14 specific genes, from which molecular markers for diverging petal-size features can be developed. Leveraging CRISPR-Cas9 technology, we successfully generated a quadruple mutant of Far-Red Elongated Hypocotyl 3 (q-bnfhy3), which exhibited smaller petals compared to the wild type. Our study provides insights into the genetic basis of petal-size regulation in rapeseed and offers abundant potential molecular markers for breeding. The q-bnfhy3 mutant unveiled a novel role of FHY3 orthologues in regulating petal size in addition to previously reported functions., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Despite major progress in mantle cell lymphoma (MCL) therapeutics, MCL remains a deadly disease with a median survival not exceeding four years. No single driver genetic lesion has been described to solely give rise to MCL. The hallmark translocation t(11;14)(q13;q32) requires additional genetic alterations for the malignant transformation. A short list of recurrently mutated genes including ATM, CCND1, UBR5, TP53, BIRC3, NOTCH1, NOTCH2, and TRAF2 recently emerged as contributors to the pathogenesis of MCL. Notably, NOTCH1 and NOTCH2 were found to be mutated in multiple B cell lymphomas, including 5–10% of MCL, with most of these mutations occurring within the PEST domain of the protein. The NOTCH genes play a critical role in the early and late phases of normal B cell differentiation. In MCL, mutations in the PEST domain stabilize NOTCH proteins, rendering them resistant to degradation, which subsequently results in the upregulation of genes involved in angiogenesis, cell cycle progression, and cell migration and adhesion. At the clinical level, mutated NOTCH genes are associated with aggressive features in MCL, such as the blastoid and pleomorphic variants, a shorter response to treatment, and inferior survival. In this article, we explore in detail the role of NOTCH signaling in MCL biology and the ongoing efforts toward targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Epithelial-to-mesenchymal transition (EMT) is a complex program by which epithelial cells lose epithelial characteristics whilst acquiring mesenchymal features. EMT was coined in the 1980s and initially thought to involve a binary switch between epithelial and mesenchymal states. However, mounting work suggests that EMT involves intermediate states or hybrid epithelial/mesenchymal (E/M) phenotypes. In the context of many cancers, such as breast cancers, these hybrid states retain characteristics of both epithelial and mesenchymal cells, and have been linked to poor survival, metastasis, and resistance to treatment. In this Review, the authors examine the complex layers of molecular interactions governing EMT in cancer. The underlying drivers of these states, namely EMT-transcription factors, epigenetic regulators, and non-coding RNAs, as well as the influence of EMT on the immune response, are discussed, and in doing so, this Review outlines valuable mechanistic insights for the reversion of EMT and potential avenues for therapeutic intervention. Cellular plasticity in cancer enables adaptation to selective pressures and stress imposed by the tumor microenvironment. This plasticity facilitates the remodeling of cancer cell phenotype and function (such as tumor stemness, metastasis, chemo/radio resistance), and the reprogramming of the surrounding tumor microenvironment to enable immune evasion. Epithelial plasticity is one form of cellular plasticity, which is intrinsically linked with epithelial–mesenchymal transition (EMT). Traditionally, EMT has been regarded as a binary state. Yet, increasing evidence suggests that EMT involves a spectrum of quasi-epithelial and quasi-mesenchymal phenotypes governed by complex interactions between cellular metabolism, transcriptome regulation, and epigenetic mechanisms. Herein, we review the complex cross-talk between the different layers of epithelial plasticity in cancer, encompassing the core layer of transcription factors, their interacting epigenetic modifiers and non-coding RNAs, and the manipulation of cancer immunogenicity in transitioning between epithelial and mesenchymal states. In examining these factors, we provide insights into promising therapeutic avenues and potential anti-cancer targets. [ABSTRACT FROM AUTHOR]

Simple Summary: As a solid tumor, melanoma is not only a tumor mass of monolithic tumor cells, but it also contains supporting stroma, extracellular matrix (ECM), and soluble molecules forming the widely recognized tumor microenvironment. The main components of the tumor microenvironment include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), ECM, and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). The tumor microenvironment has been suggested to play a central role in tumor progression and treatment resistance. Accumulated evidence indicates that tumor maintenance, progression, and treatment resistance are determined by components of the microenvironment. Thus, targeting the components of the tumor microenvironment may have a therapeutic impact on melanoma treatment. The main topic of this paper deals with the main components of the tumor microenvironment and their impact as therapeutic targets in melanoma treatment. The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic tumor cells, but it also contains supporting stroma, ECM, and soluble molecules. Melanoma cells are continuously in interaction with the components of the microenvironment. In the present review, we focus on the role of the tumor microenvironment components in the modulation of tumor progression and treatment resistance as well as the impact of the tumor microenvironment as a therapeutic target in melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy for non-small cell lung cancer (NSCLC) is a clinical reality with impressive efficacy for some patients. However, less than half of them will benefit from this therapeutic regime, and finding indicators of response is necessary for selecting the patients likely to respond. So far, detection of PD-L1 in tumors by immunohistochemistry is the only validated predictive biomarker. In recent years, certain changes in the tumor cells (intrinsic alterations), including mutations, epigenetic changes and metabolic rewiring, have been shown to modify the type of tumor microenvironment (TME) where such a tumor grows. This TME may determine response or refractoriness to immunotherapy. Examples of key mutations are KRAS, SKT11(LKB1), KEAP1 and TP53, as well as co-mutations of these genes. Reshaping the TME with novel strategies in these particular TMEs could increase the efficacy of immunotherapy in lung cancer patients. Despite the great clinical success of immunotherapy in lung cancer patients, only a small percentage of them (<40%) will benefit from this therapy alone or combined with other strategies. Cancer cell-intrinsic and cell-extrinsic mechanisms have been associated with a lack of response to immunotherapy. The present study is focused on cancer cell-intrinsic genetic, epigenetic, transcriptomic and metabolic alterations that reshape the tumor microenvironment (TME) and determine response or refractoriness to immune checkpoint inhibitors (ICIs). Mutations in KRAS, SKT11(LKB1), KEAP1 and TP53 and co-mutations of these genes are the main determinants of ICI response in non-small-cell lung cancer (NSCLC) patients. Recent insights into metabolic changes in cancer cells that impose restrictions on cytotoxic T cells and the efficacy of ICIs indicate that targeting such metabolic restrictions may favor therapeutic responses. Other emerging pathways for therapeutic interventions include epigenetic modulators and DNA damage repair (DDR) pathways, especially in small-cell lung cancer (SCLC). Therefore, the many potential pathways for enhancing the effect of ICIs suggest that, in a few years, we will have much more personalized medicine for lung cancer patients treated with immunotherapy. Such strategies could include vaccines and chimeric antigen receptor (CAR) cells. [ABSTRACT FROM AUTHOR]

