Observation of high-order imaginary Poynting momentum optomechanics in structured light.

The imaginary Poynting momentum (IPM) of light has been captivated as an unusual origin of optical forces. However, the IPM force is predicted only for dipolar magnetoelectric particles that are hardly used in optical manipulation experiments. Here, we report a whole family of high-order IPM forces for not only magnetoelectric but also generic Mie particles, assisted with their excited higher multipoles within. Such optomechanical manifestations derive from a nonlocal contribution of the IPM to the optical force, which can be remarkable even when the incident IPM is small. We observe the high-order optomechanics in a structured light beam, which, despite carrying no angular momentum, is able to set normal microparticles into continuous rotation. Our results provide unambiguous evidence of the ponderomotive nature of the IPM, expand the classification of optical forces, and open new possibilities for levitated optomechanics and micromanipulations.

Enantioselective Optical Trapping of Multiple Pairs of Enantiomers by Focused Hybrid Polarized Beams.

Enantiomers (opposite chiral molecules) usually exhibit different effects when interacting with chiral agents, thus the identification and separation of enantiomers are of importance in pharmaceuticals and agrochemicals. Here an optical approach is proposed to enantioselective trapping of multiple pairs of enantiomers by a focused hybrid polarized beam. Numerical results indicate that such a focused beam shows multiple local optical chirality of opposite signs in the focal plane, and can trap the corresponding enantiomers near the extreme value of optical chirality density according to the handedness of enantiomers. The number and positions of trapped enantiomers can be changed by altering the value and sign of polarization orders of hybrid polarized beams, respectively. The key to realizing enantioselective optical trapping of enantiomers is that the chiral optical force exerted on enantiomers in this focused field is stronger than the achiral optical force. The results provide insight into the optical identification and separation of multiple pairs of enantiomers and will find applications in chiral detection and sensing.

Peroxynitrite-activated fluorescent probe with two reaction triggers for pathological diagnosis and therapeutic evaluation of inflammation.

Excessive peroxynitrite (ONOO-) is closely related to the occurrence and progression of inflammation. Therefore, the development of an efficacious ONOO- activatable probe holds great potential for the early diagnosis of pathological inflammation, and the direct evaluation of the therapeutic efficacy of active protectants. In this work, a new ONOO--activated fluorescent probe (SZP) which greatly improved the specificity and sensitivity (LOD = 8.03 nM) with large Stokes shift (150 nm) through introducing two reaction triggers (diphenyl phosphinate moiety, CC unsaturated bond) was rationally designed for rapid detecting ONOO- (within 2 min). The excellent properties of probe SZP enable it to realize the fluorescence-guided diagnosis of inflammation. More importantly, probe SZP has also been utilized to assess the anti-inflammatory efficacy of traditional Chinese medicines (TCMs) active ingredients for the remediation of inflammation by monitoring ONOO- fluctuation for the first time.

Effect of vaccine hesitancy on female college students' willingness to receive the HPV vaccine in China: a multicenter cross-sectional study.

OBJECTIVE: To analyse the influencing factors of vaccine hesitancy on HPV vaccination willingness of female college students in order to promote the promotion of HPV vaccine in female college student population. METHODS: From September-October 2022, a convenience sampling method was used to conduct a questionnaire survey among freshman female students from four higher vocational colleges in Henan Province, China. The survey comprised a general information questionnaire, as well as inquiries regarding vaccine hesitancy and willingness to receive the human papillomavirus (HPV) vaccine. In PSM analyses, vaccine-hesitant students were matched with non-vaccine-hesitant students at a 1:1 ratio; subsequently, both univariate and multivariatble logistic regression analyses were applied to assess the impact of vaccine hesitancy on female university students' willingness to receive the HPV vaccine. RESULTS: The results revealed a vaccine hesitancy rate of 44.75% among female university students, with 82.9% expressing willingness to receive the HPV vaccine. The results of the multivariable ordinal logistic regression analysis indicated vaccine hesitancy is a risk factor for HPV vaccination intentions among female university students [OR = 4.38, 95% CI (2.74, 6.99), P < 0.001]. Furthermore, the field of study (P = 0.01) and independently seeking information about the HPV vaccine (P = 0.04) were identified as factors influencing female university students' willingness to receive the HPV vaccine. CONCLUSIONS: Non-vaccine-hesitant students were more likely to be willing to receive the HPV vaccine than vaccine-hesitant students. Healthcare providers and educators should focus on vaccine attitudes among female college students to reduce vaccine hesitancy and enhance community education on cervical cancer, HPV infection and prevention through multichannel campaigns.

