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Marine microbial secondary metabolites with diversified structures have been found as promising sources of anti-inflammatory lead compounds. This review summarizes the sources, chemical structures, and pharmacological properties of anti-inflammatory natural products reported from marine microorganisms in the past three years (2021-2023). Approximately 252 anti-inflammatory compounds, including 129 new ones, were predominantly obtained from marine fungi and they are structurally divided into polyketides (51.2%), terpenoids (21.0%), alkaloids (18.7%), amides or peptides (4.8%), and steroids (4.3%). This review will shed light on the development of marine microbial secondary metabolites as potential anti-inflammatory lead compounds with promising clinical applications in human health.

Macrolactins have attracted considerable attention due to their value and application in medicine and agriculture. However, poor yields severely hinder their broader application in these fields. This study aimed to improve macrolactins production in Bacillus siamensis using a combined atmospheric and room-temperature plasma mutagenesis and a microbial microdroplet culture system. After 25 days of treatment, a desirable strain with macrolactins production 3.0-fold higher than that of the parental strain was successfully selected. The addition of 30 mg/L ZnSO 4 further increased macrolactins production to 503 ± 37.6 μg/mL, representing a 30.9 % improvement in production compared to controls. Based on transcriptome analysis, the synthesis pathways of amino acids, fengycin, and surfactin were found to be downregulated in IMD4036. Further fermentation experiments confirmed that inhibition of the comparative fengycin synthesis pathway was potentially driving the increased production of macrolactins. The strategies and possible mechanisms detailed in this study can provide insight into enhancing the production of other secondary metabolites toxic to the producer strains., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Personalized medicine has gained more attention for cancer precision treatment due to patient genetic heterogeneity in recent years. However, predicting the efficacy of antitumor drugs in advance remains a significant challenge to achieve this task., Objective: This study aims to predict the efficacy of antitumor drugs in individual cancer patients based on clinical data., Methods: This paper proposes to predict personalized antitumor drug efficacy based on clinical data. Specifically, we encode the clinical text of cancer patients as a probability distribution vector in hidden topics space using the Latent Dirichlet Allocation (LDA) model, named LDA representation. Then, a neural network is designed, and the LDA representation is input into the neural network to predict drug response in cancer patients treated with platinum drugs. To evaluate the effectiveness of the proposed method, we gathered and organized clinical records of lung and bowel cancer patients who underwent platinum-based treatment. The prediction performance is assessed using the following metrics: Precision, Recall, F1-score, Accuracy, and Area Under the ROC Curve (AUC)., Results: The study analyzed a dataset of 958 patients with non-small cell cancer treated with antitumor drugs. The proposed method achieved a stratified 5-fold cross-validation average Precision of 0.81, Recall of 0.89, F1-score of 0.85, Accuracy of 0.77, and AUC of 0.81 for cisplatin efficacy prediction on the data, which most are better than those of previous methods. Of these, the AUC value is at least 4% higher than those of the previous. At the same time, the superior result over the previous method persisted on an independent dataset of 266 bowel cancer patients, showing the generalizability of the proposed method. These results demonstrate the potential value of precise tumor treatment in clinical practice., Conclusions: Combining LDA and neural networks can help predict the efficacy of antitumor drugs based on clinical text. Our approach outperforms previous methods in predicting drug clinical efficacy., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: The aim of this study was to study the risk factors influencing the occurrence of moderate to severe post-thrombotic syndrome (PTS) within 2 years in patients with subacute lower extremity deep vein thrombosis (DVT)., Methods: Seventy patients who developed moderate to severe PTS within 2 years after subacute lower extremity DVT from June 2018 to June 2022 were retrospectively selected as the case group. They were matched 1:1 by sex and age (±5 years) with 70 patients who did not develop moderate to severe PTS during the same follow-up period as the control group. Multiple logistic regression, stratified analysis, and interaction analyses were used to explore the risk factors for moderate to severe PTS., Results: The multiple logistic regression model showed that patients with iliofemoral vein thrombosis had a significantly increased risk of developing moderate to severe PTS within 2 years. Patients who underwent intraluminal intervention treatment during hospitalization had a significantly reduced risk. The odds ratios were 4.000 (95% confidence interval, 1.597-10.016) for the femoral-popliteal vein thrombosis and 0.262 (95% confidence interval, 0.106-0.647) for the anticoagulation treatment group. The stratified analysis showed that intraluminal intervention treatment was a protective factor against moderate to severe PTS within 2 years across different strata of hypertension, thrombus type, body mass index, duration of anticoagulation, and wearing compression stockings. Additionally, there was an interaction between thrombus type and treatment method, with intraluminal intervention treatment having a more pronounced effect on preventing moderate to severe PTS in patients with iliofemoral vein thrombosis., Conclusions: Iliofemoral vein thrombosis is a risk factor for the development of moderate to severe PTS within 2 years in patients with subacute lower extremity DVT. Intraluminal intervention treatment can reduce the risk of moderate to severe PTS, especially in patients with iliofemoral vein thrombosis., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

B7-H3 (CD276), an immune checkpoint molecule, is overexpressed in various types of cancer and their tumor vasculature, demonstrating significant associations with adverse clinical outcomes. In addition to its well-known immune functions, B7-H3 exhibits dual co-stimulatory/co-inhibitory roles in normal physiology and the tumor microenvironment. The non-immune functions of B7-H3 in tumor cells and the tumor vasculature, including promoting tumor cell anti-apoptosis, proliferation, invasion, migration, drug resistance, radioresistance, as well as affecting cellular metabolism and angiogenesis, have increasingly gained attention from researchers. Particularly, the co-expression of B7-H3 in both tumor cells and tumor endothelial cells highlights the higher potential and clinical utility of therapeutic strategies targeting B7-H3. This review aims to summarize the recent advances in understanding the non-immune functions of B7-H3 in tumors and provide insights into therapeutic approaches targeting B7-H3, focusing on its co-expression in tumor cells and endothelial cells. The aim is to establish a theoretical foundation and practical reference for the development and optimization of B7-H3-targeted therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Hu, Hui and Jiang.)

