Covalent Tethering of Cobalt Porphyrins on Phenolic Resins for Electrocatalytic Oxygen Reduction and Evolution Reactions.

Using functionalized supporting materials for the immobilization of molecular catalysts is an appealing strategy to improve the efficiency of molecular electrocatalysis. Herein, we report the covalent tethering of cobalt porphyrins on phenolic resins (PR) for improved electrocatalytic oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). A cobalt porphyrin bearing an alkyl bromide substituent was covalently tethered on phenolic resins, through the substitution reaction of alkyl bromides with phenolic hydroxyl groups, to afford molecule-engineered phenolic resins (Co-PR). The resulted Co-PR was efficient for electrocatalytic ORR and OER by displaying an ORR half-wave potential of E1/2=0.78 V versus RHE and an OER overpotential of 420 mV to get 10 mA/cm2 current density. We propose that the many residual phenolic hydroxyl groups on PR will surround the tethered Co porphyrin and play critical roles in facilitating proton and electron transfers. Importantly, Co-PR outperformed unmodified PR and PR loaded with Co porphyrins through simple physical adsorption (termed Co@PR). The zinc-air battery assembled using Co-PR displayed a performance comparable to that using Pt/C+Ir/C. This work is significant to present phenolic resins as a functionalized material to support molecular electrocatalysts and demonstrate the strategy to improve molecular electrocatalysis with the use of phenolic resin residues.

Covalent Tethering of Cobalt Porphyrins on Phenolic Resins for Electrocatalytic Oxygen Reduction and Evolution Reactions.

The front cover artwork is provided by Rui Cao's group at Shaanxi Normal University. The image shows the design of Co-porphyrin-engineered phenolic resins with intramolecular phenolic hydroxyl groups to facilitate proton and electron transfers for efficient oxygen electrocatalysis, which is bioinspired by cytochrome c oxidases, and shows the excellent performance of Zn-air batteries assembled with the hybrid material. Read the full text of the Research Article at 10.1002/cphc.202400017.

A Highly Reversible Lithium Metal Anode by Constructing Lithiophilic Bi-Nanosheets.

As a favorable candidate for the next-generation anode materials, metallic lithium is faced with two crucial problems: uncontrollable lithium plating/stripping process and huge volume expansion during cycling. Herein, a 3D lithiophilic skeleton modified with nanoscale Bi sheets (Ni@Bi Foam, i.e., NBF) through one-step facile substitution reaction is constructed. Benefiting from the nanoscale modification, smooth and dense lithiophilic Li3 Bi layer is in situ formed, which improves the uniform deposition of Li subsequently. Meanwhile, the 3D structure inhibits the growth of Li dendrites effectively by reducing local areal current density. Consequently, the NBF exhibits outstanding cycling stability with a high average Coulombic efficiency of 98.46% at 1 mA cm-2 with 1 mAh cm-2 (>500 cycles). Symmetrical cell with NBF exhibits a high reversibility at 1 mA cm-2 with 1 mAh cm-2 (>2000 h). Moreover, superior long-term cycling and rate performance of NBF@Li anode are also acquired when assembled with high areal loading of LiFePO4 (10.1 mg cm-2 ) cathode (Negative/Positive ratio: 2.91). Even in anode-free metal lithium batteries, NBF has higher capacity during cycling compared with NF. To conclude, NBF shows excellent electrochemical performance and provides an idea of facile preparation method which can be extend to other metal batteries.

Research progress review on long non-coding RNA in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies globally, and the morbidity and mortality rates associated with it are among the highest around the world. Not even great advances in colorectal cancer diagnosis and treatment technologies have been able to increase the 5-year survival rate in this disease. Recidivation and metastasis are the main causes of death in CRC, although the underlying mechanism remains unknown. Long non-coding RNA (lncRNA) is a type of non-coding RNA that is greater than 200 nt in length. LncRNAs are involved in cell proliferation, apoptosis, metastasis, and differentiation. Abnormal expression of lncRNAs is reported in various diseases. Relevant studies have demonstrated that lncRNAs are capable of interacting with DNAs, RNAs, and proteins, thereby regulating the Wnt, p53, and other signaling pathways and playing an important role in the biogenesis, progression, metastasis, and drug resistance in CRC. In the present report, recent progress in the research related to lncRNAs in colorectal cancer is reviewed.

miR-378a-5p inhibits the proliferation of colorectal cancer cells by downregulating CDK1.