Influence of Family-Learned Fear-of-Pain on Patients.

BACKGROUND: Fear-of-pain is a common feeling of patients and their family who experience or witness severe or chronic pain. Fear-of-pain may disturb patient's recovery, and also influence family support to assist patients' recovery. AIM: This study is to measure the level of family support for each patient; evaluate the extent of the supporting families' fear-of-pain; and identify possible interventions in family support and family fear-of-pain. METHODS: This cross-sectional descriptive research involved 77 participants in the orthopedics department of a tertiary hospital by convenience sampling. The online questionnaire includes general information, and scales of fear-of-pain, pain anxiety, pain vigilance and awareness, pain catastrophizing, and family support. T-test, Pearson correlation analysis and Spearman correlation analysis were used to analyze data. RESULTS: Most participants reported that they experienced a moderate-to-high level of fear-of-pain, pain anxiety, pain vigilance and awareness. A total of 15.6% of participants are at risk of pain catastrophizing. The family's pain vigilance and awareness, and fear-of-pain were often similar to those of the patient, and their levels of pain anxiety and catastrophizing were often higher than the patient's. Family support and families' fear-of-pain affect patients' feelings of pain and families' behavior in decision-making for patient recovery, necessitating the development of interventions for patients' families. CONCLUSIONS: Family members can develop the fear-of-pain from witnessing painful experiences and may exhibit fear-avoidance behaviors in deciding on patients' rehabilitation plan. Family support, including the type of relationship with families, and length of time family spent with the patient, had an effect on patients' pain and fear-of-pain.

Comparative Analysis of Chloroplast Pan-Genomes and Transcriptomics Reveals Cold Adaptation in Medicago sativa.

Alfalfa (Medicago sativa) is a perennial forage legume that is widely distributed all over the world; therefore, it has an extremely complex genetic background. Though population structure and phylogenetic studies have been conducted on a large group of alfalfa nuclear genomes, information about the chloroplast genomes is still lacking. Chloroplast genomes are generally considered to be conservative and play an important role in population diversity analysis and species adaptation in plants. Here, 231 complete alfalfa chloroplast genomes were successfully assembled from 359 alfalfa resequencing data, on the basis of which the alfalfa chloroplast pan-genome was constructed. We investigated the genetic variations of the alfalfa chloroplast genome through comparative genomic, genetic diversity, phylogenetic, population genetic structure, and haplotype analysis. Meanwhile, the expression of alfalfa chloroplast genes under cold stress was explored through transcriptome analysis. As a result, chloroplast genomes of 231 alfalfa lack an IR region, and the size of the chloroplast genome ranges from 125,192 bp to 126,105 bp. Using population structure, haplotypes, and construction of a phylogenetic tree, it was found that alfalfa populations could be divided into four groups, and multiple highly variable regions were found in the alfalfa chloroplast genome. Transcriptome analysis showed that tRNA genes were significantly up-regulated in the cold-sensitive varieties, while rps7, rpl32, and ndhB were down-regulated, and the editing efficiency of ycf1, ycf2, and ndhF was decreased in the cold-tolerant varieties, which may be due to the fact that chloroplasts store nutrients through photosynthesis to resist cold. The huge number of genetic variants in this study provide powerful resources for molecular markers.