The KCNQ1 gene encodes a voltage-gated potassium channel, which plays an important role in the repolarization of myocardial action potentials. Mutations in this gene often result in type 1 long QT syndrome (LQT1). Here, we generated a KCNQ1 (c.1032 + 2 T > C) mutant human embryonic stem cell line (WAe009-A-1D) based on the transient expression adenine base editing system that converts base A to G. The WAe009-A-1D cell maintains the morphology, pluripotency, and normal karyotype of the stem cells and is capable of differentiating into all three germ layers in vivo., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was financially supported by Henan Provincial Health Committee Foundation (number SBGJ202202009)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The clinical significance of plasma soluble programmed cell death ligand 1 (sPD-L1) and vascular endothelial growth factor (VEGF) for non-small cell lung cancer (NSCLC) treated with the combination of anti-angiogenic therapy and anti-PD-L1 antibody (Ab) remain unknown. This study aimed to explore the association between plasma sPD-L1 and VEGF levels and the prognosis of NSCLC patients treated with the combination of Envafolimab and Endostar. Peripheral blood samples were collected from 24 NSCLC patients at baseline and after 6 weeks of treatment and were detected for sPD-L1 and VEGF levels. Both baseline and posttreatment sPD-L1 were significantly higher in progressive disease (PD) group than in controlled disease (CD) group (median: 77.5 pg/ml vs. 64.6 pg/ml, P  = 0.036, median: 8451 pg/ml vs. 5563 pg/ml, P  = 0.012). In multivariate analysis, lower baseline sPD-L1 levels were significantly associated with longer progression-free survival (PFS) (HR = 6.834, 95% CI: 1.350-34.592, P  = 0.020). There were significantly higher posttreatment VEGF levels in PD group compared with CD group (median: 323.7 pg/ml vs. 178.5 pg/ml, P  = 0.009). Higher posttreatment VEGF levels were significantly associated with shorter PFS in multivariate analysis (HR = 5.911, 95% CI: 1.391-25.122, P  = 0.016). Plasma sPD-L1 and VEGF levels are associated with the clinical response and prognosis of NSCLC patients treated with the combination of PD-L1 inhibitors and anti-angiogenetic therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The laser-induced damage of ultraviolet fused silica optics is a critical factor that limits the performance enhancement of high-power laser facility. Currently, wet etching technology based on hydrofluoric acid (HF) can effectively eliminate absorbing impurities and subsurface defects, thereby significantly enhancing the damage resistance of fused silica optics. However, with an increase in the operating fluence, the redeposition defects generated during wet etching gradually become the primary bottleneck that restricts its performance improvement. The composition and morphology of redeposition defects were initially identified in this study, followed by an elucidation of their formation mechanism. A mitigation strategy was then proposed, which combines a reduction in the generation of precipitation with an acceleration of the precipitation dissolution process. Additionally, we systematically investigated the influence of various process parameters such as extrinsic impurity, etching depth, and megasonic excitation on the mitigation of deposition defects. Furthermore, a novel multiple-step dynamic etching method was developed. Through comprehensive characterization techniques, it has been confirmed that this new etching process not only effectively mitigate redeposition defects under low fluence conditions but also exhibits significant inhibition effects on high fluence precursors. Consequently, it significantly enhances the laser damage resistance performance of fused silica optics.

Anti-tumor drug efficacy prediction poses an unprecedented challenge to realizing personalized medicine. This paper proposes to predict personalized anti-tumor drug efficacy based on clinical data. Specifically, we encode the clinical text as numeric vectors featured with hidden topics for patients using Latent Dirichlet Allocation model. Then, to classify patients into two classes, responsive or non-responsive to a drug, drug efficacy predictors are established by machine learning based on the Latent Dirichlet Allocation topic representation. To evaluate the proposed method, we collected and collated clinical records of lung and bowel cancer patients treated with platinum. Experimental results on the data sets show the efficacy and effectiveness of the proposed method, suggesting the potential value of clinical data in cancer precision medicine. We hope that it will promote the research of drug efficacy prediction based on clinical data., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Carapace color plays an important role in the communication, reproduction, and self-defense of crustaceans, which is also related to their economic value. Chinese mitten crab (Eriocheir sinensis) is an important aquaculture species in China, and there are different strains with heritable carapace colors, i.e. Green, White, and Red. However, there is a lack of research on the formation mechanism of carapace color of this species. This study was conducted to compare the histology and transcriptome in the inner membrane of three carapace color strains of E. sinensis. Histological comparisons revealed that the inner membrane of green and red carapace crabs contained more melanin, appearing in clusters, and had a higher presence of yellow or orange pigments. In contrast, the inner membrane of white carapace crabs had smaller and fewer melanin particles, as well as a lower presence of yellow or orange pigments. Observation under an electron microscope showed that the inner membrane of E. sinensis contained a large number of collagen fibers and various types of cells, including fibroblasts, melanocytes, and other tissue cells, which exhibited different levels of activity. Transcriptome analysis showed that the Green, Red, and White strains of E. sinensis had approximately 80.3 K, 81.6 K and 80.3 K expressed unigenes in their inner membranes, respectively. When comparing Green and Red crabs, there were 2, 850 upregulated genes and 2, 240 downregulated genes. In the comparison between Red and White crabs, there were 2, 853 upregulated genes and 2, 583 downregulated genes. Furthermore, there were 2, 336 upregulated genes and 2, 738 downregulated genes in the inner membranes between White and Green crabs. Among these genes, some members of the solute carriers family, which are involved in carotenoid transportation, showed differential expression among the three carapace color strains. Additionally, significant differences were observed in the expression of genes related to melanin synthesis, including wingless/integrate, tyrosinase, guanine nucleotide-binding protein inhibitory subunit, cell adhesion molecule, adenylyl cyclase, and creb-binding protein. there were no differences in the gene expression levels of the crustacyanin family. In conclusion, this study identified several candidate genes associated with carapace color in the inner membrane of E. sinensis, suggesting a close relationship between the heritable carapace colors and the transport of the carotenoids as well as the synthesis of melanin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Numerous studies have demonstrated that regulatory T (Treg) cells play an important role in the tumour microenvironment (TME). The aim of this study was to investigate whether VEGFR2 affects the expression of miR-3200-3p in exosomes secreted by tumour cells, thereby influencing Treg senescence in the TME. The results showed that VEGFR2 expression level was the highest in Calu-1 cells, and after transfection with si-VEGFR2, the exosomes secreted from Calu-1 cells were extracted and characterised with no significant difference from the exosomes of the untransfected group, but the expression of miR-3200-3p in the exosomes of the transfected si-VEGFR2 group was elevated. The Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) results suggested that exosomes highly expressing miR-3200-3p could inhibit Treg cell viability and promote apoptosis levels when treated with Treg cells. Detection of the senescence-associated proteins p16 INK4A and MMP3 by western blot (WB) revealed that exosomes highly expressing miR-3200-3p were able to elevate their protein expression levels. Tumour xenograft experiments demonstrated that exosomes with high miR-3200-3p expression promoted Treg cell senescence and inhibited subcutaneous tumour growth in nude mice. Dual-luciferase reporter assays and RNA pull-down assays showed that miR-3200-3p could be linked with DDB1. Overexpression of DDB1 reverses changes in DCAF1/GSTP1/ROS protein expression caused by exosomes with high miR-3200-3p expression. In conclusion, inhibition of VEGFR2 expression in tumour cells promotes the expression of miR-3200-3p in exosomes secreted by tumour cells. miR-3200-3p enters the TME through exosomes and acts on DDB1 in Treg cells to promote senescence of Treg cells to inhibit tumour progression., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The mounting body of evidence demonstrates the growing importance of long noncoding RNAs in the advancement of tumors. This study aimed to investigate the molecular mechanism of lnc-SNAPC5-3:4 in non-small cell lung cancer (NSCLC). We investigated the expression of miR-224-3p and lnc-SNAPC5-3:4 in clinical NSCLC samples and NSCLC cell lines using reverse transcription polymerase chain reaction (RT-PCR). In vitro studies, A549 cell growth was estimated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EDU), and flow cytometry assays. In vivo studies, NSCLC tumorigenesis was determined using xenograft tumor mouse models, tumor growth was evaluated using antigen Kiel 67 (Ki67) staining, and tumor apoptosis was detected through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The relationship between lnc-SNAPC5-3:4 and miR-224-3p was determined by luciferase reporter gene assay. Results indicated that the expression of lnc-SNAPC5-3:4 was observed to be downregulated in NSCLC tissues and cell lines. After overexpression of lnc-SNAPC5-3:4 in cultured A549 cells, proliferation decreased and apoptosis increased. Furthermore, the expression of miR-224-3p was targeted and negatively regulated by lnc-SNAPC5-3:4. The lnc-SNAPC5-3:4 upregulation inhibited cell proliferation and promoted apoptosis, which was partially blocked by miR-224-3p overexpression in A549 cells. In addition, we constructed a subcutaneous inoculation model using BALB/c nude mice, and the results indicated that lnc-SNAPC5-3:4 overexpression restrained the growth of subcutaneous tumors, decreased Ki67 expression levels, and increased apoptosis, as indicated by TUNEL staining in nude mice. However, miR-224-3p transfection resulted in the reversal of the inhibitory effect of lnc-SNAPC5-3:4 on tumor growth. In conclusion, our study revealed that lnc-SNAPC5-3:4 inhibits tumor progression in NSCLC by targeting miR-224-3p. This study provides a potential therapeutic target for inhibiting NSCLC progression., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The present study aimed to investigate the interactive effects of dietary supplementation to the feed with astaxanthin and/or DHA on the color and odor of Eriocheir sinensis ovaries. The results revealed that astaxanthin supplementation significantly increased redness of E. sinensis ovaries (P < 0.05). Moreover, the addition of either astaxanthin or DHA alone to the feed affected the deposition of carotenoids and fatty acids in E. sinensis ovaries. More importantly, the simultaneous supplementation of astaxanthin and DHA significantly improved color, carotenoid content, and polyunsaturated fatty acid content (P < 0.05) in E. sinensis ovaries, as well as increased the content of aroma compounds during thermal processing. Based on the present findings, the optimal combination of dietary astaxanthin and DHA is 100 mg/kg of synthetic astaxanthin and 0.15% of DHA, respectively, which could improve color and odor quality of ovaries for E. sinensis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Membrane separation is considered an effective approach to water purification. Nevertheless, membrane fouling dramatically decreases the separation efficiency and lifetime of membranes, thus limiting its further development and application. Herein, a multifunctional self-cleaning MIL-88A(Fe) decorated polyvinyl alcohol/sodium alginate (MIL-88A(Fe)@PVA-SA) nanofiber membrane was prepared by electrospinning and in-situ growth methods for the separation of oil/water emulsions and photo-Fenton degradation of dyes. The membrane possesses superhydrophilicity with a water contact angle (WCA) of 0° and superoleophobicity with underwater oil contact angle (UCA) of 161.7°, and exhibits superior separation efficiency (>99.5 %) and permeation flux (1140-2455 L/m 2 /h) for different oil/water emulsions. Moreover, the membrane exhibited an outstanding photo-Fenton performance under visible light, with degradation efficiencies (~99.9 %) towards methylene blue (MB) and reactive red 24 (RR24) within 90 min. Importantly, the membrane can be easily regenerated by simple rinsing and photo-Fenton self-cleaning treatment. In this study, MIL-88A(Fe)@PVA-SA nanofiber membrane has a promising application in dye removal and oil/water separation, providing a new idea to develop novel membrane materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