Construction solid waste and agricultural waste, as renewable resources, have gained increasing attention recently. This research aims to explore the mechanical and thermal properties of recycled-straw insulating concrete commonly made with construction waste and straw in northern Fujian, which can provide useful suggestions for the practical use of recycled-straw insulating concrete. The effects of recycled coarse aggregate, fly ash, and straw on the mechanical and thermal properties of recycled-straw insulating concrete were investigated by orthogonal tests. The results of the orthogonal tests were optimized by the total efficacy coefficient method to obtain the optimal mix ratio of recycled-straw insulating concrete. Combined with the finite element analysis software ANSYS Workbench, the heat transfer performance of the recycled-straw insulating concrete walls was analyzed to simulate the insulation performance of the walls. The compressive strength of the recycled-straw insulating concrete with the optimal ratio was found to be 30.93 MPa, and the thermal conductivity was 0.5051 W/(m·K). The steady-state thermal analysis of the recycled-straw insulating concrete wall and the plain concrete wall was carried out by finite element software, and the simulation results showed that the insulation performance of the recycled-straw insulating concrete walls was improved by 145% compared with the plain concrete wall. These results indicate that the recycled-straw insulating concrete wall has better thermal insulation performance and can be applied to building envelopes to save heating costs in winter and reduce carbon dioxide emissions, which has significant economic and environmental significance for areas with low outdoor temperatures in winter and long heating periods. [ABSTRACT FROM AUTHOR]

The CAD/CAM technology has been increasingly popular in manufacturing spinal braces for patients with adolescent idiopathic scoliosis (AIS) in clinics. However, whether the CAD/CAM-manufactured braces or the CAD/CAM-manufactured braces integrating with biomechanical simulation could improve the in-brace correction angle of spinal braces in AIS patients, compared to the manually manufactured braces, has remained unclear. The purpose of this systematic review and meta-analysis was to compare the in-brace correction angle of (1) computer-aided design and computer-aided manufacturing (CAD/CAM)-manufactured braces or (2) the CAD/CAM-manufactured braces integrating with biomechanical simulation with that of (3) manually manufactured braces. The Web of Science, OVID, EBSCO, PUBMED, and Cochrane Library databases were searched for relevant studies published up to March 2023. Five randomized controlled trials (RCTs) or randomized controlled crossover trials were included for qualitative synthesis, and four of them were included for meta-analysis. The meta-analysis effect sizes of the in-brace correction angle for CAD/CAM versus manual method, and CAD/CAM integrating with biomechanical simulation versus the manual method in the thoracic curve group and the thoracolumbar/lumbar curve group were 0.6° (mean difference [MD], 95% confidence intervals [CI]: −1.06° to 2.25°), 1.12° (MD, 95% CI: −8.43° to 10.67°), and 3.96° (MD, 95% CI: 1.16° to 6.76°), respectively. This review identified that the braces manufactured by CAD/CAM integrating with biomechanical simulation did not show sufficient advantages over the manually manufactured braces, and the CAD/CAM-manufactured braces may not be considered as more worthwhile than the manually manufactured braces, based on the in-brace correction angle. More high-quality clinical studies that strictly follow the Scoliosis Research Society (SRS) guidelines with long-term follow-ups are still needed to draw more solid conclusions and recommendations for clinical practice in the future. [ABSTRACT FROM AUTHOR]

The rice stem borer, Chilo suppressalis, has developed a high level of resistance to many of the compounds currently used for control. There is therefore an urgent need to develop novel control methods for C. suppressalis. Insect chitin synthases (CHS) have attracted interest as a potential target for insect pest management. However, to date, CHS have not been characterized in C. suppressalis. Two CHS genes (CsCHS1 and CsCHS2) were identified and cloned from C. suppressalis. Two transcript variants were identified for CsCHS1, CsCHS1a and CsCHS1b. Spatiotemporal expression profiling showed that both transcripts of CsCHS1 are most highly expressed on the last day of each larval instar stage and show the highest expression levels in the integument. In contrast, CsCHS2 is predominantly expressed during the larval feeding stages and shows the highest expression levels in the midgut. Knockdown of CsCHS1 by RNA interference significantly inhibited the molting and pupation of C. suppressalis, and knockdown of CsCHS2 significantly affected growth during the larval stage, but had no significant effect on the pupation. Moreover, knockout of CsCHS1 by CRISPR/Cas9 genome editing severely lowered the hatching rate, larval survivorship, pupation rate, and eclosion rate, but only larval survivorship at the G0 generation was lowered after the knockout of CsCHS2. These results demonstrate that CsCHS1 and CsCHS2 play vital roles in the growth and development of C. suppressalis, and so have potential as insecticidal targets for the control of this highly damaging pest. [ABSTRACT FROM AUTHOR]

Nontarget-site resistance (NTSR) is a complex multigenic trait that is associated with the potential mechanisms of herbicide resistance which pose a serious threat to global crop protection. However, the NTSR mechanisms of Alopecurus japonicus, a malignant weed infesting wheat fields, are less characterized. In this study, we used RNA-sequencing transcriptome and enzyme activity detection to investigate the NTSR mechanisms and candidate genes involved in fenoxaprop-P-ethyl (FE) in a previously identified resistant population compared to the sensitive population of A. japonicus. Transcriptome analysis identified nine upregulated genes, which were constitutively overexpressed and upregulated by FE application in the resistant population, and the results were validated using quantitative real-time PCR. These genes including one cytochrome P450 monooxygenase (P450) gene (CYP75B4), one ATP-binding cassette (ABC) transporter gene (ABCG36), one laccase (LAC) gene (LAC15), one 9-cis-epoxycarotenoid dioxygenase (NCED) gene (NCED5), two purple acid phosphatase (PAP) genes (PAP4, PAP15), one sucrose phosphate synthase (SPS) gene (SPS3), one protein related to disease resistance gene (RGA3) and one immune protein gene (R1B-17). The activity assay of LAC, NCED, PAP and SPS revealed that the activities of these enzymes in the resistant population were significantly higher than those in the sensitive population at 0 h and after FE application at 12 h, 24 h and 72 h. Nevertheless, whether LAC, NCED, PAP and SPS genes were involved in herbicide metabolism needs to be further validated. Our results revealed that CYP, ABC transporter and LAC genes may participate in A. japonicus resistance. These genes identified in the present study provide new insights into the resistance mechanism of weeds in response to herbicide. Our study also implies the complexity of the NTSR mechanisms of weeds. [ABSTRACT FROM AUTHOR]

