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Inactivated suppressor of mothers against decapentaplegic homolog (SMAD) 4 significantly affects cancer development in pancreatic ductal adenocarcinoma (PDAC). However, the contribution of smad4 loss to drug resistance in PDAC is largely undetermined. In the present study, we reported that the loss of SMAD4 endows PDAC cells the ability to drug resistance through upregulating histone lysine demethylase, Lysine-Specific Demethylase 5B (KDM5B, also known as JARID1B or PLU1). Upregulated KDM5B was found in PDAC, associated with poor prognosis and recurrence of PDAC patients. Upregulated KDM5B promotes PDAC tumor malignancy, i.e. cancer cells stemness and drug resistance in vitro and in vivo, while KDM5B knockout exerts opposite effects. Mechanistically, loss of Smad4-mediated upregulation of KDM5B promotes drug resistance through inhibiting the discs-large homolog 1 (DLG1), thereby facilitating nuclear translocation of YAP to induce de novo lipogenesis. Moreover, m 6 A demethylase FTO is involved in the upregulation of KDM5B by maintaining KDM5B mRNA stability. Collectively, the present study suggested FTO-mediated KDM5B stabilization in the context of loss of Smad4 activate DLG1/YAP1 pathway to promote tumorigenesis by reprogramming lipid accumulation in PDAC. Our study confirmed that the KDM5B-DLG1-YAP1 pathway axis plays a crucial role in the genesis and progression of PDAC, and KDM5B was expected to become a target for the treatment of PDAC. The schematic diagram of KDM5B-DLG1-YAP pathway axis in regulating drug resistance of PDAC to gemcitabine (GEM). In the context of SMAD4 loss PDAC cells, FTO-mediated stabilization and upregulation of KDM5B promotes drug resistance through directly targeting DLG1 to promote YAP1 translocation to nucleus to induce de novo lipogenesis (DNL)., (© 2024. The Author(s).)

Lung cancer is the leading cause of global cancer-related deaths. Platinum-based chemotherapy is the first-line treatment for the most common type of lung cancer, i.e., non-small-cell lung cancer (NSCLC), but its therapeutic efficiency is limited by chemotherapeutic resistance. Therefore, it is vital to develop effective therapeutic modalities that bypass the common molecular mechanisms associated with chemotherapeutic resistance. Ferroptosis is a form of non-apoptotic regulated cell death characterized by iron-dependent lipid peroxidation (LPO). Ferroptosis is crucial for the proper therapeutic efficacy of lung cancer-associated chemotherapies. If targeted as a novel therapeutic mechanism, ferroptosis modulators present new opportunities for increasing the therapeutic efficacy of lung cancer chemotherapy. Emerging studies have revealed that the pharmacological induction of ferroptosis using natural compounds boosts the efficacy of chemotherapy in lung cancer or drug-resistant cancer. In this review, we first discuss chemotherapeutic resistance (or chemoresistance) in lung cancer and introduce the core mechanisms behind ferroptosis. Then, we comprehensively summarize the small-molecule compounds sourced from traditional medicines that may boost the anti-tumor activity of current chemotherapeutic agents and overcome chemotherapeutic resistance in NSCLC. Cumulatively, we suggest that traditional medicines with ferroptosis-related anticancer activity could serve as a starting point to overcome chemotherapeutic resistance in NSCLC by inducing ferroptosis, highlighting new potential therapeutic regimens used to overcome chemoresistance in NSCLC., 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 Wang, Hu, Fleishman, Li, Ren, Wang, Feng, Chen and Wang.)

Sepsis-associated encephalopathy (SAE), a common neurological complication of sepsis, is a heterogenous complex clinical syndrome caused by the dysfunctional response of a host to infection. This dysfunctional response leads to excess mortality and morbidity worldwide. Despite clinical relevance with high incidence, there is a lack of understanding for its both its acute/chronic pathogenesis and therapeutic management. A better understanding of the molecular mechanisms behind SAE may provide tools to better enhance therapeutic efficacy. Mounting evidence indicates that some types of non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis, and autophagy, contribute to SAE. Targeting these types of RCD may provide meaningful targets for future treatments against SAE. This review summarizes the core mechanism by which non-apoptotic RCD leads to the pathogenesis of SAE. We focus on the emerging types of therapeutic compounds that can inhibit RCD and delineate their beneficial pharmacological effects against SAE. Within this review we suggest that pharmacological inhibition of non-apoptotic RCD may serve as a potential therapeutic strategy against SAE., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: There are three major subtypes of breast cancer, ER+, HER2+ and triple-negative breast cancer (TNBC), namely ER-, PR-, HER2-. TNBC is the most aggressive breast cancer with poor prognosis and no target drug up to now. Actinomycin D (ActD) is a bioactive metabolite of marine bacteria that has been reported to have antitumor activity. The aim of study is to investigate whether ActD has a synergetic effect on TNBC with Doxorubicin (Dox), the major chemotherapeutic drug for TNBC, and explore the underlying mechanism., Methods: TNBC cell lines HCC1937, MDA-MB-436 and nude mice were used in the study. Drug synergy determination, LDH assay, MMP assay, Hoechst 33342 staining, Flow cytometry, Flexible docking and CESTA assay were carried out. The expression of proteins associated with apoptosis was checked by Western blot and siRNA experiments were performed to investigate the role of P53 and PUMA induced by drugs., Results: There was much higher apoptosis rate of cells in the ActD + Dox group than that in ActD group or Dox group. Expression of MDM2 and BCL-2 was reduced while expression of P53, PUMA and BAX were increased in the groups treated with ActD + Dox or Dox compared to the control group. Furthermore, P53 siRNA or PUMA siRNA tremendously abrogated the cell apoptosis in the groups treated by ActD, Dox and ActD + Dox. Flexible docking and CESTA showed that ActD can bind MDM2., Conclusions: ActD had a synergetic effect on TNBC with Dox via P53-dependent apoptosis and it may be a new choice for treatment of TNBC., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

IL-1β is an important proinflammatory cytokine with multifaceted modulatory roles in immune responses. In fish, recombinant IL-1β has been employed in the control of bacterial diseases, while the antiviral mechanisms of IL-1β remain largely unknown, and the efficacy of recombinant IL-1β as an immunomodulator to prevent viral diseases is still not determined. This study evaluated the immunomodulatory effects of recombinant grass carp IL-1β against grass carp reovirus (GCRV) in vitro and in vivo. Firstly, the mature form (Ser 111 -Lys 270 ) of grass carp IL-1β was identified, and its recombinant protein (designated as rgcIL-1β) was prepared through prokaryotic expression. Then, an in vitro evaluation model for rgcIL-1β activity was established in the CIK cells, with the appropriate concentration (600 ng/mL) and effect time (1 h). In vitro, rgcIL-1β could not only induce the production of proinflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α but also a series of antiviral factors including IFN-1, IFN-2, IFN-γ, and ISG15. Mechanistically, transcriptome analysis and western blotting confirmed that rgcIL-1β activated multiple transcriptional factors, including NF-κB, IRF1, IRF3, and IRF8, and the signal pathways associated with inflammatory cytokines and antiviral factors expression. Expectedly, rgcIL-1β treatment significantly inhibited GCRV replication in vitro. In vivo administration of rgcIL-1β via intraperitoneal pre-injection significantly aroused an antiviral response to restrict GCRV replication and intense tissue inflammation in grass carp, demonstrating the immunomodulatory effects of rgcIL-1β. More importantly, rgcIL-1β administrated with 10 ng/g and 1 ng/g could improve the survival rate of grass carp during GCRV infection. This study represents the first time to comprehensively reveal the immunomodulatory and antiviral mechanisms of IL-1β in fish and may also pave the way for further developing recombinant IL-1β as an immunotherapy for the prevention and control of fish viral diseases., 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.)

Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role of copper and copper triggered cell death in the pathogenesis of cancers have attracted attentions. Cuproptosis has garnered enormous interest in cancer research communities because of its great potential for cancer therapy. Copper-based treatment exerts an inhibiting role in tumor growth and may open the door for the treatment of chemotherapy-insensitive tumors. In this review, we provide a critical analysis on copper homeostasis and the role of copper dysregulation in the development and progression of cancers. Then the core molecular mechanisms of cuproptosis and its role in cancer is discussed, followed by summarizing the current understanding of copper-based agents (copper chelators, copper ionophores, and copper complexes-based dynamic therapy) for cancer treatment. Additionally, we summarize the emerging data on copper complexes-based agents and copper ionophores to subdue tumor chemotherapy resistance in different types of cancers. We also review the small-molecule compounds and nanoparticles (NPs) that may kill cancer cells by inducing cuproptosis, which will shed new light on the development of anticancer drugs through inducing cuproptosis in the future. Finally, the important concepts and pressing questions of cuproptosis in future research that should be focused on were discussed. This review article suggests that targeting cuproptosis could be a novel antitumor therapy and treatment strategy to overcome cancer drug resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other cell death modes, plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications and posttranslational modifications (PTMs) promote anticancer drug resistance, cancer progression, and metastasis. Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases (NSDs), cardiovascular diseases (CVDs), liver diseases, lung diseases, and kidney diseases. In this review, we first summarize the core molecular mechanisms of ferroptosis. Then, the roles of epigenetic processes, including histone PTMs, DNA methylation, and noncoding RNA regulation and PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, methylation, and ADP-ribosylation, are concisely discussed. The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases, including cancers, NSD, CVDs, liver diseases, lung diseases, and kidney diseases, as well as the application of epigenetic and PTM modulators in the therapy of these diseases, are then discussed in detail. Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other diseases. In addition, these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases., (© 2023. The Author(s).)

Objective: To explore the visible near-infrared spectroscopic (VNIRS) characteristics of intracerebral hematoma, and provide experimental basis for hematoma localization and residual detection in hypertensive intracerebral hemorrhage (HICH) surgery., Methods: Using VNIRS, spectral data of cerebral hematoma and cortex were collected during HICH craniotomy, and characteristic spectra were matched with paired-sample T-test. A partial least squares (PLS) quantitative model for cerebral hematoma spectra was established., Results: The reflectance of cerebral hematoma spectra in the 500-800 nm band was lower than that of the cortex, and there were statistically significant differences in the 510, 565, and 630 nm bands (P < 0.05). The calibration correlation coefficient of the PLS quantitative model for cerebral hematoma spectra was R 2  = 0.988, the cross-validation correlation coefficient was R 2 cv = 0.982, the root mean square error of calibration was RMSEC = 0.101, the root mean square error of cross-validation was RMSEV = 0.122, the external validation correlation coefficient was CORRELATION = 0.902, and the root mean square error of prediction was RMSEP = 0.426, indicating that the model had high fitting degree and good predictive ability., Conclusions: VNIRS as a noninvasive, real-time and portable analysis technology, can be used for real-time detection of hematoma during HICH surgery, and provide reliable basis for hematoma localization and residual detection., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The double-stranded DNA (dsDNA) viruses represented by adenovirus and monkeypox virus, have attracted widespread attention due to their high infectivity. In 2022, the global outbreak of mpox (or monkeypox) has led to the declaration of a Public Health Emergency of International Concern. However, to date therapeutics approved for dsDNA virus infections remain limited and there are still no available treatments for some of these diseases. The development of new therapies for treating dsDNA infection is in urgent need. In this study, we designed and synthesized a series of novel disulfide-incorporated lipid conjugates of cidofovir (CDV) as potential candidates against dsDNA viruses including vaccinia virus (VACV) and adenovirus (AdV) 5. The structure-activity relationship analyses revealed that the optimum linker moiety was C 2 H 4 and the optimum aliphatic chain length was 18 or 20 atoms. Among the synthesized conjugates, 1c exhibited more potency against VACV (IC 50  = 0.0960 μM in Vero cells; IC 50  = 0.0790 μM in A549 cells) and AdV5 (IC 50  = 0.1572 μM in A549 cells) than brincidofovir (BCV). The transmission electron microscopy (TEM) images revealed that the conjugates could form micelles in phosphate buffer. The stability studies in the GSH environment demonstrated that the formation of micelles in phosphate buffer might protect the disulfide bond from glutathione (GSH) reduction. The dominant means of the synthetic conjugates to liberate the parent drug CDV was by enzymatic hydrolysis. Furthermore, the synthetic conjugates remained sufficiently stable in simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and pooled human plasma, which indicated the possibility for oral administration. These results indicated 1c may be a broad-spectrum antiviral candidate against dsDNA viruses with potential oral administration. Moreover, modification of the aliphatic chain attached to the nucleoside phosphonate group was involved as an efficient prodrug strategy for the development of potent antiviral candidates., 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 Masson SAS. All rights reserved.)

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.)

Background: Breast cancer (BC) is the leading cause of morbidity and the second leading cause of death among female malignant tumors. Although available drugs have been approved for the corresponding breast cancer subtypes (ER-positive, HER2 + ) currently, there are still no effective targeted drugs or treatment strategies for metastatic breast cancer or triple-negative breast cancer that lack targets. Therefore, it is urgent to discover new potential targets. ERCC6L is an essential protein involved in chromosome separation during cell mitosis. However, the effect of ERCC6L on the tumorigenesis and progression of breast cancer is unclear., Methods and Results: Here, we found that ERCC6L was highly expressed in breast cancer, especially in TNBC, which was closely related to poor outcomes of patients. An ERCC6L conditional knockout mouse model was first established in this study, and the results confirmed that ERCC6L was required for the development of the mammary gland and the tumorigenesis and progression of mammary gland cancers. In in vitro cell culture, ERCC6L acted as a tumor promoter in the malignant progression of breast cancer cells. Overexpression of ERCC6L promoted cell proliferation, migration and invasion, while knockdown of ERCC6L caused the opposite results. Mechanistically, ERCC6L accelerated the cell cycle by regulating the G 2 /M checkpoint signalling pathway. Additionally, we demonstrated that there is an interaction between ERCC6L and KIF4A, both of which are closely related factors in mitosis and are involved in the malignant progression of breast cancer., Conclusions: We first demonstrated that ERCC6L deficiency can significantly inhibit the occurrence and development of mammary gland tumors. ERCC6L was found to accelerate the cell cycle by regulating the p53/p21/CDK1/Cyclin B and PLK/CDC25C/CDK1/Cyclin B signalling pathways, thereby promoting the malignant progression of breast cancer cell lines. There was a direct interaction between KIF4A and ERCC6L, and both are closely associated with mitosis and contribute to growth and metastasis of breast tumor. To sum up, our results suggest that ERCC6L may be used as a promising target for the treatment of BC., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Emerging evidence suggests that ferroptosis, a unique regulated cell death modality that is morphologically and mechanistically different from other forms of cell death, plays a vital role in the pathophysiological process of neurodegenerative diseases, and strokes. Accumulating evidence supports ferroptosis as a critical factor of neurodegenerative diseases and strokes, and pharmacological inhibition of ferroptosis as a therapeutic target for these diseases. In this review article, the core mechanisms of ferroptosis are overviewed and the roles of ferroptosis in neurodegenerative diseases and strokes are described. Finally, the emerging findings in treating neurodegenerative diseases and strokes through pharmacological inhibition of ferroptosis are described. This review demonstrates that pharmacological inhibition of ferroptosis by bioactive small-molecule compounds (ferroptosis inhibitors) could be effective for treatments of these diseases, and highlights a potential promising therapeutic avenue that could be used to prevent neurodegenerative diseases and strokes. This review article will shed light on developing novel therapeutic regimens by pharmacological inhibition of ferroptosis to slow down the progression of these diseases in the future., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