High relative humidity (RH) and high temperature are expected more frequently due to climate change, and can severely affect the growth of chrysanthemums. In order to analyze the interactive effects of RH and high temperature on the photosynthetic performance of chrysanthemum, a completely randomized block experiment was conducted with three factors, namely temperature (Day/night temperature, 35°C/18°C, 38°C/18°C, 41°C/18°C), RH (Whole day RH, 50%, 70%, 90%), and treatment duration (3d, 6d, 9d). The control (CK) temperature was 28°C/18°C and RH was 50%. The results showed that with the increase of temperature, the apparent quantum efficiency (AQE), maximum net photosynthetic rate (P n-max ), net photosynthetic rate (P n ), transpiration rate (T r ), water use efficiency (WUE), maximal recorded fluorescence intensity (F m ), PSII maximal photochemical efficiency (F v /F m ), absorption flux per cross section (ABS/CSm), trapped energy flux per cross section (TRo/CSm), electron transport flux per cross section (ETo/CSm) and photosynthetic pigment content of leaves significantly decreased, the minimal recorded fluorescence intensity (F o ), fluorescence intensity at point J of the OJIP curve (F j ) and non-photochemical quenching per cross section (DIo/CSm) significantly increased, the fluorescence difference kinetics of the OJ phase of chrysanthemum leaves showed K-bands. P n , AQE, F m , F v , F v /F m , ABS/CSm, TRo/CSm, ETo/CSm and photosynthetic pigment content were higher at 70% RH than the other two RH conditions. The dominant factor causing the decrease of P n in leaves was stomatal limitation at 35°C,38°C, three RH conditions, 3d and 6d, but non-stomatal limitation at 41°C and 9d. There was an interaction between temperature and RH, with a significant impact on P n . The temperature had the greatest impact on P n , followed by RH. This study confirms that heat stress severely affects the photosynthesis of chrysanthemum leaves, and when the temperature reaches or exceeds 35°C, adjusting the RH to 70% can effectively reduce the impact of heat stress on chrysanthemum photosynthesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Jiang, Agathokleous, Lu, Yang and Li.)

The carapace coloration is important for the environmental adaptation and reproductive behaviors of crustaceans. We selected red, green and white three carapace color strains of Chinese mitten crab (Eriocheir sinensis) strains. These three carapace colors have stable heritability, but the mechanism for their coloration remains unclear.Through histological observations, we have found significant differences in the composition of pigment cells and pigments within the inner membrane of the three color strains, which may be one of the reasons for the color variation. The levels of various carotenoids in both the shell and inner membrane tissues of red and green strains were significantly higher than those of the white strain, while there was no significant difference between the red and green strains. Proteomics studies have identified 2, 034 and 947 different proteins in the shell and inner membrane, respectively. In the shell, there were 18, 13 and 43 differential proteins between red and white strains, green and white strains and green and red strains, respectively. In the inner membrane, there were 44, 24 and 16 differential proteins between red and white strains, green and white strains and green and red strains, respectively. It is clear that the deposited quantity of carotenoids affects the shell formation of three color strains. Some members of the hemocyanin family showed significant variation among different strains. The study yielded two crustacyanin proteins, which were extracted from both the shell and membrane. Of the two proteins, only Crustacyanin-A1 expression showed a difference between the red and green shells strains. In conclusion, these results indicated that the carapace color formation of E. sinensis may be accomplished through pigment binding proteins (PBPs) and pigment cells, which enhance the understanding of color formation mechanism for crustacean., Competing Interests: Declaration of competing interest We confirm that all research and data presented in this paper is accurate, reliable, and unbiased. We have followed all ethical guidelines and disclosed any potential conflicts of interest to ensure transparency and integrity in our research. We believe that these disclosures do not compromise the validity or integrity of our findings., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aerosol particle contamination in high-power laser facilities has become a major cause of internal optical component damage resistance and service life reduction. In general, contaminating particles primarily originate from stray light; therefore, it is crucial to investigate the mechanism and dynamics of the dynamic contaminating particle generation to control the cleanliness level. In this study, corresponding research was conducted on experiments and theory. We investigated the particle generation and surface composition modification under the action of a laser. We employed various surface analytical methods to identify the possible variations in the aluminum alloy surface during laser irradiations. A theoretical model for particle ejection from aluminum alloy surfaces was established by taking the adhesion force and laser cleaning force (due to thermal expansion) into account. The results show that the threshold energies for contamination particle generation and damage are around 0.1 and 0.2 J/cm 2 , respectively. Subsurface impurities are the primary source of particles, and particle adhesion density is related to surface roughness. Pollution particle generation and splashing processes include temperature increases, phase changes, impact diffusion, and adhesion. The results provide a reference for the normal operation of high-energy laser systems. The results also suggest that the laser irradiation pretreatment of aluminum alloy surfaces is essential to improve the cleanliness level.

