Correlation Between Thyroid-Related Hormones and Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients with Normal Thyroid Function: A Retrospective Study.

Purpose: To investigate the correlation between thyroid-related hormones and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM). Patients and Methods: Patients with T2DM admitted to our hospital between January 2023 and June 2023 were retrospectively analyzed. The patients were divided into DR and non-diabetic retinopathy (NDR) groups according to whether DR occurred. Thyroid function-related hormones (TSH, FT3, and FT4), blood glucose indices (FBG and HbA1c), and blood lipid indices (HDL-C, LDL-C, TC, and TG) of the two groups were analyzed by univariate and multivariate logistic regression to explore the risk factors for DR. Pearson correlation analysis and multiple stepwise regression analysis were used to investigate the correlation of TSH or FT3 with FBG, HbA1c, and TG in DR patients. Results: Of the 286 patients with T2DM included in this study, 101 (35.31%) developed DR and 185 (64.69%) did not. High TG, FBG, HbA1c, and TSH and low FT3 levels were independent risk factors for DR in T2DM patients. TSH positively correlated with TG, whereas FT3 negatively correlated with TG and HbA1c in T2DM patients with DR. Conclusion: Higher TSH and lower FT3 in T2DM patients with normal thyroid function may affect glucose and lipid metabolism, thereby increasing the risk of DR.

Peste des petits ruminants virus infection induces endoplasmic reticulum stress and apoptosis via IRE1-XBP1 and IRE1-JNK signaling pathways.

BACKGROUND: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial. OBJECTIVES: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication. METHODS: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway. RESULTS: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly down-regulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010. CONCLUSIONS: PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.

Single [0001]-oriented zinc metal anode enables sustainable zinc batteries.

The optimization of crystalline orientation of a Zn metal substrate to expose more Zn(0002) planes has been recognized as an effective strategy in pursuit of highly reversible Zn metal anodes. However, the lattice mismatch between substrate and overgrowth crystals has hampered the epitaxial sustainability of Zn metal. Herein, we discover that the presence of crystal grains deviating from [0001] orientation within a Zn(0002) metal anode leads to the failure of epitaxial mechanism. The electrodeposited [0001]-uniaxial oriented Zn metal anodes with a single (0002) texture fundamentally eliminate the lattice mismatch and achieve ultra-sustainable homoepitaxial growth. Using high-angle angular dark-filed scanning transmission electron microscopy, we elucidate the homoepitaxial growth of the deposited Zn following the "~ABABAB~" arrangement on the Zn(0002) metal from an atomic-level perspective. Such consistently epitaxial behavior of Zn metal retards dendrite formation and enables improved cycling, even in Zn||NH4V4O10 pouch cells, with a high capacity of 220 mAh g-1 for over 450 cycles. The insights gained from this work on the [0001]-oriented Zn metal anode and its persistently homoepitaxial mechanism pave the way for other metal electrodes with high reversibility.

Zinc Transporters Serve as Prognostic Predictors and their Expression Correlates with Immune Cell Infiltration in Specific Cancer: A Pan-cancer Analysis.

The disruption of zinc (Zn) homeostasis has been implicated in cancer development and progression through various signaling pathways. Maintaining intracellular zinc balance is crucial in the context of cancer. Human cells rely on two families of transmembrane transporters, SLC30A/ZNT and SLC39A/ZIP, to coordinate zinc homeostasis. While some ZNTs and ZIPs have been linked to cancer progression, limited information is available regarding the expression patterns of zinc homeostasis-related genes and their potential roles in predicting prognosis and developing therapeutic strategies for specific cancers. In this study, a systematic analysis was conducted to examine the expression of all genes from the SLC30A and SLC39A families at both mRNA and protein levels across different cancers. As a result, three SLC39A genes (SLC39A1, SLC39A4, and SLC39A8) were found to be significantly dysregulated in specific cancers, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), liver hepatocellular carcinoma (LIHC), pancreatic adenocarcinoma (PAAD), and kidney renal papillary cell carcinoma (KIRP). Moreover, the dysregulation of these genes was tightly associated with the prognosis of patients with those cancers. Furthermore, we found that the gene SLC39A8 exhibited the lowest mutation frequency in KIRP, whereas mutations in SLC39A4 were found to significantly impact overall survival (OS), disease-free (DF), and progress-free survival (PFS) in cancer patients, particularly in those with PAAD. Additionally, immune infiltration analysis revealed that SLC39A1, SLC39A4, and SLC39A8 may function as immune regulators in cancers. This provides new insights into understanding the complex relationship between zinc homeostasis and cancer progression.