BACKGROUND: MicroRNAs (miRNAs) play an important role in tumor occurrence. The role of miR-378a-5p and CDK1 in colorectal cancer (CRC) was investigated in this study. METHODS: Investigation of TCGA database and the detection of miR-378a-5p expression in colorectal cancer pathological tissues and colorectal cancer cell lines were undertaken by using qRT-PCR. We performed cell function experiments (CCK-8 assay, EdU assay, colony formation assay, wound healing assay, transwell assay, cell apoptosis assessment, and cell cycle assessment) and nude mouse tumor formation experiments to evaluate the effects of miR-378a-5p on proliferation, metastasis, and invasion to explore the role of miR-378a-5p in vivo and in vitro. Next, through TCGA database, immunohistochemical staining of pathological tissues, and cell function experiments, the role of the target gene CDK1 of miR-378a-5p was verified by database prediction, and dual luciferase reporter gene experiments in colorectal cancer cells were performed. Finally, whether upregulation of CDK1 restores the inhibitory effect of overexpression of miR-378a-5p on the proliferation of CRC cells was studied by overexpression of CDK1. RESULTS: Bioinformatic analysis showed significant downregulation of miR-378a-5p levels in colorectal cancer (CRC). Cell function experiments and tumor xenograft mouse models confirmed the low expression of miR-378a-5p within CRC tissues, which indicated the tumor suppressive role of miR-378a-5p in CRC. To better explore the regulation of miR-378a-5p in CRC, we predicted and validated cell cycle-dependent protein kinase 1 (CDK1) as the miR-378a-5p target gene and observed that miR-378a-5p suppressed CRC cell proliferation by targeting CDK1. CONCLUSION: The results of this study help to elucidate the mechanism by which miR-378a-5p can be used as a tumor marker to inhibit the growth of colorectal cancer and CDK1, which is related to the prognosis of colorectal cancer patients. MiR-378a-5p inhibits CRC cell proliferation by suppressing CDK1 expression, which may become a possible therapeutic target for treatment of CRC.

lncRNA CERS6-AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR-125a-5p to upregulate BAP1 expression.

Long noncoding RNAs (lncRNAs) can act as oncogene and tumor suppressor genes in many types of cancers including breast cancer (BC). Our previous study has indicated microRNA (miR)-125a-5p was downregulated and function as a tumor suppressor in BC. However, its upstream regulation mechanism is still unclear. In this study, we used bioinformatics algorithms, RNA pulldown assay, and dual-luciferase reports assay to predict and confirm lncRNA CERS6-AS1 interacted with miR-125a-5p. Then we found CERS6-AS1 was upregulated in BC tissues. Experimental results of tumor growth in nude mice show that CERS6-AS1 promotes tumor growth. Furthermore, CERS6-AS1 regulated BC susceptibility gene 1-associated protein 1 (BAP1) expression via sponging miR-125a-5p via Western blot analysis and quantitative polymerase chain reaction arrays. Finally, we showed that miR-125a-5p had opposing effects to those of CERS6-AS1 on BC cells, demonstrating that CERS6-AS1 may promote cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p. Our results indicated CERS6-AS1 promote BC cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p to upregulate BAP1 expression.

Hierarchically porous aggregates of Co-N-C nanoparticles for oxygen electrocatalysis.

Herein, a novel assembled Co-N-C (A-Co-N-C) material was reported for the first time by pyrolyzing zeolitic imidazolate framework-67 (ZIF-67) nanoparticle aggregates caused by the introduction of surfactant polystyrene sulfonic acid (PSS). The A-Co-N-C has a large surface area of 455 m2 g-1 with micropores (101 m2 g-1) and mesopores (354 m2 g-1). The A-Co-N-C exhibits good bifunctional catalytic oxygen reduction/evolution reaction (ORR/OER) and Zn-air battery activity. This work provides a simple but efficient strategy for constructing hierarchically porous aggregates of Co-N-C nanoparticles.

Design of antiviral AGO2-dependent short hairpin RNAs.

The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals. RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), which exhibits significant promise for antiviral therapy. AGO2-dependent shRNA (agshRNA) generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA. In this study, we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power. Using this model, we designed siRNA sequences targeting diverse RNA viruses, including human enterovirus A71 (EV71), Zika virus (ZIKV), dengue virus 2 (DENV2), mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and transformed them into agshRNAs. We validated the performance of our agshRNA design by evaluating antiviral efficacies of agshRNAs in cells infected with different viruses. Using the agshRNA targeting EV71 as an example, we showed that the anti-EV71 effect of agshRNA was more potent compared with the corresponding siRNA and shRNA. Moreover, the antiviral effect of agshRNA is dependent on AGO2-processed guide RNA, which can load into the RNA-induced silencing complex (RISC). We also confirmed the antiviral effect of agshRNA in vivo. Together, this work develops a novel antiviral strategy that combines machine learning-based algorithm with agshRNA design to custom design antiviral agshRNAs with high efficiency.