To evaluate the functional effects of APS (Astragalus polysaccharide) on Furong crucian carp, APS-supplemented diets (0.00 %, 0.05 %, 0.10 % and 0.15 %) were prepared and utilized in feeding experiment. The results showed that the 0.05 % APS group has the highest weight gain rate and specific growth rate, and the lowest feed coefficient rate. In addition, 0.05 % APS supplement could improve muscle elasticity, adhesiveness and chewiness. Moreover, the 0.15 % APS group had the highest spleen-somatic index and the 0.05 % group had the maximum intestinal villus length. 0.05 % and 0.10 % APS addition significantly increased T-AOC and CAT activities while MDA contents decreased in all APS groups. The plasma TNF-α levels in all APS groups significantly increased (P<0.05), and the 0.05 % group showed the highest TNF-α level in spleen. In APS addition groups, the tlr8, lgp2 and mda5 gene expressions were significantly elevated, while xbp1, caspase-2 and caspase-9 expressions decreased in uninfected and A. hydrophila-infected fish. Finally, higher survival rate and slower disease outbreak rate were observed in APS-supplemented groups after being infected by A. hydrophila. In conclusion, Furong crucian carp fed by APS-supplemented diets possesses elevated weight gain rate and specific growth rate, and improved meat quality, immunity and disease resistance., 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.)

Divergent N 6 -methyladenosine (m 6 A) modifications are dynamic and reversible posttranscriptional RNA modifications that are mediated by m 6 A regulators or m 6 A RNA methylation regulators, i.e., methyltransferases ("writers"), demethylases ("erasers"), and m 6 A-binding proteins ("readers"). Aberrant m 6 A modifications are associated with cancer occurrence, development, progression, and prognosis. Numerous studies have established that aberrant m 6 A regulators function as either tumor suppressors or oncogenes in multiple tumor types. However, the functions and mechanisms of m 6 A regulators in cancer remain largely elusive and should be explored. Emerging studies suggest that m 6 A regulators can be modulated by epigenetic modifications, namely, ubiquitination, SUMOylation, acetylation, methylation, phosphorylation, O-GlcNAcylation, ISGylation, and lactylation or via noncoding RNA action, in cancer. This review summarizes the current roles of m 6 A regulators in cancer. The roles and mechanisms for epigenetic modification of m 6 A regulators in cancer genesis are segregated. The review will improve the understanding of the epigenetic regulatory mechanisms of m 6 A regulators., (© 2023. The Author(s).)

GABA is the most common inhibitory neurotransmitter in the vertebrate central nervous system. Synthesized by glutamic acid decarboxylase, GABA could specifically bind with two GABA receptors to transmit inhibition signal stimuli into cells: GABAA receptor and GABAB receptor. In recent years, emerging studies revealed that GABAergic signaling not only participated in traditional neurotransmission but was involved in tumorigenesis as well as regulating tumor immunity. In this review, we summarize the existing knowledge of the GABAergic signaling pathway in tumor proliferation, metastasis, progression, stemness, and tumor microenvironment as well as the underlying molecular mechanism. We also discussed the therapeutical advances in targeting GABA receptors to provide the theoretical basis for pharmacological intervention of GABAergic signaling in cancer treatment especially immunotherapy., Competing Interests: Conflict of interest statement The authors declared that they had no conflict of interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Viral seasonality in the aquaculture industry is an important scientific issue for decades. While the molecular mechanisms underpinning the temperature-dependent pathogenesis of aquatic viral diseases remain largely unknown. Here we report that temperature-dependent activation of IL6-STAT3 signaling was exploited by grass carp reovirus (GCRV) to promote viral entry via increasing the expression of heat shock protein 90 (HSP90). Deploying GCRV infection as a model system, we discovered that GCRV induces the IL6-STAT3-HSP90 signaling activation to achieve temperature-dependent viral entry. Further biochemical and microscopic analyses revealed that the major capsid protein VP7 of GCRV interacted with HSP90 and relevant membrane-associated proteins to boost viral entry. Accordingly, exogenous expression of either IL6, HSP90, or VP7 in cells increased GCRV entry in a dose-dependent manner. Interestingly, other viruses (e.g., koi herpesvirus, Rhabdovirus carpio, Chinese giant salamander iridovirus) infecting ectothermic vertebrates have evolved a similar mechanism to promote their infection. This work delineates a molecular mechanism by which an aquatic viral pathogen exploits the host temperature-related immune response to promote its entry and replication, instructing us on new ways to develop targeted preventives and therapeutics for aquaculture viral diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Epilepsy is a chronic disorder of the central nervous system characterized by recurrent unprovoked seizures resulting from excessive synchronous discharge of neurons in the brain. As one of the most common complications of many neurological diseases, epilepsy is an expensive and complex global public health issue that is often accompanied by neurobehavioral comorbidities, such as abnormalities in cognition, psychiatric status, and social-adaptive behaviors. Recurrent or prolonged seizures can result in neuronal damage and cell death; however, the molecular mechanisms underlying the epilepsy-induced damage to neurons remain unclear. Ferroptosis, a novel type of regulated cell death characterized by iron-dependent lipid peroxidation, is involved in the pathophysiological progression of epilepsy. Emerging studies have demonstrated pharmacologically inhibiting ferroptosis can mitigate neuronal damage in epilepsy. In this review, we briefly describe the core molecular mechanisms of ferroptosis and the roles they play in contributing to epilepsy, highlight emerging compounds that can inhibit ferroptosis to treat epilepsy and associated neurobehavioral comorbidities, and outline their pharmacological beneficial effects. The current review suggests inhibiting ferroptosis as a therapeutic target for epilepsy and associated neurobehavioral comorbidities., 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 Jin, Ren, Jing and Wang.)