Macroscale preparation of CoS2 nanoparticles for ultra-high fast-charging performance in sodium-ion batteries.

Improving the fast-charging capabilities and energy storage capacity of electric vehicles presents a feasible strategy for mitigating the prevalent concern of range anxiety in the market. Nanostructure electrode materials play a crucial role in this process. However, the current method of preparation is arduous and yields restricted quantities. In view of this, we have devised an innovative approach that provides convenience and efficacy, facilitating the large-scale synthesis of CoS2 nanoparticles, which exhibited exceptional performance. When the current density was 1000 mA g-1, the discharging capacity reached 760 mAh g-1 after 400 cycles. Remarkably, even at an increased current density of 5000 mA g-1, the discharging capacity of CoS2 remained at 685.5 mAh g-1. The ultra-high performance could be attributed to the specific surface area, which minimized the diffusion distance of sodium-ions during the charging and discharging processes and mitigated the extent of structural damage. Our straightforward preparation techniques facilitate the mass production and present a novel approach for the development of cost-effective and high-performing anode materials for sodium-ion batteries.

Mini PROTACs: N-end rule-mediated degradation on the horizon.

Heterobifunctional proteolysis-targeting chimeras (PROTACs) offer a promising cancer treatment avenue by efficiently degrading unwanted cellular proteins. A recent study from Zhang et al. demonstrated the successful utilization of the N-end rule in PROTAC design, allowing for a modular degradation rate tailored to the oncogenic driver BCR-ABL.

Diosbulbin C, a novel active ingredient in Dioscorea bulbifera L. extract, inhibits lung cancer cell proliferation by inducing G0/G1 phase cell cycle arrest.

BACKGROUND: Despite the critical progress of non-small cell lung cancer (NSCLC) therapeutic approaches, the clinical outcomes remain considerably poor. The requirement of developing novel therapeutic interventions is still urgent. In this study, we showed for the first time that diosbulbin C, a natural diterpene lactone component extracted from traditional Chinese medicine Dioscorea bulbifera L., possesses high anticancer activity in NSCLC. METHODS: A549 and NCI-H1299 cells were used. The inhibitory effects of the diosbulbin C on NSCLC cell proliferation were evaluated using cytotoxicity, clone formation, EdU assay, and flow cytometry. Network pharmacology methods were used to explore the targets through which the diosbulbin C inhibited NSCLC cell proliferation. Molecular docking, qRT-PCR, and western blotting were used to validate the molecular targets and regulated molecules of diosbulbin C in NSCLC. RESULTS: Diosbulbin C treatment in NSCLC cells results in a remarkable reduction in cell proliferation and induces significant G0/G1 phase cell cycle arrest. AKT1, DHFR, and TYMS were identified as the potential targets of diosbulbin C. Diosbulbin C may inhibit NSCLC cell proliferation by downregulating the expression/activation of AKT, DHFR, and TYMS. In addition, diosbulbin C was predicted to exhibit high drug-likeness properties with good water solubility and intestinal absorption, highlighting its potential value in the discovery and development of anti-lung cancer drugs. CONCLUSIONS: Diosbulbin C induces cell cycle arrest and inhibits the proliferation of NSCLC cells, possibly by downregulating the expression/activation of AKT, DHFR, and TYMS.

