A nature-inspired multifunctional adhesive for cartilage tissue-biomaterial integration.

Surgical adhesives play a crucial role in tissue integration and repair, yet their application in wet conditions has been severely limited by inadequate adhesive strength and subpar biocompatibility. Furthermore, tissue adhesives have rarely been reported in cartilage tissue repair. In this study, a three-armed dopamine-modified hyaluronic acid derivative adhesive was prepared to function as a bio-inspired adhesive in moist environments. To meet the clinical requirements for cartilage tissue adhesion, we studied its chemical structure, including microscopic morphology, adhesion properties with materials and tissues, in vivo degradation rules, and biological evaluation. The OGMHA8-DOPA adhesive with the optimal aldehyde substitution degree and dopamine-grafting rate was determined by analyzing the experimental conditions. SEM results revealed that the cartilage tissue adhered to a porous interconnected structure. The excellent biocompatibility of the material not only facilitated chondrocyte adhesion but also supported their proliferation on its surface. Animal experiments have demonstrated that this material has no observable inflammatory response or incidence of fibrous capsule formation. The degradation timeline of the material extends beyond the duration of two weeks. The dopamine-modified adhesive exhibited a tight interfacial binding force between the biomaterial and cartilage tissue and excellent biocompatibility in watery tissue, revealing its potential for application in cartilage tissue repair and minimally invasive surgery.

Protoilludane-Type and Related Nor-Sesquiterpenes from Phellinus hartigii and Their Anti-Hypertrophic Activities in Rat Cardiomyocytes.

Three nor-sesquiterpenes, phellinharts A-C (1-3), isolated from Phellinus hartigii, exhibited unprecedented protoilludane and cerapicane-type structures. The structures of compounds 1-3 were elucidated via spectroscopic analysis, quantum chemical calculations, and X-ray diffraction. Potential biogenic pathways involving demethylation, ring cleavage, and rearrangement were proposed. Compounds 1-3 displayed potent anti-hypertrophic activities with low cytotoxicity (CC50 > 50 µM) in rat cardiomyocytes, underscoring their therapeutic potential.

Metabolic disparities between obese and non-obese patients with polycystic ovary syndrome: implications for endometrial receptivity indicators.

OBJECTIVE: To investigate the differences in the metabolic indicators and sex hormones between obese and non-obese patients with polycystic ovary syndrome (PCOS), and their impacts on endometrial receptivity (ER). METHODS: We selected 255 individuals with PCOS, and categorized them into the obese groups, including the OP group (obese patients with PCOS) and the ON group (obese patients without PCOS), and selected 64 individuals who were categorized in the non-obese groups, namely, the control groups, which comprise the NP group (non-obese patients with PCOS) and the NN group(non-obese patients without PCOS). The one-way analysis of variance (ANOVA) and Mann-Whitney U tests were used to compare the metabolic indicators, and sex hormone-associated and ER-associated indicators between the groups. The correlation between the aforementioned clinical markers and ER was analyzed using the Pearson's correlation coefficient. RESULTS: (1) In comparison with the NP group, the OP group exhibited higher levels (p < .01) of free androgen index (FAI), anti-müllerian hormone (AMH), fasting insulin (FINS), insulin level within 60 min, 120 min, and 180 min-60minINS, 120minINS, and 180minINS, respectively, fasting blood glucose (FBG), blood glucose level within two hours (2hGlu), homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), waist-to-hip ratio (WHR), waist circumference, hip circumference, the ratio of the maximum blood flow velocity of the uterine artery during systole to the blood flow velocity of the uterine artery at the end of diastole (uterine artery S/D), and blood flow resistance index (RI) of the uterine artery. In comparison with the NP group, the OP group exhibited lower levels (p < .01) of sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), high molecular weight adiponectin (HMWA), and high-density lipoprotein cholesterol (HDL-C). (2) In the PCOS group, RI was significantly positively correlated with FAI, FINS, 120minINS, HOMA-IR, and WHR (p < .01), and significantly negatively correlated with SHBG, HDL-C, and HMWA (p < .01); uterine artery S/D was significantly positively correlated with FAI, FINS, 2hGlu, HOMA-IR, LDL-C, and WHR (p < .01), significantly positively correlated with 120minINS and FBG (p < .05), and significantly negatively correlated with SHBG and HMWA (p < .01). CONCLUSION: (1) The OP group exhibited obvious metabolic disorders and poor ER, which was manifested as low levels of SHBG and HMWA, and high levels of FAI, HOMA-IR, WHR, uterine artery S/D, and RI. (2) In patients with PCOS, there was a substantial correlation between ER-associated indicators RI and uterine artery S/D and FAI, FINS, 120minINS, HOMA-IR, WHR, SHBG, and HMWA.

