Chemical composition and bioactivity variability of two-step extracts derived from traditional and "QiNan" agarwood (Aquilaria spp.).

One of the primary applications for agarwood lies in the extracts, instead, there are obvious differences in the demands for agarwood components with different application fields. To obtain the rough separation and clarify each part's activity, four extracts of essential oil, hydrolat, extractum, and ethanol precipitation from traditional agarwood (TraA) and "Qinan" agarwood (QinA) were obtained by steam-solvent multistage extraction and ethanol precipitation. We investigated the chemistry and biological activity of multistage extracts using gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), and in vitro activity testing. The results demonstrated that two kinds of agarwood essential oils contained mainly sesquiterpenoids, yet the sesquiterpene species were remarkably diverse in two kinds of agarwood essential oils. Then, the TraA and QinA hydrolat, all predominantly aromatic and sesquiterpene, but with differences from the essential oil ingredients. Additionally, the extractum chiefly contained chromones and the ethanol precipitation method worked well to separate the impurities in the TraA extract, however, it was ineffective for the QinA extract. Ultimately, essential oils and extractums all have antioxidant properties, with extractums outperforming essential oils. Moreover, both extractums and essential oils exhibited excellent broad-spectrum antimicrobial activity and anti-inflammatory activity. The findings pointed to the feasibility of separating the primary components from TraA and QinA using a multi-stage extraction technique, providing a scientific basis for the efficient utilization of all components of agarwood, as well as the functional product development and differentiated utilization of extract products in incense, fragrance, perfume, and daily chemicals.

Anatomical, chemical and endophytic fungal diversity of a Qi-Nan clone of Aquilaria sinensis (Lour.) Spreng with different induction times.

Recently, some new Qi-Nan clones of Aquilaria sinensis (Lour.) Spreng which intensively produces high-quality agarwood have been identified and propagated through grafting techniques. Previous studies have primarily focused on ordinary A. sinensis and the differences in composition when compared to Qi-Nan and ordinary A. sinensis. There are few studies on the formation mechanism of Qi-Nan agarwood and the dynamic changes in components and endophytic fungi during the induction process. In this paper, the characteristics, chemical composition, and changes in endophytic fungi of Qi-Nan agarwood induced after 1 year, 2 years, and 3 years were studied, and Qi-Nan white wood was used as the control. The results showed that the yield of Qi-Nan agarwood continued to increase with the induction time over a period of 3 years, while the content of alcohol extract from Qi-Nan agarwood reached its peak at two years. During the formation of agarwood, starch and soluble sugars in xylem rays and interxylary phloem are consumed and reduced. Most of the oily substances in agarwood were filled in xylem ray cells and interxylary phloem, and a small amount was filled in xylem vessels. The main components of Qi-Nan agarwood are also chromones and sesquiterpenes. With an increasing induction time, the content of sesquiterpenes increased, while the content of chromones decreased. The most abundant chromones in Qi-Nan agarwood were 2-(2-Phenethyl) chromone, 2-[2-(3-Methoxy-4-hydroxyphenyl) ethyl] chromone, and2-[2-(4-Methoxyphenyl) ethyl] chromone. Significant differences were observed in the species of the endophytic fungi found in Qi-Nan agarwood at different induction times. A total of 4 phyla, 73 orders, and 448 genera were found in Qi-Nan agarwood dominated by Ascomycota and Basidiomycota. Different induction times had a significant effect on the diversity of the endophytic fungal community in Qi-Nan. After the induction of agarwood formation, the diversity of Qi-Nan endophytic fungi decreased. Correlation analysis showed that there was a significant positive correlation between endophytic fungi and the yield, alcohol extract content, sesquiterpene content, and chromone content of Qi-Nan agarwood, which indicated that endophytic fungi play a role in promoting the formation of Qi-Nan agarwood. Qi-Nan agarwood produced at different induction times exhibited strong antioxidant capacity. DPPH free radical scavenging activity and reactive oxygen species clearance activity were significantly positively correlated with the content of sesquiterpenes and chromones in Qi-Nan agarwood.

Identification and characterization of two O-methyltransferases involved in biosynthesis of methylated 2-(2-phenethyl)chromones in agarwood.