Time-resolved proteomic profiling reveals compositional and functional transitions across the stress granule life cycle.

Stress granules (SGs) are dynamic, membrane-less organelles. With their formation and disassembly processes characterized, it remains elusive how compositional transitions are coordinated during prolonged stress to meet changing functional needs. Here, using time-resolved proteomic profiling of the acute to prolonged heat-shock SG life cycle, we identify dynamic SG proteins, further segregated into early and late proteins. Comparison of different groups of SG proteins suggests that their biochemical properties help coordinate SG compositional and functional transitions. In particular, early proteins, with high phase-separation-propensity, drive the rapid formation of the initial SG platform, while late proteins are subsequently recruited as discrete modules to further functionalize SGs. This model, supported by immunoblotting and immunofluorescence imaging, provides a conceptual framework for the compositional transitions throughout the acute to prolonged SG life cycle. Additionally, an early SG constituent, non-muscle myosin II, is shown to promote SG formation by increasing SG fusion, underscoring the strength of this dataset in revealing the complexity of SG regulation.

Assessment of degradability and endothelialization of modified poly L-lactic acid (PLLA) atrial septal defect (ASD) occluders over time in vivo.

OBJECTIVE: To evaluate the fiber-degradation and endothelialization of a modified poly L-lactic acid (PLLA) atrial septal defect (ASD) occluder for a long time in vivo. METHODS: A total of 57 New Zealand rabbits were selected to establish the vasculature implantation model, which would be used to characterize the mechanical properties and pathological reaction of PLLA filaments (a raw polymer of ASD occluder). In total, 27 Experimental piglets were used to create the ASD model for the catheter implantation of PLLA ASD occluders. Then, X-ray imaging, transthoracic echocardiography, histopathology, and scanning electron microscope (SEM) were performed in the experimental animals at 3, 6, 12, and 24 months after implantation. RESULTS: In the rabbit models, the fibrocystic grade was 0 and the inflammatory response was grade 2 at 6 months after vasculature implantation of the PLLA filaments. The mass loss of PLLA filaments increased appreciably with the increasing duration of implantation, but their mechanical strength was decreased without broken. In the porcine models, the cardiac gross anatomy showed that all PLLA ASD occluders were stable in the interatrial septum without any vegetation or thrombus formation. At 24 months, the occluders had been embedded into endogenous host tissue nearly. Pathological observations suggested that the occluders degraded gradually without complications at different periods. SEM showed that the occluders were endothelialized completely and essentially became an integral part of the body over time. CONCLUSION: In the animal model, the modified PLLA ASD occluders exhibited good degradability and endothelialization in this long-term follow-up study.

Post-translational modifications in stress granule and their implications in neurodegenerative diseases.

Stress granules (SGs) arise as formations of mRNAs and proteins in response to translation initiation inhibition during stress. These dynamic compartments adopt a fluidic nature through liquid-liquid phase separation (LLPS), exhibiting a composition subject to constant change within cellular contexts. Research has unveiled an array of post-translational modifications (PTMs) occurring on SG proteins, intricately orchestrating SG dynamics. In the realm of neurodegenerative diseases, pathological mutant proteins congregate into insoluble aggregates alongside numerous SG proteins, manifesting resilience against disassembly. Specific PTMs conspicuously label these aggregates, designating them for subsequent degradation. The strategic manipulation of aberrant SGs via PTMs emerges as a promising avenue for therapeutic intervention. This review discerns recent strides in comprehending the impact of PTMs on LLPS behavior and the assembly/disassembly kinetics of SGs. By delving into the roles of PTMs in governing SG dynamics, we augment our cognizance of the molecular underpinnings of neurodegeneration. Furthermore, we offer invaluable insights into potential targets for therapeutic intervention in neurodegenerative afflictions, encompassing conditions like amyotrophic lateral sclerosis and frontotemporal dementia.