Constructing Co4(SO4)4 Clusters within Metal-Organic Frameworks for Efficient Oxygen Electrocatalysis.

Multinuclear metal clusters are ideal candidates to catalyze small molecule activation reactions involving the transfer of multiple electrons. However, synthesizing active metal clusters is a big challenge. Herein, on constructing an unparalleled Co4(SO4)4 cluster within porphyrin-based metal-organic frameworks (MOFs) and the electrocatalytic features of such Co4(SO4)4 clusters for the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is reported. The reaction of CoII sulfate and metal complexes of tetrakis(4-pyridyl)porphyrin under solvothermal conditions afforded Co4-M-MOFs (M═Co, Cu, and Zn). Crystallographic studies revealed that these Co4-M-MOFs have the same framework structure, having the Co4(SO4)4 clusters connected by metalloporphyrin units through Co─Npyridyl bonds. In the Co4(SO4)4 cluster, the four CoII ions are chemically and symmetrically equivalent and are each coordinated with four sulfate O atoms to give a distorted cube-like structure. Electrocatalytic studies showed that these Co4-M-MOFs are all active for electrocatalytic OER and ORR. Importantly, by regulating the activity of the metalloporphyrin units, it is confirmed that the Co4(SO4)4 cluster is active for oxygen electrocatalysis. With the use of Co porphyrins as connecting units, Co4-Co-MOF displays the highest electrocatalytic activity in this series of MOFs by showing a 10 mA cm-2 OER current density at 357 mV overpotential and an ORR half-wave potential at 0.83 V versus reversible hydrogen electrode (RHE). Theoretical studies revealed the synergistic effect of two proximal Co atoms in the Co4(SO4)4 cluster in OER by facilitating the formation of O─O bonds. This work is of fundamental significance to present the construction of Co4(SO4)4 clusters in framework structures for oxygen electrocatalysis and to demonstrate the cooperation between two proximal Co atoms in such clusters during the O─O bond formation process.

Hierarchical Piezoelectric Composites for Noninvasive Continuous Cardiovascular Monitoring.

Continuous monitoring of blood pressure (BP) and multiparametric analysis of cardiac functions are crucial for the early diagnosis and therapy of cardiovascular diseases. However, existing monitoring approaches often suffer from bulky and intrusive apparatus, cumbersome testing procedures, and challenging data processing, hampering their applications in continuous monitoring. Here, a heterogeneously hierarchical piezoelectric composite is introduced for wearable continuous BP and cardiac function monitoring, overcoming the rigidity of ceramic and the insensitivity of polymer. By optimizing the hierarchical structure and components of the composite, the developed piezoelectric sensor delivers impressive performances, ensuring continuous and accurate monitoring of BP at Grade A level. Furthermore, the hemodynamic parameters are extracted from the detected signals, such as local pulse wave velocity, cardiac output, and stroke volume, all of which are in alignment with clinical results. Finally, the all-day tracking of cardiac function parameters validates the reliability and stability of the developed sensor, highlighting its potential for personalized healthcare systems, particularly in early diagnosis and timely intervention of cardiovascular disease.

Modulating piezoelectricity and mechanical strength via three-dimensional gradient structure for piezoelectric composites.

Advanced flexible electronic devices make urgent demand for wearing comfort and data accuracy. Piezoelectric composites exhibit great potential, but mutually constrained mechanical strength and electrical output limit their further applications. Here, we design a gradient PMN-PT/PVDF nanocomposite via a non-equilibrium process integrated with a modified electrospinning and hot-pressing process to modulate the piezoelectric output and mechanical strength. The enhanced piezoelectric output together with the mechanical strength of the gradient structure are verified from both the experimental and simulation results. Ascribed to a unique three-dimensional gradient distribution, the prepared PMN-PT/PVDF nanocomposite exhibits an excellent mechanical strength (830 MPa) and piezoelectric performance (1.08 V), which are substantially higher than those of a randomly dispersed nanocomposite. The enhancement mechanism is revealed in terms of polarization, stress and crystallinity. These results of the gradient structure offer new opportunities to understand the structure-related mechanical and electrical behaviors of a nanocomposite, and support the design of a nanocomposite with overall performance.