Vascular Electrical Stimulation with Wireless, Battery-Free, and Fully Implantable Features Reduces Atherosclerotic Plaque Formation Through Sirt1-Mediated Autophagy.

Electrical stimulation (ES) is a safe and effective procedure in clinical rehabilitation with few adverse effects. However, studies on ES for atherosclerosis (AS) are scarce because ES does not provide a long-term intervention for chronic disease processes. Battery-free implants and surgically mounted them in the abdominal aorta of high-fat-fed Apolipoprotein E (ApoE-/- ) mice are used, which are electrically stimulated for four weeks using a wireless ES device to observe changes in atherosclerotic plaques. Results showed that there is almost no growth of atherosclerotic plaque at the stimulated site in AopE-/- mice after ES. RNA-sequencing (RNA-seq) analysis of Thp-1 macrophages reveal that the transcriptional activity of autophagy-related genes increase substantially after ES. Additionally, ES reduces lipid accumulation in macrophages by restoring ABCA1- and ABCG1-mediated cholesterol efflux. Mechanistically, it is demonstrated that ES reduced lipid accumulation through Sirtuin 1 (Sirt1)/Autophagy related 5 (Atg5) pathway-mediated autophagy. Furthermore, ES reverse autophagic dysfunction in macrophages of AopE-/- mouse plaques by restoring Sirt1, blunting P62 accumulation, and inhibiting the secretion of interleukin (IL)-6, resulting in the alleviation of atherosclerotic lesion formation. Here, a novel approach is shown in which ES can be used as a promising therapeutic strategy for AS treatment through Sirt1/Atg5 pathway-mediated autophagy.

Convergent molecular evolution of thermogenesis and circadian rhythm in Arctic ruminants.

The muskox and reindeer are the only ruminants that have evolved to survive in harsh Arctic environments. However, the genetic basis of this Arctic adaptation remains largely unclear. Here, we compared a de novo assembled muskox genome with reindeer and other ruminant genomes to identify convergent amino acid substitutions, rapidly evolving genes and positively selected genes among the two Arctic ruminants. We found these candidate genes were mainly involved in brown adipose tissue (BAT) thermogenesis and circadian rhythm. Furthermore, by integrating transcriptomic data from goat adipose tissues (white and brown), we demonstrated that muskox and reindeer may have evolved modulating mitochondrion, lipid metabolism and angiogenesis pathways to enhance BAT thermogenesis. In addition, results from co-immunoprecipitation experiments prove that convergent amino acid substitution of the angiogenesis-related gene hypoxia-inducible factor 2alpha (HIF2A), resulting in weakening of its interaction with prolyl hydroxylase domain-containing protein 2 (PHD2), may increase angiogenesis of BAT. Altogether, our work provides new insights into the molecular mechanisms involved in Arctic adaptation.

Intratumoral and peritumoral radiomics nomograms for the preoperative prediction of lymphovascular invasion and overall survival in non-small cell lung cancer.

OBJECTIVES: To evaluate the predictive value of intratumoral and peritumoral radiomics and radiomics nomogram for preoperative lymphovascular invasion (LVI) status and overall survival (OS) in patients with non-small cell lung cancer (NSCLC). METHODS: In total, 240 NSCLC patients from our institution were randomly divided into the training cohort (n = 145) and internal validation cohort (n = 95) with a ratio of 6:4, and 65 patients from the Cancer Imaging Archive were enrolled as the external validation cohort. We extracted 1217 CT-based radiomics features from the gross tumor volume (GTV) and gross tumor volume incorporating peritumoral 3, 6, and 9 mm regions (GPTV3, GPTV6, GPTV9). A radiomics nomogram based on clinical independent predictors and radiomics score (Radscore) of the best radiomics model was constructed. The correlation between factors and OS was evaluated with the Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. RESULTS: Compared with GTV, GPTV3, and GPTV6 radiomics models, GPTV9 radiomics model exhibited better prediction performance with the AUCs of 0.82, 0.75, and 0.67 in the training, internal validation, and external validation cohorts, respectively. In the clinical model, smoking and clinical stage were independent predictors. The nomogram incorporating independent predictors and GPTV9-Radscore was clinically useful, with the AUCs of 0.89, 0.83, and 0.66 in three cohorts. Pathological LVI, GPTV9-Radscore-predicted, and Nomoscore-predicted LVI were associated with poor OS (p < 0.05). CONCLUSIONS: CT-based radiomics nomogram can predict LVI and OS in patients with NSCLC and may help in making personalized treatment strategies before surgery. KEY POINTS: • Compared with GTV, GPTV3, and GPTV6 radiomics models, GPTV9 radiomics model showed better prediction performance for LVI status in NSCLC. • The radiomics nomogram based on GPTV9 radiomics features and clinical independent predictors could effectively predict LVI status and OS in NSCLC and outperformed the clinical model. • The radiomics nomogram had a wider scope of clinical application.