Circ-RNF111 Promotes Proliferation of Ovarian Cancer Cell SKOV-3 by Targeting the MiR-556-5p/CCND1 Axis.

The aim of this study was to investigate the role and mechanism of circ-RNF111 in the human ovarian cancer cell line SKOV-3. First, qRT-PCR was used to detect circ-RNF111 and miR-556-5p expression levels in human normal ovarian epithelial cells IOSE80 and human ovarian cancer cells SKOV-3. CCK-8 and colony formation assays were adopted to determine the proliferation rate and cell viability of SKOV-3 cells, respectively. Additionally, in an attempt to reveal the mechanism of circ-RNF111, we predicted the targeting relationship between miR-556-5p and circ-RNF111 as well as miR-556-5p and CCND1 using the circinteractome and TargetScan databases, respectively, and validated their relationship by dual-luciferase reporter assay. The protein expression levels of CCND1 in SKOV-3 cells were detected by Western blot. Based on the above experiments, the expression of circ-RNF111 was found to be up-regulated in SKOV-3, and the knockdown of circ-RNF111 significantly inhibited the proliferation and viability of SKOV-3 cells. Then we confirmed that circ-RNF111 sponged miR-556-5p in SKOV-3 cells to up-regulate CCND1 expression. In addition, simultaneous inhibition of miR-556-5p or overexpression of CCND1 in SKOV-3 cells with knockdown of circ-RNF111 reversed the inhibitory effect of knockdown of circ-RNF111 on the protein expression level of CCND1, cell proliferation rate, and cell viability. In summary, circ-RNF111 promotes the proliferation of SKOV-3 cells by targeting the miR-556-5p/CCND1 axis. Circ-RNF111 may serve as a potential target for ovarian cancer therapy.

Three Undescribed Protoilludane-type Sesquiterpene Aryl Esters from Armillaria gallica.

Three previously undescribed protoilludane-type sesquiterpene aryl esters, armillanals A-C (1-3), along with seven known ones (4-10) were obtained from Armillaria gallica Marxm. & Romagn. Compounds 1 and 2 were a rare class of sesquiterpenes featuring the Δ2(3) and Δ12(13)-protoilludane skeleton. Their structures were established by extensive spectroscopic methods. Based on electronic circular dichroism (ECD) calculations, the absolute configurations of three new compounds (1-3) were determined. The anti-inflammatory activity of compounds 1-10 was screened and compound 3 could dose-dependently decrease the level of lactate dehydrogenase, showing IC50 value of 4.525 µM.

Two new oleanane triterpenes from Maytenus hookeri.

Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36-3.44 µM.

Pruritus Anesis in Dystrophic Epidermolysis Bullosa Pruriginosa with Dupilumab.

ABSTRACT: Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of dystrophic epidermolysis bullosa, and traditional treatments have limited efficacy. Dupilumab has demonstrated remarkable efficacy in relieving pruritus. In this case study, after traditional treatment failed, providers recommended the patient begin dupilumab to treat his pruritus. The patient was administrated a loading dose of 600 mg of dupilumab and a dose of 300 mg every 2 weeks. The Dermatology Life Quality Index and Pruritic Numeric Rating Scale were used to assess the patient's situation. After several months, the patient's DEB-Pr was considered in remission. Dupilumab may be a better choice than immunosuppressants for the treatment of pruritus in patients with DEB-Pr.

Recent advances in network-based methods for disease gene prediction.