The 2-(2-phenethyl)chromones (PECs) are the signature constituents responsible for the fragrance and pharmacological properties of agarwood. O-Methyltransferases (OMTs) are necessary for the biosynthesis of methylated PECs, but there is little known about OMTs in Aquilaria sinensis. In this study, we identified 29 OMT genes from the A. sinensis genome. Expression analysis showed they were differentially expressed in different tissues and responded to drill wounding. Comprehensive analysis of the gene expression and methylated PEC content revealed that AsOMT2, AsOMT8, AsOMT11, AsOMT16, and AsOMT28 could potentially be involved in methylated PECs biosynthesis. In vitro enzyme assays and functional analysis in Nicotiana benthamiana demonstrated that AsOMT11 and AsOMT16 could methylate 6-hydroxy-2-(2-phenylethyl)chromone to form 6-methoxy-2-(2-phenylethyl)chromone. A transient overexpression experiment in the variety 'Qi-Nan' revealed that AsOMT11 and AsOMT16 could significantly promote the accumulation of three major methylated PECs. Our results provide candidate genes for the mass production of methylated PECs using synthetic biology.

Salty treatment increased bioactive compounds accumulation during agarwood development in Aquilaria sinensis trees.

To compare the bioactive compounds in agarwood induced by different methods in Aquilaria sinensis(Lour.) Gilg trees, a two dimensional thin layer chromatograph(2D-TLC) combined with effect directive analysis(EDA) was developed. Three antioxidants were found by 2D-TLC-DPPH and further identified as 2-(2-phenylethyl) chromones(PECs) with LC-MS/MS. The 3 antioxidants decreased along agarwood formation and their compositions in drilling induced agarwood differed with those in microbe culture induced agarwood. Further study showed NaCl treatment promoted antioxidants accumulation in agarwood induced by drilling or hot drilling. Hot drilling combined with salty stimulation was most efficient in some chemicals accumulation, which were identified as PECs with antioxidant, tyrosinase or ß-glucosidase inhibiting activities by 2D-TLC-EDA-LC-MS/MS. This study provided a 2D-TLC-EDA-LC-MS/MS method for bioactive compounds screen and qualification of agarwood. Based on this method, non-conventional methods were found to accelerate the accumulation of some bioactive PECs in A. sinensis trees.

The Impact of high-performance work system perceived by medical staff on job satisfaction: the mediating role of self-efficacy.

As the mainstay of healthcare, the job satisfaction of medical staff deserves attention. This study aimed to explore the correlation between the perception of the high-performance work system (P-HPWS) and job satisfaction of medical staff in public hospitals and to further investigate the mediating effect of self-efficacy. From November 2019 to January 2020, a cross-sectional survey on working doctors and nurses was conducted in five tertiary public hospitals in China. A total of 520 participants were surveyed. The P-HPWS, job satisfaction, and self-efficacy were assessed using the 25-item self-administered scale, six-item job satisfaction questionnaire, and the General Self-Efficacy Scale, respectively. Linear regression and mediation effects models were used to identify the associations between primary variables. The results showed a significant positive correlation between P-HPWS and job satisfaction (P < 0.01), while self-efficacy played a mediating role between P-HPWS and job satisfaction. This finding reveals the benefits of improving employees' P-HPWS and self-efficacy on their job satisfaction, and that hospitals can improve their management systems by implementing and refining HPWS.

Toward well-defined colloidal particles: Efficient fractionation of lignin by a multi-solvent strategy.

Colloidal lignin particles (CLPs) have sparked various intriguing insights toward bio-polymeric materials and triggered many lignin-featured innovative applications. Here, we report a multi-solvent sequential fractionation methodology integrating green solvents of acetone, 1-butanol, and ethanol to fractionate industrial lignin for CLPs fabrication. Through a rationally designed fractionation strategy, multigrade lignin fractions with variable hydroxyl group contents, molecular weights, and high purity were obtained without altering their original chemical structures. CLPs with well-defined morphology, narrow size distribution, excellent thermal stability, and long-term colloidal stability can be obtained by rational selection of lignin fractions. We further elucidated that trace elements (S, N) were reorganized onto the near-surface area of CLPs from lignin fractions during the formation process in the form of -SO42- and -NH2. This work provides a sustainable and efficient strategy for refining industrial lignin into high-quality fractions and an in-depth insight into the CLPs formation process, holding great promise for enriching the existing libraries of colloidal materials.

