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The investigation of the effects of electrical and mechanical stimulations on chondrogenesis in tissue engineering scaffolds is essential for realizing successful cartilage repair and regeneration. The aim of articular cartilage tissue engineering is to enhance the function of damaged or diseased articular cartilage, which has limited regenerative capacity. Studies have shown that electrical stimulation (ES) promotes mesenchymal stem cell (MSC) chondrogenesis, while mechanical stimulation (MS) enhances the chondrogenic differentiation capacity of MSCs. Therefore, understanding the impact of these stimuli on chondrogenesis is crucial for researchers to develop more effective tissue engineering strategies for cartilage repair and regeneration. This study focuses on the preparation of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conductive polymer (CP) scaffolds using the freeze-drying method. The scaffolds were fabricated with varying concentrations (0, 1, 3, and 10 wt %) of (3-glycidyloxypropyl) trimethoxysilane (GOPS) as a crosslinker and an additive to tailor the scaffold properties. To gain a comprehensive understanding of the material characteristics and the phase aggregation phenomenon of PEDOT:PSS scaffolds, the researchers performed theoretical calculations of solubility parameters and surface energies of PSS, PSS-GOPS, and PEDOT polymers, as well as conducted material analyses. Additionally, the study investigated the potential of promoting chondrogenic differentiation of human adipose stem cells by applying external ES or MS on a PEDOT:PSS CP scaffold. Compared to the group without stimulation, the group that underwent stimulation exhibited significantly up-regulated expression levels of chondrogenic characteristic genes, such as SOX9 and COL2A1. Moreover, the immunofluorescence staining images exhibited a more vigorous fluorescence intensity of SOX9 and COL II proteins that was consistent with the trend of the gene expression results. In the MS experiment, the strain excitation exerted on the scaffold was simulated and transformed into stress. The simulated stress response showed that the peak gradually decreased with time and approached a constant value, with the negative value of stress representing the generation of tensile stress. This stress response quantification could aid researchers in determining specific MS conditions for various materials in tissue engineering, and the applied stress conditions could be further optimized. Overall, these findings are significant contributions to future research on cartilage repair and biophysical ES/MS in tissue engineering.

In this study, we examined the influence of functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) nanostructures decorated on the channel layer of an organic electrochemical transistor (OECT) for the detection of sweat cortisol, an adrenocorticosteroid stress hormone. The OECT device featured a bilayer channel confined by a PEDOT:polystyrenesulfonate (PSS) underlayer and a nanostructure-decorated upper layer engineered from the monomers EDOT-COOH and EDOT-EG3 through template-free electrochemical polymerization. This molecular design allowed antibody conjugation using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysulfosuccinimide coupling through the carboxylic acid side chain, with EDOT-EG3 known to minimize nonspecific binding of biomolecules. We also engineered an OECT device having a channel area without any nanostructures to gain insight into the effect of the nanostructures on cortisol sensing. Our new nanostructure-embedded OECT device facilitated real-time detection of cortisol at concentrations ranging from 1 fg/mL to 1 μg/mL with a detection limit of 0.0088 fg/mL with good linearity (R2= 0.9566), in addition to excellent selectivity toward cortisol among other structurally similar interfering compounds and high stability and reproducibility. With its rapid response for the detection of 100 ng/mL cortisol-spiked artificial sweat, this nanostructure-decorated OECT device has potential clinical practicality and utility in wearable sensors for future healthcare applications.

The incidence of opioid use disorder (OUD) is increasing worldwide, and the opioid-related overdose crisis is currently a major global challenge. This study investigated the effects of adjuvant laser meridian massage (LMM) in men with OUD undergoing methadone maintenance treatment (MMT).