Multichannel Gradient Piezoelectric Transducer Assisted with Deep Learning for Broadband Acoustic Sensing.

As an important part of human-machine interfaces, piezoelectric voice recognition has received extensive attention due to its unique self-powered nature. However, conventional voice recognition devices exhibit a limited response frequency band due to the intrinsic hardness and brittleness of piezoelectric ceramics or the flexibility of piezoelectric fibers. Here, we propose a cochlear-inspired multichannel piezoelectric acoustic sensor (MAS) based on gradient PVDF piezoelectric nanofibers for broadband voice recognition by a programmable electrospinning technique. Compared with the common electrospun PVDF membrane-based acoustic sensor, the developed MAS demonstrates the greatly 300%-broadened frequency band and the substantially 334.6%-enhanced piezoelectric output. More importantly, this MAS can serve as a high-fidelity auditory platform for music recording and human voice recognition, in which the classification accuracy rate can reach up to 100% in coordination with deep learning. The programmable bionic gradient piezoelectric nanofiber may provide a universal strategy for the development of intelligent bioelectronics.

Activating transcription factor 3 protects alveolar epithelial type II cells from Mycobacterium tuberculosis infection-induced inflammation.

Activating transcription factor 3 (ATF3) is a stress-inducible gene reported with anti-inflammatory response effects against bacterial infections. This study focuses on the function of ATF3 in alveolar epithelial type II cells (A549) following Mycobacterium tuberculosis (MTB) infection. First, RT-qPCR results detected reduced ATF3 expression in broncho-alveolar lavage fluid (BALF) of MTB-infected patients, whereas the ATF3 level was upregulated in A549 cells at early stages after MTB infection but decreased later. The binding relationship between ATF3 and TIMP metallopeptidase inhibitor 2 (TIMP2) promoter was predicted via bioinformatic prediction and validated by ChIP and luciferase assays. ATF3 bound to TIMP2 promoter for transcriptional activation. Overexpression of ATF3 or TIMP2 enhanced autophagy activity, elevated p62 levels and the LC3BII/LC3BI ratio, and decreased IL-6 and TNF-α levels in A549 cells. The ATF3/TIMP2 axis suppressed the NF-κB pathway to alleviate inflammatory responses in A549 cells. Mice were exposed to MTB aerosol for in vivo experiments. Increased ATF3 expression was correlated with increased autophagy activity, clearance of bacteria as well as inflammation resolution in mouse lung tissues. In conclusion, this study demonstrates that ATF3 promotes cell autophagy and suppresses inflammatory response in MTB-infected A549 cells via TIMP2 activation and NF-κB suppression.

Overexpression of microRNA-340-5p Ameliorates Inflammatory Response and Intracellular Survival of Mycobacterium Tuberculosis in Alveolar Type II Cells.

BACKGROUND: The importance of microRNAs (miRs) has been documented in infections. This study estimated the role of miR-340-5p in Mycobacterium tuberculosis (Mtb)-infected alveolar type II cells. METHODS: The microarray of GEO database was analyzed to find the differentially expressed miRs caused by Mtb infection, and miR-340-5p was selected as the research object. The effects of Mtb infection on A549 cells were studied by MTT, CFU, EdU, flow cytometry and ELISA assays. miR-340-5p expression was altered in Mtb-infected A549 cells. The downstream target of miR-340-5p was found by bioinformatics analysis and verified by the rescue experiment. The pathways regulated by miR-340-5p and its target gene were further studied. RESULTS: Mtb infection suppressed the activity of A549 cells and promoted the release of inflammatory factors. Mtb infection inhibited miR-340-5p expression. Overexpression of miR-340-5p enhanced the resistance of A549 cells to Mtb infection. Moreover, miR-340-5p targeted TMED7. Overexpression of TMED7 reversed the protective effect of miR-340-5p on Mtb-infected A549 cells. miR-340-5p inhibited the activation of NF-κB by targeting TMED7. CONCLUSION: miR-340-5p inhibits the activation of NF-κB by targeting TMED7, thus alleviating the injury of A549 cells caused by Mtb infection. This study may offer a novel approach to Mtb infection.

The prognostic and predictive significance of cytokeratin 5/6 and epidermal growth factor receptor in metastatic triple-negative breast cancer treated with maintenance capecitabine.