Pancreatic cancer is a malignant disease characterized by low survival and high recurrence rate, whose patients are mostly at the stage of locally advanced or metastatic disease when first diagnosed. Early diagnosis is particularly important because prognostic/predictive markers help guide optimal individualized treatment regimens. So far, CA19-9 is the only biomarker for pancreatic cancer approved by the FDA, but its effectiveness is limited by low sensitivity and specificity. With recent advances in genomics, proteomics, metabolomics, and other analytical and sequencing technologies, the rapid acquisition and screening of biomarkers is now possible. Liquid biopsy also occupies a significant place due to its unique advantages. In this review, we systematically describe and evaluate the available biomarkers that have the greatest potential as vital tools in diagnosing and treating pancreatic cancer., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2023 YANG et al.)

Clinoptilolite based zeolite-geopolymer foams (abbreviated as CFs) were prepared from natural clinoptilolite and calcined clinoptilolite, using H 2 O 2 solution as pore former through a straightforward process. Natural clinoptilolite and CFs are characterized by analytical techniques including optical microscope, XRF, FTIR, XRD, BET, MIP and SEM. The obtained CFs possesses micropores of zeolite and meso/macropores of geopolymer matrix. The porosities range from 66.7 to 69.5%. Clinoptilolite (partially dissolved) and impurity minerals (montmorillonite, illite and albite) contribute to the formation of geopolymer. CFs shows a good static sorption performance for toxic heavy metals at pH = 5 and sorption time of 24 h. Results show that the adsorption amount of CFs for Cr 3+ , Pb 2+ , Ni 2+ , Cu 2+ and Cd 2+ in the 50 mg/L working solutions are 6.21 mg/g, 6.11-6.13 mg/g, 5.92-6.07 mg/g, 5.53-5.93 mg/g and 5.44-5.79 mg/g, respectively. In addition, CFs could reach a high removal rate (Cr removal rate >80% and Cd > 60%) for different heavy metals after three cycles. The elimination order of toxic metals is Cr 3+  > Pb 2+  > Ni 2+  > Cu 2+  > Cd 2+ . The sequence is in accordance with Hard-Soft-Acid-Base principle, it is also related to the speciation and the ionic radii of the hydrated metal ions. This research provides a feasible approach for preparation of promising foams sorbent based on natural zeolite for wastewater management., 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 © 2022 Elsevier Ltd. All rights reserved.)

Background: There lacks a sufficient research on the tumorigenesis of clear cell renal cell carcinoma (ccRCC), causing that the prognosis of ccRCC was not effectively improved. Micall2 contributes to the malignancy of cancer. Moreover, Micall2 is considered a typical cell mobility-promoting factor. However, the relationship between Micall2 and ccRCC malignancy is unknown., Methods: In this study, we first investigated the expression patterns of Micall2 in ccRCC tissues and cell lines. Next, we explored the in vitro and in vivo roles of Micall2 in ccRCC tumorigenesis based on ccRCC cell lines with different Micall2 expression and gene manipulation assays., Results: Our study showed that ccRCC tissues and cell lines expressed higher level of Micall2 than paracancerous tissues and normal renal tubular epithelial cell, and Micall2 expression was overexpressed on cancerous tissue with significant metastasis and enlargement. Among three ccRCC cell lines, the expression of Micall2 was the highest in 786-O cells and the lowest in CAKI-1 cells. Moreover, 786-O cells showed the highest malignancy in vitro and in vivo (including proliferation, migration, invasion, reduced E-cadherin expression and tumorigenicity of nude mice in vivo ), while CAKI-1 cells showed the contrary results. Furthermore, the upregulated Micall2 by Gene overexpression promoted the proliferation, migration and invasion of ccRCC cells while the downregulated Micall2 by Gene silencing showed the opposite effect., Conclusion: Micall2, as a pro-tumorigenic gene marker of ccRCC, contributes the malignancy of ccRCC., Competing Interests: The authors declare no conflict of interest., (©2023 Tottori University Medical Press.)

Development of resistance to chemotherapy in cancer continues to be a major challenge in cancer management. Ferroptosis, a unique type of cell death, is mechanistically and morphologically different from other forms of cell death. Ferroptosis plays a pivotal role in inhibiting tumour growth and has presented new opportunities for treatment of chemotherapy-insensitive tumours in recent years. Emerging studies have suggested that ferroptosis can regulate the therapeutic responses of tumours. Accumulating evidence supports ferroptosis as a potential target for chemotherapy resistance. Pharmacological induction of ferroptosis could reverse drug resistance in tumours. In this review article, we first discuss the key principles of chemotherapeutic resistance in cancer. We then provide a brief overview of the core mechanisms of ferroptosis in cancer chemotherapeutic drug resistance. Finally, we summarise the emerging data that supports the fact that chemotherapy resistance in different types of cancers could be subdued by pharmacologically inducing ferroptosis. This review article suggests that pharmacological induction of ferroptosis by bioactive compounds (ferroptosis inducers) could overcome chemotherapeutic drug resistance. This article also highlights some promising therapeutic avenues that could be used to overcome chemotherapeutic drug resistance in cancer., Competing Interests: Declaration of Competing Interest The authors report no competing interests., (Copyright © 2023 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.)

Background: Exploiting cancer metabolism during nutrient availability holds immense potential for the clinical and therapeutic benefits of hepatocellular carcinoma (HCC) patients. Dietary methionine is a metabolic dependence of cancer development, but how the signal transduction integrates methionine status to achieve the physiological demand of cancer cells remains unknown., Methods: Low or high levels of dietary methionine was fed to mouse models with patient-derived xenograft or diethyl-nitrosamine induced liver cancer. RNA sequence and metabolomics were performed to reveal the profound effect of methionine restriction on gene expression and metabolite changes. Immunostaining, sphere formation assays, in vivo tumourigenicity, migration and self-renewal ability were conducted to demonstrate the efficacy of methionine restriction and sorafenib., Results: We discovered that mTORC1-c-Myc-SIRT4 axis was abnormally regulated in a methionine-dependent manner and affected the HCC progression. c-Myc rewires methionine metabolism through TRIM32 mediated degradation of SIRT4, which regulates MAT2A activity by ADP-ribosylation on amino acid residue glutamic acid 111. MAT2A is a key enzyme to generate S-adenosylmethionine (SAM). Loss of SIRT4 activates MAT2A, thereby increasing SAM level and dynamically regulating gene expression, which triggers the high proliferation rate of tumour cells. SIRT4 exerts its tumour suppressive function with targeted therapy (sorafenib) by affecting methionine, redox and nucleotide metabolism., Conclusions: These findings establish a novel characterization of the signaling transduction and the metabolic consequences of dietary methionine restriction in malignant liver tissue of mice. mTORC1, c-Myc, SIRT4 and ADP ribosylation site of MAT2A are promising clinical and therapeutic targets for the HCC treatment., (© 2022. The Author(s).)

Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are deregulated in hepatocellular carcinoma (HCC) and play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the current understanding of the role of lncRNAs in NAFLD-associated HCC is limited. In this study, transcriptomic profiling analysis of three paired human liver samples from patients with NAFLD-driven HCC and adjacent samples showed that LINC01468 expression was significantly upregulated. In vitro and in vivo gain- and loss-of-function experiments showed that LINC01468 promotes the proliferation of HCC cells through lipogenesis. Mechanistically, LINC01468 binds SHIP2 and promotes cullin 4 A (CUL4A)-linked ubiquitin degradation, thereby activating the PI3K/AKT/mTOR signaling pathway, resulting in the promotion of de novo lipid biosynthesis and HCC progression. Importantly, the SHIP2 inhibitor reversed the sorafenib resistance induced by LINC01468 overexpression. Moreover, ALKBH5-mediated N 6 -methyladenosine (m 6 A) modification led to stabilization and upregulation of LINC01468 RNA. Taken together, the findings indicated a novel mechanism by which LINC01468-mediated lipogenesis promotes HCC progression through CUL4A-linked degradation of SHIP2. LINC01468 acts as a driver of HCC progression from NAFLD, highlights the potential of the LINC01468-SHIP2 axis as a therapeutic target for HCC., (© 2022. The Author(s).)