Metagenomic next-generation sequencing for rapid detection of pulmonary infection in patients with acquired immunodeficiency syndrome.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is associated with a high rate of pulmonary infections (bacteria, fungi, and viruses). To overcome the low sensitivity and long turnaround time of traditional laboratory-based diagnostic strategies, we adopted metagenomic next-generation sequencing (mNGS) technology to identify and classify pathogens. RESULTS: This study enrolled 75 patients with AIDS and suspected pulmonary infections who were admitted to Nanning Fourth People's Hospital. Specimens were collected for traditional microbiological testing and mNGS-based diagnosis. The diagnostic yields of the two methods were compared to evaluate the diagnostic value (detection rate and turn around time) of mNGS for infections with unknown causative agent. Accordingly, 22 cases (29.3%) had a positive culture and 70 (93.3%) had positive valve mNGS results (P value < 0.0001, Chi-square test). Meanwhile, 15 patients with AIDS showed concordant results between the culture and mNGS, whereas only one 1 patient showed concordant results between Giemsa-stained smear screening and mNGS. In addition, mNGS identified multiple microbial infections (at least three pathogens) in almost 60.0% of patients with AIDS. More importantly, mNGS was able to detect a large variety of pathogens from patient tissue displaying potential infection and colonization, while culture results remained negative. There were 18 members of pathogens which were consistently detected in patients with and without AIDS. CONCLUSIONS: In conclusion, mNGS analysis provides fast and precise pathogen detection and identification, contributing substantially to the accurate diagnosis, real-time monitoring, and treatment appropriateness of pulmonary infection in patients with AIDS.

Glp-1 Receptor Agonists Regulate the Progression of Diabetes Mellitus Complicated with Fatty Liver by Down-regulating the Expression of Genes Related to Lipid Metabolism.

Non-alcoholic fatty liver disease is mostly associated with diabetes mellitus. Dulaglutide is approved in type 2 diabetes as a hypoglycemic agent. However, its effects on liver fat and pancreatic fat contents are not evaluated yet. The objectives of the study were to evaluate the effects of dulaglutide on liver fat content, pancreatic fat content, liver stiffness, and liver enzyme levels. Patients have taken 0.75 mg subcutaneous dulaglutide each week for 4 weeks, then 1.5 mg weekly for 20 weeks plus standard treatment (metformin plus sulfonylurea and/or insulin; DS group, n = 25), or patients have taken standard treatment (metformin plus sulfonylurea and/or insulin) alone (ST group, n = 46) for type 2 diabetes management. Both groups reported a decrease in liver fat content, pancreatic fat content, and liver stiffness after interventions (p < 0.001 for all). After interventions, the DS group reported a higher decrease in liver fat content, pancreatic fat content, and liver stiffness than that of the ST group (p < 0.001 for all). After interventions, the DS group reported a higher decrease in body mass index than that of the ST group (p < 0.05). There were significant improvements in liver function tests, kidney function tests, lipid profiles, and blood counts after interventions (p < 0.05 for all). Both groups reported a decrease in body mass index after interventions (p < 0.001 for both). The DS group significantly decrease body mass index after interventions (p < 0.05) than the ST group.

The interconnection of endoplasmic reticulum and microtubule and its implication in Hereditary Spastic Paraplegia.

The endoplasmic reticulum (ER) and microtubule (MT) network form extensive contact with each other and their interconnection plays a pivotal role in ER maintenance and distribution as well as MT stability. The ER participates in a variety of biological processes including protein folding and processing, lipid biosynthesis, and Ca2+ storage. MTs specifically regulate cellular architecture, provide routes for transport of molecules or organelles, and mediate signaling events. The ER morphology and dynamics are regulated by a class of ER shaping proteins, which also provide the physical contact structure for linking of ER and MT. In addition to these ER-localized and MT-binding proteins, specific motor proteins and adaptor-linking proteins also mediate bidirectional communication between the two structures. In this review, we summarize the current understanding of the structure and function of ER-MT interconnection. We further highlight the morphologic factors which coordinate the ER-MT network and maintain the normal physiological function of neurons, with their defect causing neurodegenerative diseases such as Hereditary Spastic Paraplegia (HSP). These findings promote our understanding of the pathogenesis of HSP and provide important therapeutic targets for treatment of these diseases.