Non-Pharmacological Interventions in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To determine the effectiveness of non-pharmacologic interventions and the additional benefits of their combination in patients with heart failure with reduced ejection fraction (HFrEF). DATA SOURCES: We searched PubMed, Embase, and the Cochrane Clinical Trials Register from the date of database inception to April 22, 2023. STUDY SELECTION: Randomized controlled trials involving non-pharmacologic interventions conducted in patients with HFrEF were included. DATA EXTRACTION: Data were extracted by 2 independent reviewers based on a pre-tested data extraction form. The quality of evidence was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation method. DATA SYNTHESIS: A total of 82 eligible studies (4574 participants) were included. We performed a random-effects model within a Bayesian framework to calculate weighted mean differences (WMDs) and 95% credibility intervals. High or moderate certainty evidence indicated that high-intensity aerobic interval training (HIAIT) was best on improving 6-minute walk distance (6MWD; 68.55 m [36.41, 100.47]) and left ventricular ejection fraction (6.28% [3.88, 8.77]), while high-intensity aerobic continuous training (HIACT) is best on improving peak oxygen consumption (Peak VO2; 3.48 mL/kg•min [2.84, 4.12]), quality of life (QOL; -17.26 [-29.99, -7.80]), resting heart rate (-8.20 bpm [-13.32, -3.05]), and N-terminal pro-B-type natriuretic peptide (-600.96 pg/mL [-902.93, -404.52]). Moderate certainty evidence supported the effectiveness of inspiratory muscle training to improve peak oxygen consumption and functional electrical stimulation to improve QOL. Moderate-intensity aerobic continuous training (MIACT) plus moderate-intensity resistance training (MIRT) had additional benefits in Peak VO2, 6MWD, and QOL. This review did not provide a comprehensive evaluation of adverse events. CONCLUSIONS: Both HIAIT and HIACT are the most effective single non-pharmacologic interventions for HFrEF. MIACT plus MIRT had additional benefits in improving peak oxygen consumption, 6MWD, and QOL.

Clinical Observation of Anatomical and Visual Outcomes of Macular Hole after Inverted Internal Limiting Membrane Flap in Patients with Idiopathic Macular.

Objective: To investigate anatomical and visual outcomes of macular hole (MH) after inverted internal limiting membrane (ILM) flap technique for idiopathic macular hole (IMH). Methods: A total of 13 IMH cases diagnosed in Shanxi Eye Hospital between January 2015 and June 2016 were included in the study. All patients underwent vitrectomy combined with indocyanine green-assisted inverted ILM flap technique. The MH closure rate, best-corrected visual acuity (BCVA), changes of ellipsoid zone (EZ), and external limiting membrane (ELM) were examined before operation and one, three, and six months after operation. Furthermore, 488 nm fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) were used to observe the dynamic changes in function of macular area after surgery. Results: One month after the surgery, the MH closure rate was 100% and the visual acuity (VA) was stable, with no recurrence. Additionally, the average logMAR BCVA before operation was 1.208 ± 0.158, and this value became 0.877 ± 0.105 one month after the operation, showing a significant decrease. Three months after surgery, the average logMAR BCVA was 0.792 ± 0.103, which was significantly lower than the level one month after the surgery but much higher than that six months after surgery (0.708 ± 0.131). Besides, the diameter of the EZ defect of the postoperative one month, three months, and six months was (1377.46 ± 198.65) µm, (964.62 ± 336.26) µm, and (817.08 ± 442.99) µm, respectively. In postoperative one month, three months, and six months, the diameter of the ELM defect diameter was (969.62 ± 189.92) µm, (649.92 ± 413.15) µm, and (557.62 ± 412.50) µm, respectively. The diameter of both EZ and ELM defects was significantly reduced with the passage of time after surgery. Conclusion: Inverted ILM flap technique can reconstruct macular anatomical structure and improve VA. This technique is effective for the treatment of IMH with large MH minimum diameter and base diameter.

Non-pharmacological interventions for older patients with hypertension: A systematic review and network meta-analysis.