Disease-gene association through genome-wide association study (GWAS) is an arduous task for researchers. Investigating single nucleotide polymorphisms that correlate with specific diseases needs statistical analysis of associations. Considering the huge number of possible mutations, in addition to its high cost, another important drawback of GWAS analysis is the large number of false positives. Thus, researchers search for more evidence to cross-check their results through different sources. To provide the researchers with alternative and complementary low-cost disease-gene association evidence, computational approaches come into play. Since molecular networks are able to capture complex interplay among molecules in diseases, they become one of the most extensively used data for disease-gene association prediction. In this survey, we aim to provide a comprehensive and up-to-date review of network-based methods for disease gene prediction. We also conduct an empirical analysis on 14 state-of-the-art methods. To summarize, we first elucidate the task definition for disease gene prediction. Secondly, we categorize existing network-based efforts into network diffusion methods, traditional machine learning methods with handcrafted graph features and graph representation learning methods. Thirdly, an empirical analysis is conducted to evaluate the performance of the selected methods across seven diseases. We also provide distinguishing findings about the discussed methods based on our empirical analysis. Finally, we highlight potential research directions for future studies on disease gene prediction.

Helicity-resolved Raman scattering of MoS2 bulk crystal.

Helicity-resolved Raman spectroscopy (HRRS) can effectively distinguish the Raman modes of two-dimensional (2D) layered materials by phonon symmetry. In this paper, we systematically investigated the phonon helicity selection of basal and edge planes of MoS2 bulk by HRRS. We find that the symmetry of the crystal structure changes the helicity selection of the E1g, E1 2g, and A1g modes in the edge plane. The theoretical calculation results confirm that the E1 2g and A1g modes of the basal plane exhibit a perfect helicity exchange, and the helicity selections of the E1 2g and A1g modes of the edge plane are eliminated or weakened. Our study provides references for phonon helicity selection of 2D layered materials represented by MoS2.

Evolutionary research trend of Polygonatum species: a comprehensive account of their transformation from traditional medicines to functional foods.

With the advances in Polygonatum research, there is a huge interest in harnessing the valuable functional ingredients of this genus with the potential for functional foods. This review emphasizes the different aspects of Ploygonatum based research starting from its bioactive compounds, their structural characterization, various extraction methods, as well as biological activities. In view of its integral use as an essential medicinal plant, our review emphasizes on its promising food applications both as an ingredient and as a whole food, and its improved health benefits with potential for agricultural and environmental relevance are also discussed. As we collated the recent research information, we present the main challenges and limitations of the current research trend in this area which can upgrade the further expansion of Polygonatum-related research that will strengthen its economic and accessible nutritional value in the food and health industries. By highlighting the need for the unattended species, this review not only fills existing research gaps, but also encourages the researchers to find new avenues for the natural production of bio-based functional materials and the development of highly functional and health-promoting foods for disease prevention and treatment.

High-dose amoxicillin-proton pump inhibitor dual therapy as first-line treatment for Helicobacter pylori infection in Northwest China: A prospective, randomised controlled trial.

AIMS: We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China. METHODS: A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by 13 C urea breath test (13 C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method. RESULTS: The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of 13 C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured. CONCLUSION: The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of 13 C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.

Strophioblachins A-K, Structurally Intriguing Diterpenoids from Strophioblachia fimbricalyx with Potential Anticardiac Hypertrophic Inhibitory Activity.

Three new rearranged diterpenoids, strophioblachins A-C (1-3), eight new diterpenoids, strophioblachins D-K (4-11), and seven previously described diterpenoids (12-18) were purified from the aerial parts of Strophioblachia fimbricalyx. Compounds 1 and 2 contain a rare 6/6/5/6 ring system, while 3 has an uncommon tricyclo[4.4.0.08,9]tridecane-bridged unit, and their diterpenoid skeletons are being reported for the first time. Utilizing spectroscopic and HRESIMS data analysis, the structures of the new compounds (1-11) were established, and ECD and 13C NMR calculations were used to confirm the relative and absolute configurations of 11 and 9. The absolute configurations of compounds 1, 3, and 10 were established using single-crystal X-ray diffraction. The results of testing for anticardiac hypertrophic activity demonstrated that compounds 10 and 15 dose-dependently lowered the mRNA expression of Nppa and Nppb. Protein levels were confirmed by Western blotting, which also demonstrated that compounds 10 and 15 lowered the expression of the hypertrophic marker ANP. The cytotoxic activity against neonatal rat cardiomyocytes was assayed in vitro by the CCK-8 and ELISA methods, and the results showed that compounds 10 and 15 were only very weakly active in the range.

