Room-temperature magnetocapacitance spanning 97 K hysteresis in molecular material.

Magnetic capacitor, as a new type of device, has broad application prospects in fields such as magnetic field sensing, magnetic storage, magnetic field control, power electronics and so on. Traditional magnetic capacitors are mostly assembled by magnetic and capacitive materials. Magnetic capacitor made of a single material with intrinsic properties is very rare. This intrinsic property is magnetocapacitance (MC). The studies on MC effect have mainly focused on metal oxides so far. No study was reported in molecular materials. Herein, two complexes: (CETAB)2[CuCl4] (1) and (CETAB)2[CuBr4] (2) (CETAB = (2-chloroethyl)trimethylammonium) are reported. There exist strong H-Br and Br-Br interactions and other weak interactions in complex 2, so the phase transition energy barrier is high, resulting in the widest thermal hysteresis loop on a molecular level to date. Furthermore, complexes 1 and 2 show large MC parameters of 0.247 and 1.614, respectively, which is the first time to observe MC effect in molecular material.

PDK3 drives colorectal carcinogenesis and immune evasion and is a therapeutic target for boosting immunotherapy.

Pyruvate Dehydrogenase Kinase 3 (PDK3) has emerged as a significant player in various cancer types, yet its specific impact on cancers including colon cancer remains ambiguous. Through pan-cancer analysis using TCGA data, we found that the expression of PDK3 and the composition of the immune microenvironment for different tumors were highly heterogeneous across tumors. PDK3 is highly expressed in colorectal cancer and may promote tumor proliferation by activating PI3K-AKT signaling. In addition, we found that PDK3 was able to inhibit tumor antigen presentation signals to suppress immune killing. High PDK3 expression predicts less CD8+ T cell infiltration and effector function. Moreover, inhibition of PDK3 expression bolstered CD8+ T cell-mediated cytotoxicity CD8+ T cell infiltration and activation in vivo. Notably, PDK3 was found to facilitate STAT1 activation and elevate programmed death-ligand 1 (PD-L1) expression in colon cancer cells. Importantly, PDK3 inhibition combination with PD-1 blockade significantly activates the infiltrated CD8+ T cells to suppress tumor growth and improves the survival benefit in several murine tumor models. In summary, these findings underscore PDK3's role in fueling colon cancer growth by orchestrating PI3K-AKT signaling and PD-L1 expression and dampening CD8+ T cell function.

Chemical Constituents from the deep-sea-derived Fungus Aureobasidium melanogenum LUO5.

Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3 nM.

Imaging phenotyping using 18F-FDG PET/CT radiomics to predict micropapillary and solid pattern in lung adenocarcinoma.

OBJECTIVES: To develop and validate a machine learning model using 18F-FDG PET/CT radiomics signature and clinical features to predict the presence of micropapillary and solid (MP/S) components in lung adenocarcinoma. METHODS: Eight hundred and forty-six patients who underwent preoperative PET/CT with pathologically confirmed adenocarcinoma were enrolled. After segmentation, 1688 radiomics features were extracted from PET/CT and selected to construct predictive models. Then, we developed a nomogram based on PET/CT radiomics integrated with clinical features. Receiver operating curves, calibration curves, and decision curve analysis (DCA) were performed for diagnostics assessment and test of the developed models for distinguishing patients with MP/S components from the patients without. RESULTS: PET/CT radiomics-clinical combined model could well distinguish patients with MP/S components from those without MP/S components (AUC = 0.87), which performed better than PET (AUC = 0.829, p < 0.05) or CT (AUC = 0.827, p < 0.05) radiomics models in the training cohort. In test cohorts, radiomics-clinical combined model outperformed the PET radiomics model in test cohort 1 (AUC = 0.859 vs 0.799, p < 0.05) and the CT radiomics model in test cohort 2 (AUC = 0.880 vs 0.829, p < 0.05). Calibration curve indicated good coherence between all model prediction and the actual observation in training and test cohorts. DCA revealed PET/CT radiomics-clinical model exerted the highest clinical benefit. CONCLUSION: 18F-FDG PET/CT radiomics signatures could achieve promising prediction efficiency to identify the presence of MP/S components in adenocarcinoma patients to help the clinician decide on personalized treatment and surveillance strategies. The PET/CT radiomics-clinical combined model performed best. CRITICAL RELEVANCE STATEMENT: 18F-FDG PET/CT radiomics signatures could achieve promising prediction efficiency to identify the presence of micropapillary and solid components in adenocarcinoma patients to help the clinician decide on personalized treatment and surveillance strategies.