Codonopsis pilosula is a medicinal and edible herb with a rich nutritional value. In Gansu Province, China, its production quality and yield differ during the four seasons. Here, we investigated the differences in the microfloral composition and metabolic functions in the rhizospheric soil and roots of C. pilosula during the four seasons, and we also analyzed their dynamic and synergistic effects on C. pilosula growth and carbohydrate content change. The C. pilosula samples were analyzed for plant physiology, microfloral composition and metabolic functions in the rhizospheric soil and roots using high-throughput sequencing technology. Environmental indices including soil physiochemistry and meteorological conditions were also determined by the coupled chromatography–spectroscopy technique. The results revealed that the C. pilosula growth was affected by temperature, precipitation and light intensity, with the bacterial structures and functions of the soil and root samples showing obvious seasonal changes. Due to the diversity of microbial composition and community metabolic function, and the synergistic effect of microbial and environmental factors, there are significant differences in stress resistance, physiological status and metabolites of C. pilosula in different seasons. Furthermore, the change in seasons was significantly correlated with the quality and yield of C. pilosula. This study provides a scientific basis for soil improvement and the refinement of local Radix C. pilosula cultivation methods. [ABSTRACT FROM AUTHOR]

Simple Summary: Nucleases are highly diverse enzymes that cleave phosphodiester bonds of nucleic acids with highly diverse enzymes. A widespread superfamily of nucleases contains PIN-like domains, which are identified in eukaryotes and prokaryotes. The domesticated silkworm Bombyx mori, as a lepidoptera model insect, has numerous advantages in life science and can be used as an important model in various research areas. However, few nucleases on RNA insensitivity or virus defense have been studied in B. mori. In this study, we identified a protein asteroid (BmAst) in silkworm B. mori, containing the PIN domain and XPG domain. BmAst gene was highest expressed in hemocytes and fat body of the 5th larvae. The BmAst gene expression was significantly induced by Bombyx mori nucleopolyhedrovirus (BmNPV) or dsRNA. By interference with BmAst gene expression, the proliferation of BmNPV in B. mori was significantly increased, whereas the survival rate of silkworm larvae was significantly lower when compared with the control. Our results indicate that BmAst is involved in silkworm resistance to BmNPV infection. Nuclease is a type of protein that degrades nucleic acids, which plays an important role in biological processes, including RNA interference efficiency and antiviral immunity. However, no evidence of a link between nuclease and Bombyx mori nucleopolyhedrovirus (BmNPV) infection in silkworm B. mori has been found. In this study, a protein asteroid (BmAst) containing the PIN domain and XPG domain was identified in silkworm B. mori. BmAst gene was highest expressed in hemocytes and fat body of the 5th instar larvae, and high expression in the pupa stage. The transcriptional levels of the BmAst gene in 5th instar larvae were significantly induced by BmNPV or dsRNA. After knocking down BmAst gene expression by specific dsRNA, the proliferation of BmNPV in B. mori was increased significantly, whereas the survival rate of larvae was significantly lower when compared with the control. Our findings indicate that BmAst is involved in silkworm resistance to BmNPV infection. [ABSTRACT FROM AUTHOR]

Resistant starch appears to have promising effects on hypertension, cardiovascular and enteric illness. The influence of resistant starch on intestinal physiological function has drawn great attention. In this study, we first analyzed the physicochemical characteristics, including the crystalline properties, amylose content, and anti-digestibility among different types of buckwheat-resistant starch. The influence of resistant starch on the physiological functions of the mouse intestinal system, contained defecation, and intestinal microbes were also evaluated. The results showed that the crystalline mold of buckwheat-resistant starch changed from A to B + V after acid hydrolysis treatment (AHT) and autoclaving enzymatic debranching treatment (AEDT). The amylose content in AEDT was higher than in AHT and raw buckwheat. Moreover, the anti-digestibility of AEDT was also stronger than that in AHT and raw buckwheat. The buckwheat-resistant starch can promote bowel intestinal tract movement. The quantity of intestinal microbe was regulated by buckwheat-resistant starch. Our research demonstrates an effective preparation method for improving the quality of buckwheat-resistant starch and found that buckwheat-resistant starch has the role of adjusting the distribution of the intestinal flora and maintaining the health of the body. [ABSTRACT FROM AUTHOR]

The clinical management of small cell lung cancer (SCLC) treatment remains a major challenge for thoracic oncologists, with very few therapeutic advances significantly impacting patients' survival. The recent introduction of immunotherapy in the clinical setting produced a marginal benefit for a limited subset of metastatic patients, while the therapeutic scenario for relapsing extended-disease small cell lung cancers (ED-SCLCs) remains almost deserted. Recent efforts clarified the molecular features of this disease, leading to the identification of key signalling pathways which may serve as potential targets for clinical use. Despite the large number of molecules tested and the numerous therapeutic failures, some targeted therapies have recently shown interesting preliminary results. In this review, we describe the main molecular pathways involved in SCLC development/progression and provide an updated summary of the targeted therapies currently under investigation in SCLC patients. [ABSTRACT FROM AUTHOR]

This paper investigates the synchronization problem of network systems (NSs) via finite‐time (FIT) control techniques. First, the network systems include two complex networks with linear couplings, nonlinear couplings and different rates of evolution. In order to realize the goal of synchronization, intermittent‐adaptive control schemes with quantizer are designed. Then, several FIT synchronization criteria are established by using the designed controllers whose parameters could be adjusted automatically according to the adaptive laws. At the rest of this article, the numerical simulations are provided to illustrate our results. [ABSTRACT FROM AUTHOR]

Changes in the DNA damage response (DDR) and cellular metabolism are two important factors that allow cancer cells to proliferate. DDR is a set of events in which DNA damage is recognized, DNA repair factors are recruited to the site of damage, the lesion is repaired, and cellular responses associated with the damage are processed. In cancer, DDR is commonly dysregulated, and the enzymes associated with DDR are prone to changes in ubiquitination. Additionally, cellular metabolism, especially glycolysis, is upregulated in cancer cells, and enzymes in this metabolic pathway are modulated by ubiquitination. The ubiquitin–proteasome system (UPS), particularly E3 ligases, act as a bridge between cellular metabolism and DDR since they regulate the enzymes associated with the two processes. Hence, the E3 ligases with high substrate specificity are considered potential therapeutic targets for treating cancer. A number of small molecule inhibitors designed to target different components of the UPS have been developed, and several have been tested in clinical trials for human use. In this review, we discuss the role of ubiquitination on overall cellular metabolism and DDR and confirm the link between them through the E3 ligases NEDD4, APC/CCDH1, FBXW7, and Pellino1. In addition, we present an overview of the clinically important small molecule inhibitors and implications for their practical use. [ABSTRACT FROM AUTHOR]

Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue and associated factors in patients with IBD. A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Among 97 ulcerative colitis patients and 50 Crohn's disease patients, the mean total MFI-K score was 59.0 ± 5.5, which corresponded to a moderate-to-severe level of fatigue. Moderate-to-severe disease activity was found to be significantly associated with a higher general and physical fatigue subscale MFI-K score compared to remission-to-mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, p = 0.009), while the use of biologics was associated with a lower total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, p = 0.031). In multiple linear regression, the total MFI-K score was positively correlated with a history of surgery for IBD, while it was negatively correlated with the use of biologics. Depression was positively correlated with the reduced motivation subscale score. The degree of fatigue in patients with IBD was high. Disease activity, the use of biologics, a history of surgery for IBD, and depression were associated with fatigue. [ABSTRACT FROM AUTHOR]

An efficient photodetector (PD) is a key component in silicon-based photonic integrated circuits (PICs). III–V PDs with low dark current density, large bandwidth, and wide operation wavelength range have become increasingly important for Si photonics in various applications. Monolithic integration of III–V PDs on Si by direct heteroepitaxy exhibits the lowest cost, the largest integration density, and the highest throughput. As the research of integrating III–V lasers on Si flourishes in the last decade, various types of III–V PDs on Si with different device structures and absorption materials have also been developed. While the integration of III–V lasers on Si using various technologies has been systematically reviewed, there are few reviews of integrating III–V PDs on Si. In this article, we review the most recent advances in III–V PDs directly grown on Si using two different epitaxial techniques: blanket heteroepitaxy and selective heteroepitaxy. [ABSTRACT FROM AUTHOR]

With the rise of the fourth industrial revolution, traditional methods of analyzing investment have been transformed into intelligent methods under big data and the Internet of Things. This has created a new approach to solving practical engineering problems. This paper examines the formation and evolution of the application of inversion theory in tunnel and underground engineering, summarizing research progress using traditional and intelligent inversion analysis methods to identify three types of target unknown quantities in tunnels and underground projects: initial ground stress, support structure load, and tunnel characteristic parameters. It also offers an outlook on how to optimize inversion analysis methods to solve more challenging and complex tunneling problems in the context of informatization, digitalization, and intelligence. In the current research process of tunnel and underground space engineering problems, the inversion theory system has been improved, but inversion analysis methods still face many challenges. These include the low reliability of initial ground stress inversion under complex geological conditions, the lack of indicators to objectively evaluate the accuracy of inversion analysis, and the high costs of intelligent inversion analysis means. Moving forward in the context of big data and the information era, the future development direction for inversion theory and inversion methods in tunnel and underground space engineering is to combine new monitoring technology, computer vision technology, and simulation analysis technology to establish multifaceted intelligent inversion analysis models. [ABSTRACT FROM AUTHOR]

The core collection is a small subset that minimizes genetic redundancy while preserving the maximum genetic diversity of the entire population. Research on the core collection is crucial for the efficient management and utilization of germplasm resources. In this paper, the concept of the core collection and the research progress of its construction have briefly been summarized. Subsequently, some perspectives have been proposed in this research field for the near future. Four novel opinions have been presented, (1) the effective integration of multiple data types and accurate phenotyping methods need to be focused on; (2) the sampling strategy and bioinformatics software should be given attention; (3) the core collection of afforestation tree and bamboo species, with a wide natural distribution range and a large planting area, need to be carried out as soon as possible; (4) we should place a high priority on the study of genes discoveries and utilize these with a rapid, precise and high-throughput pattern based on re-sequencing technology. This paper provides a theoretical and technological reference for further study and the application of the plant core collection. [ABSTRACT FROM AUTHOR]

erg4 is a key gene for ergosterol biosynthesis in filamentous fungi, but its function in Penicillium expansum remains unknown. Our results showed that P. expansum contains three erg4 genes, including erg4A, erg4B and erg4C. The expression levels of the three genes showed differences in the wild-type (WT) strain, and the expression level of erg4B was the highest, followed by erg4C. Deletion of erg4A, erg4B or erg4C in the WT strain revealed functional redundancy between them. Compared to the WT strain, erg4A, erg4B or erg4C knockout mutants reduced ergosterol levels, with erg4B deletion having the greatest effect. Furthermore, deletion of the three genes reduced sporulation of the strain, and Δerg4B and Δerg4C mutants showed defective spore morphology. In addition, Δerg4B and Δerg4C mutants were found to be more sensitive to cell wall integrity and oxidative stress. However, deletion of erg4A, erg4B or erg4C had no significant effect on colony diameter, spore germination rate, conidiophore structure of P. expansum or pathogenicity to apple fruit. Taken together, erg4A, erg4B and erg4C have redundant functions and are all involved in ergosterol synthesis and sporulation in P. expansum. In addition, erg4B and erg4C contribute to spore morphogenesis, cell wall integrity and response to oxidative stress in P. expansum. [ABSTRACT FROM AUTHOR]

The artificial neural network (ANN) was used to predict the modulus of rupture (MOR) of the laminated wood products adhered by melamine/urea formaldehyde (MUF) resin with different formaldehyde to melamine/urea molar ratios combined with different weight ratios of the protein adhesive resulting from the alkaline treatment (NaOH) of the soybean oil meal to MUF resin pressed at different temperatures according to the central composite design (CCD). After making the boards and performing the mechanical test to measure the MOR, based on experimental data, different statistics such as determination coefficient (R2), root mean square error (RMSE), mean absolute error (MAE) and sum of squares error (SSE) were determined, and then the suitable algorithm was selected to determine the estimated values. After comparing estimated values with the experimental values, the direct and interactive effects of the independent variables on MOR were determined. The results indicated that using suitable algorithms to train the ANN well, a very good estimate of the bending strength of the laminated wood products can be offered with the least error. In addition, based on the estimated and measured strengths and FTIR and TGA diagnostic analyses, it was found that the replacement of the MUF resin by the protein bio-based adhesive when using low F to M/U molar ratios, the MOR is maximized if a high range of temperature is used during the press. [ABSTRACT FROM AUTHOR]

Target ranging is the premise for manipulators to complete agronomic operations such as picking and field management; however, complex environmental backgrounds and changing crop shapes increase the difficulty of obtaining target distance information based on binocular vision or depth cameras. In this work, a method for ranging large-sized fruit based on monocular vision was proposed to provide a low-cost and low-computation alternative solution for the fruit thinning or picking robot. The regression relationships between the changes in the number of pixels occupied by the target area and the changes in the imaging distance were calculated based on the images of square-shaped checkerboards and circular-shaped checkerboards with 100 cm2, 121 cm2, 144 cm2, 169 cm2, 196 cm2, 225 cm2, 256 cm2, 289 cm2, and 324 cm2 as the area, respectively. The 918 checkerboard images were collected by the camera within the range from 0.25 m to 1.5 m, with 0.025 m as the length of each moving step, and analyzed in MATLAB to establish the ranging models. A total of 2448 images of four oval watermelons, four pyriform pomelos, and four oblate pomelos, as the representatives of large fruit with different shapes, were used to evaluate and optimize the performance of the models. The images of the front were the input, while the imaging distances were the output. The results showed that the absolute error would be less than 0.06 m for both models and would linearly increase with a decrease in the distance. The relative error could be controlled at 5%. The results proved the proposed monocular method could be a solution for the ranging of large fruit targets. [ABSTRACT FROM AUTHOR]