The psychometric properties of the Chinese version of the Parkinson Anxiety Scale (C-PAS) among Parkinson's disease.

BACKGROUND: Anxiety disorder is a common non-motor symptom among individuals with Parkinson's disease (PD). At present, there are no specific tools in China for assessing the anxiety level of patients with PD. This study aimed to test the reliability and validity of the Chinese version of the Parkinson Anxiety Scale (C-PAS) in Chinese patients with PD. METHODS: A total of 158 patients with PD at one hospital in Nanjing were recruited through convenience sampling. The C-PAS was translated into Chinese using a classic 'forward-backward' translation method. Reliability tests included internal consistency and test-reliability. And in addition to content, structure and criterion-related validity were performed for the validity tests. Criterion-related validity was evaluated with the Hospital Anxiety and Depression Scale-Anxiety Subscale (HADS-A). RESULTS: Results confirmed the three-factor structure of the original C-PAS with 12 items, including persistent anxiety (5 items), episodic anxiety (4 items) and avoidance behavior (3 items). Significant and positive correlations were obtained between C-PAS and HADS-A (r = 0.82, P<0.01). The Cronbach's α and test-retest reliability of the total scale were 0.89 and 0.84, respectively. CONCLUSION: The C-PAS has demonstrated good psychometric properties. Therefore, it can be employed in patients with PD to evaluate the condition of anxiety.

Helicobacter pylori CagA Interacts with SHP-1 to Suppress the Immune Response by Targeting TRAF6 for K63-Linked Ubiquitination.

Helicobacter pylori is the major etiological agent for most gastric cancer. CagA has been reported to be an important virulence factor of H. pylori, but its effect on the immune response is not yet clear. In this study, wild-type C57BL/6 mice and Ptpn6me-v/me-v mice were randomly assigned for infection with H. pylori We demonstrated that CagA suppressed H. pylori-stimulated expression of proinflammatory cytokines in vivo. Besides, we infected mouse peritoneal macrophages RAW264.7 and AGS with H. pylori Our results showed that CagA suppressed expression of proinflammatory cytokines through inhibiting the MAPKs and NF-κB pathways activation in vitro. Mechanistically, we found that CagA interacted with the host cellular tyrosine phosphatase SHP-1, which facilitated the recruitment of SHP-1 to TRAF6 and inhibited the K63-linked ubiquitination of TRAF6, which obstructed the transmission of signal downstream. Taken together, these findings reveal a previously unknown mechanism by which CagA negatively regulates the posttranslational modification of TRAF6 in innate antibacterial immune response and provide molecular basis for new therapeutics to treat microbial infection.

Effect of the change of mechanical ventilation mode on cerebral oxygen saturation level in neonates.

