Apical papilla stem cell-derived exosomes regulate lipid metabolism and alleviate inflammation in the MCD-induced mouse NASH model.

Stem cells from the apical papilla(SCAPs) exhibit remarkable tissue repair capabilities, demonstrate anti-inflammatory and pro-angiogenic effects, positioning them as promising assets in the realm of regenerative medicine. Recently, the focus has shifted towards exosomes derived from stem cells, perceived as safer alternatives while retaining comparable physiological functions. This study delves into the therapeutic implications of exosomes derived from SCAPs in the methionine-choline-deficient (MCD) diet-induced mice non-alcoholic steatohepatitis (NASH) model. We extracted exosomes from SCAPs. During the last two weeks of the MCD diet, mice were intravenously administered SCAPs-derived exosomes at two distinct concentrations (50 µg/mouse and 100 µg/mouse) biweekly. Thorough examinations of physiological and biochemical indicators were performed to meticulously evaluate the impact of exosomes derived from SCAPs on the advancement of NASH in mice induced by MCD diet. This findings revealed significant reductions in body weight loss and liver damage induced by the MCD diet following exosomes treatment. Moreover, hepatic fat accumulation was notably alleviated. Mechanistically, the treatment with exosomes led to an upregulation of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) levels in the liver, enhancing hepatic fatty acid oxidation and transporter gene expression while inhibiting genes associated with fatty acid synthesis. Additionally, exosomes treatment increased the transcription levels of key liver mitochondrial marker proteins and the essential mitochondrial biogenesis factor. Furthermore, the levels of serum inflammatory factors and hepatic tissue inflammatory factor mRNA expression were significantly reduced, likely due to the anti-inflammatory phenotype induced by exosomes in macrophages. The above conclusion suggests that SCAPs-exosomes can improve NASH.

Design, synthesis, and biological evaluation of dinuclear bismuth(III) complexes with Isoniazid-derived Schiff bases.

Four dinuclear bismuth(III) Schiff-base complexes bearing Schiff-base ligands have been synthesized and structurally characterized by single-crystal X-ray diffraction, elemental analysis, and spectral techniques (FT-IR, NMR and MS). The analytical data reveal the bismuth(III) complexes possess 1:1 metal-ligand ratios. In vitro biological studies have revealed that bismuth(III) complexes displayed much higher antibacterial and antitumor activities than their parent ligands, which involves two gram-negative (S. aureus, B. subtili) and two gram-positive (E. coli, P. aeruginosa) bacteria, and human gastric cancer SNU-16 cells. The power-time curves of S. pombe exposed to tested compounds were detected by bio-microcalorimetry. Some thermokinetic parameters (k, Pmax,tG and Qtotal) were derived based on the metabolic power-time curves, and their quantitative relationships with the concentrations (c) were further discussed.

Construction of Electrochemical and Photoelectrochemical Sensing Platform Based on Porphyrinic Metal-Organic Frameworks for Determination of Ascorbic Acid.