Interleukin-2 (IL-2) is one of the most important regulators in immune system, as it plays an essential part both in immune activation and suppression. However, as the first immunotherapy drug approved for the treatment of cancer, IL-2 is limited in clinical application by the serious adverse reactions. The long-felt needs in clinical practice, including prolonged half-lives, T cell subset specificity, and toxicity reduction can be achieved by polyethylene glycol (PEG) modification, Fc fusing, or protein mutation of IL-2. NKTR-214, the most advanced IL-2 pathway-targeted agent in clinical development for oncology, shows exciting results in treatment of melanoma in combination with nivolumab. At the same time, many more other modified molecules against cancer and autoimmune diseases are being tested in clinical research, an exciting future lying ahead for IL-2 therapeutics.

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.)

Background: Chemoresistance is a major factor contributing to the poor prognosis of patients with pancreatic cancer, and cancer stemness is one of the most crucial factors associated with chemoresistance and a very promising direction for cancer treatment. However, the exact molecular mechanisms of cancer stemness have not been completely elucidated., Methods: m 6 A-RNA immunoprecipitation and sequencing were used to screen m 6 A-related mRNAs and lncRNAs. qRT-PCR and FISH were utilized to analyse DDIT4-AS1 expression. Spheroid formation, colony formation, Western blot and flow cytometry assays were performed to analyse the cancer stemness and chemosensitivity of PDAC cells. Xenograft experiments were conducted to analyse the tumour formation ratio and growth in vivo. RNA sequencing, Western blot and bioinformatics analyses were used to identify the downstream pathway of DDIT4-AS1. IP, RIP and RNA pulldown assays were performed to test the interaction between DDIT4-AS1, DDIT4 and UPF1. Patient-derived xenograft (PDX) mouse models were generated to evaluate chemosensitivities to GEM., Results: DDIT4-AS1 was identified as one of the downstream targets of ALKBH5, and recruitment of HuR onto m 6 A-modified sites is essential for DDIT4-AS1 stabilization. DDIT4-AS1 was upregulated in PDAC and positively correlated with a poor prognosis. DDIT4-AS1 silencing inhibited stemness and enhanced chemosensitivity to GEM (Gemcitabine). Mechanistically, DDIT4-AS1 promoted the phosphorylation of UPF1 by preventing the binding of SMG5 and PP2A to UPF1, which decreased the stability of the DDIT4 mRNA and activated the mTOR pathway. Furthermore, suppression of DDIT4-AS1 in a PDX-derived model enhanced the antitumour effects of GEM on PDAC., Conclusions: The ALKBH5-mediated m 6 A modification led to DDIT4-AS1 overexpression in PDAC, and DDIT-AS1 increased cancer stemness and suppressed chemosensitivity to GEM by destabilizing DDIT4 and activating the mTOR pathway. Approaches targeting DDIT4-AS1 and its pathway may be an effective strategy for the treatment of chemoresistance in PDAC., (© 2022. The Author(s).)

Grafting organic molecules onto an insoluble matrix is an effective way to improve the electronic conductivity and insolubility in electrolyte of organic electrode materials. The active group of CN in DAP@C composites synthesized by chemical grafting of 2,3-diaminophenazine (DAP) with carbon felt through amide bonds (-CO-NH-) displays excellent electrochemical behavior.

The high interface impedance between inorganic material electrodes and solid electrolytes results in a high Li + diffusion energy barrier, which limits the electrochemical performance of active materials. To solve this issue, an integrated configuration of organic active material electrode-solid polymer electrolyte (SPE) is synthesized via in situ polymerization. In the integrated aminoanthraquinone-solid polymer electrolyte (AQ-SPE), the naphthalene urethane bond acts as a bridge that links the organic material electrode and the SPE and acts as a channel for Li + transport at the electrode/SPE interface. Compared to the activation energy of the conventional aminoanthraquinone/solid polymer electrolyte (AQ/SPE), the activation energy of the charge transfer process for the integrated AQ-SPE decreases from 71.2 to 42.1 kJ mol -1 , and the charge transfer impedance decreases from 1140 to 198 Ω at 50 °C. The first and 625th discharge capacity densities of AQ in the integrated AQ-SPE at 0.1 mA cm -1 and 50 °C are 139.7 and 125.3 mAh g -1 , respectively. Moreover, pouch batteries with the integrated AQ-SPE show excellent safety performance. The in situ fabrication of integrated electrode-SPE provides an enlightening and extended method for realizing efficient, safe, and environmentally friendly batteries.

The literature on cases of acute disseminated encephalomyelitis (ADEM) associated with SARS-CoV-2 infection has been rapidly increasing. However, the specific clinical features of ADEM associated with SARS-CoV-2 (SARS-CoV-2-ADEM) have not been previously evaluated. We screened all articles resulting from a search of PubMed and Web of Science databases looking for reports of ADEM published between December 01, 2019, and June 5, 2021. Of the 48 ADEM cases identified from 37 studies, 34 (71%) had ADEM while 14 (29%) were of AHLE. RT-PCR for SARS-CoV-2 was positive in 83% (n = 19) of patients. 26 patients (54%) were male, and 18 patients (38%) were female, with a male to female sex ratio of 1.4:1; median age was 44 (1.4-71) years. 9 patients (19%, 9/48) were children. Of the 9 children patients, their median age was 9 years (range 1.4-13 years), 6 patients (67%) were female, and 2 patients (22%) were male, with a female to male sex ratio of 3:1.39 patients (81%) was performed CSF analysis. PCR for SARS-CoV-2 tested positive in 3 patients (14%, 3/22) on CSF sample. 31 (64%) of patients had a poor outcome on discharge from hospital. Five (10%) patients died in hospital. Compared to classic ADEM, SARS-CoV-2-ADEM have a more longer duration between the onset of the antecedent infective symptoms and the start of ADEM symptoms, the older age distribution of the patients, relatively poor outcome, a lower full recovery rate, a more frequently brain lesions involved the periventricular white matter and corpus callosum, and less frequently affected the deep gray matter. Taken together, the present comprehensive review reveals that although rare, ADEM can be associated with SARS-CoV-2 infection. SARS-CoV-2-ADEM seems to share most features of classic ADEM, with moderate discrepancies from the classical ADEM., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Soils contamination with Cd result in detriment to the environmental quality. In-situ immobilization methods by applying clay minerals have been gaining prominence. The effects on sepiolite of thermal activation at different temperatures (300-750 °C), for removing Cd from aqueous solutions were evaluated, in order to consider their further application for soil remediation. The influence of activation temperature was investigated using XRD, SEM, and N 2 adsorption-desorption measurements. The S-600 exhibited the maximum adsorption capacity (21.28 mg/g), despite its lower SSA, and Langmuir model described the adsorption isotherms better than the Freundlich equation. TCLP was used to quantify the remediation effects of thermal-activated sepiolite on simulated soils artificially polluted with Cd. The results indicated that the mobility of Cd in soil was effectively reduced after treating with thermal-activated sepiolite and the use of S-600 was the most efficient, reducing the TCLP-Cd by approximately 73% compared with the control test. The main remediation mechanism was considered as the cation exchange of Cd by Mg at the edges of octahedral sheet. This study showed that thermal-activated sepiolite could be promising amendments for remediation of Cd-contaminated soil., (Copyright © 2021 Elsevier B.V. All rights reserved.)