BACKGROUND: This study aimed to apply near-infrared spectroscopy (NIRS) to monitor cerebral oxygen saturation (SrO2) level in neonates before and after the change of mechanical ventilation mode, and thus, the effects of the change of mechanical ventilator mode on SrO2 level in neonates were assessed. METHODS: This trial was designed as an observational study .A total of 70 neonates who were admitted to the Department of Neonatology of Beijing Luhe Hospital Affiliated to Capital Medical University (Beijing, China) between September 2019 and October 2021 and required respiratory support were included. The variations of SrO2 level before and after the change of mechanical ventilation mode, including changing from Synchronized intermittent mandatory ventilation (SIMV) to noninvasive ventilation (NIV, group 1), and from NIV to oxygen inhalation (group 2), were monitored by Enginmed EGOS-600 A. The changes of SrO2 level at 30 min before and 1 h after the change of ventilation mode were compared between the two groups. RESULTS: The SrO2 level in the group 1 30 min before, as well as 10 min, 30 min, and 1 h after the change of ventilation mode was 62.54 ± 3.36%, 65.43 ± 3.98%, 64.38 ± 4.23%, and 64.63 ± 3.71%, respectively. The SrO2 level at all the points after the change of ventilation mode increased compared with 30 min before the change (P < 0.05). The SrO2 level in the group 2 at each time point was 62.67 ± 4.69%, 64.61 ± 5.00%, 64.04 ± 4.48%, and 64.55 ± 4.32%, respectively. Compared with 30 min before ventilator weaning, the SrO2 level at all the points after ventilator weaning increased (P < 0.05). Peak inspiratory pressure (PIP) excluding Nasal Continuous Positive Airway Pressure (NCPAP)) in group 1 was lower than that before extubation, and the difference was statistically significant (P = 0) (Table 7). CONCLUSIONS: SrO2 level showed an increasing trend after the change of ventilation mode, and the increase of SrO2 level at 10 min after the change of ventilation mode was the most prominent. From SIMV to NIV, increased SrO2 levels may be associated with decreased PIP.

Convergent Genomic Signatures of Cashmere Traits: Evidence for Natural and Artificial Selection.

Convergent evolution provides powerful opportunities to investigate the genetic basis of complex traits. The Tibetan antelope (Pantholops hodgsonii) and Siberian ibex (Capra sibirica) belong to different subfamilies in Bovidae, but both have evolved similar superfine cashmere characteristics to meet the cold temperature in plateau environments. The cashmere traits of cashmere goats underwent strong artificial selection, and some traces of domestication also remained in the genome. Hence, we investigated the convergent genomic signatures of cashmere traits between natural and artificial selection. We compared the patterns of convergent molecular evolution between Tibetan antelope and Siberian ibex by testing positively selected genes, rapidly evolving genes and convergent amino acid substitutions. In addition, we analyzed the selected genomic features of cashmere goats under artificial selection using whole-genome resequencing data, and skin transcriptome data of cashmere goats were also used to focus on the genes involved in regulating cashmere traits. We found that molecular convergent events were very rare, but natural and artificial selection genes were convergent enriched in similar functional pathways (e.g., ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway) in a variety of gene sets. Type IV collagen family genes (COL4A2, COL4A4, COL4A5, COL6A5, COL6A6) and integrin family genes (ITGA2, ITGA4, ITGA9, ITGB8) may be important candidate genes for cashmere formation and development. Our results provide a comprehensive approach and perspective for exploring cashmere traits and offer a valuable reference for subsequent in-depth research on the molecular mechanisms regulating cashmere development and fineness.

Dithienylethene-Bridged Fluoroquinolone Derivatives for Imaging-Guided Reversible Control of Antibacterial Activity.