OBJECTIVE: To determine the most effective non-pharmacological interventions to control the blood pressure variation in older hypertensive patients. METHODS: Primary endpoints were office systolic blood pressure (SBP) and diastolic blood pressure (DBP). The quality of evidence was assessed using the "risk of bias 2″ tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. We performed a Bayesian network meta-analysis using R-4.0.2 software to compare the efficacy of interventions. RESULTS: 36 eligible studies (3,531 patients) with a median follow-up of 12 weeks, assessing 18 non-pharmacological interventions, were included. The percentages of high, moderate, low, and very low certainty evidence were 16.7%, 38.9%, 33.3%, and 11.1%, respectively. CONCLUSION: High certainty evidence suggests that self-management education is most effective in lowering SBP and DBP in older patients with hypertension, followed by moderate-intensity aerobic exercise. Moderate-intensity resistance training is the most effective exercise for lowering SBP. REGISTRATION: PROSPERO, #CRD42020209850.

Diverse tumorigenic consequences of human papillomavirus integration in primary oropharyngeal cancers.

Human papillomavirus (HPV) causes 5% of all cancers and frequently integrates into host chromosomes. The HPV oncoproteins E6 and E7 are necessary but insufficient for cancer formation, indicating that additional secondary genetic events are required. Here, we investigate potential oncogenic impacts of virus integration. Analysis of 105 HPV-positive oropharyngeal cancers by whole-genome sequencing detects virus integration in 77%, revealing five statistically significant sites of recurrent integration near genes that regulate epithelial stem cell maintenance (i.e., SOX2, TP63, FGFR, MYC) and immune evasion (i.e., CD274). Genomic copy number hyperamplification is enriched 16-fold near HPV integrants, and the extent of focal host genomic instability increases with their local density. The frequency of genes expressed at extreme outlier levels is increased 86-fold within ±150 kb of integrants. Across 95% of tumors with integration, host gene transcription is disrupted via intragenic integrants, chimeric transcription, outlier expression, gene breaking, and/or de novo expression of noncoding or imprinted genes. We conclude that virus integration can contribute to carcinogenesis in a large majority of HPV-positive oropharyngeal cancers by inducing extensive disruption of host genome structure and gene expression.

Effect of intravitreal conbercept injection on VEGF-A and -B levels in the aqueous and vitreous humor of patients with proliferative diabetic retinopathy.

The present study aimed to investigate the mechanisms of anti-VEGF treatment prior to eye surgery to reduce intraoperative bleeding. A total of 30 patients with proliferative vitreoretinopathy after clinical diagnosis were enrolled in the present study as the surgical group. Furthermore, 30 patients underwent intravitreal injection of the anti-VEGF drug conbercept and were considered the drug pretreatment group. The aqueous and vitreous humors from the eyes of patients in the surgical group were drawn during pars plana vitrectomy surgery. The aqueous humor in the eyes of patients in the drug pretreatment group was drawn prior to conbercept treatment and seven days after conbercept treatment immediately prior to surgery. The vitreous humor in this group was only taken during surgery. Furthermore, ELISA was used to detect the levels of VEGF-A and -B in the aqueous and vitreous humors. Semi-quantitative determination of VEGF-A and VEGF-B levels in fibrovascular proliferative membranes was performed using immunohistochemical staining. The results indicated that in the drug group, the levels of VEGF-A in the aqueous humor of patients prior to and after conbercept injection were 197.66±48.00 and 3.39±2.54 pg/ml, respectively. The levels of VEGF-A in the vitreous humor of patients in the surgical and drug groups were 267.53±179.60 and 21.43±5.81 pg/ml after injection, respectively. The levels of VEGF-B in the aqueous humor of patients prior to and after conbercept injection were 13.66±3.30 (before injection) and 2.17±0.94 pg/ml (after injection), respectively. The levels of VEGF-B in the vitreous humor of patients in the surgical and drug groups were 127.36±16.72 and 18.56±9.82 pg/ml after injection, respectively (P<0.05). Furthermore, in the drug group, the surgery time, bleeding and capillary formation were significantly reduced compared with those in the surgical group. Taken together, these results suggested that the levels of VEGF-A and -B decreased significantly in the aqueous humor of patients with PDR after conbercept injection. Furthermore, the levels of VEGF-A and -B in the vitreous humor of patients dropped significantly in the drug group compared with those in the surgical group. These results provide theoretical clinical support for the preoperative application of conbercept for patients with PDR.

Superelastic, Hygroscopic, and Ionic Conducting Cellulose Nanofibril Monoliths by 3D Printing.