Soil microbes play an important role in the microbial circulation and energy flow of ecosystems. In order to understand the change in the rhizosphere soil microbial community structure and function in the heterogeneous karst habitats, the nutrient content and enzyme activity were analyzed, and Illumina MiSeq high-throughput sequencing technology was used to detect the composition, quantity and functional types of the rhizosphere soil microbial community in Rhododendron pudingense under three kinds of karst microhabitats (soil surface, rock gully and rock surface) in Wangmo Country (WM), Zhenning Country (ZN) and Qinglong Country (QL). The results showed that SS and RG microhabitats had a higher nutrient content and enzyme activity, while RS had the lowest. At the phylum level, Proteobacteria and Actinomycetes were dominant in terms of bacteria, while Ascomycota and Basidiomycotina were dominant in terms of fungi. There was no significant difference in microbial diversity among different karst microhabitats (p > 0.05). At the microbial genus level, there were some differences in species composition among the three karst microhabitats, which may lead to soil heterogeneity in karst microhabitats. WM was a little different from ZN and QL. The results of PCoA showed that the community composition of RG and RS was more similar to that of SS. There was no significant difference in microbial functional types among different microhabitats (p > 0.05). Only the abundance of pathothoph-symbiothoph fungi in RG was significantly higher than that in RS (p < 0.05). The main function of bacteria was metabolism, and saprophytic and symbiotic fungi were the dominant fungal group. In conclusion, soil organic carbon and alkaline phosphatase are important factors affecting the level distribution of microflora in different karst microhabitats. R. pudingense in the SS and RG microhabitats has better soil conditions, which may require protection for the plants in the RS microhabitat. The current study results can provide a theoretical basis for the adaptation mechanism of Rhododendron pudingense to the karst microhabitat. [ABSTRACT FROM AUTHOR]

The innate immune response is highly dependent on the action of macrophages. They are abundant in the intestine subepithelial lamina propria of the mucosa, where they deploy multiple tasks and play a critical role. The balance between the gut microbiota and M2 macrophages is critical for gut health and homeostasis. Gut microbiota has the power to change macrophage phenotype and replenish the resident macrophage niche during and post infection. As far as the extracellular enteric parasitic infections invasive amebic colitis and giardiasis are concerned, a change of macrophages phenotype to a pro-inflammatory state is dependent on direct contact of the protozoan parasites with host cells. Macrophages induce strong pro-inflammatory response by inflammasome activation and secretion of interleukin IL-1β. Inflammasomes play a key role in the response to cellular stress and microbe attacks. The balance between gut mucosal homeostasis and infection is dependent on the crosstalk between microbiota and resident macrophages. Parasitic infections involve NLRP1 and NLRP3 inflammasome activation. For Entamoeba histolytica and Giardia duodenalis infections, inflammasome NLRP3 activation is crucial to promote the host defenses. More studies are needed to further elucidate possible therapeutic and protective strategies against these protozoan enteric parasites' invasive infections in humans. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent of vaccines and potent antiviral agents able to suppress viral replication, recovery from chronic HBV infection is still an extremely difficult goal to achieve. Complex interactions between virus and host are responsible for HBV persistence and the risk of oncogenesis. Through multiple pathways, HBV is able to silence both innate and adaptive immunological responses and become out of control. Furthermore, the integration of the viral genome into that of the host and the production of covalently closed circular DNA (cccDNA) represent reservoirs of viral persistence and account for the difficult eradication of the infection. An adequate knowledge of the virus–host interaction mechanisms responsible for viral persistence and the risk of hepatocarcinogenesis is necessary for the development of functional cures for chronic HBV infection. The purpose of this review is, therefore, to analyze how interactions between HBV and host concur in the mechanisms of infection, persistence, and oncogenesis and what are the implications and the therapeutic perspectives that follow. [ABSTRACT FROM AUTHOR]

Amomum tsaoko (AT) is a dietary botanical with laxative properties; however, the active ingredients and mechanisms are still unclear. The active fraction of AT aqueous extract (ATAE) for promoting defecation in slow transit constipation mice is the ethanol-soluble part (ATES). The total flavonoids of ATES (ATTF) were the main active component. ATTF significantly increased the abundance of Lactobacillus and Bacillus and reduced the dominant commensals, such as Lachnospiraceae, thereby changing the gut microbiota structure and composition. Meanwhile, ATTF changed the gut metabolites mainly enriched in pathways such as the serotonergic synapse. In addition, ATTF increased the serum serotonin (5-HT) content and mRNA expression of 5-hydroxytryptamine receptor 2A (5-HT2A), Phospholipase A2 (PLA2), and Cyclooxygenase-2 (COX2), which are involved in the serotonergic synaptic pathway. ATTF increased Transient receptor potential A1 (TRPA1), which promotes the release of 5-HT, and Myosin light chain 3(MLC3), which promotes smooth muscle motility. Notably, we established a network between gut microbiota, gut metabolites, and host parameters. The dominant gut microbiota Lactobacillus and Bacillus, prostaglandin J2 (PGJ2) and laxative phenotypes showed the most significant associations. The above results suggest that ATTF may relieve constipation by regulating the gut microbiota and serotonergic synaptic pathway and has great potential for laxative drug development in the future. [ABSTRACT FROM AUTHOR]

Belt tearing is the main safety accident of belt conveyor. The main cause of tearing is the doped bolt and steel in the conveying belt. In this paper, the bolt and steel are identified as the Hazard source of tear. In this paper, bolt and steel are defined as the risk sources of tearing. Effective detection of the source of danger can effectively prevent the occurrence of conveyor belt tearing accidents. Here we use deep learning to detect the hazard source image. We improved on the SSD(Single Shot MultiBox Detector) model. Replace the original backbone network with an improved Shufflenet_V2, and replace the original position loss function with the CIoU loss function. Additionally, it compares this new approach to previous methods. The proposed model has surpassed other state-of-art methods with more than 94% accuracy. In addition, when deployed without GPU acceleration, the detection speed can reach 20fps. It can meet the requirements of real-time detection. The experimental results show that the proposed model can realize the online detection of hazard sources, so as to prevent longitudinal tearing of conveyor belt. [ABSTRACT FROM AUTHOR]