Buffalo yogurt fermented with commercial starter and Lactobacillus plantarum originating from breast milk lowered blood pressure in pregnant hypertensive rats.

Nutritional therapy, which may have advantages over medication, is being investigated as a novel treatment for pregnancy-induced hypertension. Several studies have shown that probiotic yogurt supplementation during pregnancy has beneficial effects on maternal and fetal health. In this study, fermented buffalo milk was produced with yogurt culture and Lactobacillus plantarum B, a probiotic isolated from healthy breast milk with high angiotensin-converting enzyme inhibitory activity. The fermentation conditions under which the angiotensin-converting enzyme (ACE) inhibitory activity reached 84.51% were optimized by the response surface method as follows: 2 × 106 cfu/mL of L. plantarum B, yogurt culture 2.5 × 105 cfu/mL, and 8 h at 37°C. The distribution of ACE inhibitory peptides from fermented buffalo milk and fermented cow milk were further analyzed by liquid chromatography-mass spectrometry. By searching according to the structural features of ACE inhibitory peptides, 29 and 11 peptides containing ACE inhibitory peptide features were found in fermented buffalo milk and fermented cow milk, respectively. To investigate the in vivo antihypertensive activity of fermented buffalo milk, 18 pregnant rats were divided into 3 groups (n = 6 in each group) and administered 10 mL of normal saline, yogurt (20 mg/kg), or labetalol hydrochloride (4 mg/kg) daily from the beginning of pregnancy to parturition. To induce hypertension, methyl nitrosoarginine (125 mg/kg) was injected subcutaneously every day from d 15 of pregnancy to the day of delivery. Blood pressure was not significantly changed in the yogurt and labetalol groups after induction of hypertension and was lower compared with the normal saline group, but there was no difference between the yogurt and labetalol groups. This implied that the buffalo yogurt had a preventive and antihypertensive effect in the pregnancy-induced hypertensive rat model. Further studies to determine the mechanism of action, as well as a randomized control trial, are warranted.

Compression Degree of Trigeminal Nerve and Type of Conflicting Vessels Determine Short- and Long-Term Complete Pain Relief in Adult Patients with Primary Trigeminal Neuralgia After Microvascular Decompression: A Three-Year Retrospective Study of 200 Adult Patients with Primary Trigeminal Neuralgia.

Objective: In this study, we aimed to explore the demographic and clinical factors that could determine short- and long-term complete pain relief (CPR) in adult patients with primary trigeminal neuralgia (PTN) after microvascular decompression (MVD) to guide clinical practice. Methods: This single-center retrospective study included adult patients with PTN who underwent MVD as their initial neurosurgical procedure in the Department of Neurosurgery at the Second Affiliated Hospital of Harbin Medical University from January 2017 to December 2019 and completed a 3-year post-surgery follow-up. Demographic and clinical information was obtained from medical records. Pain relief of adult patients with PTN at various time points after sufficient decompression of trigeminal nerve (TN) during MVD was determined and classified by the patient's subjective response and medications use. Pain relief of local patients was evaluated by outpatient follow-up at various time points, whereas that of local cases who could not return to outpatient or non-local cases was assessed through telephone or WeChat. Results: In univariate analysis, compression degree of TN and type of conflicting vessels constantly showed significant differences between the two groups at 3 months, 6 months, 1 year, 2 years, and 3 years after MVD. Compression degree of TN and type of conflicting vessels at various time points after MVD were always the related factors to CPR in logistic regression analysis, with the former having the greatest impact. The areas under the receiver operating characteristic (ROC) curve of CPR at various time points after MVD were 0.937, 0.874, 0.879, 0.864, and 0.869, respectively. Conclusion: In summary, compression degree of TN and type of conflicting vessels can determine short- and long-term CPR in adult patients with PTN after MVD.

Hepialiamides A-C: Aminated Fusaric Acid Derivatives and Related Metabolites with Anti-Inflammatory Activity from the Deep-Sea-Derived Fungus Samsoniella hepiali W7.

A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A-C (1-3) and one novel hybrid polyketide hepialide (4), together with 18 known miscellaneous compounds (5-22). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8, 11, 13, 21, and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC50 value of 426.2 nM.