Competing Interests: The authors declare no conflict of interest.

A 46-year-old male visited our hospital with blood stool and constipation. Colonoscopy revealed a broad-based protruded lesion in the rectum.The endoscopic ultrasonography showed the lesion invaded the submucosa, and the boundary between the local and intrinsic muscular layer was not clear. Transanal local excision was conducted, the pathology showed a rare case of mucosal prolapse syndrome merging chronic suppurative inflammation.

The pinion-streaked snout Schrankia costaestrigalis is a new potato pest that has recently been recorded in China. In this study, we analyzed the complete mitochondrial genome of S. costaestrigalis . The results revealed the mitogenome (GenBank: OQ181231) to occur as a circular DNA molecule of 16,376 bp with 51.001% AT content, including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and 1 control region. Notably, the PCGs exhibited typical ATN (Met) start codons, including cox1 , which deviated from the usual CGA start codon observed in other lepidopteran mitogenomes, and followed the conventional TAN stop codons. The 22 tRNA genes demonstrated the ability to form a cloverleaf structure, with the exception of trnS1-NCU, which lacked the DHU arm present in other Erebidae mitogenomes. Additionally, conserved motifs like "ATAGA + poly-T (19 bp) stretch" and five microsatellite-like elements (TA) were identified in the AT-rich region. The phylogenetic trees revealed that the Hypenodinae subfamily forms an independent lineage closely related to Erebinae and Catocalinae. The comprehensive mitogenome of S. costaestrigalis will greatly enhance future studies focused on the molecular classification and phylogenetic understanding of the Hypenodinae subfamily within the larger family Erebidae.

Malignant melanoma (MM) is the most common and deadliest type of skin cancer and is associated with high mortality rates across all races and ethnicities. Although present treatment options combined with surgery provide short-term clinical benefit in patients and early diagnosis of non-metastatic MM significantly increases the probability of survival, no efficacious treatments are available for MM. The etiology and pathogenesis of MM are complex. Acquired drug resistance is associated with a pool prognosis in patients with advanced-stage MM. Thus, these patients require new therapeutic strategies to improve their treatment response and prognosis. Multiple studies have revealed that ferroptosis, a non-apoptotic form of regulated cell death (RCD) characterized by iron dependant lipid peroxidation, can prevent the development of MM. Recent studies have indicated that targeting ferroptosis is a promising treatment strategy for MM. This review article summarizes the core mechanisms underlying the development of ferroptosis in MM cells and its potential role as a therapeutic target in MM. We emphasize the emerging types of small molecules inducing ferroptosis pathways by boosting the antitumor activity of BRAFi and immunotherapy and uncover their beneficial effects to treat MM. We also summarize the application of nanosensitizer-mediated unique dynamic therapeutic strategies and ferroptosis-based nanodrug targeting strategies as therapeutic options for MM. This review suggests that pharmacological induction of ferroptosis may be a potential therapeutic target for MM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ta, Jiang, Zhang and Wang.)

Unsupervised domain adaptation (UDA) has attracted increasing attention in recent years, which adapts classifiers to an unlabeled target domain by exploiting a labeled source domain. To reduce the discrepancy between source and target domains, adversarial learning methods are typically selected to seek domain-invariant representations by confusing the domain discriminator. However, classifiers may not be well adapted to such a domain-invariant representation space, as the sample- and class-level data structures could be distorted during adversarial learning. In this article, we propose a novel transferable feature learning approach on graphs (TFLG) for unsupervised adversarial domain adaptation (DA), which jointly incorporates sample- and class-level structure information across two domains. TFLG first constructs graphs for minibatch samples and identifies the classwise correspondence across domains. A novel cross-domain graph convolutional operation is designed to jointly align the sample- and class-level structures in two domains. Moreover, a memory bank is designed to further exploit the class-level information. Extensive experiments on benchmark datasets demonstrate the effectiveness of our approach compared to the state-of-the-art UDA methods.

Nitrate is the main form of inorganic nitrogen that crop absorbs, and nitrate transporter 2 (NRT2) is a high affinity transporter using nitrate as a specific substrate. When the available nitrate is limited, the high affinity transport systems are activated and play an important role in the process of nitrate absorption and transport. Most NRT2 cannot transport nitrates alone and require the assistance of a helper protein belonging to nitrate assimilation related family (NAR2) to complete the absorption or transport of nitrates. Crop nitrogen utilization efficiency is affected by environmental conditions, and there are differences between varieties, so it is of great significance to develop varieties with high nitrogen utilization efficiency. Sorghum bicolor has high stress tolerance and is more efficient in soil nitrogen uptake and utilization. The S . bicolor genome database was scanned to systematically analyze the gene structure, chromosomal localization, physicochemical properties, secondary structure and transmembrane domain, signal peptide and subcellular localization, promoter region cis -acting elements, phylogenetic evolution, single nucleotide polymorphism (SNP) recognition and annotation, and selection pressure of the gene family members. Through bioinformatics analysis, 5 NRT2 gene members (designated as SbNRT2 - 1a , SbNRT2 - 1b , SbNRT2 - 2, SbNRT2 - 3, and SbNRT2 - 4 ) and 2 NAR2 gene members (designated as SbNRT3 - 1 and SbNRT3 - 2 ) were identified, the number of which was less than that of foxtail millet. SbNRT2 / 3 were distributed on 3 chromosomes, and could be divided into four subfamilies. The genetic structure of the same subfamilies was highly similar. The average value of SbNRT2/3 hydrophilicity was positive, indicating that they were all hydrophobic proteins, whereas α-helix and random coil accounted for more than 70% of the total secondary structure. Subcellular localization occurred on plasma membrane, where SbNRT2 proteins did not contain signal peptides, but SbNRT3 proteins contained signal peptides. Further analysis revealed that the number of transmembrane domains of the SbNRT2s family members was greater than 10, while that of the SbNRT3s were 2. There was a close collinearity between NRT2 / 3s of S . bicolor and Zea mays . Protein domains analysis showed the presence of MFS&#95;1 and NAR2 protein domains, which supported executing high affinity nitrate transport. Phylogenetic tree analysis showed that SbNRT2 / 3 were more closely related to those of Z . mays and Setaria italic . Analysis of gene promoter cis -acting elements indicated that the promoter region of SbNRT2 / 3 had several plant hormones and stress response elements, which might respond to growth and environmental cues. Gene expression heat map showed that SbNRT2 - 3 and SbNRT3 - 1 were induced by nitrate in the root and stem, respectively, and SbNRT2 - 4 and SbNRT2 - 3 were induced by low nitrogen in the root and stem. Non-synonymous SNP variants were found in SbNRT2 - 4 and SbNRT2 - 1a . Selection pressure analysis showed that the SbNRT2 / 3 were subject to purification and selection during evolution. The expression of SbNRT2 / 3 gene and the effect of aphid infection were consistent with the expression analysis results of genes in different tissues, and SbNRT2 - 1b and SbNRT3 - 1 were significantly expressed in the roots of aphid lines 5-27sug, and the expression levels of SbNRT2 - 3 , SbNRT2 - 4 and SbNRT3 - 2 were significantly reduced in sorghum aphid infested leaves. Overall, genome-wide identification, expression and DNA variation analysis of NRT2/3 gene family of Sorghum bicolor provided a basis for elucidating the high efficiency of sorghum in nitrogen utilization.