Stress granule homeostasis is modulated by TRIM21-mediated ubiquitination of G3BP1 and autophagy-dependent elimination of stress granules.

Eukaryotic stress granules (SGs) are highly dynamic assemblies of untranslated mRNAs and proteins that form through liquid-liquid phase separation (LLPS) under cellular stress. SG formation and elimination process is a conserved cellular strategy to promote cell survival, although the precise regulation of this process is poorly understood. Here, we screened six E3 ubiquitin ligases present in SGs and identified TRIM21 (tripartite motif containing 21) as a central regulator of SG homeostasis that is highly enriched in SGs of cells under arsenite-induced oxidative stress. Knockdown of TRIM21 promotes SG formation whereas overexpression of TRIM21 inhibits the formation of physiological and pathological SGs associated with neurodegenerative diseases. TRIM21 catalyzes K63-linked ubiquitination of the SG core protein, G3BP1 (G3BP stress granule assembly factor 1), and G3BP1 ubiquitination can effectively inhibit LLPS, in vitro. Recent reports suggested the involvement of macroautophagy/autophagy, as a stress response pathway, in the regulation of SG homeostasis. We systematically investigated well-defined autophagy receptors and identified SQSTM1/p62 (sequestosome 1) and CALCOCO2/NDP52 (calcium binding and coiled-coil domain 2) as the primary receptors that directly interact with G3BP1 during arsenite-induced stress. Endogenous SQSTM1 and CALCOCO2 localize to the periphery of SGs under oxidative stress and mediate SG elimination, as single knockout of each receptor causes accumulation of physiological and pathological SGs. Collectively, our study broadens the understanding in the regulation of SG homeostasis by showing that TRIM21 and autophagy receptors modulate SG formation and elimination respectively, suggesting the possibility of clinical targeting of these molecules in therapeutic strategies for neurodegenerative diseases.Abbreviations: ACTB: actin beta; ALS: amyotrophic lateral sclerosis; BafA1: bafilomycin A1; BECN1: beclin 1; C9orf72: C9orf72-SMCR8 complex subunit; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; Co-IP: co-immunoprecipitation; DAPI: 4',6-diamidino-2-phenylindole; FTD: frontotemporal dementia; FUS: FUS RNA binding protein; G3BP1: G3BP stress granule assembly factor 1; GFP: green fluorescent protein; LLPS: liquid-liquid phase separation; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NBR1: NBR1 autophagy cargo receptor; NES: nuclear export signal; OPTN: optineurin; RFP: red fluorescent protein; SQSTM1/p62: sequestosome 1; SG: stress granule; TAX1BP1: Tax1 binding protein 1; TOLLIP: toll interacting protein; TRIM21: tripartite motif containing 21; TRIM56: tripartite motif containing 56; UB: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; WT: wild-type.

Intelligent fault diagnosis of helical gearboxes with compressive sensing based non-contact measurements.