Penidihydrocitrinins A-C: New Polyketides from the Deep-Sea-Derived Penicillium citrinum W17 and Their Anti-Inflammatory and Anti-Osteoporotic Bioactivities.

Three new polyketides (penidihydrocitrinins A-C, 1-3) and fourteen known compounds (4-17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1-17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on LPS-stimulated nitric oxide production in murine brain microglial BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Additionally, compounds 6, 7, and 8 significantly enhanced osteoblast mineralization, which was comparable to that of the positive control, purmorphamine. Furthermore, these three compounds also suppressed osteoclastogenesis in a dose-dependent manner under the concentrations of 2.5 µM, 5.0 µM, and 10 µM.

Near-Room-Temperature Synergetic Response of Magnetism, Dielectricity and Luminescence Based on (C5 NH13 Cl)2 MnBr4.

Multifunctional materials with working temperatures near room temperature are crucial for practical applications. Until now, it is still a great challenge to obtain such materials. In this paper, a complex of (C5 NH13 Cl)2 MnBr4 (1) with a structural phase transition near room temperature is reported. The phase transition induces switchable magnetic properties, dielectric anomalies and luminescent response over the same range of temperatures. It is the first time the synergetic effect of magnetism, dielectricity and luminescence near room temperature have been observed in the same molecular complex.

In Vivo Analysis of Extract of Leaves of Mistletoe as a Benalu Duku: Clinical Chemical Value Associated with Histopathology, Liver, Kidneys, and Lethal Dose Determinate.

The active compounds from the leaves of Dendrophthoe pentandra L. Miq., also known as, Benalu Duku (in Indonesia), are known to contain progesterone-like compounds (PLCs). This study aims to determine the effect of giving a single dose of PLCs on liver and kidney function in rats and the dose limit that causes the death of experimental animals. The PLCs were analyzed for chemical and physical characterization and compared to a pure standard of progesterone using HPLC, IR spectrometry, thermogravimetry, and NMR. The research was carried out in two sections. In section one, thirty-five healthy adult male rats were divided into six experimental groups and a control group of five rats each. The groups received, respectively, 50 to 75 mg/kg of PLCs (i.p.). The control group was given a 0.5 mL Aqua Pro injection. Alanine aminotransferase, aspartate aminotransferase, creatinine, and blood urea nitrogen were assessed using the clinical chemistry of blood serum analysis. Cell disruptions were analyzed to determine the degeneration effects of PLCs on the liver and kidney in the experimental and control groups. In section two, thirty healthy adult male rats were divided into 6 groups, each group of 5 rats, and injected with PLCs at a dose of 0.9-2.1 g/kg BW, followed by a lethal dose test. The control groups were available for 5 individual rats at 0 g/kg BW of PLCs. Our findings indicated that PLCs have a similarity chemical and physical characterized each other compounds, then the following administration of 50 to 75 mg/kg of PLCs did not affect the parameters of clinical chemistry. Histopathology analysis of the liver and kidney revealed normal subcellular levels in the experimental group, with the nonlethal dose at 0.9 g/kg BW.

A computational method for large-scale identification of esophageal cancer-related genes.

The incidence of esophageal cancer has obvious genetic susceptibility. Identifying esophageal cancer-related genes plays a huge role in the prevention and treatment of esophageal cancer. Through various sequencing methods, researchers have found only a small number of genes associated with esophageal cancer. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. This method fuses graph convolutional network and logical matrix factorization to effectively identify esophageal cancer-related genes through the association between genes. We call this method GCNLMF which achieved AUC as 0.927 and AUPR as 0.86. Compared with other five methods, GCNLMF performed best. We conducted a case study of the top three predicted genes. Although the association of these three genes with esophageal cancer has not been reported in the database, studies by other reseachers have shown that these three genes are significantly associated with esophageal cancer, which illustrates the accuracy of the prediction results of GCNLMF.

Synthesis, dielectric, magnetic, and photoluminescence properties of two new hybrid rare-earth double perovskites.