Wulfenioidins D-N, Structurally Diverse Diterpenoids with Anti-Zika Virus Activity Isolated from Orthosiphon wulfenioides.

Eleven diterpenoids, wulfenioidins D-N (1-11), classified into five distinct carbon skeletons with one unreported framework, and four modified abietane diterpenoids were isolated from the whole plant of Orthosiphon wulfenioides. The structures and absolute configurations were characterized by spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analyses. Compounds 3 and 5 exhibited activity against Zika virus (ZIKV) with EC50 values of 8.07 and 8.50 µM, respectively, and showed no significant cytotoxicity toward Vero cells at 100 µM. Western blot and immunofluorescence experiments showed that compounds 3 and 5 interfered with the replication of the ZIKV by inhibiting the expression of the ZIKV envelope (E) protein.

Abietane diterpenoids from Orthosiphon wulfenioides with NLRP3 inflammasome inhibitory activity.

Wulfenioidones A - K (1-11) were abietane diterpenoids with highly oxidized 6/6/6 aromatic tricyclic skeleton isolated from the whole plant of Orthosiphon wulfenioides, and their planar structures and absolute configurations were elucidated by spectroscopic data interpretation, electronic circular dichroism calculation as well as X-ray crystallography analysis. Bioactivity screening indicated that compounds 1-4, 6 and 8 exhibited lactate dehydrogenase (LDH) inhibition effect with IC50 values ranging from 0.23 to 3.43 µM by preventing the mononuclear macrophage cell pyroptosis induced by double signal stimulation of LPS and nigericin. Western Blot analyses of Caspase-1 and IL-1ß down-regulation exhibited that compound 1 could selectively inhibit NLRP3 inflammasome, and the cell morphological observation further supported that compound 1 prevented macrophage cell pyroptosis.

Effects of intravenous administration of magnesium sulfate in propofol-based sedation for ERCP in elderly patients: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Propofol-based sedations are widely used in elderly patients for endoscopic retrograde cholangiopancreatography (ERCP) procedure, but respiratory depression and cardiovascular adverse events commonly occur. Magnesium administered intravenously can alleviate pain and decrease propofol requirements during surgery. We hypothesized that intravenous magnesium was used as adjuvant to propofol might be beneficial in elderly patients undergoing ERCP procedures. METHODS: Eighty patients aged from 65 to 79 years who were scheduled for ERCP were enrolled. All patients were intravenously administered 0.1 µg/kg sufentanil as premedication. The patients were randomized to receive either intravenous magnesium sulfate 40 mg/kg (group M, n = 40) or the same volume of normal saline (group N, n = 40) over 15 min before the start of sedation. Intraoperative sedation was provided by propofol. Total propofol requirement during ERCP was the primary outcome. RESULTS: The total propofol consumption were reduced by 21.4% in the group M compared with the group N (151.2 ± 53.3 mg vs. 192.3 ± 72.1 mg, P = 0.001). The incidences of respiratory depression episodes and involuntary movement were less in the group M than those in the group N (0/40 vs. 6/40, P = 0.011; 4/40 vs. 11/40, P = 0.045; respectively). In the group M, the patients experienced less pain than those in the group N at 30 min after the procedure (1 [0-1] vs. 2 [1-2], P < 0.001). Correspondingly, the patients' satisfaction was clearly higher in the group M (P = 0.005). There was a tendency towards lower intraoperative heart rate and mean arterial pressure in group M. CONCLUSIONS: A single bolus of 40 mg/kg of intravenous magnesium can significantly reduce propofol consumption during ERCP, with higher sedation success and lower adverse events. TRIAL REGISTRATION: ID UMIN000044737. Registered 02/07/2021.

Chemical Constituents of the Branches and Leaves of Picrasma chinensis P.Y. Chen and Tyrosinase Inhibiting Activity.