Stormwater runoff from roadways is a global threat to water quality, aquatic organisms, and ecosystems. Tire tread wear particles (TWP) from roadway runoff may lead to urban runoff mortality syndrome (URMS) in some aquatic organisms. We tested the hypothesis that urban runoff from roadways can kill zooplankton. Both roadway runoff and TWP leachate were acutely lethal to a model species, the water flea Daphnia pulex. Life table experiments further revealed the lowered survival rates, intrinsic rate of increase, average life span, and net productive rate of D. pulex when exposed to roadway runoff and TWP leachate. The tire rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) mainly contributed to the TWP toxicity. The toxicity of TWP and 6PPD extracted varied with time in nature. Cladocerans and rotifers were more sensitive to TWP and 6PPD than copepods. These results demonstrate the presence of URMS in zooplankton, which may cascade through food webs and affect aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tumor-associated macrophages (TAMs) can be widely heterogeneous, based on their ontogeny and function, and driven by the tissue-specific niche. TAMs are highly abundant in the melanoma tumor microenvironment (TME), usually correlating with worse prognoses. However, the understanding of their diversity may be harnessed for therapeutic purposes. Here, we used the clinically relevant YUMM1.7 model to study melanoma TAM origin and dynamics during tumor progression. In i.d. YUMM1.7 tumors, we identified distinct TAM subsets based on F4/80 expression, with the F4/80 high fraction increasing over time and displaying a tissue-resident-like phenotype. While skin-resident macrophages showed mixed ontogeny, F4/80 + TAM subsets in the melanoma TME originated almost exclusively from bone-marrow precursors. A multiparametric analysis of the macrophage phenotype showed a temporal divergence of the F4/80 + TAM subpopulations, which also differed from the skin-resident subsets and their monocytic precursors. Overall, the F4/80 + TAMs displayed co-expressions of M1- and M2-like canonical markers, while RNA sequencing showed differential immunosuppressive and metabolic profiles. Gene-set enrichment analysis (GSEA) revealed F4/80 high TAMs to rely on oxidative phosphorylation, with increased proliferation and protein secretion, while F4/80 low cells had high pro-inflammatory and intracellular signaling pathways, with lipid and polyamine metabolism. Overall, we provide an in-depth characterization of and compelling evidence for the BM-dependency of melanoma TAMs. Interestingly, the transcriptomic analysis of these BM-derived TAMs matched macrophage subsets with mixed ontogeny, which have been observed in other tumor models. Our findings may serve as a guide for identifying potential ways of targeting specific immunosuppressive TAMs in melanoma.

Graph, as an important data representation, is ubiquitous in many real world applications ranging from social network analysis to biology. How to correctly and effectively learn and extract information from graph is essential for a large number of machine learning tasks. Graph embedding is a way to transform and encode the data structure in high dimensional and non-euclidean feature space to a low dimensional and structural space, which is easily exploited by other machine learning algorithms. We have witnessed a huge surge of such embedding methods, from statistical approaches to recent deep learning methods such as the graph convolutional networks (GCN). Deep learning approaches usually outperform the traditional methods in most graph learning benchmarks by building an end-to-end learning framework to optimize the loss function directly. However, most of the existing GCN methods can only perform convolution operations with node features, while ignoring the handy information in edge features, such as relations in knowledge graphs. To address this problem, we present CensNet, Convolution with Edge-Node Switching graph neural network, for learning tasks in graph-structured data with both node and edge features. CensNet is a general graph embedding framework, which embeds both nodes and edges to a latent feature space. By using line graph of the original undirected graph, the role of nodes and edges are switched, and two novel graph convolution operations are proposed for feature propagation. Experimental results on real-world academic citation networks and quantum chemistry graphs show that our approach achieves or matches the state-of-the-art performance in four graph learning tasks, including semi-supervised node classification, multi-task graph classification, graph regression, and link prediction.

Background: Attention deficit/hyperactivity disorder (ADHD) has been identified as a risk factor for obesity in both children and adolescents. However, the mechanisms underlying the relationship between ADHD and obesity are still unclear. This study aimed to test a theoretical model of whether anxiety/depression is an intermediary factor in the ADHD-obesity relationship., Methods: Data were derived from the National Health Interview Survey (NHIS), a principal source of information on the health of the civilian noninstitutionalized population of the United States. A total of 35,108 adolescents aged 12-17 years old from 2010-2015 NHIS and 2016-2018 NHIS representing 46,550,729 individuals in the weighted population, had a parent-reported previous ADHD diagnosis, emotional problems, and height and weight data. Mediation analyses were used to explore whether anxiety/depression is an intermediary factor in the relationship between ever having ADHD and obesity. Mediation analyses were performed using multiple logistic regressions., Results: The findings showed that ADHD was a predictor of obesity. This relationship was partially mediated by depression(2010-2015: β=0.28, 95%CI:0.13-0.43; 2016-2018: β=0.26, 95%CI:0.03-0.49), as well as anxiety (2010-2015: β=0.28, 95%CI:0.18-0.38)., Conclusions: Our study suggests the hypothetical role of depression and anxiety as underlying mechanisms in the association between ever having ADHD and obesity in adolescents. When treating children with ADHD, clinicians need to be particularly attentive to whether they show emotional problems and use interventions to eliminate anxiety/depression to protect against obesity., (© 2023. The Author(s).)

Introduction: In CameL phase 3 study (ClinicalTrials.gov: NCT03134872), addition of camrelizumab to first-line chemotherapy significantly improved the progression-free survival in patients with stages IIIB to IV nonsquamous NSCLC. Here, we present outcomes after a minimum follow-up of 43.9 months since last patient randomization., Methods: Eligible patients were randomized 1:1 to 4 to 6 cycles of camrelizumab plus carboplatin and pemetrexed or chemotherapy alone every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only (n = 205 and 207, respectively). Total camrelizumab exposure was up to 2 years., Results: As of January 31, 2022, camrelizumab plus chemotherapy exhibited substantially improved overall survival over chemotherapy alone (median, 27.1 versus 19.8 mo; hazard ratio = 0.72 [95% confidence interval: 0.57-0.92]). In the chemotherapy-alone group, 95 patients (45.9%) crossed over to camrelizumab monotherapy. After adjustment for crossover, the survival benefit with camrelizumab plus chemotherapy was more pronounced (adjusted hazard ratio = 0.55 [95% confidence interval: 0.42-0.71]). In camrelizumab plus chemotherapy group, 33 patients completed 2 years of camrelizumab. Objective response rate was 97.0%, with ongoing responses in 17 of the 32 responses (53.1%), and 93.9% (31 of 33) of the patients were alive at data cutoff. Safety profiles were consistent with the previous report, and no obvious evidence of cumulative toxicity was found with long exposure to camrelizumab., Conclusions: Camrelizumab plus carboplatin and pemetrexed provides long-term survival benefit over chemotherapy, with manageable toxicity and remarkable and durable response in patients receiving 2 years of camrelizumab, further supporting camrelizumab combination as first-line treatment for advanced nonsquamous NSCLC., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The main objective of this study was to compare the pharmacokinetic (PK) bioequivalence of two capecitabine tablets and explore the different PK profiles of various tumors in Chinese patients with cancer. All 76 patients with a confirmed cancer diagnosis were included in this study. A single dose of 2000 mg of test or reference capecitabine (Xeloda, Hoffmann-La Roche) was orally administered postprandially. After 24 hours of washout, the patients were administered the test or the reference capecitabine alternately. PK samples were taken at the time of predose up to 6 hours postdose. Bioequivalence evaluation was performed using the geometric mean ratios of peak concentration in plasma (C max) , area under the concentration-time curve from time 0 to 6 h (AUC 0-t) , and area under the concentration-time curve from time 0 to infinity (AUC 0-∞ ) for capecitabine and 5-fluorouracil (5-FU). In this study, 90% confidence intervals of test/reference mean ratios of C max , AUC 0-t , AUC 0-∞ of capecitabine and 5-FU were in the range of 80%-125%. Both the test and reference capecitabine regimens were well tolerated in this study. Furthermore, we found that patients with esophageal-gastrointestinal cancers had higher exposure to capecitabine and a shorter time to C max (T max) than those with breast cancer. In conclusion, a single oral dose of 2000 mg of test capecitabine tablets after postprandial administration was bioequivalent to the reference drug., (© 2022, The American College of Clinical Pharmacology.)