Pyridoxal phosphate (PLP)-dependent enzymes can catalyze transformations of l-amino acids at α, β, and γ positions. These enzymes are frequently involved in the biosynthesis of nonproteinogenic amino acids as building blocks of natural products and are attractive biocatalysts. Here, we report the discovery of a two-step enzymatic synthesis of (2S,6S)-6-methyl pipecolate 1, from the biosynthetic pathway of citrinadin. The key enzyme CndF is PLP-dependent and catalyzes the synthesis of (S)-2-amino-6-oxoheptanoate 3that is in equilibrium with the cyclic Schiff base. The second enzyme CndE is a stereoselective imine reductase that gives 1. Biochemical characterization of CndF showed this enzyme performs γ-elimination of O-acetyl-l-homoserine to generate the vinylglycine ketimine, which is subjected to nucleophilic attack by acetoacetate to form the new Cγ–Cδbond in 3and complete the γ-substitution reaction. CndF displays promiscuity toward different β-keto carboxylate and esters. With use of an Aspergillusstrain expressing CndF and CndE, feeding various alkyl-β-keto esters led to the biosynthesis of 6-substituted l-pipecolates. The discovery of CndF expands the repertoire of reactions that can be catalyzed by PLP-dependent enzymes.

The intestinal microbiome plays an important role in the pathogenesis of liver diseases. Alcohol intake induces gut microbiota dysbiosis and alters its function. This study investigated the antibiotic effect of allicin in mice with hepatic steatosis. Male C57BL/6 mice were administered an ethanol diet supplemented with allicin (5 and 20 mg/(kg bw day)) for 4 weeks. Allicin modified the gut microbiota composition. Cecal microbiota exhibited a positive correlation with alcohol and hepatic triacylglycerol, but were suppressed with allicin. Ethanol diet with 5 mg of allicin induced a lower intestinal permeability compared to the ethanol diet alone. Allicin mediated the lipopolysaccharide (LPS)–CD14–toll-like receptor 4 (TLR4)-induced hepatic inflammation pathway by reducing LPS, CD14, TLR4, and pro-inflammatory cytokines—tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. However, hepatic inflammation primarily resulted from alcohol toxicity rather than LPS production in the gut. The prediction of functional profiles from metagenomic 16S ribosomal RNA (rRNA) data revealed different functional profiles in each group. The predicted aldehyde dehydrogenase tended to increase in alcoholic mice administered allicin. The predicted LPS-related pathway and LPS biosynthesis protein results exhibited a similar trend as plasma LPS levels. Thus, alcohol and allicin intake shapes the gut microbiota and its functional profile and improves the CD14–TLR4 pathway to alleviate inflammation in the liver.

The association between Chinese herbal medicine (CHM) and the risk of developing major adverse cardiovascular events (MACEs) in patients with dialysis hypotension is unclear and has not yet been investigated. This study aimed to determine whether CMH intervention could reduce the risk of MACEs in patients with dialysis hypotension.

Glyoxal is an oxoaldehyde generated from the degradation of glucose-protein conjugates and from lipid peroxidation in foods and in vivo, and it is also present in the environment (e.g., cigarette smoke). The major endogenous source of glyoxal is glucose autoxidation, and the glyoxal concentrations in plasma are higher in diabetic patients than in nondiabetics. Glyoxal reacts with biomolecules forming covalently modified DNA and protein adducts. We previously developed sensitive and specific assays based on nanoflow liquid chromatography-nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) for quantification of DNA cross-linked adducts (dG-gx-dC and dG-gx-dA) and for hemoglobin adducts derived from glyoxal. In this study, we isolated and analyzed both leukocyte DNA and hemoglobin from the blood of diabetic patients and compared the adduct levels with those from nondiabetic subjects using the modified assays. The results indicated that the extents of glyoxal-induced hemoglobin modifications on α-Lys-11, α-Arg-92, β-Lys-17, and β-Lys-66 were statistically higher in diabetic patients than nondiabetics and they correlated with HbA1c significantly. Moreover, the levels of dG-gx-dC in leukocyte DNA correlated positively with the extents of globin modification at α-Lys-11 and β-Lys-17, while levels of dG-gx-dA correlated with those at α-Lys-11 and α-Arg-92 in nonsmoking subjects. Comparing the levels and the correlation coefficients of these hemoglobin and DNA adducts including or excluding smokers, it appears that smoking is not a major contributor to glyoxal-induced adduction of hemoglobin and leukocyte DNA. To the best of our knowledge, this is one of the few reports of positive correlation between DNA and protein adducts of the same compound (glyoxal) in the blood from the same subjects. Because of the high abundance of hemoglobin in blood, the results indicate that quantification of glyoxal-modified peptides in hemoglobin might serve as a dosimetry for glyoxal and a practical surrogate biomarker for assessing glyoxal-induced DNA damage and its prevention.