Two new organic-inorganic hybrid double perovskites (R3HQ)4CsSm(NO3)8 (1) (R3HQ = (R)-(-)-3-quinuclidinol) and (R3HQ)4CsEu(NO3)8 (2) were synthesized and characterized. Compounds 1 and 2 exhibit obvious phase transitions at 379 and 375 K, respectively, confirmed by differential scanning calorimetry (DSC) and variable temperature powder X-ray diffraction. The rapid switching between high- and low-dielectric states makes it a typical dielectric material with a switchable dielectric constant for thermal stimulus response. Furthermore, 1 and 2 show attractive photoluminescence and paramagnetic behavior, and the fluorescence quantum yield of 2 reached 14.6%. These results show that compounds 1 and 2 can be used as excellent candidates for multifunctional intelligent materials, which also provides a new way for development of multifunctional materials.

Efficacy of subthreshold micropulse laser for chronic central serous chorioretinopathy: A meta-analysis.

PURPOSE: To evaluate the efficacy of subthreshold micropulse laser (SML) treatment for chronic central serous chorioretinopathy (CSC). METHODS: PubMed, Cochrane Library, and Embase were comprehensively searched for studies published up to April 19, 2021. Randomized controlled trials (RCTs), retrospective and prospective cohort studies that compared SML with any other intervention for chronic CSC were selected. The primary outcomes were best corrected visual acuity (BCVA) and central macular thickness (CMT). Meta-analysis was performed using Review Manager 5.3. Random-effect model was used for pooled analysis. RESULTS: Eleven studies including 834 eyes were included, with 428 eyes undergoing SML treatment and 406 eyes receiving other interventions. Pooled results showed no significant differences between SML and control with respect to BCVA, CMT, or complete resolution of subretinal fluid, while SML treatment was inferior to control in terms of subfoveal choroidal thickness (SFCT) reduction [weighted mean difference (WMD)=44.75, 95% Cl, 14.31-75.20, P<0.05, I2=72%]. However, SML was not superior to photodynamic therapy with respect to SFCT (WMD=61.29, 95% Cl, 29.50-93.08, P<0.05, I2=56%), retinal sensitivity (WMD=-1.85, 95% Cl, -3.05--0.65, P<0.01, I2=0) or NEI-VFQ25 score (WMD=-2.44, 95% Cl, -4.72--0.16, P<0.05, I2=0). No serious side effects of SML treatment were observed. CONCLUSION: Available evidence suggests that the clinical efficacy of SML therapy is similar to other treatment modalities for chronic CSC. However, because of the lack of serious side effects, SML may be the most promising alternative therapy for chronic CSC. The study protocol was registered on PROSPERO (CRD42021 258837).

577 nm subthreshold micropulse laser treatment for acute central serous chorioretinopathy: a comparative study.

BACKGROUND: To assess the efficacy of 577 nm subthreshold micropulse laser (SML) treatment for acute central serous chorioretinopathy (CSC). METHODS: This retrospective comparative case-series included 34 eyes of 34 patients with acute CSC who received either 577 nm SML treatment (SML group, n = 16 eyes) or were only monitored (observation group, n = 18 eyes). Acute CSC was defined as disease course < 3 months. Eyes with any history of treatment in the past were excluded. Data were collected over a period of 6 months. The best corrected visual acuity (BCVA), central macular thickness (CMT), and subfoveal choroidal thickness (SFCT) were observed. RESULTS: SML group showed significantly greater improvement in the BCVA (logMAR) compared to observation group at 1 month (0.20 ± 0.10 vs 0.30 ± 0.12, P < 0.01), 3 months (0.13 ± 0.06 vs 0.21 ± 0.06, P < 0.01) and 6 months (0.01 ± 0.06 vs 0.09 ± 0.66, P < 0.01). The CMT reduction was significantly greater in the SML group at 1 month (337.19 ± 62.96 µm vs 395.11 ± 91.30 µm, P < 0.05), 3 months (312.94 ± 49.50 µm vs 364.50 ± 70.30 µm, P < 0.05) and 6 months (291.38 ± 26.46 µm vs 348.56 ± 54.65 µm, P < 0.05). In the SML group, the SFCT did not show a significant decrease at 1 month (468.88 ± 42.19 µm, P > 0.05) but showed a significant reduction at 3 months (451.75 ± 39.36 µm, P < 0.05) and 6 months (450.50 ± 34.24 µm, P < 0.05) from baseline (489.94 ± 45.86 µm). In the observation group, there was no significant change in SFCF during follow-up. No adverse events occurred in the SML group. CONCLUSIONS: Although some patients with acute CSC show spontaneous healing, timely intervention with 577 nm SML can shorten the disease course, improve visual acuity, and reduce the risk of chronic transformation without adverse events.