This study aimed to determine the expression and investigate the role of chemokine 26 (CCL26) in colon cancer cells. The Cancer Genome Atlas (TCGA) analysis, qRT-PCR, and western blotting were used to detect CCL26 expression while the Kaplan-Meier plotter was used to analyze the survival of patients with colon cancer. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and Transwell assays were performed to measure the viability, proliferation, apoptosis, and migration and invasion of colon cancer cells, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to analyze the signaling pathways regulated by CCL26. Western blotting, used to measure protein expression in this study, found overexpression of CCL26 in colon tumors. Low CCL26 levels were associated with better survival of patients as CCL26 siRNAs markedly reduced viability and proliferation, accelerated apoptosis, decreased migration and invasion, enhanced E-cadherin expression, and reduced N-cadherin and vimentin expression in cancer cells. The opposite results were obtained in CCL26-overexpressed colon cancer cells. In addition, CCL26 activated the epithelial-mesenchymal transition (EMT) pathway. CCL26 siRNAs suppressed the expression of tissue inhibitor matrix metalloproteinase 1 (TIMP1), nicotinamide N-methyltransferase (NNMT), and fibromodulin (FMOD), while CCL26 overexpression significantly increased the expression of all. EMT inhibition using the EMT inhibitor C19 eliminated the effect of CCL26 overexpression on colon cancer cells. In summary, CCL26 is involved in colon cancer progression through regulation of the EMT signaling pathway., Competing Interests: Conflict of interest The authors declare that they have no competing interests exist., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroiso-quinoline (Salsolinol, SAL) is a dopamine metabolite that is toxic to dopaminergic neurons in vitro and in vivo, and is involved in the pathogenesis of Parkinson's disease (PD). However, the molecular mechanism by which SAL induces neurotoxicity in PD remains challenging for future investigations. This study found that SAL induced neurotoxicity in SH-SY5Y cells and mice. RNA sequencing (RNAseq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to detect differentially expressed genes in SAL-treated SH-SY5Y cells. We found that NLR family pyrin domain-containing 3 (NLRP3)-dependent pyroptosis was enriched by SAL, which was validated by in vitro and in vivo SAL models. Further, NLRP3 inflammasome-related genes (ASC, NLRP3, active caspase 1, IL-1β, and IL-18) were increased at the mRNA and protein level. Acteoside mitigates SAL-induced neurotoxicity by inhibiting NLRP3 inflammasome-related pyroptosis in in vitro and in vivo PD models. In summary, the present study suggests for the first time that NLRP3-dependent pyroptosis plays a role in the pathogenesis of SAL-induced PD, and acteoside mitigates SAL-induced pyroptosis-dependent neurotoxicity in in vitro and in vivo PD models. The present results demonstrated a new mechanism whereby SAL mediates neurotoxicity by activating NLRP3-dependent pyroptosis, further highlighting SAL-induced pyroptosis-dependent neurotoxicity as a potential therapeutic target in PD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The liver is a highly metabolic organ and plays a crucial role in the transportation, storage, and/or detoxication of xenobiotics. Liver damage induced by xenobiotics (e.g., heavy metal, endocrine disrupting chemicals, Chinese herbal medicine, or nanoparticles) has become a pivotal reason for liver diseases, leading to great clinical challenge and much attention for the past decades. Given that endoplasmic reticulum (ER) is the prominent organelle involved in hepatic metabolism, ER dysfunction, namely, ER stress, is clearly observed in various liver diseases. In response to ER stress, a conserved adaptive signaling pathway known as unfolded protein response (UPR) is activated to restore ER homeostasis. However, the prolonged ER stress with UPR eventually leads to the death of hepatocytes, which is a pathogenic event in many hepatic diseases. Therefore, analyzing the perturbation in the activation or inhibition of ER stress and the UPR signaling pathway is likely an effective marker for investigating the molecular mechanisms behind the toxic effects of xenobiotics on the liver. We review the role of ER stress in hepatic diseases and xenobiotic-induced hepatotoxicity, which not only provides a theoretical basis for further understanding the pathogenesis of liver diseases and the mechanisms of hepatotoxicity induced by xenobiotics but also presents a potential target for the prevention and treatment of xenobiotic-related liver diseases., Competing Interests: The authors declare that they have no conflicting interests., (Copyright © 2022 Yujing Zhang et al.)