Compressible and superelastic 3D printed monoliths have shown great promise in various applications including energy storage, soft electronics, and sensors. Although such elastic monoliths have been constructed using some limited materials, most notably graphene, it has not yet been achieved in nature's most abundant material, cellulose, partly due to the strong hydrogen-bonding network within cellulose. Here, we report a 3D-printed cellulose nanofibril monolith that demonstrates superb elasticity (over 91% strain recovery after 500 cycles of compressive test), compressibility (up to 90% compressive strain), and pressure sensitivity (0.337 kPa-1) at 43% relative humidity. Such a high-performance CNF monolith is achieved through both hierarchical architecture design by 3D printing and freeze-drying and incorporation of hygroscopic salt for water absorption. The facile and efficient design strategy for a highly flexible CNF monolith is expected to expand to materials beyond cellulose and can realize much broader applications in flexible sensors, thermal insulation, and many other fields.

Effect of Furfurylation on Hierarchical Porous Structure of Poplar Wood.

Some wood properties (such as permeability and acoustic properties) are closely related to its hierarchical porous structure, which is responsible for its potential applications. In this study, the effect of wood impregnation with furfuryl alcohol on its hierarchical porous structure was investigated by microscopy, mercury intrusion porosimetry and nuclear magnetic resonance cryoporometry. Results indicated decreasing lumina diameters and increasing cell wall thickness of various cells after modification. These alterations became serious with enhancing weight percent gain (WPG). Some perforations and pits were also occluded. Compared with those of untreated wood, the porosity and pore volume of two furfurylated woods decreased at most of the pore diameters, which became more remarkable with raising WPG. The majority of pore sizes (diameters of 1000~100,000 nm and 10~80 nm) of macrospores and micro-mesopores of two furfurylated woods were the same as those of untreated wood. This work could offer thorough knowledge of the hierarchical porous structure of impregnatedly modified wood and pore-related properties, thereby providing guidance for subsequent wood processing and value-added applications.

Lignin-based fluorescence hollow nanoparticles: Their preparation, characterization, and encapsulation properties for doxorubicin.

Lignin shows strong adsorption, biodegradability and non-toxicity, and has opened a research hotspot in the design and manufacture of controllable nanomaterials for drug delivery. However, lignin-based materials, with both diagnostic and therapeutic functions, have yet to be developed. In this work, enzymatically hydrolysable lignin (EHL) was used to prepare blue fluorescent lignin copolymer by grafting 1-Pyrenebutyric acid onto lignin via amidation reaction and then formed self-assembled nanoparticles. The results show that such lignin-based hollow nanoparticles exhibit characteristics of fluorescent functions, size controlled and stable structure within 15 days. For anticancer drug Doxorubicin, the encapsulation efficiency and drug loading reached, respectively, 50% and 10%. This encapsulation had no cytotoxicity, and sustained-release effect on the drug. The aim of this study was to develop the multifunctional bio-nanomaterials for medical applications, through simple, environmentally friendly, low-cost methods.

Clinical analysis and predictive factors associated with improved visual acuity of infectious endophthalmitis.

BACKGROUND: To describe the clinical characteristics and analyze the predictive factors associated with improved visual acuity of 359 patients with infectious endophthalmitis. METHODS: This study retrospectively analyzed 359 eyes of 359 patients with infectious endophthalmitis from January 2014 to December 2018. The findings summarized some epidemiological characteristics of these patients, including age, sex, occupation, patient visit time, etiology, causative organisms, therapy, and best-corrected visual acuity. Multivariate logistic regression was performed to predict the relative factors of improved visual acuity (VA). RESULTS: Overall, 283 (78.83%) patients were male. The mean age was 48.0 ± 18.27 years. Ocular trauma, especially open globe injuries (246, 68.5%) was the most common etiology of infectious endophthalmitis in this study. The etiologies of infectious endophthalmitis were open globe injuries (68.5%), intraocular surgery (22.6%), and corneal ulcer-associated (6.7%) and endogenous causes (2.2%). In the etiology classification and visual acuity improvement group, had statistically significant differences in factors such as age, sex, patient visit time, pre-therapy visual acuity, etc. The average Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity on pre-therapy was 2.28 ± 0.60, and it had significantly improved to 1.67 ± 0.83 post-therapy (P < 0.05). Logistic regression analysis showed that visit time > 7 day (P = 0.034, OR = 0.522, 95% CI: 0.286-0.953), pre-therapy VA ≦logMAR 2.3 (P = 0.032, OR = 1.809, 95% CI: 1.052-3.110), post-surgical (vs. posttraumatic; P = 0.023, OR = 2.100, 95% CI: 1.109-3.974), and corneal ulcer-associated etiologies (vs. posttraumatic; P = 0.005, OR = 0.202, 95%CI: 0.066-0.621) were significantly associated with improved visual acuity after adjusting for possible confounding factors. CONCLUSIONS: Among the patients with infectious endophthalmitis, middle-aged male, especially farmers and workers, accounted for a large proportion. Open globe injuries were the main cause and the gram-positive bacteria were the major causative organisms. The final visual outcomes seemed to vary according to the type of endophthalmitis, but early treatment and good initial visual acuity were important factors for visual acuity improvement.