BACKGROUND: Capecitabine is the most widely used agent for maintenance chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). However, there are no biomarkers for identifying mTNBC patients who could benefit from capecitabine maintenance. METHODS: The prognostic roles of cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), and maintenance therapy were evaluated in mTNBC patients. Both CK5/6 and EGFR were detected using immunohistochemistry. Of 115 patients who achieved disease control, 56 received capecitabine maintenance therapy and 59 underwent observation. The progression-free survival (PFS) and overall survival (OS) of the patients were evaluated. RESULTS: The median PFS and OS were longer in the maintenance group than that in the observation group (7.3 versus 5.7 months, P=0.0016; 22.4 versus 17.9 months, P=0.0055). Patients with basal-like TNBC had a poorer survival times than in those with non-basal-like TNBC (P=0.0062). Capecitabine maintenance significantly prolonged the OS of non-basal-like TNBC patients (P=0.0257), while in the basal-like TNBC patients, the difference was not significant (P=0.0541). Multivariate analysis revealed that the prolonged OS was related to age >50 years (P=0.005), presence of visceral metastases (P=0.035), response to initial therapy (P=0.017), maintenance therapy (P=0.033), and CK5/6 and EGFR status (P=0.032). Compared with the observation group, toxicities of all grades were more frequently observed in the maintenance group, including neutropenia, 85.71% vs. 25.87%, P<0.001; thrombocytopenia, 55.36% vs. 11.86%, P<0.001; anemia, 82.14% vs. 52.54%, P= 0.001; nausea 83.47% vs. 11.86%, P<0.001; vomiting 69.64% vs. 8.47%, P<0.001; and hand-foot syndrome (HFS) 32.14% vs. 1.69%, P<0.001. CONCLUSIONS: Our study revealed that patients with non-basal-like TNBC had a better clinical outcome than those with basal-like TNBC, and capecitabine maintenance treatment significantly prolonged PFS and OS in patients with TNBC. Patients with non-basal-like TNBC could benefit from maintenance therapy with capecitabine and CK5/6 and EGFR are biomarkers for TNBC prognosis.

Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer.

INTRODUCTION: Although the survival rate of colorectal cancer (CRC) patients can be improved by surgery, radiotherapy, and chemotherapy, the resistance to 5-fluorouracil (5-Fu) affects the effect of chemotherapy and the prognosis of patients. An increasing number of studies showed that 5-Fu resistance was the main reason for the failure of colorectal cancer treatment. The poor prognosis of colorectal cancer greatly harms people's health. This study aimed to clarify the correlation between cyclin-dependent kinase 1 (CDK1) and 5-Fu-induced tumor resistance. MATERIALS AND METHODS: Cell proliferation and invasion experiments showed that down-regulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation. The expression level of CDK1 was detected in 5-Fu-resistant CRC cells in vitro. Tumor growth was inhibited by down-regulation of CDK1 in tumor xenograft mouse models. RESULTS: We found that CDK1 was highly expressed in tumor tissues, especially in fluorouracil-resistant tissues. We also confirmed that the differential expression of 5-Fu in tumor tissues was related to tumor site, lymph node metastasis and stage. CDK1 promoted migration, invasion and inhibited apoptosis in 5-Fu-resistant CRC cells. Down-regulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation and tumorigenesis in vivo. CONCLUSION: High expression of CDK1 may lead to poor clinical prognosis, and inhibition of CDK1 enhances 5-Fu sensitivity in CRC. Our research suggested that CDK1 may be used to predict 5-Fu efficacy and as a therapeutic target for CRC.

Three-dimensional printing of shape memory hydrogels with internal structure for drug delivery.

Hydrogels with shape memory behavior and internal structure have wide applications in fields ranging from tissue engineering and medical instruments to drug delivery; however, creating the hydrogels has proven to be extremely challenging. This study presents a three-dimensional (3D) printing technology to fabricate the shape memory hydrogels with internal structure (SMHs) by combining sodium alginate (alginate) and pluronic F127 diacrylate macromer (F127DA). SMHs were constituted by a dual network structure. One is a stable network which is formed by F127DA photo-crosslinking; the other one is a reversible network which is formed by Ca2+ cross-linked alginate. SMHs recovery ratio was 98.15% in 10min after Ca2+ was removed in the Na2CO3 solution, and the elastic modulus remains essentially stable after the shape memory cycle. It showed that the drug releasing rate is more rapid compared with traditional drug-loaded hydrogels in in vitro experiments. The viability of 3T3 fibroblasts remained intact which revealed its excellent biocompatibility. Therefore, SMHs have a huge prospect for application in drug carriers and tissue engineering scaffold.