Study on risk factors, bacterial species, and drug resistance of acute pyelonephritis associated with ureteral stent after percutaneous nephrolithotomy.

The purpose of this study is to explore the risk factors, bacterial species, and drug resistance of acute pyelonephritis (AP) associated with ureteral stent after percutaneous nephrolithotomy (PCNL) and to provide reference for clinical intervention. The clinical data of 415 patients with indwelling ureteral stent after PCNL from December 2016 to May 2019 were analyzed retrospectively. The patients were divided into infection group (n = 54) and non-infection group (n = 361) according to whether patients had AP. Patients' clinical data, blood and urine bacterial culture, and drug sensitivity were collected and analyzed. The incidence of AP associated with ureteral stent after PCNL was 13.01% and diabetes mellitus (P = 0.001), postoperative stone residue (P = 0.002), urinary leucocytes ≥ 100/HP (P = 0.018), positive urine culture results (P = 0.001), ureteral stent retention time ≥ 8 weeks (P = 0.004), and high S.T.O.N.E. score (P = 0.014) are independent risk factors for it. Escherichia coli (40.54%, 47.82%), Klebsiella pneumoniae (16.21%, 15.21%), Pseudomonas aeruginosa (10.81%, 4.34%), Enterococcus faecalis (21.6%, 19.56%), and epidermis Staphylococci (10.81%, 13.33%) are the main pathogens in blood and urine. The main sensitive drugs of pathogenic bacteria are imipenem, meropenem, tigecycline, piperacillin/tazobactam, ceftazidime, linezolid, teicoplanin, levofloxacin, vancomycin, tigecycline, etc., while levofloxacin, norfloxacin, penicillin G, first, and second-generation cephalosporins showed a strong drug resistance rate (> 70%). This study found that diabetes, postoperative stone residuals, urinary leukocytes ≧ 100 cells/HP, positive urine culture results, ureteral stent indwelling time ≧ 8 weeks, and high S.T.O.N.E. score were independent of AP associated with ureteral stent after PCNL risk factors and Escherichia coli is the main pathogenic bacteria and shows drug resistance.

Corrigendum to "miR-375 Inhibits the Proliferation and Invasion of Nasopharyngeal Carcinoma Cells by Suppressing PDK1".

[This corrects the article DOI: 10.1155/2020/9704245.].

Propofol inhibits the expression of Abelson nonreceptor tyrosine kinase without affecting learning or memory function in neonatal rats.

OBJECTIVE: Propofol is one of the most commonly used intravenous drugs to induce and maintain general anesthesia. In vivo and in vitro studies have shown that propofol can affect neuronal growth, leading to apoptosis and impairing cognitive function. The Abelson nonreceptor tyrosine kinase (c-Abl) is associated with both neuritic plaques and neurofibrillary tangles in the brains of patients with Alzheimer's disease and other neurodegenerative diseases. This study aimed to explore the effect of propofol on apoptosis and neurocognition through its regulation of c-Abl expression in vivo and in vitro. MATERIALS AND METHODS: In this study, primary hippocampal neurons were cultured and exposed to propofol at different concentrations. Protein expression was measured by Western blotting and coimmunoprecipitation. The c-Abl transcription level was verified by fluorescence quantitative PCR. Reactive oxygen species (ROS) levels were detected by flow cytometry. In addition, an animal experiment was conducted to assess neuronal apoptosis by immunofluorescence staining for caspase-3 and to evaluate behavioral changes by the Morris water maze (MWM) test. RESULTS: The in vitro experiment showed that propofol significantly decreased c-Abl expression and ROS levels. In addition, propofol has no cytotoxic effect and does not affect cell activity. Moreover, in the animal experiment, intraperitoneal injection of 50 mg/kg propofol for 5 days obviously decreased the expression of c-Abl in the neonatal rat brain (p < .05) but did not significantly increase the number of caspase-3-positive cells. Propofol treatment did not significantly reduce the number of platform crossings (p > .05) or prolong the escape latency of neonatal rats (p > .05) in the MWM test. CONCLUSIONS: The present data suggest that reduced expression of this nonreceptor tyrosine kinase through consecutive daily administration of propofol did not impair learning or memory function in neonatal rats.

miR-375 Inhibits the Proliferation and Invasion of Nasopharyngeal Carcinoma Cells by Suppressing PDK1.