Aromatic l-amino acid decarboxylases (AAADs) are a phylogenetically diverse group of enzymes responsible for the decarboxylation of aromatic amino acid substrates into their corresponding aromatic arylalkylamines. AAADs have been extensively studied in mammals and plants as they catalyze the first step in the production of neurotransmitters and bioactive phytochemicals, respectively. Unlike mammals and plants, the hallucinogenic psilocybin mushroom Psilocybe cubensisreportedly employs an unrelated phosphatidylserine-decarboxylase-like enzyme to catalyze l-tryptophan decarboxylation, the first step in psilocybin biosynthesis. To explore the origin of this chemistry in psilocybin mushroom, we generated the first de novotranscriptomes of P. cubensisand investigated several putative l-tryptophan-decarboxylase-like enzymes. We report the biochemical characterization of a noncanonical AAAD from P. cubensis(PcncAAAD) that exhibits substrate permissiveness toward l-phenylalanine, l-tyrosine, and l-tryptophan, as well as chloro-tryptophan derivatives. The crystal structure of PcncAAAD revealed the presence of a unique C-terminal appendage domain featuring a novel double-β-barrel fold. This domain is required for PcncAAAD activity and regulates catalytic rate and thermal stability through calcium binding. PcncAAAD likely plays a role in psilocybin production in P. cubensisand offers a new tool for metabolic engineering of aromatic-amino-acid-derived natural products.

Twelve new flavan derivatives including four pairs of enantiomers, daphnegiralins A1–A4(1) and daphnegiralins B1–B4(2), and two pairs of epimers, daphnegiralins C1/C2(3) and daphnegiralins D1/D2(4), were isolated from the stem bark and roots of Daphne giraldii. Their structures were elucidated using spectroscopic analyses, computational approaches, and chemical methods. Separation of the enantiomeric mixtures (1a, 1b, 2a, and 2b) was achieved using chiral HPLC. The compounds were evaluated against a small panel of human cancer cell lines, and 1b-2, 2a, and 2bwere cytotoxic against Hep3B human hepatoma cells.

Objective To systematically review scientific reports on the effectiveness of acupuncture to treat male sexual dysfunction.Methods The Medline database was searched for published clinical trials of acupuncture for erectile dysfunction (ED) and premature ejaculation (PE) with English abstracts. Risk of bias was assessed for randomised controlled trials (RCTs).Results Seven studies on two conditions of male sexual dysfunction met the inclusion criteria. Three out of four RCTs were patient-blinded, but all had a high risk of bias. Three suggested that acupuncture has a therapeutic effect as compared with sham acupuncture. Comparisons with paroxetine were inconsistent. Other uncontrolled studies and case series suggested satisfactory improvements of ED and PE after acupuncture.Conclusions Acupuncture appears to have promise for treating male sexual dysfunction, but in view of the small number of studies and their variable quality, doubts remain about its effectiveness. Further studies are justified.

Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic 大 蒜 Dà Suàn; Allium sativum), is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.