Highly sensitive and specific detection of biomolecular markers is of great importance to the diagnosis and treatment of related diseases. Herein, Cu-TCPP@MOFs thin films were synthesized with tetrakis(4-carboxyphenyl) porphyrin (H2TCPP) as organic ligands and copper ions as metal nodes. The as-synthesized Cu-TCPP@MOFs thin films as electrode modifiers were used to modify the pre-treated glassy carbon electrode (GCE) and the electrochemical performances of Cu-TCPP@MOFs/GCE were evaluated by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Furthermore, as the working electrode, the constructed Cu-TCPP@MOFs/GCE was used for the investigation of ascorbic acid (AA) due to its outstanding electrocatalytic activities towards AA by several electrochemical methods, including cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry (CA). The well-linear relationship was established based on different AA concentration ranges and the ideal detection limits (LOD) were obtained in the above-mentioned electrochemical methods, respectively. Furthermore, a Cu-TCPP MOFs@GCE sensing platform was used as a photoelectrochemical (PEC) sensor to quantitatively detect AA based on the strong absorption properties of Cu-TCPP ingredients in Cu-TCPP MOFs in a visible light band of 400~700 nm. PEC sensing platform based on Cu-TCPP@MOFs exhibited a more extensive linear concentration range, more ideal detection limit, and better sensitivity relative than the other electrochemical methods for AA. The well linear regression equations were established between the peak current intensity and AA concentrations in different electrochemical technologies, including CV, DPV, and CA, and PEC technology. AA concentration ranges applicable to various electrochemical equations were as follows: 0.45~2.10 mM of CV, 0.75~2.025 mM of DPV, 0.3~2.4 mM of CA, 7.5~480 µM of PEC, and the corresponding detection limits for AA were 1.08 µM (S/N = 3), 0.14 µM (S/N = 3), 0.049 µM (S/N = 3), and 0.084 nA/µM. Moreover, the proposed Cu-TCPP MOFs@GCE electrochemical and photoelectrochemical sensing platform was applied to determine the AA concentration of a real human serum sample; the results reveal that Cu-TCPP MOFs@GCE sensing platform could accurately determine the concentration of AA of the human serum under other potential interferences contained in the human serum samples.

Recent Advances on the Applications of Luminescent Pb2+-Containing Metal-Organic Frameworks in White-Light Emission and Sensing.

Luminescent Pb2+-based metal-organic frameworks (MOFs) belong to a new class of multifunctional molecular materials with interesting luminescence properties and potential applications within a single crystalline phase. In this mini review, we present the recent advances that have been achieved in their applications as single-phase white-light emitting materials and chemosensors in the last decade. We focus on the trends in the modification of their structures and luminescence by various bridging ligands, and subsequently their multifunctional applications, which may affect the future development of the field.

Development of Apremilast Solid Dispersion Using TPGS and PVPVA with Enhanced Solubility and Bioavailability.

Apremilast (APST) is an effective inhibitor of phosphodieasterase 4 (PDE4) which is the first oral drug for the treatment of adult patients with active psoriatic arthritis. However, Apremilast's low solubility restricts its dissolution and bioavailability. In this study, APST solid dispersion with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) was developed to improve the dissolution and bioavailability of APST by spray drying. A series of TPGS were synthesized to elucidate the effect of the ratio of monoester to diester on solubilizing capacity. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were used to characterize the solid dispersion, and the results showed that APST was amorphous in solid dispersion. In vitro dissolution study showed that the dissolution rate of solid dispersion in phosphate buffered saline (pH 6.8) was remarkably increased, reaching a release of 90% within 10 min. Moreover, in vivo pharmacokinetics study revealed that the bioavailability of solid dispersion in rats had significant improvement. In particular, its Cmax and AUClast were nearly 22- and 12.9-fold greater as compared to APST form B, respectively. In conclusion, APST solid dispersion with TPGS and PVPVA is an alternative drug delivery system to improve the solubility and oral bioavailability of APST.

Transcriptome sequencing analysis of the MSDIN gene family encoding cyclic peptides in lethal Amanita fuligineoides.

Amanita fuligineoides, a lethal mushroom discovered in China, contains abundant cyclic peptide toxins that can cause fatal poisoning. However, the MSDIN gene family encoding for these cyclic peptides in A. fuligineoides has not been systematically studied. In this research, the transcriptome sequencing of A. fuligineoides was performed and its MSDIN family members were analyzed. A total of 4.41 Gb data containing 30833 unigenes was obtained; sequence alignments throughout several databases were done to obtain their functional annotations. Based on these annotations, MSDIN genes were found and verified by RT-PCR. A total of 29 different core peptides were obtained: 3 toxin genes, encoding ß-amanitin (ß-AMA), phalloidin (PHD), and phallacidin (PCD), and 26 genes encoding unknown cyclic peptides, 20 of which are reported for the first time and may encode for novel cyclic peptides. Analysis of the predicted precursor peptides indicated that octocyclic peptides were the main MSDIN peptides synthesized by A. fuligineoides, accounting for the 45%. A phylogenetic analysis suggested that studied precursor peptides could be clustered into 7 clades, which might represent different functionalities. Results suggested that A. fuligineoides might have a strong capacity to synthesize cyclopeptides, laying the foundation for their excavation and utilization.