COVID-19 has spread around the world and caused serious public health and social problems. Although several vaccines have been authorized for emergency use, new effective antiviral drugs are still needed. Some repurposed drugs including Chloroquine, Hydroxychloroquine and Remdesivir were immediately used to treat COVID-19 after the pandemic. However, the therapeutic effects of these drugs have not been fully demonstrated in clinical studies. In this paper, we found an antimalarial drug, Naphthoquine, showed good broad-spectrum anti-coronavirus activity. Naphthoquineinhibited HCoV-229E, HCoV-OC43 and SARS-CoV-2 replication in vitro, with IC 50 = 2.05 ± 1.44 μM, 5.83 ± 0.74 μM, and 2.01 ± 0.38 µM, respectively. Time-of-addition assay was also performed to explore at which stage Naphthoquine functions during SARS-CoV-2 replication. The results suggested that Naphthoquine may influence virus entry and post-entry replication. Considering the safety of Naphthoquine was even better than that of Chloroquine, we think Naphthoquine has the potential to be used as a broad-spectrum drug for coronavirus infection.

Background: Cerebrovascular diseases associated with SARS-CoV-2 are being increasingly reported in the literature as the coronavirus disease 2019 (COVID-19) pandemic continues. However, a case-based retrospective analysis of the literature about SARS-CoV-2-cerebrovascular disease (SCVD) is not yet well established. Thus, we reviewed the literature on SCVD covering a comprehensive range of topics spanning the clinical features, mechanism, treatment, and outcomes of patients with SCVD., Methods: We searched PubMed ® and included single-case reports and case series with full text in English that reported original data of patients with CVD and a confirmed recent SARS-CoV-2 infection. Clinical data were extracted., Results: We included all 51 articles indexed in PubMed ® that were published between January 1, 2020, and June 20, 2020. The selected studies reported a total of 167 cerebrovascular events including ischemic stroke, cerebral hemorrhage, subarachnoid hemorrhage, and cerebral venous thrombosis in patients with confirmed COVID-19. The detailed demographic and clinical characteristics of patients with CVD are summarized., Conclusion: This summary of patient characteristics may help clinicians better anticipate SCVD outcomes and complications in their COVID-19 patients., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 Yu et al.)

Parkinson's disease (PD) is a complex neurodegenerative disorder featuring both motor and nonmotor symptoms associated with a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress (OS) has been implicated in the pathogenesis of PD. Genetic and environmental factors can produce OS, which has been implicated as a core contributor to the initiation and progression of PD through the degeneration of dopaminergic neurons. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) orchestrates activation of multiple protective genes, including heme oxygenase-1 (HO-1), which protects cells from OS. Nrf2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis. Recently, a series of studies have reported that different bioactive compounds were shown to be able to activate Nrf2/antioxidant response element (ARE) and can ameliorate PD-associated neurotoxin, both in animal models and in tissue culture. In this review, we briefly overview the sources of OS and the association between OS and the pathogenesis of PD. Then, we provided a concise overview of Nrf2/ARE pathway and delineated the role played by activation of Nrf2/HO-1 in PD. At last, we expand our discussion to the neuroprotective effects of pharmacological modulation of Nrf2/HO-1 by bioactive compounds and the potential application of Nrf2 activators for the treatment of PD. This review suggests that pharmacological modulation of Nrf2/HO-1 signaling pathway by bioactive compounds is a therapeutic target 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 © 2021 Wang, Gao, Chen, Li, Huo, Wang, Wang and Du.)

Complement factor D (Df) is a serine protease well known for activating the alternative pathway (AP) in mammals by promoting the cleavage of complement component 3 (C3), thus becoming involved in innate defense. In teleost fish, however, the functional mechanisms of Df in the AP and against pathogen infection are far from clear. In the present study, we cloned and characterized the Df gene, Ci Df, from grass carp ( Ctenopharyngodon idella ) and analyzed its function in promoting C3 cleavage and expression changes after grass carp reovirus (GCRV) infection. The open reading frame of Ci Df was found to be 753 bp, encoding 250 amino acids with a molecular mass of 27.06 kDa. Ci Df harbors a conserved Tryp&#95;SPc domain, with three conserved residues representing the catalytic triad and three conserved binding sites in the substrate specificity pocket. Pairwise alignment showed that Ci Df shares the highest identity (96%) and similarity (98%) with Df from Anabarilius grahami . Phylogenetic analysis indicated that Ci Df and other fish Dfs formed a distinct evolutionary branch. Similar to most Dfs from other vertebrates, the Ci Df gene structure is characterized by four introns and five exons. The incubation of recombinant Ci Df protein with grass carp serum significantly increased the C3b content, demonstrating the conserved function of Ci Df in the AP in promoting C3 cleavage, similar to Dfs in mammals. Ci Df mRNA expression was widely detected in various tissues and levels were relatively higher in the liver, spleen, and intestine of grass carp. During GCRV infection over a 168-hour period, a high level of Ci Df mRNA expression in the liver, spleen, and intestine was maintained at 144 and 168 h, suggesting AP activity at the late stage of GCRV infection. Collectively, the above results reveal the conserved structure and function of Ci Df and its distinct expression patterns after GCRV infection, which provide a key basis for studying the roles of Df and AP during GCRV infection in the grass carp C. idella .

As one kind of reactive carbonyl species (RCS), formaldehyde (FA) with a high concentration could be extremely toxic to living bodies as well as the environment. This paper reports a three-dimensional (3D) Tb 3+ @Ag-MOFs-based fluorescent probe for fast sensing of FA, which uses a novel turn-on mechanism based on the luminescence induced by Tb 3+ . The MOF sensor shows broad dynamic ranges of 0.1-1 mM for FA with the detection limit of 1.9 μM. For online and real-time detection of FA, a portable smartphone platform was employed to analyze the RGB values of the fluorescence by a smartphone application. By incorporating this probe into a polyacrylonitrile (PAN) layer, we synthesized a film composite that could effectively remove FA in real samples including milk and chemical factory wastewater, and the removal rate reached 98.52% and 95.38% respectively. Moreover, the potential of the film to remove gaseous FA was confirmed by experiments as well., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Melanoma, the most aggressive skin cancer, is mainly treated with BRAF inhibitors or immunotheareapy. However, most patients who initially responded to BRAF inhibitors or immunotheareapy become resistant following relapse. Ferroptosis is a form of regulated cell death characterized by its dependence on iron ions and the accumulation of lipid reactive oxygen species (ROS). Recent studies have demonstrated that ferroptosis is a good method for tumor treatment, and iron homeostasis is closely associated with ferroptosis. Iron regulatory protein (IRP)1 and 2 play important roles in maintaining iron homeostasis, but their functions in ferroptosis have not been investigated. The present study reported that the expression of IRP1 and IRP2 was increased by the ferroptosis inducers erastin and RSL3 in melanoma cells. Depletion of IRP1 significantly suppressed erastin- and RSL3-induced ferroptosis. IRP2 had a weak effect but could enhance the promoting function of IRP1 on ferroptosis. Further, erastin and RSL3 promoted the transition of aconitase 1 to IRP1, which regulated downstream iron metabolism proteins, including transferrin receptor (TFRC), ferroportin (FPN) and ferritin heavy chain 1 (FTH1). Moreover, overexpression of TFRC and knockdown of FPN and FTH1 significantly promoted erastin- and RSL3-induced ferroptosis in IRP1 knockdown melanoma cells. Collectively, the present findings indicate that IRP1 plays an essential role in erastin- and RSL3-induced ferroptosis by regulating iron homeostasis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yao et al.)