The emerging field of photopharmacology has offered a promising alternative to guard against the bacterial resistance by effectively avoiding antibiotic accumulation in the body or environment. However, the degradation, toxicity, and thermal reversibility have always been an ongoing concern for potential applications of azobenzene-based photopharmacology. Developing novel photopharmacological agents based on a more matched switch is highly in demand and remains a major challenge. Herein, two novel dithienylethene-bridged dual-fluoroquinolone derivatives have been developed by introducing two fluoroquinolone drugs into both ends of the dithienylethene (DTE) switch, in which the fluoroquinolone acts as a fluorophore except for the pharmacodynamic component. For comparison, two monofluoroquinolone-DTE hybrids were also prepared by a similar strategy. As expected, these resultant DTE-based antibacterial agents displayed efficient photochromism and fluorescence switching behavior in dimethyl sulfoxide. Moreover, improved antibacterial activities compared to those of monofluoroquinolone derivatives and a maximum fourfold active difference against Escherichia coli (E. coli) for open and closed isomers and photoswitchable bacterial imaging for Staphylococcus aureus and E. coli were observed. The molecular docking to DNA gyrase gave a rationale for the discrepancies in antibacterial activity for both isomers. Therefore, these fluoroquinolone derivatives can act as interesting imaging-guided photopharmacological agents for further in vivo studies.

Anti-inflammation of isoliquiritigenin via the inhibition of NF-κB and MAPK in LPS-stimulated MAC-T cells.

BACKGROUND: The application of plant extracts has received great interest for the treatment of bovine mastitis. Isoliquiritigenin (ISL) is a rich dietary flavonoid that has significant antioxidative, anti-inflammatory and anticancer activities. This study was conducted to explore the protective efficacy and related mechanism of ISL against lipopolysaccharide (LPS)-stimulated oxidation and inflammation in bovine mammary epithelial cells (MAC-T) by in vitro experiments. RESULTS: Real-time PCR and ELISA assays indicated that ISL treatment at 2.5, 5 and 10 µg/mL significantly reduced the mRNA and protein expression of the oxidative indicators cyclooxygenase-2 and inducible nitric oxide synthase (P < 0.01), and of the inflammatory cytokines interleukin-6 (P < 0.05), interleukin-1ß (P < 0.01) and tumor necrosis factor-α (P < 0.01) in LPS-stimulated MAC-T cells. Moreover, Western blotting and immunofluorescence tests indicated that the phosphorylation levels of nuclear factor kappa (NF-κB) p65 and the inhibitor of NF-κB were significantly decreased by ISL treatment, thus blocking the nuclear transfer of NF-κB p65. In addition, ISL attenuated the phosphorylation levels of p38, extracellular signal-regulated kinase and c-jun NH2 terminal kinase. CONCLUSIONS: Our data demonstrated that ISL downregulated the LPS-induced inflammatory response in MAC-T cells. The anti-inflammatory and antioxidative activity of ISL involves the NF-κB and MAPK cascades.

Identification and separation of chiral particles by focused circularly polarized vortex beams.

The identification and separation of chiral substances are of importance in the biological, chemical, and pharmaceutical industries. Here, we demonstrate that a focused circularly polarized vortex beam can, in the focal plane, selectively trap and rotate chiral dipolar particles via radial and azimuthal optical forces. The handedness and topological charge of the incident beam have strong influence on identifying and separating behavior: left- and right-handed circular polarizations lead to opposite effects on the particle of trapping and rotating, while the sign of topological charge will change the particle's rotation direction. Such effects are a direct result of the handedness and topological charge manifesting themselves in the directions of the spin angular momentum (SAM) and Poynting vector. The research provides insight into the chiral light-matter interaction and may find potential application in the identification and separation of chiral nanoparticles.

Spirally rotating particles with structured beams generated by phase-shifted zone plates.

The emerging field of structured beams has led to optical manipulation with tremendous progress. Beyond various methods for structured beams, we use phase-shifted zone plates known as beam-shaping diffractive optical elements to generate beams whose phase exclusively or both phase and intensity are twisted along a curve. These beams can trap and guide particles on open curved trajectories for continuous motion, not necessarily requiring a closed symmetric intensity distribution. We show the feasibility and versatility of the proposed method as a promising technique in optical manipulation in which the trajectory of the spiral rotation and the rate of rotation of trapped particles can be controlled.

Knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination among college students in China.