Tilianin Protects Diabetic Retina through the Modulation of Nrf2/TXNIP/NLRP3 Inflammasome Pathways.

Oxidative stress and inflammation are regarded as prime reasons for the progression and development of diabetic retinopathy. Currently, nuclear factor erythroid-2-related factor 2 (Nrf2), thioredoxin interacting protein (TXNIP) and NLRP3 inflammasome pathways are under increasing focus in research on oxidative stress and inflammation-related diseases. On the other hand, tilianin (TN) has received much attention because of its various pharmacological properties. Based on results of these studies, this investigation was performed to inspect the therapeutic efficiency of TN on the retina in diabetic rats. Rats were arbitrarily assigned to three groups: control group, diabetic group, and diabetic plus TN (20 mg/ kg body weight for 42 days, orally) group. TN supplementation in diabetic rats, their food intake, fasting blood glucose status, glycosylated hemoglobin (HbA1c) levels were drastically reduced, and there was a marked augmentation in serum insulin status. TN treatment of diabetic rats increased mRNA expression of Nrf2 and its target gene, HO-1, and noticeably decreased the malondialdehyde status. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX) were increased relative to diabetic rats. Furthermore, administering TN to the diabetic rats resulted in decreased expression of TXNIP, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1ß proteins and decreased distribution of TXNIP, NLRP3, ASC, and caspase-1 proteins in retinas. In addition, TN treatment ameliorated morphological and morphometric changes in the retinas of diabetic rats. Together, all of these findings provide clear evidence that TN treatment of diabetic rats attenuated diabetic retinal changes through its hypoglycemic, antioxidant, and anti-inflammatory properties. The antioxidant and anti-inflammatory effects in diabetic retinas occur at least in part through the modulation of Nrf2/TXNIP/NLRP3 inflammasome pathways, which may have remedial benefits in the healing of diabetic retinopathy.

Characterization of the incense ingredients of cultivated grafting Kynam by TG-FTIR and HS-GC-MS.

Agarwood is a resinous wood of Aquilaria species and has been used for various applications. Burning agarwood incense is a common practice in temples and homes in Asia. Kynam is widely regarded as high-quality agarwood in the market. Recently, cultivated grafting Kynam (CGK) has emerged as a new agarwood product in the market, which greatly affects the price of high grading Kynam agarwood. In this study, the morphology, ethanol extract content, and incense chemical profile of CGK was investigated and compared with those of wild Kynam (WK) and cultivated common agarwood (CCA). The incense smoke of CGK was analyzed by thermogravimetric Fourier transform infrared spectroscopy (TG-FTIR) and headspace gas chromatography-mass spectrometry (HS-GC-MS). The results showed that the heating of most incenses occurred below 200 °C, and the mass-loss rate value of CGK was between those of WK and CCA. The HS-GC-MS analysis showed the chemical compounds of incense smoke of CGK at 40, 100, and 180 °C, corresponding to the head, middle, and tail of the heating process, respectively. The results suggested that the sesquiterpenes compounds were the major contributors to the mysterious and elegant odoriferous character of agarwood incense. However, a peak area percentage analysis revealed a significant difference in the predominant compounds between CGK and WK, especially at lower temperatures. Therefore, it is not straightforward to substitute WK with CGK. The results are helpful for the study and usage of the new cultivated grafting Kynam agarwood and the development of the agarwood incense industry.

Lignin-Based Hollow Nanoparticles for Controlled Drug Delivery: Grafting Preparation Using ß-Cyclodextrin/Enzymatic-Hydrolysis Lignin.