One new alkaloid, picrasine A, two new quassinoids, picralactones A-B, together with eleven known compounds were isolated from Picrasma chinensis P.Y. Chen. The structures of these compounds were determined using 1D and 2D NMR, HR-ESI-MS, and IR spectroscopic data, and by comparison with published data. Some compounds were tested for tyrosinase inhibiting activity, however, none of them exhibited strong inhibitory effects.

Three New Clerodane Diterpenoids and Their NLRP3 Inflammasome Activation Inhibitory Activity from Callicarpa arborea Roxb.

Three new compounds callicarpenoids A-C (1-3), were isolated from the stems of Callicarpa arborea Roxb together with fifteen known compounds (4-18). The structures of these compounds were elucidated using advanced spectroscopic techniques, including 1D and 2D NMR, UV, IR, HR-ESI-MS, ECD, ORD, and quantum chemical calculations. Compound 3, a rare rearranged diterpenoid with a fused 5/6-ring system demonstrated strong potential as an inhibitor of the NLRP3 inflammasome activation with an IC50 value of 3.153 µM. It effectively reduced GSDMD-NT production, inhibited caspase-1 activation, and suppressed IL-1ß secretion, thereby mitigating NLRP3 inflammasome-induced pyroptosis in J774A.1 cells. These findings suggest that compound 3 warrants further research and development as a promising NLRP3 inflammasome inhibitor.

Two New Prostaglandin-Like Compounds from Callicarpa arborea Roxb and Their NLRP3 Inflammasome Activation Inhibitory Activity.

Two new prostaglandin-like compounds callicarboric acids A-B (1-2), along with six known compounds (3-8) were isolated from the stems of Callicarpa arborea Roxb. Their structures were determined with the help of modern spectroscopic techniques such as NMR, UV, IR, HR-ESI-MS, ECD, and ORD with the assistance of quantum chemical calculations. Compound 1 exhibited remarkable anti-NLRP3 inflammasome activation potential, demonstrating an IC50 value of 0.74 µM. Additionally, by reducing GSDMD-NT production, inhibiting caspase-1 activation, and suppressing IL-1ß secretion, it effectively mitigated NLRP3 inflammasome-induced pyroptosis in J774A.1 cells. These findings indicate that compound 1 possesses the capability to be a valuable candidate for further research and development as an NLRP3 inflammasome inhibitor.

Highly Oxygenated Labdane Diterpenoids from Stevia rebaudiana and Their Anti-Atherosclerosis Activities.

Five unknown labdane diterpenoids Stevelins A-E (1-5), three known labdane diterpenoids (6-8) and three labdane norditerpenoids (9-11) were isolated from the Stevia rebaudiana. The structures were determined primarily via NMR spectroscopic data and HR-ESI-MS experiments. X-ray crystallography using CuKα radiation was used to determine the absolute configurations of 1, and the absolute configurations of 2-5 were deduced by electronic circular dichroism (ECD) calculations. The potential anti-atherosclerosis activities of all compounds were evaluated by measuring their inhibitory effects on the macrophage foam cell formation. As a result, most isolated compounds could significantly inhibit oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment for atherosclerosis.

Callicarpanes A-L, Twelve New Clerodane Diterpenoids with NLRP3 Inflammasome Inhibitory Activity from Callicarpa integerrima.

Twelve new clerodane diterpenoids named callicarpanes A-L (1-12), together with eight known compounds (13-20), were isolated from Callicarpa integerrima. Their structures were determined by comprehensive spectroscopic data. The calculated chemical shifts were used to identify relative configurations using DP4+ analysis. The absolute configurations (AC) were assigned based on quantum chemical calculations and X-ray single-crystal diffraction methods. Compounds 1, 3, 5, 9, 10, 12, 15, 16, and 19 showed significant inhibitory activity for NLRP3 inflammasome activation, with the IC50 against lactate dehydrogenase (LDH) release ranging from 0.08 to 4.78 µM. Further study revealed that compound 10 repressed IL-1ß secretion and caspase-1 maturation in J774A.1 cell as well as blocked macrophage pyroptosis.