Purpose: Anlotinib is an oral small-molecule multitarget tyrosine kinase inhibitor that hampers neovascularization thus providing antitumor effect. The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical study to evaluate the efficacy of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). The ALTER 0303 results showed that patients in the anlotinib group had a median progression-free survival of 5.4 months, a significant improvement compared with 1.4 months in the placebo group; however, median overall survival was only extended by 3.3 months (9.6 vs 6.3 months). The problem of anlotinib resistance cannot be ignored, and an in-depth exploration of biomarkers of anlotinib treatment response is urgently needed to further improve the efficacy of anlotinib in the treatment of NSCLC. This study aimed to identify plasma exosome markers that could be used to monitor the efficacy of anlotinib., Methods: We enrolled 5 patients with advanced NSCLC, and 15 blood samples were collected before anlotinib treatment, when the treatment was effective, and when the treatment was ineffective. The plasma exosomal RNA profiles were analyzed by whole-transcriptome sequencing at three different stages. The expression of dysregulated exosomal RNAs in 43 additional patients was also verified by real-time quantitative PCR., Results: In the plasma exosomal RNA profiles of the 5 patients with advanced NSCLC during treatment with anlotinib, 7 miRNAs, 3 lncRNAs, and 83 mRNAs were significantly dysregulated. The regulation trend was opposite when the treatment was effective and ineffective, showing dynamic changes. After validation, we finally found that plasma exosomal lnc-SNAPC5-3:4 was significantly upregulated when anlotinib treatment was effective, and it was significantly downregulated when the treatment failed (p < 0.05). Thus, it can be used as a potential biomarker for monitoring the efficacy of anlotinib., Conclusion: Our results demonstrate the potential of plasma exosomal lnc-SNAPC5-3:4 as a biomarker for monitoring anlotinib efficacy., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Gastrointestinal bleeding (GIB) is a potential contributing factor for poor prognosis of spontaneous basal ganglia hemorrhage (BGH). This study aimed to investigate the predictive value of new inflammatory biomarkers including neutrophil to lymphocytes (NLR) on admission and construct a nomogram for rapidly predicting GIB in acute BGH., Methods: The retrospective study included all patients with acute BGH admitted from the emergency department in Huashan Hospital from July 2017 to January 2019. Multivariate analysis was conducted to evaluate the correlation between factors within 24 h and the occurrence of GIB within 7 days after BGH. The receiver operating characteristic (ROC) curve was performed to estimate the prediction ability of inflammatory biomarkers. A nomogram based on significant predictors was validated by ROC curve and calibration curve., Results: A total of 122 patients were enrolled in this study, and the incidence of GIB was 23.0%. Patients with GIB had larger hematoma volume (≥30 ml), lower Glasgow Coma Scale (GCS) score (≤8) and increased inflammatory biomarkers on admission. ROC curve revealed that NLR had a high predictive value to the complication (area under the curve = 0.87). According to multivariate analysis, NLR, GCS score, and hematoma volume were main factors for nomogram, with good calibration and discrimination., Conclusions: Neutrophil-to-lymphocyte ratio and GCS score within 24 h after the onset of acute BGH are the independent risk factors for GIB. The nomogram developed by these predictors may assist surgeons in rapidly assessing and preventing of GIB for BGH patients in earlier stage., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Xanthone-containing natural products display diverse pharmacological properties. The biosynthetic mechanisms of the xanthone formation have not been well documented. Here we show that the flavoprotein monooxygenase FlsO1 in the biosynthesis of fluostatins not only functionally compensates for the monooxygenase FlsO2 in converting prejadomycin to dehydrorabelomycin, but also unexpectedly converts prejadomycin to xanthone-containing products by catalyzing three successive oxidations including hydroxylation, epoxidation and Baeyer-Villiger oxidation. We also provide biochemical evidence to support the physiological role of FlsO1 as the benzo[b]-fluorene C5-hydrolase by using nenestatin C as a substrate mimic. Finally, we resolve the crystal structure of FlsO1 in complex with the cofactor flavin adenine dinucleotide close to the "in" conformation to enable the construction of reactive substrate-docking models to understand the basis of a single enzyme-catalyzed multiple oxidations. This study highlights a mechanistic perspective for the enzymatic xanthone formation in actinomycetes and sets an example for the versatile functions of flavoproteins., (© 2022. The Author(s).)

Epigallocatechin 3-gallate (EGCG), an abundant polyphenolic component derived from green tea extract, possesses versatile bioactivities that can combat many diseases. During the last decade, EGCG was shown to be effective in experimental models of Parkinson's disease (PD). Several experimental studies have suggested that it has pleiotropic neuroprotective effects, which has enhanced the appeal of EGCG as a therapeutic strategy in PD. In this review, we compiled recent updates and knowledge of the molecular mechanisms underlying the neuroprotective effects of EGCG in PD. We focused on the effects of EGCG on apoptosis, oxidative stress, inflammation, ferroptosis, modulation of dopamine production, and the aggregation of α-synuclein. The review highlights the pharmacological features of EGCG and its therapeutic implications in PD. Taken together, the accumulated data indicate that EGCG is a promising neuroprotective compound for the treatment of PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wu, Li, Lang, Li, Jiang, Wan, Chen and Wang.)

The incorporation of montmorillonite (MMT) into Nylon 6 can endow advantages like improved mechanical strength and thermal stability, making Nylon 6/MMT a possible ideal alternative for Nylon 66. However, the relationship between the microstructure and physical properties of nylon 6/MMT nanocomposites is unclear so far due to the complicated system, including the highly asymmetric geometry of the exfoliated MMT layer and the complicated interaction between MMT layers and entangled nylon 6 chains. Herein, we focus on two processes, namely the impact of MMT on the solidification procedure during molding and the toughness-brittleness transition during the tensile stretch, in order to elucidate the structure-property relationship of nylon 6/MMT composites. We firstly studied the solidification process of nylon 6/MMT with bending height experiments. The results showed that the solidification process occurs prior to the crystallization of nylon 6, indicating that a physical crosslinked network rather than a crystalline structure is the reason for the solidification process. Furthermore, the solidification speed has a step change at around 2 wt% MMT content, indicating that the MMT percolation network is related to the transition. We further studied the influence of MMT inclusion on the mechanical properties, and found the tensile strain at break showed a similar step change at around 2 wt% MMT content, which further confirms the existence of an MMT percolation network above 2 wt% MMT content. It was generally believed that the main effect of MMT on nylon 6 is the nanofiller enforcement; we found that the percolation effect of the highly asymmetric 2-D nanofiller plays a central role in influencing the mechanical properties and solidification behavior during molding.

In recent years, progressive application of convolutional neural networks in image processing has successfully filtered into medical diagnosis. As a prerequisite for images detection and classification, object segmentation in medical images has attracted a great deal of attention. This study is based on the fact that most of the analysis of pathological diagnoses requires nuclei detection as the starting phase for obtaining an insight into the underlying biological process and further diagnosis. In this paper, we introduce an embedded attention model in multi-bridge Wnet (AMB-Wnet) to achieve suppression of irrelevant background areas and obtain good features for learning image semantics and modality to automatically segment nuclei, inspired by the 2018 Data Science Bowl. The proposed architecture, consisting of the redesigned down sample group, up-sample group, and middle block (a new multiple-scale convolutional layers block), is designed to extract different level features. In addition, a connection group is proposed instead of skip-connection to transfer semantic information among different levels. In addition, the attention model is well embedded in the connection group, and the performance of the model is improved without increasing the amount of calculation. To validate the model's performance, we evaluated it using the BBBC038V1 data sets for nuclei segmentation. Our proposed model achieves 85.83% F1-score, 97.81% accuracy, 86.12% recall, and 83.52% intersection over union. The proposed AMB-Wnet exhibits superior results compared to the original U-Net, MultiResUNet, and recent Attention U-Net architecture., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Macrolactins, a type of macrolide antibiotic, are toxic to the producer strains. As such, its level is usually maintained below the lethal concentration during the fermentation process. To improve the production of macrolactins, we applied adaptive laboratory evolution technology to engineer a saline-resistant mutant strain. The hypothesis that strains with saline resistance show improved macrolactins production was investigated., Results: Using saline stress as a selective pressure, we engineered a mutant strain with saline resistance coupled with enhanced macrolactins production within 60 days using a self-made device. As compared with the parental strain, the evolved strain produced macrolactins with 11.93% improvement in non-saline stress fermentation medium containing 50 g/L glucose, when the glucose concentration increased to 70 g/L, the evolved strain produced macrolactins with 71.04% improvement. RNA sequencing and metabolomics results revealed that amino acid metabolism was involved in the production of macrolactins in the evolved strain. Furthermore, genome sequencing of the evolved strain revealed a candidate mutation, hisD D41Y , that was causal for the improved MLNs production, it was 3.42 times higher than the control in the overexpression hisD D41Y strain. Results revealed that saline resistance protected the producer strain from feedback inhibition of end-product (macrolide antibiotic), resulting in enhanced MLNs production., Conclusions: In the present work, we successfully engineered a mutant strain with enhanced macrolactins production by adaptive laboratory evolution using saline stress as a selective pressure. Based on physiological, transcriptomic and genetic analysis, amino acid metabolism was found to benefit macrolactins production improvement. Our strategy might be applicable to improve the production of other kinds of macrolide antibiotics and other toxic compounds. The identification of the hisD mutation will allow for the deduction of metabolic engineering strategies in future research., (© 2022. The Author(s).)