Helical gearboxes play a critical role in power transmission of industrial applications. They are vulnerable to various faults due to long-term and heavy-duty operating conditions. To improve the safety and reliability of helical gearboxes, it is necessary to monitor their health conditions and diagnose various types of faults. The conventional measurements for gearbox fault diagnosis mainly include lubricant analysis, vibration, airborne acoustics, thermal images, electrical signals, etc. However, a single domain measurement may lead to unreliable fault diagnosis and the contact installation of transducers is not always accessible, especially in harsh and dangerous environments. In this article, a Compressive Sensing (CS)-based Dual-Channel Convolutional Neural Network (CNN) method was proposed to accurately and intelligently diagnose common gearbox faults based on two complementary non-contact measurements (thermal images and acoustic signals) from a mobile phone. The raw acoustic signals were analysed by the Modulation Signal Bispectrum (MSB) to highlight the coupled modulation components relating to gear faults and suppress the irrelevant components and random noise, which generates a series of two-dimensional matrices as sparse MSB magnitude images. Then, CS was used to reduce the image redundancy but retain key information owing to the high sparsity of thermal images and acoustic MSB images, which significantly accelerates the CNN training speed. The experimental results convincingly demonstrate that the proposed CS-based Dual-Channel CNN method significantly improves the diagnostic accuracy (99.39% on average) of industrial helical gearbox faults compared to the single-channel ones.

Ribavirin inhibits peste des petits ruminants virus proliferation in vitro.

Peste des petits ruminants virus (PPRV), a member of the family Paramyxoviridae, belongs to the genus Morbillivirus. It causes devastating viral diseases in small ruminants and has been rapidly spreading over various regions in Africa, the Middle East, and Asia. Although vaccination is thought to be an effective management strategy against PPR infections, the heat sensitivity of PPRV vaccines severely restricts their use in regions with hot climates. In this research, we studied the antiviral activities of ribavirin and aimed to understand the potential mechanisms of action of ribavirin in the African green monkey kidney cells (Vero cells). In brief, the adsorption, intrusion, replication, and release of PPRV, as well as the mRNA expression level of RNA-dependent RNA polymerase (RdRp), were significantly inhibited in the ribavirin-treated Vero cells compared to those in the PPRV-infected cells that were not treated with ribavirin. Additionally, ribavirin has potential as an antiviral drug against PPRV, and its antiviral activity is mediated by the Janus kinase signal transducer and activator of transcription (JAK/STAT) and PI3K/AKT pathways.

The Role and Therapeutic Potential of Macropinocytosis in Cancer.

Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis. Conversely, overexpression of the RAS gene alongside drug treatment can lead to methuosis, a novel mode of cell death. The survival and proliferation of cancer cells is closely related to macropinocytosis in the tumor microenvironment (TME), but identifying how these cells interface with the TME is crucial for creating drugs that can limit cancer progression and metastasis. Substantial progress has been made in recent years on designing anticancer therapies that utilize the effects of macropinocytosis. Both the induction and inhibition of macropinocytosis are useful strategies for combating cancer cells. This article systematically reviews the general mechanisms of macropinocytosis, its specific functions in tumor cells, its occurrence in nontumor cells in the TME, and its application in tumor therapies. The aim is to elucidate the role and therapeutic potential of macropinocytosis in cancer treatment.

Enhanced removal of diclofenac via coupling Pd catalytic and microbial processes in a H2-based membrane biofilm reactor: Performance, mechanism and biofilm microbial ecology.

Diclofenac (DCF) is a most widely used anti-inflammatory drug, which has attracted worldwide attention given its low biodegradability and ecological damage, especially toxic effects on mammals including humans. In this study, a H2-based membrane biofilm reactor (H2-MBfR) was constructed with well-dispersed Pd nanoparticles generated in situ. The Pd-MBfR was applied for catalytic reductive dechlorination of DCF. In batch tests, DCF concentration had significantly effect on the rate and extent DCF removal, and NO3- had negative impact on DCF reductive dechlorination. Over 67% removal of 0.5 mg/L DCF and 99% removal of 10 mg/L NO3--N were achieved in 90 min, and the highest removal of 97% was obtained at 0.5 mg/L DCF in the absence of NO3-. Over 78 days of continuous operation, the highest steady-state removal flux of DCF was 0.0097 g/m2/d. LC-MS analysis indicated that the major product was 2-anilinephenylacetic acid (APA). Dechlorination was the main removal process of DCF mainly owing to the catalytic reduction by PdNPs, microbial reduction, and the synergistic reduction of microbial and PdNPs catalysis using direct delivery of H2. Moreover, DCF reductive Dechlorination shifted the microbial community in the biofilms and Sporomusa was responsible for DCF degradation. In summary, this work expands a remarkable feasibility of sustainable catalytic removal of DCF.