Cobalt(III)-Catalyzed Oxidative Annulation of Benzaldehydes with Internal Alkynes via C-H Functionalization in Poly(ethylene glycol).

A novel Co(III)-catalyzed oxidative annulation of aromatic aldehydes with internal alkynes for accessing isocoumarins is described, which is achieved by oxidation, weak chelation-assisted C-H bond functionalization, and annulation cascades with excellent functional group compatibility, high atom economy, and step efficiency. By using environmentally benign and inexpensive poly(ethylene glycol)-400 (PEG-400), the Co/Cu/PEG-400 system could be recycled and reused.

The Reliability of DNA Sequences in Public Databases Belonging to the Most Economically Important Shiitake Culinary-Medicinal Mushroom Lentinus edodes (Agaricomycetes) in Asia.

Large numbers of DNA sequences deposited in the International Nucleotide Sequence Databases (INSD) are erroneously annotated. The erroneous information may lead to misleading conclusions or cause great economic losses to farmers. Lentinus edodes (= Lentinula edodes (Berk.) Pegler) is one of the most important and popular culinary-medicinal mushrooms with a high nutritional value. In this study, experimental and in silico methods were used to correct the sequences annotated as L. edodes in the INSD. A total of 3,426 nucleotide entries were retrieved from public databases, including 140 different types of genetic sequences. Excluding 1,893 genome sequences, the most abundant signatures represented by ITS (258) and IGS1 (259) sequences accounted for 33.23% of the total entries. A total of 3,058 sequences were annotated correctly, 350 were indeterminate, and 18 were annotated erroneously based on the two methods. Correction of sequences will be beneficial for species identification and annotation. Phylogenic analysis based on ITS sequences suggested that L. edodes segregate in four clades in the tree based on ITS sequences. The isolates from China were distributed into two clades. In L. edodes, the intraspecific variation of the ITS2 sequences was much higher than that of the ITS1 sequences. In addition, the genetic diversity of the L. edodes sequences from China was much higher than that of any other regions included in this study. The northwest and southwest regions of China were L. edodes diversity centers.

ITS1/5.8S/ITS2, a Good Marker for Initial Classification of Shiitake Culinary-Medicinal Lentinus edodes (Agaricomycetes) Strains in China.

China is home to rich wild and cultivated strains of Lentinus edodes, an important edible and medicinal mushroom. Artificial selection of L. edodes has a long history, and the widely cultivated strains belong to populations different from those of most wild strains. Internal transcribed spacer (ITS) regions have been used as good markers to identify L. edodes populations. But because ITS regions exhibit incomplete concerted evolution, the use of an ITS to identify L. edodes populations has been questioned. The objective of this study was to determine whether the ITS region is suitable for identifying L. edodes populations and which populations the widely cultivated strains and the most wild strains belong to by investigating intraindividual and differential ITS polymorphisms between 44 cultivars and 44 wild strains of L. edodes in China. Intraindividual ITS polymorphism is common in L. edodes strains, and most strains possessed 2 different ITS sequences, which came from their heterokaryons. The genetic polymorphisms of ITS1, 5.8S, and ITS2 in L. edodes strains are distinct. All strains were divided into one 5.8S type (5.8S-A), 2 ITS1 types (ITS1-A and ITS1-B), and 2 ITS2 types (ITS2-A and ITS2-B), which were subdivided into 2 branches (ITS2-A1 and ITS2-A2; ITS2-B1 and ITS2-B2). ITS1/5.8S/ITS2 could be used as a good marker in preliminary classification of L. edodes strains in China. It not only exhibited classified information of ITS1, 5.8S, and ITS2 for each strain at the same time, it also indicated whether the strain was heterozygous. The 44 cultivated strains were mainly the A/A/A1 type, and the 44 wild strains were mainly the A/A/A2 and other mixed types.