This work was to investigate the impact of drying on the physical, chemical stability and character properties of P. aibuhitensis hydrolysate. Properties including amino acid composition, color stability, molecular weight distribution, powder morphology, etc. were compared between the freeze drying powder (FD) and spray drying powder (SD). They were fractionated with ultra filtration in antioxidant activities test. FD and SD contained amounts of amino acids and umami amino acids. SD exhibited the higher lightness and whiteness. SD had more compounds between 451 Da and 6511 Da. The surface morphology of FD was porous and flaky while SD was microsphere. SD had more volatile flavor substances and higher antioxidant activities on DPPH, hydroxyl, and superoxide radical-scavenging. In summary, results demonstrated that drying methods indeed affected the characteristics of hydrolysate, and the one prepared by spray drying method had the potential to be utilized for antioxidant food development and seafood seasoning., (Copyright © 2022. Published by Elsevier Ltd.)

A new cyclo-heptadepsipeptide xanthostatin B ( 1 ), together with isobutyryl hexapeptide ( 2 ), xanthostatin ( 3 ), TXS-1 ( 4 ) and TXS-2 ( 5 ), were isolated from the marine sponge derived Streptomyces sp. SCSIO 40064. The structures were elucidated by comprehensive spectroscopic data analyses and comparison with the literatures. The D-Val unit in 1 was assigned by Marfey's method. The absolute configuration of 4 was determined by X-ray crystallographic analysis. Compounds 1 ‒ 5 were evaluated for the inhibitory activities against four pharmaceutical targets and six antibacterial indicator strains. Compound 5 displayed α -glucosidase inhibitory activity with IC 50 value of 18.67 ± 1.27 µM.

Background: Leftover food consumption is very prevalent among the Chinese older adults, however, the potential effects of leftover eating consumption on depression have not yet been investigated., Objectives: The study aims to determine the association between leftover consumption on depression among older adults., Methods: Data of leftover consumption frequency was collected in a cross-sectional study with a provincial representative sample of 5992 older adults (aged 60 or older) in 2019. Depression symptoms were assessed by the 9-item screener Patient Health Questionnaire (PHQ-9). Multiple logistic regression models were applied to analyze the association of the frequency of leftover eating consumption and the presence and the severity of depression., Results: After controlling for all the covariates, the participants who consume leftover food everyday had higher risk of having depression symptom comparing to those who had the lowest frequency of leftover eating (OR: 1.675, 95% CI: 1.435-1.956, p < 0.001). The participants who consume leftover food every day was also associated with more severe depression symptoms (OR: 1.621, 95% CI: 1.397-1.881, p < 0.001), when comparing to the reference group. The associations seemed stronger in men than women., Limitations: The causal relationship between leftover consumption behavior and depression could not be determined due to the cross-sectional design. Moreover, the variety or handling method of the leftover food was not specified., Conclusion: Leftovers eating frequency was associated with the presence and severity of depression symptoms among older adults., (Copyright © 2022. Published by Elsevier B.V.)

This study aims to investigate the immunoglobulin superfamily containing leucine-rich repeat (ISLR) expression in gastric cancer (GC) and ISLR's underlying mechanisms regulation of GC progression. Through The Cancer Genome Atlas (TCGA) cohort datasets, we analyzed the ISLR expression in GC tumor tissues and normal tissues. ISLR expression in GC tissues and cells was determined using quantitative real-time polymerase chain reaction. Cell viability, proliferation, migration, and invasion assays were performed in GC cells transfected with sh-ISLR, ISLR plasmids, or controls. TCGA results showed that ISLR expression was higher in GC tumor tissues compared to normal tissues, and its expression levels were related to lymph node metastasis, tumor size, and clinical stage. ISLR was highly expressed in tumor cells. ISLR knockdown suppressed cell viability, proliferation, migration, and invasion in HGC-27 cells, whereas ISLR overexpression led to opposite effects in AGS cells. Gene Set Enrichment Analysis showed that ISLR could activate the epithelial-mesenchymal transition (EMT) signaling pathway. Silencing of ISLR suppressed EMT in HGC-27 cells and overexpression of ISLR promoted EMT in AGS cells. ISLR was overexpressed in both GC cell lines and tumor tissues, and our study first showed that silencing of ISLR inhibited GC cell growth and metastasis by reversing EMT.

Two new piericidins A5 ( 1 ) and G1 ( 2 ), a previously synthesized piericidin G2 ( 3 ), and two known piericidins A1 ( 4 ) and A2 ( 5 ) were isolated from the marine-derived Streptomyces sp. SCSIO 40063. The structures of 1 - 5 were elucidated by HRESIMS, 1 D, 2 D NMR data analyses and comparisons with the known compounds. Compound 2 showed moderate cytotoxicities against four human tumor cell lines SF-268, MCF-7, HepG2 and A549 with IC 50 values between 10.0 and 12.7 μM.

A photo-thermal absorption distribution probability curve based on a normal distribution model was proposed to describe the distribution of absorptive defects on fused silica surfaces under different processing conditions. Simultaneously, the maximum distribution probability absorption coefficient (MPA) and absorption distribution deviation (ADD) were used to quantitatively describe the overall absorption level and the uniformity of the absorption distribution on the fused silica surface. Based on this, the MPA (μ) and ADD (δ) were used to establish a statistical numerical relationship with the surface damage density of fused silica. The results showed that when μ ≤ 0.095 ± 0.015 and δ ≤ 0.045 ppm, the fused silica optics met the manufacturing process requirements for high laser-induced damage performance. Thus, a non-destructive approximate evaluation of the laser-induced damage density on the fused silica surface was achieved. This evaluation method provides a new, to the best of our knowledge, technology for evaluating the manufacturing process quality related to the damage performance of fused silica optics in high-power solid-state laser facilities and is an important supplement to popular destructive laser-induced damage testing methods.

Background: Anlotinib resistance is a challenge for advanced non-small cell lung cancer (NSCLC). Understanding the underlying mechanisms against anlotinib resistance is of great importance to improve prognosis and treatment of patients with advanced NSCLC., Methods: RT-qPCR assay was used to assess the level of miR-136-5p in anlotinib-resistant NSCLC cells and exosomes derived from anlotinib-resistant NSCLC cells. In addition, miR-136-5p level in tumor tissues from patients who exhibited a poor response to anlotinib therapy and patients who were therapy naïve or patients who exhibited a positive response to anlotinib therapy was detected by RT-qPCR assay., Results: In this study, we found that high levels of plasma exosomal miR-136-5p is correlated with clinically poor anlotinib response. In addition, anlotinib-resistant NSCLC cells promoted parental NSCLC cell proliferation via transferring functional miR-136-5p from anlotinib-resistant NSCLC cells to parental NSCLC cells via exosomes. Moreover, exosomal miR-136-5p could endow NSCLC cells with anlotinib resistance by targeting PPP2R2A, leading to the activation of Akt pathway. Furthermore, miR-136-5p antagomir packaging into anlotinib-resistant NSCLC cell-derived exosomes functionally restored NSCLC cell anlotinib sensitivity in vitro. Animal studies showed that A549/anlotinib cell-derived exosomal miR-136-5p agomir promoted A549 cell anlotinib resistance in vivo., Conclusion: Collectively, these findings indicated that anlotinib-resistant NSCLC cell-derived exosomal miR-136-5p confers anlotinib resistance in NSCLC cells by targeting PPP2R2A, indicating miR-136-5p may act as a potential biomarker for anlotinib response in NSCLC., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2021 Gu et al.)