Due to its abundance, degradability, and low toxicity, lignin is a promising raw material for the preparation of nanomaterials. However, efficient encapsulation using lignin-nanomaterial for sustained-release medications remains a challenge. This study involves grafting ß-cyclodextrin (ß-CD), with a hollow toroidal structure, onto the enzymatic-hydrolysis lignin (EHL) to form CD-EHL. The modified lignin was next used to prepare hollow nanoparticles (LHNPs) via self-assembly to encapsulate the antitumor drug hydroxycamptothecin (HCPT). The results indicated that ß-CD improved the network structure of modified lignin molecules. Moreover, LHNPs that self-assembled using CD-EHL had an increased specific surface area and greater porosity, and exhibited a spherical hollow structure and stability in phosphate-buffered saline. The drug loading and encapsulation efficiency of HCPT were 70.6 ± 9% and 22.02 ± 2%, respectively. An in vitro study showed that lignin-based nanoparticles have low toxicity, and the modified LHNPs demonstrated a good sustained-release capability. This study broadened the potential application of lignin as a renewable biomass material.

IL-21-based therapies induce clearance of hepatitis B virus persistence in mouse models.

Chronic hepatitis B virus (HBV) infection causes hepatitis, liver cirrhosis and hepatocellular carcinoma. Covalently closed circular DNA (cccDNA) is the sole viral transcription template and not affected by current treatment options, constituting a key determinant of HBV persistence. Novel therapeutics with demonstrable effectiveness against cccDNA are required. Methods: Previously, we established an HBV persistence mouse model using replicon plasmid derived from a clinical isolate (termed BPS) and identified IL-21 as a potent clearance-inducer. We also described another persistence mouse model based on cccDNA mimics produced in vivo termed recombinant cccDNA (rcccDNA). In this work, effectiveness of IL-21-based gene and cellular therapies was tested using these models. Results: In both models of HBV persistence, single injections with adeno-associated virus (AAV) expressing murine IL-21 highly efficiently induced clearance of both HBV markers from serum, and more importantly, BPS DNA and rcccDNA from mouse liver. Mechanistically, IL-21-induced clearance was associated with activation and liver infiltration of CD8+ T cells, and CD8 antibody injections negatively affected AAV-IL-21 effectiveness. More notably, adoptive transfer of CD8+ T cells from AAV-IL-21-cured mice engendered clearance in acceptor HBV persistence mice. Furthermore, cured mice were protected against re-challenge with long-lived memory. Most significantly, infusion of splenocytes from treatment-naïve mice stimulated ex vivo with IL-21 protein and HBV antigen could also induce clearance in treatment-naïve mice. Conclusion: These data demonstrate IL-21-based gene and cellular therapies as valid candidates for treating chronic HBV infections, with potential in removing cccDNA-harboring hepatocytes via activated CD8+ T cells accompanied by long-term protective memory.

Chemical Profiles of Cultivated Agarwood Induced by Different Techniques.

Agarwood is the resinous wood produced in some Aquilaria species and is highly valued for wide usages in medicine, incense, and perfume. To protect the threatened Aquilaria species, the cultivation of Aquilaria sinensis and artificial agarwood induction techniques have been effectively established in China. To evaluate the quality of agarwood induced by different techniques, patterns of chemical constituents in artificial agarwood by four methods (wounding using an axe, burning-chisel-drilling, chemical inducer, and biological inoculation) were analyzed and compared by UPLC-ESI-MS/MS and GC-EI-MS in this study. Results of GC-MS gave a panorama of chemical constituents in agarwood, including aromatic compounds, steroids, fatty acids, sesquiterpenoids, and 2-(2-phenlyethyl)-chromones (PECs). Sesquiterpenoids were dominant in agarwood induced by wounding using an axe. PEC comprised over 60% of components in agarwood produced by biological inoculation and chemical inducers. PECs were identified by UPLC-ESI-MS/MS in all artificial agarwood and the relative contents varied in different groups. Tetrahydro-2-(2-phenylethyl)-chromones (THPECs) in wounding by axes induced agarwood were lower while 2-(2-phenylethyl)-chromones (FPECs) were higher than other groups. The results showed that methods used for inducing agarwood formation in Aquilaria sinensis affect the chemical constituents of agarwood.