PINK1/Parkin-mediated mitophagy is activated to protect against AFB1-induced immunosuppression in mice spleen.

Aflatoxin B1 (AFB1) can cause mitochondrial malfunction and immunosuppression in spleen. Mitochondrial damage can lead to oxidative stress and aggravate immune cell dysfunction. Phosphatase and tensin homolog (PTEN)-induced putative kinase1 (PINK1)/ E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy can scavenge damaged mitochondria and alleviate oxidative stress to maintain cellular homeostasis. However, the role of PINK1/Parkin-mediated mitophagy in AFB1-induced immunosuppression in spleen is unclear. In this study, sixty male mice were sensibilized orally with AFB1 at different concentrations [0, 0.5, 0.75, and 1 mg/kg body weight (BW)] for 28 days, and AFB1 caused splenic structure injury and immunosuppression, also led to upregulation of PINK1/Parkin-mediated mitophagy in a dose-dependent manner. Subsequently, thirty male WT C57BL/6 N mice and thirty male Parkin knockout (Parkin-/-) C57BL/6 N mice were sensibilized orally with AFB1 at 0 or 1 mg/kg BW for 28 days, and Parkin-/- inhibited mitophagy and further aggravated AFB1-induced splenic structure injury, immunosuppression, mitochondrial damage and oxidative stress. Collectively, these results indicate that AFB1 exposure activates PINK1/Parkin-mediated mitophagy, which protects against immunosuppression in spleen.

Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology.

Erianin is a major bisbenzyl compound extracted from Dendrobium chrysotoxum Lindl., an important traditional Chinese herb. In recent years, a growing body of evidence has proved the potential therapeutic effects of erianin on various cancers, including hepatoma, melanoma, non-small-cell lung carcinoma, myelogenous leukemia, breast cancer, and osteosarcoma. Especially, the pharmacological activities of erianin, such as antioxidant and anticancer activity, have been frequently demonstrated by plenty of studies. In this study, we firstly conducted a systematic review on reported anticancer activity of erianin. All updated valuable information regarding the underlying action mechanisms of erianin in specific cancer was recorded and summarized in this paper. Most importantly, based on the molecular structure of erianin, its potential molecular targets were analyzed and predicted by means of the SwissTargetPrediction online server (http://www.swisstargetprediction.ch). In the meantime, the potential therapeutic targets of 10 types of cancers in which erianin has been proved to have anticancer effects were also predicted via the Online Mendelian Inheritance in Man (OMIM) database (http://www.ncbi.nlm.nih.gov/omim). The overlapping targets may serve as valuable target candidates through which erianin exerts its anticancer activity. The clinical value of those targets was subsequently evaluated by analyzing their prognostic role in specific cancer using Kaplan-Meier plotter (http://Kmplot.com/analysis/) and Gene Expression Profiling Interactive Analysis (GEPIA) (http://gepia.cancer-pku.cn/). To better assess and verify the binding ability of erianin with its potential targets, molecular flexible docking was performed using Discovery Studio (DS). The valuable targets obtained from the above analysis and verification were further mapped to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway using the Database for Annotation, Visualization and Integrated Discovery (DAVID) (http://david.abcc.ncifcrf.gov/) to explore the possible signaling pathways disturbed/regulated by erianin. Furthermore, the in silico prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of erianin was also performed and provided in this paper. Overall, in this study, we aimed at 1) collecting all experiment-based important information regarding the anticancer effect and pharmacological mechanism of erianin, 2) providing the predicted therapeutic targets and signaling pathways that erianin might act on in cancers, and 3) especially providing in silico ADMET properties of erianin.