Nano-oleanolic acid alleviates metabolic dysfunctions in rats with high fat and fructose diet.

Obesity, diabetes and related metabolic disorders are among the top prevalent metabolism-related diseases with increasing threat to human health throughout the world. Oleanolic acid (OA) is a natural triterpenoid and an aglycone of many saponins possessing anti-diabetic, antioxidant, hypolipidemic and anti-inflammatory activities. A nano-formulation of OA was recently developed to evaluate the efficiency of nano-OA in the treatment of insulin-resistance and metabolic disorders in high fat and fructose (HFF) diet-fed rats. This study further identified that nano-OA could reduce the increase of body weights, serum insulin, insulin sensitivity index, serum triglycerides, and cholesterol in HFF-fed rats. In consistence, nano-OA was able to attenuate HFF diet-induced lipid accumulation in the liver and improve the structural integrity of mitochondria and endoplasmic reticulum in liver and pancreas in animals fed with HFF diet. In addition, nan-OA can efficaciously mitigate the increase of levels of malondialdehyde (MDA) and nitric oxide (NO), and serum superoxide dismutase (SOD) and catalase (CAT) activities in blood samples. The beneficial effects of nano-OA was further evidenced to be superior to OA formulated in arabic gum and rosiglitazone treatment. Together, this study provides the evidence that nano-OA can effectively improve HFF diet-induced metabolic dysfunctions in rats by improving its bioavailability and pharmacodynamic properties and thus nano-OA may be a potentially efficient agent to treat obesity-related diabetes and metabolic disorders.

Hepatocyte nuclear factor 1b is a novel negative regulator of white adipocyte differentiation.

Hepatocyte nuclear factor 1b (HNF1b) is a transcription factor belonging to the HNF family. We aimed to investigate the role of HNF1b in white adipocyte differentiation. The expression of HNF1b was reduced in white adipose tissue (WAT) of both diet-induced and genetic obese mice and decreased during the process of 3T3-L1 adipocyte differentiation. Downregulation of HNF1b enhanced 3T3-L1 adipocyte differentiation and upregulation of HNF1b inhibited this process. Upregulation of HNF1b inhibited peroxisome proliferator-activated receptor γ (PPARγ) and its target gene expression, while downregulation of HNF1b increased those genes expression. Overexpression of PPARγ suppressed HNF1b upregulation-induced inhibition of adipocyte differentiation. HNF1b can directly bind with the promoter of PPARγ in 3T3-L1 cells, which was decreased after adipogenic differentiation. HNF1b promoted apoptotic and autophagic cell death in early differentiated adipocytes through regulation of cell cycle progress and cell death-related factors, and thus inhibited the process of mitotic clonal expansion (MCE). HNF1b acted as an antioxidant regulator through regulating various antioxidant enzymes via binding with antioxidant response element. Oxidant treatment suppressed HNF1b upregulation-induced inhibition of adipocyte differentiation. Overall, our results suggest that HNF1b is a novel negative regulator of adipocyte differentiation through regulation of PPARγ signaling, MCE and redox state.

[Effects of different phosphorus sources on the growth and toxin production of Prorocentrum lima].

To explore the nutrient properties of Prorocentrum lima and biosynthesis mechanism of diarrhetic shellfish poison (DSP), the growth and activities of alkaline phosphatase of Prorocentrum lima were observed under different phosphorus sources. DSP productions were also analyzed. The maximum growth rate (micro(max)) was slightly lower under beta-sodium glycerophosphate than those under NaH2PO4 and ATP as phosphorus sources, respectively. The maximum biomass (X) under ATP was higher than those under NaH2PO4 and beta-sodium glycerophosphate as the phosphorus sources, respectively. When the concentration of NaH2PO4 was below 2 micromol/L, the activity of alkaline phosphatase increased significantly. However, the activities were much low in the all treatments when beta-sodium glycerophosphate used as phosphorus source, whereas the activities increased with the concentration of ATP when ATP used as phosphorus source. The level of okadaic acid (OA) in Prorocentrum lima at the stationary phase under beta-sodium glycerophosphate was higher than those under NaH2PO4 and ATP. These suggested that beta-sodium glycerophosphate could be utilized directly by Prorocentrum lima with lower efficiency; ATP could induce alkaline phosphatase to produce inorganic phosphate for algae. DSP production in Prorocentrum lima were different under various phosphate sources, beta-sodium glycerophosphate enhanced production of DSP. The difference in DSP production might be related with the physiological state of Prorocentrum lima.