The naphthalene derivative fluorescent probe F6 was synthesized and a 1 × 10−3 mol/L solution of Al3+ and other metals to be tested was prepared for the subsequent experiments. The Al3+ fluorescence system of the naphthalene derivative fluorescent probe F6 was successfully constructed as demonstrated by fluorescence emission spectroscopy. The optimal time, temperature and pH of the reaction were investigated. The selectivity and anti-interference ability of the probe F6 for Al3+ were investigated by fluorescence spectroscopy in a methanol solution. The experiments showed that the probe has high selectivity and anti-interference ability for Al3+. The binding ratio of F6 to Al3+ was 2:1, and the binding constant was calculated to be 1.598 × 105 M−1. The possible mechanism of the binding of the two was speculated. Different concentrations of Al3+ were added to Panax Quinquefolium and Paeoniae Radix Alba. The results showed that the recoveries of Al3+ were 99.75–100.56% and 98.67–99.67%, respectively. The detection limit was 8.73 × 10−8 mol/L. The experiments demonstrated that the formed fluorescence system can be successfully adapted for the determination of Al3+ content in two Chinese herbal medicines, which has good practical application. [ABSTRACT FROM AUTHOR]

Aberrant expression of the phosphatidylinositol 3-kinase (PI3K) signalling pathway is often associated with tumourigenesis, progression and poor prognosis. Hence, PI3K inhibitors have attracted significant interest for the treatment of cancer. In this study, a series of new 6-(imidazo[1,2-a]pyridin-6-yl)quinazoline derivatives were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS spectra analyses. In the in vitro anticancer assay, most of the synthetic compounds showed submicromolar inhibitory activity against various tumour cell lines, among which 13k is the most potent compound with IC50 values ranging from 0.09 μΜ to 0.43 μΜ against all the tested cell lines. Moreover, 13k induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC50 value of 1.94 nM. These results suggested that compound 13k might serve as a lead compound for the development of PI3Kα inhibitor. [ABSTRACT FROM AUTHOR]

With the development in agricultural mechanization and information technology, orchard agricultural machinery is also constantly pursuing the goal of intelligence and efficiency. Fruit picking is the most labor-intensive part of the orchard harvesting process. In order to resolve the problems of high labor intensity, low picking efficiency, and labor shortage when harvesting dwarf high-density orchards, an automatic navigation fruit-picking platform with voice control was developed in the present study. First, the platform utilized a voice-controlled high-level extendable working platform and a fruit-box-lifting device to adapt to varying orchard planting row spacing and enable convenient fruit box loading and unloading. Second, an automatic navigation system, which employed China's Beidou navigation satellite system to acquire positional data and the Stanley algorithm for path-tracking control, was implemented. Third, the fruit-picking platform with automatic navigation system was fabricated and assembled, its outer wheel steering was measured to have a maximum angle of 30.3° and an average minimum turning radius of 4.5 m, meeting the turning radius requirements under orchard conditions. Finally, automatic navigation tests of the developed platform were performed in the orchard conditions. The results indicated that the platform could maintain a straight-line path with a maximum lateral deviation of 101.5 mm and a maximum absolute average deviation of 44.1 mm at 0.4 m/s. Under the U-shaped paths, the measured maximum lateral deviation was 148.6 mm and the maximum absolute average deviation was 57.2 mm. The navigation accuracy was sufficient to meet the requirements for the harvesting platform's routine operation in the orchards. [ABSTRACT FROM AUTHOR]

The construction of high-rise oblique grid buildings requires a large amount of concrete. To save resources, an oblique grid of intersecting nodes composed of steel outer tubes and steel fiber, recycled concrete inner tubes (OGSFRCIN) has been proposed. ABAQUS is used to study the mechanical properties of the nodes under axial pressure, accounting for the effects of six parameters: the oblique angle, the thickness of the stiffening ring, the thickness of the connecting plate, the concrete strength, the recycled aggregate replacement rate, and the steel fiber content. The results show that the oblique angle, connecting plate thickness, concrete strength, and steel fiber content significantly affect the ultimate bearing capacity of specimens. The reinforcing ring thickness has a significant effect on the evolution of lateral displacement. It is not advisable to use components with a replacement rate of 100% recycled aggregate in engineering practice because of insufficient lateral stiffness and ultimate strength. The specimen's out-of-plane displacement is tightly restricted when the connecting plate's thickness is greater than or equal to 10 mm. In practical engineering, the connecting plate and reinforcing ring thickness should not be less than 10 mm, and the recommended steel fiber content is 1.0% to 2.0%. Through the analysis of the mechanical properties of the OGSFRCIN under monotonic axial compression and reciprocating axial tension and compression loads, it can be seen that OGSFRCIN have good mechanical properties and can be applied in engineering practice. Here, the modified formulas for calculating the bearing capacity of OGSFRCIN are put forward. [ABSTRACT FROM AUTHOR]

This study investigated, in detail, the characteristics of the Late Triassic fine-grained sediments in the third member of the Xujiahe Formation (Xu-3 Member), in the Western Sichuan Depression, and the paleoenvironmental evolution during their deposition through petrological interpretation, mineralogical composition characterization, and element geochemical analysis. According to the mineralogical composition, the Xu-3 Member can be divided into two petrological types, namely clayey fine-grained felsic sedimentary rocks and lime fine-grained felsic sedimentary rocks. The main mineral components are siliceous, clay, and carbonate minerals. Through the cluster analysis of major elements, all samples could be divided into two types with different major elemental characteristics. Trace elements exhibited distinct Sr depletion, relative enrichment of large ion lithophile elements, and high field strength elements. Two REE enrichment patterns were observed, which could be attributed to differences in the provenance area and tectonic background. The paleoclimate of the sedimentary area was warm and humid, but it was hotter and drier in the southern and central parts of the depression. The change trend of paleo-productivity was consistent with the paleoclimate. The waters in the sedimentary environment were mainly brackish water to saline water, with fresh water in the southern part of the depression. The paleo-redox conditions of the waters were mainly sub-oxidation to sub-reduction, but the southern part of the depression was more oxidative. The provenance area experienced a moderate degree of chemical weathering under a warm and humid paleoclimate, same as the depositional area. However, the depositional environments differed between the northern and south-central parts of the depression. [ABSTRACT FROM AUTHOR]