PURPOSE: In patients with nasopharyngeal carcinoma (NPC), the expression of PDK1 is remarkably improved in NPC tissue and correlated with the clinicopathological severity of NPC. We expressed miR-375 in NPC cells to study the effects on PDK1 gene expression. We also investigated the mechanism by which miR-375 affects the biological behavior of NPC cells through effects on PDK1. METHODS: qRT-PCR was carried out to analyze miR-375 and PDK1 levels in NPC cells. NPC cells were transfected with miR-375 inhibitor or miR-375 mimic. CCK-8 testing, colony formation testing, transwell testing, and flow cytometry analysis were carried out to quantify the cells' biological behavior. Rescue experiments demonstrated that the recovery of PDK1 expression was able to reverse the influence of miR-375 inhibition on NPC diffusion and intrusion. The interaction between miR-375 and PDK1 was verified by dual-luciferase reporter gene testing. RESULTS: The results revealed that miR-375 has a negative regulatory effect on PDK1 expression in NPC cells. Furthermore, PDK1 is a target gene for miR-375. The empirical results obtained demonstrated a negative correlation between tumor development and the level of miR-375 expression in NPC tissues. The excessive expression of miR-375 and the downregulation of PDK1 facilitated the diffusion and invasion of NPC cells. CONCLUSION: The diffusion and incursion of NPC cells may be inhibited by direct targeting of PDK1 and decreasing the expression of miR-375. Our study highlights efforts to target PDK1 and miR-375 as potential therapeutic strategies for use in the treatment of NPC.

Aphidicolin Chemistry of the Deep-Sea-Derived Fungus Botryotinia fuckeliana MCCC 3A00494.

Aphidicolin, a potent DNA polymerase α inhibitor, has been explored in clinical trials for the treatment of cancer. So far, about 300 modified aphidicolins have been discovered. However, none have shown a stronger effect. Herein, we report 71 new (aphidicolins A1-A71, 1-71) and eight known (72-79) aphidicolin congeners from Botryotinia fuckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (-5572 m). The structures of 1-71 were determined through extensive spectroscopic analysis, X-ray crystallography, chemical derivatization, modified Mosher's method, and the ECD exciton chirality method. Compounds 54-57 and 58-64 are novel 6/6/5/6/5 pentacyclic aphidicolins featuring tetrahydrofuran and dihydrofuran rings, respectively, while compounds 65-71 are rare noraphidicolins. Aphidicolin A8 (8) significantly induced apoptosis in T24 (IC50 = 2.5 µM) and HL-60 (IC50 = 6.1 µM) cancer cells by causing DNA damage. By docking its structure to the human DNA polymerase α binding pocket, 8 was found to form tight intermolecular contacts, elaborating aphidicolin A8 as a potently cytotoxic lead compound.

Realgar transforming solution-induced differentiation of NB4 cell by the degradation of PML/RARα partially through the ubiquitin-proteasome pathway.

PML/retinoic acid receptor alpha (RARα), as a hallmark of acute promyeloid leukemia (APL), is directly related to the outcome of clinical APL remedy. It is reported that arsenicals can effectively degrade PML/RARα, such as arsenic trioxide and realgar. However, the high toxicity or insolubility have hampered their clinical applications. Realgar transforming solution (RTS) was produced from realgar by bioleaching process in our lab. Previous studies demonstrated that RTS had a significant anti-cancer ability on chronic myeloid leukemia through oncoprotein degradation. The capacity of RTS on treating APL is what is focused on in this study. The results showed that RTS had a noticeable sensitivity in NB4 cell, and RTS remarkably down-regulated PML/RARα expression and induced cell differentiation. Further, RTS could accumulate PML/RARα into the nuclear bodies and then execute degradation, which could be reversed by proteasome inhibitor MG132. The results also exhibited that the reduction of RTS-induced PML/RARα expression accompanied by the elevation of ubiquitin and SUMO-1 protein expression. Finally, PML and SUMO-1 had been demonstrated to be co-localized after RTS treatment by immunofluorescence co-localization assay and immunoprecipitation assay. In conclusion, these results suggested that RTS-induced cell differentiation may attribute to the PML/RARα degradation partially through the ubiquitin-proteasome pathway.