Background: Aggregation and neurotoxicity of the presynaptic protein α-synuclein and the progressive loss of nigral dopaminergic neurons are believed to be the key hallmarks of Parkinson's disease (PD). A53T mutant α-synuclein causes early onset PD and more severe manifestations. A growing body of evidence shows that misfolding or deposition of α-synuclein is linked to the maintenance of mitochondrial dynamics, which has been proven to play an important role in the pathogenesis of PD. It has been observed that Dl-3-n-butylphthalide (NBP) may be safe and effective in improving the non-tremor-dominant PD. However, the potential mechanism remains unclear. This study aimed to investigate whether NBP could decrease the loss of dopaminergic neurons and α-synuclein deposition and explore its possible neuroprotective mechanisms., Methods: A total of 20 twelve-month-old human A53T α-synuclein transgenic mice and 10 matched adult C57BL/6 mice were included in the study; 10 adult C57BL/6 mice were selected as the control group and administered with saline (0.2 ml daily for 14 days); 20 human A53T α-synuclein transgenic mice were randomly divided into A53T group (treated in the same manner as in the control group) and A53T + NBP group (treated with NBP 0.2 ml daily for 14 days). Several markers of mitochondrial fission and fusion and mitophagy were determined, and the behavioral, olfactory, and cognitive symptoms were assessed as well., Results: In the present study, it was observed that the A53T-α-synuclein PD mice exhibited anxiety-like behavioral disturbance, impairment of coordination ability, memory deficits, and olfactory dysfunction, loss of dopaminergic neurons, and α-synuclein accumulation. Meanwhile, the mitofusin 1 expression was significantly decreased, and the mitochondrial number and dynamin-related protein 1, Parkin, and LC3 levels were increased. The detected levels of all markers were reversed by NBP treatment, and the mitochondrial morphology was partially recovered., Conclusion: In the present study, a valuable neuropharmacological role of NBP has been established in the A53T-α-synuclein PD mouse model. Possible neuroprotective mechanisms might be that NBP is involved in the maintenance of mitochondrial dynamics including mitochondrial fission and fusion and clearance of damaged mitochondria. It is essential to perform further experiments to shed light on the precise mechanisms of NBP on mitochondrial homeostasis., 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 © 2021 Li, Wang, Zhang, Wang and Li.)

It has been established that scar acellular matrices (AMs), which allow cell proliferation, have similar characteristics. The aim of this study was to investigate the repair effect of scar AMs on animals, thus providing a reference for clinical application. Selected mature and immature scar AMs were implanted into animals, and then a negative control group was set for comparison. The effect of scar AMs on wound healing was observed through tissue staining, RT-qPCR, and immunohistochemistry. The materials showed milder inflammation and faster extracellular matrix (ECM) deposition than the negative control group. The ECM deposition and new vessels increased over time. However, the arrangement of ECM in mature scar AM was more regular than in immature scar AM and the negative control group, and more new vessels grew in the mature scar AM group than in the immature scar AM group and negative control group over the same period. The transforming growth factor-β level was elevated at one month, two months, and six months. COLA1 and vimentin levels all peaked at six months. Matrix metalloproteinase and TIMP1 were also elevated at different months. Collectively, scar AMs can effectively promote wound healing and vascularization. Mature scar AMs have a better regeneration effect.

Growth hormone (ScGH) and growth hormone receptor (ScGHR) genes from the barbel chub (Squaliobarbus curriculus), in addition to their cDNAs, were cloned. The associations between their mRNA expression levels and growth-related traits were analysed, and the differences in the levels of expression of growth regulation-related genes between the largest and smallest individuals were compared. The full-length 1182-bp cDNA of ScGH contained a 633-bp open reading frame (ORF), and the length of the gene had 2492 bp. The full-length 2825-bp cDNA of ScGHRa contained a 1818-bp ORF, and the gene had 6970 bp. The full-length 2822-bp cDNA of ScGHRb contained a 1737-bp ORF, and the gene had 8149 bp. Quantitative real-time PCR revealed that ScGH was only expressed in the pituitary. ScGHRa was expressed predominantly in muscle, and the expression level of ScGHRb was the highest in the liver. The ScGHRa mRNA levels in the muscle were significantly negatively correlated with the caudal peduncle length. However, no correlation between growth-related traits and ScGH and ScGHRb expression levels were found. Pituitary ScGH, liver GHRb and liver insulin-like growth factor I (igf-1) expression levels were significantly higher in the largest individuals than those in the smallest S. curriculus individuals. Contrarily, the largest individuals had significantly lower expression levels of muscle igf-1 and liver myog than the smallest individuals. Overall, our results provide novel molecular information for growth-regulation study of S. curriculus., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Autophagy is a self-proteolytic process that degrades intracellular material to maintain cellular homeostasis. Transcription factor EB (TFEB) is the master activator that regulates the transcription of genes involved in autophagy and lysosomal biogenesis. However, the cotranscriptional factors of TFEB are rarely identified. Here, we found that Yin Yang 1 (YY1) regulated autophagy and lysosome biogenesis in melanoma cells. YY1 cooperates with TFEB to regulate autophagy through controlling the transcription of autophagy and lysosome biogenesis related genes. Moreover, suppression of YY1 enhanced the antitumor efficiency of vemurafenib both in vitro and in vivo. Collectively, these studies identify YY1 as a novel cotranscription factor of TFEB in regulating autophagy and lysosomal functions and suggest YY1 could be a therapeutic target in cancer treatment., (© 2019 Wiley Periodicals, Inc.)

Brain-derived neurotrophic factor (BDNF) is a growth factor crucial for neuronal survival, while its role in subarachnoid hemorrhage (SAH)-induced neuronal apoptosis remains unclear. The aim of the present study was to investigate whether administering exogenous BDNF can protect against neuronal apoptosis and neurological deficits following SAH in a rat model. The BDNF level was found to be significantly decreased in the basal cortex at 6, 12, 24, 48 and 72 h following SAH. Exogenous BDNF significantly decreased the expression of Bax and reduced activation of caspase-3 and caspase-9 and the number of apoptotic neurons. Moreover, exogenous BDNF treatment significantly improved the neurological deficits at 72 h and long-term behavioral deficits (day 14) following SAH in a rat model. These findings indicate that exogenous BDNF attenuated SAH-induced neuronal injury in rats., (Copyright: © Chen et al.)