The emergence of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) revolutionized the treatment of advanced-stage non-small cell lung cancer (NSCLC). Detected in more than 50% of late-stage lung adenocarcinoma in Asian patients, the EGFR mutation was regarded as a golden mutation for Asians. However, resistance to TKIs seems inevitable and severely hinders patients from getting further benefits from treatment. Even though resistance caused by EGFR T790M could be effectively managed by third-generation EGFR-TKIs currently, resistance to third-generation EGFR-TKIs is still a troublesome issue faced by both clinicians and patients. Various efforts have been made to maximize the benefits of patients from EGFR-TKIs therapy. Thus, new requirements and challenges have been posed to clinicians of this era. In this review, we summarized the clinical evidence on the efficacy of third-generation EGFR-TKIs in patients with EGFR-mutated NSCLC. Then, we discussed advancements in sequential treatment aiming to delay the onset of resistance. Moreover, the resistance mechanisms and features were depicted to help us better understand our enemies. Lastly, we put forward future strategies, including recent approaches involving the utilization of antibody drug conjugates against resistance and research directions about shaping the evolution of NSCLC as a core idea in the management of NSCLC. [ABSTRACT FROM AUTHOR]

Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflammation players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent Literature about this topic. First, we update conditions and mechanisms, including RNAs, extracellular vesicles/exosomes, endogenous compounds, and ethnic/pharmacological agents/extracts regulating NLRP3 function. Second, we pinpoint NLRP3-activating mechanisms and known NLRP3 inhibition effects in acute (ischemia, stroke, hemorrhage), chronic (Alzheimer's disease, Parkinson's disease, Huntington's disease, MS, ALS), and virus-induced (Zika, SARS-CoV-2, and others) human brain diseases. The available data show that (i) disease-specific divergent mechanisms activate the (mainly animal) brains NLRP3; (ii) no evidence proves that NLRP3 inhibition modifies human brain diseases (yet ad hoc trials are ongoing); and (iii) no findings exclude that concurrently activated other-than-NLRP3 inflammasomes might functionally replace the inhibited NLRP3. Finally, we highlight that among the causes of the persistent lack of therapies are the species difference problem in disease models and a preference for symptomatic over etiologic therapeutic approaches. Therefore, we posit that human neural cell-based disease models could drive etiological, pathogenetic, and therapeutic advances, including NLRP3's and other inflammasomes' regulation, while minimizing failure risks in candidate drug trials. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON), one of the main mycotoxins with enteric toxicity, genetic toxicity, and immunotoxicity, and is widely found in corn, barley, wheat, and rye. In order to achieve effective detoxification of DON, the least toxic 3-epi-DON (1/357th of the toxicity of DON) was chosen as the target for degradation. Quinone-dependent dehydrogenase (QDDH) reported from Devosia train D6-9 detoxifies DON by converting C3-OH to a ketone group with toxicity of less than 1/10 that of DON. In this study, the recombinant plasmid pPIC9K-QDDH was constructed and successfully expressed in Pichia pastoris GS115. Within 12 h, recombinant QDDH converted 78.46% of the 20 μg/mL DON to 3-keto-DON. Candida parapsilosis ACCC 20221 was screened for its activity in reducing 86.59% of 3-keto-DON within 48 h; its main products were identified as 3-epi-DON and DON. In addition, a two-step method was performed for epimerizing DON: 12 h catalysis by recombinant QDDH and 6 h transformation of the C. parapsilosis ACCC 20221 cell catalyst. The production rates of 3-keto-DON and 3-epi-DON were 51.59% and 32.57%, respectively, after manipulation. Through this study, effective detoxification of 84.16% of DON was achieved, with the products being mainly 3-keto-DON and 3-epi-DON. [ABSTRACT FROM AUTHOR]

Early heat and drought priming may increase the plant's ability to resist later drought and heat stress. However, it remains unclear whether combined heat and drought priming can enhance the acclimation of plants to later combined stress by improving physiological activities. In this study, maize seedlings were first pre-exposed twice to heat, drought, and a combination of stresses followed by recovery, and then subjected to six days of more severe stresses. A considerable reduction in photosynthetic pigment content, stomatal size, and photosynthesis was observed under heat and drought conditions, and the changes in the above indicators were amplified under combined stress conditions. Stress priming improves antioxidant defense and cellular osmoregulation, as indicated by improved superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione reductase (GR), and ascorbate peroxidase activities, as well as elevated soluble sugar (SS) and proline (Pro) contents. Lower superoxide anion and malondialdehyde contents and injury index in the primed seedlings demonstrated the mitigation of oxidative stress. ROC analysis revealed that SOD and POD had considerable reliability in determining that maize seedlings were experiencing heat stress (AUC = 0.941–0.971); GR and SS were capable of accurately monitoring drought stress that was being experienced by plants (AUC = 0.919–0.958); and SOD, GR, and Pro had more capability for detecting the combination of heat and drought stress (AUC = 0.907–0.958). Collectively, the primed seedlings exhibited better performance than the non-primed seedlings, exhibiting stronger stress acclimation supported by an effective antioxidant defense system and osmoregulatory function. [ABSTRACT FROM AUTHOR]

Background and Objectives: The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in the antitumor immune response (IR). By interacting both with each other and with tumor cells, different immune mechanisms are activated or inhibited, which can suppress or promote the development and progression of cervical cancer (CC). Our aim was to investigate some of the main components of the cellular immune response in TME—tumor-infiltrating cytotoxic T cells (Tc, CD8+) and tumor-associated macrophages (TAMs, CD68+)—in patients with CC. Materials and Methods: We analyzed 72 paraffin-embedded tumor tissues of patients diagnosed and treated at Medical University Pleven, Bulgaria. Patients were classified according to the 2018 FIGO (International Federation of Gynaecology and Obstetrics) classification. From each patient, we selected one histological slide with hematoxylin eosin staining. In a microscopic evaluation, CD8+ T lymphocytes and CD68+-positive macrophages were counted in the tumor and stroma of five randomly selected fields at ×40 magnification (HPF). We analyzed the relationship between intratumoral and stromal CD8 and CD68 expression and FIGO stage and N status. Results: There was no significant association between the expression levels of intratumoral and stromal CD68+ cells in the different FIGO stages and according to the lymph nodes' involvement. For CD8+ cells, the association of stromal infiltration was also not found, but T intratumor infiltration was associated with a higher FIGO stage, despite the fact that the results did not reach significance (p = 0.063, Fisher test). Intratumoral CD8+ cells were significantly associated with positive N status, (p = 0.035). Discussion: The separation of tumor-infiltrating cytotoxic T cells and tumor-associated macrophages into intratumoral and stromal is inconsequential. In our study, the level of infiltration of CD68+ cells in tumors and stromata was not significantly associated with tumor progression or lymph node involvement. The results were different for CD8+ cells, in which levels of infiltration were associated with lymph nodes' statuses. Conclusions: The separate evaluation of CD68+ immune cells in the TME as intratumoral and stromal is not beneficial for defining prognoses, since the presence of these cells is not associated with the patient's stage. In our study, the presence of CD8+ cells was significantly associated with lymph node metastases. The prognostic value of the obtained results can be enriched with an additional study of the lymphocyte phenotype, including B and other subtypes of T lymphocytes, NK cells, as well as molecules involved in the immune response, such as HLA subtypes. [ABSTRACT FROM AUTHOR]