BACKGROUND: Cervical cancer is the fourth most common cancer in women. Up to 99% of cervical cancer cases are associated with high-risk human papillomavirus (HPV). Sexual behavior is a direct risk factor for HPV infection, and sexually active college students, therefore, receive attention for HPV vaccination. At present, most Chinese studies lack of in-depth research on influencing factors, and are limited to cervical cancer, HPV, or HPV vaccine, without comprehensive consideration. This study investigated Chinese college students' cervical cancer prevention and treatment knowledge level, and explored the influencing factors, and understood their willingness to receive HPV vaccination. The findings of this study will lay a foundation for promoting the early screening of cervical cancer and vaccination process. METHODS: A total of 800 college students from four universities in Zhengzhou, China were selected by multistage random sampling method. A self-administered questionnaire on the knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination was carried out. A logistic regression model was conducted to analyze factors influencing knowledge of cervical cancer prevention and treatment among college students. RESULTS: Up to 87.9% of college students said they had heard of cervical cancer. The proportion of college students with good knowledge of cervical cancer prevention and treatment was 46.7%. Logistic regression showed that gender, major, grade, level of education, the father's level of education, premarital sex attitude, and mother cervical cancer screening participation had a significant influence on cervical cancer prevention and treatment knowledge level (P < 0.05). In addition, 589 (74.0%) of college students had heard of HPV vaccine, and 92.8% of college students said they were willing to get vaccinated or recommended that their relatives and friends get vaccinated. CONCLUSIONS: The knowledge level of cervical cancer prevention and treatment knowledge among college students in Zhengzhou is low. Many of them had poor knowledge about HPV vaccine, but their willingness to vaccination is high. Various health education modes should be carried out for people with different characteristics, to improve their knowledge of cervical cancer prevention and promote the vaccination process.

Phenolic Glucosides from the Leaves of Vitex negundo var. cannabifolia.

Four new phenolic glucosides, cannabifolins G-J (1-4), together with four known ones (5-8), were isolated from the leaves of Vitex negundo var. cannabifolia. Their structures were established by comprehensive analysis of 1D and 2D NMR data and comparison of their spectroscopic and physical data with the literature values. Compound 7 exhibited weak inhibition of nitric oxide production stimulated by lipopolysaccharide in BV-2 microglial cells with IC50 value of 132.8 µM.

Metformin Hydrochloride Mucosal Nanoparticles-Based Enteric Capsule for Prolonged Intestinal Residence Time, Improved Bioavailability, and Hypoglycemic Effect.

Metformin hydrochloride enteric-coated capsule (MH-EC) is a commonly used clinical drug for the treatment of type 2 diabetes. In this study, we described a metformin hydrochloride mucosal nanoparticles enteric-coated capsule (MH-MNPs-EC) based on metformin hydrochloride chitosan mucosal nanoparticles (MH-CS MNPs) and its preparation method to improve the bioavailability and hypoglycemic effect duration of MH-EC. In intestinal adhesion study, the residue rates of free drugs and mucosal nanoparticles were 10.52% and 67.27%, respectively after cleaned with PBS buffer. MH-CS MNPs could significantly improve the efficacy of MH and promote the rehabilitation of diabetes rats. In vitro release test of MH-MNPs-EC showed continuous release over 12 h, while commercial MH-EC released completely within about 1 h in intestinal environment (pH 6.8). Pharmacokinetic study was performed in beagle dogs compared to the commercial MH-EC. The durations of blood MH concentration above 2 µg/mL were 9 h for MH-MNPs-EC versus 2 h for commercial MH-EC. The relative bioavailability of MH-MNPs-EC was determined as 185.28%, compared with commercial MH-EC. In conclusion, MH-CS MNPs have good intestinal adhesion and can significantly prolong the residence time of MH in the intestine. MH-MNPs-EC has better treatment effect compared with MH-EC, and it is expected to be a potential drug product for the treatment of diabetes because of its desired characteristics.