Synthesis, crystal structure and spectroscopic studies of bismuth(III) complex with 2-substituted benzimidazole ligands.

Reaction of BiCl3 with 2-(2-hydroxy-3-methoxyphenyl)benzimidazole (HL) in tetrahydrofuran (THF) under reflux gave mononuclear complex of formula [Bi(HL)2Cl3·H2O]. The binding interaction of the complex with bovine serum albumin (BSA) was investigated using the fluorescence quenching method. The experimental results showed that the complex could bind to BSA in the proportion of about 1:1. The binding reaction was spontaneous and hydrophobic force played major role in the reaction. The binding of the complex to BSA could change the microenvironment and conformation of BSA.

Nutritional Composition of Three Domesticated Culinary-Medicinal Mushrooms: Oudemansiella sudmusida, Lentinus squarrosulus, and Tremella aurantialba.

The nutritional composition of three recently domesticated culinary-medicinal mushroom species (Oudemansiella sudmusida, Lentinus squarrosulus, and Tremella aurantialba) was evaluated for contents of protein, fiber, fat, total sugar content, amino acid, carbohydrate, and nucleotide components. The data indicated that fruiting bodies of these three mushroom species contained abundant nutritional substances. The protein contents of L. squarrosulus and O. submucida were 26.32% and 14.70%, which could be comparable to other commercially cultivated species. T. aurantialba contained 74.11% of carbohydrate, of which soluble polysaccharide was 40.55%. Oudemansiella sudmusida contained 15.95% of arabitol as the highest sugar alcohol in three mushrooms. These mushrooms also possessed distinct taste by their flavor component composition. Among them, L. squarrosulus contained 10.68% and 9.25% of monosodium glutamate-like and sweet amino acids, which were higher than the other two mushrooms. However, the nucleotide amounts of the three mushrooms were all lower than those of other commercially cultivated mushrooms. Among them, L. squarrosulus contained the highest amount of flavor nucleotides, which was 1.01‰. Results revealed that these three mushroom species are potentially suitable resources for commercial cultivation and healthy food.

Synthesis of nordihydroguaiaretic acid derivatives and their bioactivities on S. pombe and K562 cell lines.

Nordihydroguaiaretic acid (NDGA) and its synthetic analogues are potentially useful in treating diseases related to cancers, diabetes, viral and bacterial infections, and inflammation. In this paper, we report the optimal synthetic methods and the bioactivity study of terameprocol 2, NDGA derivative 3, and its cyclized analogue 4. The IC50 of these three compounds 2, 3 and 4 on the growth metabolism of Schizosacchromyces pombe and K562 cell lines were determined by microcalorimetry. The preliminary results showed that the compounds 2, 3 and 4 possessed good inhibition activities on S. pombe and K562 cell lines, and exhibited bidirectional biological effect and Hormesis effect. In particular, terameprocol 2 was found to possess the most potent inhibitory effect on K562 cell lines.

[Discoveries of avian influenza A(H9N2) virus in chickens and men infected by H9N2 virus in Guangzhou area].

OBJECTIVE: To understand the epidemic status of avian influenza A virus in chickens and men in Guangzhou area and to prevent men suffering from avian influenza A (H5N1) virus. METHODS: Etiologic and serological surveys were conducted in chickens and men who were working in the poultry farms and slaughter house. Viruses were isolated with both MDCK cells and embryonated chicken eggs. Hemagglutination inhibition tests were performed by routine method. RESULTS: Anti-H9N2 antibody was found in 12.8% of the chickens and 5.1% of the workers. CONCLUSIONS: Avian influenza virus H9N2 subtype existed in chickens and this subtype of influenza A virus might infect men.