Expansins are pH-dependent enzymatic proteins that irreversibly and continuously facilitate cell-wall loosening and extension. The identification and comprehensive analysis of Ginkgo biloba expansins (GbEXPs) are still lacking. Here, we identified and investigated 46 GbEXPs in Ginkgo biloba. All GbEXPs were grouped into four subgroups based on phylogeny. GbEXPA31 was cloned and subjected to a subcellular localization assay to verify our identification. The conserved motifs, gene organization, cis-elements, and Gene Ontology (GO) annotation were predicted to better understand the functional characteristics of GbEXPs. The collinearity test indicated segmental duplication dominated the expansion of the GbEXPA subgroup, and seven paralogous pairs underwent strong positive selection during expansion. A majority of GbEXPAs were mainly expressed in developing Ginkgo kernels or fruits in transcriptome and real-time quantitative PCR (qRT-PCR). Furthermore, GbEXLA4, GbEXLA5, GbEXPA5, GbEXPA6, GbEXPA8, and GbEXPA24 were inhibited under the exposure of abiotic stresses (UV-B and drought) and plant hormones (ABA, SA, and BR). In general, this study expanded our understanding for expansins in Ginkgo tissues' growth and development and provided a new basis for studying GbEXPs in response to exogenous phytohormones. [ABSTRACT FROM AUTHOR]

In this study, the basalt fiber content (0%, 0.075%, and 0.15%) and replacement ratio of recycled coarse aggregate (0%, 50%, and 100%) were used as parameters, and the compressive strength of 15 cubes and 15 prisms was analyzed. The failure morphology of the specimens was characterized, and the cubic compressive strength, axial compressive strength, elastic modulus, Poisson's ratio, and other mechanical property indices of the specimens were measured. Upon increasing the replacement ratio, the degree of damage of the specimens gradually increased, whereas the cubic compressive strength, axial compressive strength, and elastic modulus gradually decreased. As the replacement ratio was increased from 50% to 100%, the cubic compressive strength and elastic modulus were noted to decrease the most by about 9.07% and 9.87%, respectively. On the other hand, the Poisson's ratio first decreased, followed by an increase. Upon increasing the fiber content, the degree of damage of the specimens was gradually reduced, whereas the cubic compressive strength, axial compressive strength, and elastic modulus gradually increased. As the fiber content increased from 0.075% to 0.15%, the axial compressive strength and elastic modulus increased the most by about 6.65% and 10.19%, respectively. On the other hand, the Poisson's ratio gradually decreased. Based on the test data, the functional relationships between the strength indices and different variables, as well as the conversion value of each strength index and different variables were established; after comparison and verification, the formula calculation results were found to be in good agreement with the test results. The microstructural changes in the basalt fiber reinforced recycled aggregate concrete were characterized by scanning electron microscopy (SEM), and the changes in the mechanical properties of the basalt fiber reinforced recycled aggregate concrete as well as the mechanism of fiber modification and reinforcement were explained from a micro perspective. [ABSTRACT FROM AUTHOR]

With an emphasis on environmental protection and the sustainable development of resources, the reuse of waste concrete has long been a research hotspot, and the study of WCP is the key to improving the efficiency of waste concrete utilization. In this study, in which we reviewed the relevant literature at home and abroad in recent years, we first used Citespace software to visualize and analyze the research on the reuse and activation methods of WCP in recent years. In this paper, we explain the characteristics of WCP and the influence of different activation methods on the activity index of WCP. We summarize the mechanical properties and working properties of WCP mortar products, and finally, the optimal activation method of WCP and the optimal amount of WCP in mortar preparation are analyzed. In addition, some problems in the current research are determined. [ABSTRACT FROM AUTHOR]

Thin−walled parts are widely used in many important fields because of performance and structural lightweight requirements. They are critical parts because they usually carry the core functions of high−end equipment. However, their high−performance machining has been facing severe challenges, among which the dynamics problem is one of the most important obstacles. The machining system is easily subjected to chatter due to the weak rigidity of the thin−walled structure and slender cutting tool, which significantly deteriorates the surface quality and reduces the machining efficiency. Extensive studies aiming at eliminating machining chatter have been carried out in the recent decades. This paper systematically reviews previous studies on the identification of system dynamic characteristics, modeling and prediction of chatter stability, and chatter elimination/suppression methods and devices. Finally, existing problems are summarized, and future research is concluded. [ABSTRACT FROM AUTHOR]

Based on the modified KM (Kock–Mecking) model, a cutting constitutive model of AA7050-T7451 considering anisotropy is established in this article. With the aid of high-speed cutting FEM simulation and experiment, the micro-influence mechanism of anisotropy on high-speed cutting hardening of AA7050-T7451 was studied from three aspects: micro-morphology, residual strain, and plastic deformation. By analyzing the macro-micro correlation mechanism of dislocation density, work hardening, and cutting temperature, a "Three-Stage" model of work hardening is put forward. The results show that the work-hardening behavior of high-speed cutting AA7050-T7451 shows obvious anisotropic characteristics. And the work hardening degree is less than 0° and 90° at the material forming angle of 45°. At the 45° forming angle, the material dislocation density is the highest, and the grains are most prone to the dislocation slip. The macroscopic properties show that the microhardness of the material is small. The "Three-stage" model reveals the micro-evolution mechanism of work-hardening behavior. It is found that the dislocation density dominates the work-hardening behavior in stages I and II, and cutting temperature dominates the work-hardening behavior in stage III. The microhardness of the material increases sharply at first and then tends to be flat. [ABSTRACT FROM AUTHOR]

Daylily (Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of daylily from the perspective of gastro-intestinal transit, defecation parameters, short-chain organic acids, gut microbiome, transcriptomes and network pharmacology. The results show that dried daylily (DHC) intake accelerated the defecation frequency of mice, while it did not significantly alter the levels of short-chain organic acids in the cecum. The 16S rRNA sequencing showed that DHC elevated the abundance of Akkermansia, Bifidobacterium and Flavonifractor, while it reduced the level of pathogens (such as Helicobacter and Vibrio). Furthermore, a transcriptomics analysis revealed 736 differentially expressed genes (DEGs) after DHC treatment, which are mainly enriched in the olfactory transduction pathway. The integration of transcriptomes and network pharmacology revealed seven overlapping targets (Alb, Drd2, Igf2, Pon1, Tshr, Mc2r and Nalcn). A qPCR analysis further showed that DHC reduced the expression of Alb, Pon1 and Cnr1 in the colon of constipated mice. Our findings provide a novel insight into the anti-constipation effects of DHC. [ABSTRACT FROM AUTHOR]