To analysis the fracture mechanism and breaking location of the stick. By using ANSYS software to establish the model of excavator stick, and focus on analyzing the force changes of excavator stick in largest excavating force. By the modal analysis and transient dynamic analysis, stick stress and deformation distribution are obtained, further poses that reasonable to add the ribs, appropriate to strengthen cover thickness and the welding process of the stick will help prevent cracks. The results provide a reliable theoretical basis to improve the life of stick.

Antrodia cinnamomea, a Taiwan-specific medicinal mushroom, can manipulate biological activities, including hepatoprotection, anti-inflammation, anti-hepatitis B virus activity, anticancer activity, etc. In this study, the anti-liver cancer activity and molecular mechanisms of eburicoic acid, the second most abundant triterpenoid from the fruiting bodies of basswood cultivated Antrodia cinnamomeawas investigated using the human hepatoma Hep 3B cells. The results show that eburicoic acid effectively reduced Hep 3B cell viability within 24 hours, and the IC50was 18.4 μM, which was equivalent to 8.7 μg/mL. Besides, eburicoic acid induced conversion of LC3-I to LC3-II and a large number of autophagosomes/autolysosomes formation. In depth investigation for the molecular mechanisms, revealed that eburicoic acid firstly promoted reactive oxygen species generation and ATP depletion, leading to endoplasmic reticulum stress, followed by elevated cytosolic calcium ion concentration and BiP expression, downregulated phosphorylation of DAPK, upregulated phosphorylation of Beclin-1, JNK, and Bcl-2, and finally induced autophagy in Hep 3B cells. These results indicate that eburicoic acid has significant anti-liver cancer effects and more distinctive mechanisms.

Alcoholic liver disease (ALD) is a complex chronic disease and is associated with a spectrum of liver injury ranging from steatosis and steatohepatitis to fibrosis and cirrhosis. Since effective therapies for ALD are still limited, Chinese herbal medicine is thought to be an important and alternative approach. This review focuses on the current scientific evidence of ALD by ten Chinese Materia Medica (中藥 zhōng yào), including Salviae Miltiorrhizae Radix (丹參 dān shēn), Notoginseng Radix (三七 sān qī), Lycii Fructus (枸杞子 gǒu qǐ zǐ), Cnidii Fructus (蛇床子 shé chuáng zǐ), Gentianae Radix (龍膽 lóng dǎn), Puerariae Radix (葛根 gé gēn), Puerariae Flos (葛花 gé huā), Magnoliae Officinalis Cortex (厚朴 hòu pò), Platycodonis Radix (桔梗 jié gěng), and Trigonellae Semen (胡蘆巴 hú lú bā). Potential mechanisms of these herbal medicines in ALD are involved in amelioration of enhanced inflammation, reduction of hepatic oxidative stress and lipogenesis, and enhancement of intestinal permeability in alcohol-induced liver injury models in vitroand in vivo. Accordingly, the evidenced therapeutic potential suggests that these herbs are promising candidates for prevention and development of new drugs for ALD in the future.

Whole genome amplification (WGA) is a crucial procedure for genomic DNA analysis from limited sources, such as in forensic analysis, embryo biopsy for preimplantation genetic diagnosis, or needle aspiration biopsies. Several strategies for WGA have been developed for either genotyping or microarray-based comparative genome hybridization (array-CGH) during the past decade. Nevertheless, there were few studies in which various WGA methods had been performed side-by-side and results evaluated with multiple methods.

Researchers from the Second Hospital of Shandong University have conducted a study on the potential protective effect of 3-Hydroxybutyrate against aortic dissection. They utilized publicly accessible data from a genome-wide association study (GWAS) to examine the relationship between ketone bodies and aortic dissection. The Mendelian randomization analysis showed a negative correlation between 3-Hydroxybutyrate and the risk of aortic dissection. The findings suggest that genetically predicted 3-Hydroxybutyrate may have a protective effect against aortic dissection. [Extracted from the article]

2024 OCT 12 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Investigators discuss new findings in aortic dissection. According to news originating from [...]