Hypertrophic olivary degeneration (HOD) is a rare form of trans-synaptic degeneration characterized by hypertrophy of the inferior olivary nucleus situated in the olivary body, part of the medulla oblongata, representing a major source of input to the cerebellum. HOD typically results from focal lesions interrupting connections from the inferior olive within the dentato-rubro-olivary pathway (DROP), a region also known as the Guillain-Mollaret triangle (GMT) (red nucleus, inferior olivary nucleus, and contralateral dentate nucleus). Clinically, HOD presents classically as palatal tremor and can include dentatorubral tremor and/or ocular myoclonus. Oppenheim first described the enlargement of the ION in his post-mortem study. Since then, a limited number of cases have been reported in the literatures. Thus, we intended to describe the definition, pathophysiology, clinical features, radiological features, diagnosis, and current management of HOD. We provide a comprehensive review of HOD focusing on etiology. The present review may lead to a better understanding of HOD clinical characteristic with the goal of contributing to existing knowledge of this rare disease., (Copyright © 2019. Published by Elsevier B.V.)

The European Space Agency (ESA) Climate Change Initiative (CCI) project combines multi-sensors at different microwave frequencies to derive three harmonized soil moisture products using active, passive and combined approaches. These long-term soil moisture products assist in understanding the global water and carbon cycles. However, extensive validations are a prerequisite before applying the retrieved soil moisture into climatic or hydrological models. To fulfill this objective, we assess the performances of three CCI soil moisture products (active, passive and combined) with respect to in-situ soil moisture networks located in China, Spain and Canada. In order to compensate the scale differences between ground stations and the CCI product's coarse resolution, we adopted two upscaling approaches of Inverse Distance Weighting (IDW) interpolation and simple Arithmetic Mean (AM). The temporal agreements between the satellite retrieved and ground-measured soil moisture were quantified using the unbiased root mean square error (ubRMSE), RMSE, correlation coefficients (R) and bias. Furthermore, the temporal variability of the CCI soil moisture is interpreted and verified with respect to the Tropical Rainfall Measuring Mission (TRMM) precipitation observations. The results show that the temporal variations of CCI soil moisture agreed with the in-situ ground measurements and the precipitation observations over the China and Spain test sites. In contrast, a significant overestimation was observed over the Canada test sites, which may be due to the strong heterogeneity in soil and vegetation characteristics in accordance with the reported poor performance of soil moisture retrieval there. However, despite a retrieval bias, the relatively temporal variation of the CCI soil moisture also followed the ground measurements. For all the three test sites, the soil moisture retrieved from the combined approach outperformed the active-only and passive-only methods, with ubRMSE of 0.034, 0.050, and 0.050-0.054 m 3 /m 3 over the test sites in China, Spain and Canada, respectively. Thus, the CCI combined soil moisture product is suggested to drive the climatic and hydrological studies.

Introduction: Acellular dermal matrix (ADM) is commonly used to treat burn injuries and wounds. In this study, we aimed to analyze the structural and biomechanical characteristics of an ADM from human scars., Methods: We randomly selected human mature scars, human proliferative scars, and human normal skin as experimental specimens. Split-thickness dermal grafts were obtained using a free-hand graft knife. Samples were subjected to cell lysis to obtain ADMs. Structural analysis was performed via light microscopy, fluorescence microplate reader and scanning electron microscopy. Thereafter, human epithelial stem cells were incubated on these ADMs. Finally, the biomechanical characteristics of the ADMs were analyzed using a tensile machine., Results: Normal skin ADM fibers were arranged in order, whereas proliferative scar ADM fibers were dense and disordered, and mature scar ADM fibers were porous and slightly disordered. The residual DNA of three ADM meet the residual DNA standard of biological material. After incubating human epithelial stem cells on ADMs, cells grew in an aggregated state in both normal skin ADMs and mature scar ADMs; however, cells adhered only on the surface of proliferative scar ADMs. No significant differences were observed in the Young's modulus, relaxation slope, creep slope, creep, or maximum tensile stress among the three ADMs, although significant differences in stress-strain elongation and relaxation were noted., Conclusions: Our findings showed that mature scar ADMs were similar to proliferative scar ADMs, showing a slight lag compared with normal skin ADMs, providing insights into the biomechanical features of these scar tissues. Abbreviations ADM Acellular dermal matrix H&E Hematoxylin and eosin PBS Phosphate-buffered saline SEM Scanning electron microscopy.

The grass carp reovirus (GCRV) has been shown to cause lethal infections in the grass carp Ctenopharyngodon idella (C. idella). In order to investigate the immune response to GCRV infection, the full-length cDNA sequences of coagulation factor VIII (CiFVIII) and plasminogen (CiPLG) from C. idella were cloned and their involvement in the immune response was studied. The immunity factor levels in C. idella with different GCRV resistances were also analyzed. The full-length 2478 bp cDNA of CiFVIII contained an open reading frame of 1965 bp and encoded a putative polypeptide of 654 amino acid residues. The full-length 2907 bp cDNA of CiPLG contained an open reading frame of 2133 bp and encoded a putative polypeptide of 710 amino acid residues. CiFVIII was closely clustered with that of Clupea harengus. CiPLG was first clustered with those of Cyprinus carpio and Danio rerio. CiFVIII transcripts were most abundant in the liver and least in the skin. The highest expression level of CiPLG was observed in liver and the lowest in muscle. Expression levels of CiFVIII in gill, head kidney and spleen, and expression levels of CiPLG in gill, intestine and liver all reached the maximum at 72 h post GCRV infection. In spleen, expression levels of CiFVIII and CiPLG were significantly positively correlated. The activities of T-AOC, LSZ and IgM in R♂ were significantly higher than those in O♂. Likewise, T-AOC and LSZ activities in F1 were significantly higher than f1 individuals (P < 0.01). These results indicated that CiFVIII and CiPLG may play important roles in the immune response to GCRV infection. In addition, antioxidant ability and serum immune factor activity may confer a different viral resistance to C. idella., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Titania has recently been identified as a new and effective nonlight-driven catalyst for degradation of organic pollutant with the use of H 2 O 2 as an oxidant; however, either relatively low surface area or lack of diversity in chemical composition largely limits its catalytic performance. In this work, a series of transition-metal ion (Mn 2+ , Co 2+ , Ni 2+ , and Cu 2+ )-doped titania nanomaterials with regular flower-like morphology, good crystallinity (anatase), and large specific surface areas (71.4-124.4 m 2 g -1 ) were facilely synthesized and utilized as catalysts for methylene blue (MB) degradation in the presence of H 2 O 2 without light irradiation. It was revealed that the doping of transition-metal ions (especially Mn 2+ ) into titania could significantly improve the catalytic efficiency. At 30 °C, 10 mL of MB with a concentration of 50 mg L -1 could be completely degraded within 60-100 min for these doped samples, whereas the removal rate was only 35.1% within 100 min with the use of pure flower-like titania. Temperature-dependent kinetic studies indicated that the presence of transition-metal ion dopants could markedly lower the activation energy and thus resulted in enhanced catalytic performances. Test of reusability exhibited that these doped catalysts could well keep their original catalytic activities after reuse for several cycles, indicating their excellent catalytic durability., Competing Interests: The authors declare no competing financial interest.