A novel gelatin composite film with melt extrusion for walnut oil packaging.

Gelatin have excellent film-forming and barrier properties, but its lack of biological activity limits its application in packaging. In this study, fish gelatin incorporated with apple polyphenol/cumin essential oil composite films were successfully prepared by melt extrusion. The cross-linking existed in gelatin and apple polyphenol improved the thermal stability and oxidation resistance of the film. The synergistic effect of apple polyphenols and cumin essential oil decreased the sensitivity of the film to water, especially the water solubility decreased from 41.60 % to 26.07 %. The plasticization of essential oil nearly doubled the elongation at break while maintaining the tensile strength of the film (11.45 MPa). Furthermore, the FG-CEO-AP film can inhibit peroxide value to extend the shelf life about 20 days in the walnut oil preservation. In summary, the apple polyphenol/cumin essential oil of FG film exhibits excellent comprehensive properties and high preparation efficiency for utilization as an active packaging material.

Chemical Synergic Stabilization of High Br-Content Mixed-Halide Wide-Bandgap Perovskites for Durable Multi-Terminal Tandem Solar Cells with Minimized Pb Leakage.

High Br-content mixed-halide perovskites with wide-bandgap (WBG) of 1.6-2.0 eV have showcased vast potential to be used in tandem solar cells. However, they often suffer from severe halide segregation, phase separation and ion migration issues, which would accelerate the decomposition of perovskites films, deteriorate the photovoltaic performance and even aggravate the lead leakage from damaged devices. Here, we report a novel chemical synergic interaction strategy to mitigate the abovementioned issues. A small amount of cationic ß-cyclodextrin, composed of multiple ammonium cations, chlorine ions and abundant hydroxyl functional groups, was introduced into WBG perovskites, which effectively stabilized the halide ions and homogenized the phase distribution, comprehensively passivated the defects,and efficiently immobilized the Pb2+ ions. Encouragingly, the cationic ß-cyclodextrin was universal and useful for different WBG perovskites, which favorably boosted the efficiencies by 10%-36% and extended the device operational stability to 2680 h. The integrated four-terminal or six-terminal all-perovskite tandem solar cells exhibited efficiencies up to 24.39% and 22.42%, respectively. We demonstrated the cationic ß-cyclodextrin-assisted internal chemical encapsulation effectively prevented the Pb leakage from severely damaged devices with only 5.63 ppb Pb leaching out. The target tandem solar cells with cationic ß-cyclodextrin modification also realized a Pb sequestration efficiency of 93.4%.

[Benefit-risk assessment of three oral Chinese patent medicines for activating blood and eliminating mass in treating primary liver cancer based on network Meta-analysis and multi-criteria decision analysis].

Network Meta-analysis and multi-criteria decision analysis(MCDA) model were performed to evaluate the benefit-risk of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in the adjuvant treatment of primary liver cancer(PLC). The randomized controlled trial(RCT) of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in treating PLC were retrieved from CNKI, Wanfang, VIP, Web of Science, PubMed, and Cochrane Library. R 4.2 was employed to conduct a network Meta-analysis, on the basis of which the effect values of the three medicines were obtained by indirect comparison. MCDA was performed to establish the value tree based on the benefit-risk indexes. Hiview 3.2 was used to calculate the benefit values, risk values, and benefit-risk values of the three medicines in treating PLC, and a sensitivity analysis was carried out to evaluate the robustness of the results. Oracle Crystal Ball 11.1 was employed to optimize the evaluation results by Monte Carlo simulation. A total of 39 RCTs were included. The results showed that Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules combined with transcatheter arterial chemoembolization(TACE) had the benefit values of 45, 51 and 45, the risk values of 59, 47, and 41, and the benefit-risk values of 52, 49, and 43, respectively. The benefit-risk differences and [95%CI] of Compound Cantharis Capsules vs Huisheng Oral Solution, Compound Cantharis Capsules vs Jinlong Capsules, and Huisheng Oral Solution vs Jinlong Capsules were 3.00[-13.09, 21.82], 9.00[-4.39, 24.62], and 6.00[-8.84, 20.28], respectively. Based on the results of MCDA, Huisheng Oral Solution, Jinlong Capsules, and Compound Cantharis Capsules combined with TACE had the greatest benefit, the greatest risk, and the best overall benefit, respectively. Considering the efficacy and safety, the priority of the three oral Chinese patent medicines combined with TACE for treating PLC followed the trend of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules.

Blade-Coating (100)-Oriented α-FAPbI3 Perovskite Films via Crystal Surface Energy Regulation for Efficient and Stable Inverted Perovskite Photovoltaics.

Photoactive black-phase formamidinium lead triiodide (α-FAPbI3) perovskite has dominated the prevailing high-performance perovskite solar cells (PSCs), normally for those spin-coated, conventional n-i-p structured devices. Unfortunately, α-FAPbI3 has not been made full use of its advantages in inverted p-i-n structured PSCs fabricated via blade-coating techniques owing to uncontrollable crystallization kinetics and complicated phase evolution of FAPbI3 perovskites during film formation. Herein, a customized crystal surface energy regulation strategy has been innovatively developed by incorporating 0.5 mol % of N-aminoethylpiperazine hydroiodide (NAPI) additive into α-FAPbI3 crystal-derived perovskite ink, which enabled the formation of highly-oriented α-FAPbI3 films. We deciphered the phase transformation mechanisms and crystallization kinetics of blade-coated α-FAPbI3 perovskite films via combining a series of in-situ characterizations and theoretical calculations. Interestingly, the strong chemical interactions between the NAPI and inorganic Pb-I framework help to reduce the surface energy of (100) crystal plane by 42 %, retard the crystallization rate and lower the formation energy of α-FAPbI3. Benefited from multifaceted advantages of promoted charge extraction and suppressed non-radiative recombination, the resultant blade-coated inverted PSCs based on (100)-oriented α-FAPbI3 perovskite films realized promising efficiencies up to 24.16 % (~26.5 % higher than that of the randomly-oriented counterparts), accompanied by improved operational stability. This result represented one of the best performances reported to date for FAPbI3-based inverted PSCs fabricated via scalable deposition methods.

P-CAB versus PPI in the eradication of Helicobacter pylori: a systematic review and network meta-analysis.

Background: The efficacy and safety of potassium-competitive acid blockers (P-CABs) in the eradication of Helicobacter pylori (Hp) remains controversial when compared with proton pump inhibitors (PPIs). Objectives: The current study set out to compare the differences in the eradication rate and adverse reactions between eradication regimens based on P-CAB or PPI drugs and the differences between the vonoprazan-based and the tegoprazan-based regimens to explore the efficacy and safety of different Hp eradication regimens. Data sources and methods: Databases including PubMed, EMBASE, Cochrane Library, and WOS were searched from the inception of these databases up to July 2023, and eligible randomized controlled trials (RCTs) were included. The outcome measures were the eradication rate and the incidence of adverse reactions of different regimens in treating Hp. The results were estimated as relative risk (RR) and its 95% confidence interval (CI), and R 4.2.1 software was used to perform the network meta-analysis (NMA). Results: A total of 20 studies were included in the analysis, involving 5815 patients with Hp. In terms of eradication rate, the 2-week vonoprazan-based triple regimen (V-Tri-2w) was the best, which was superior to the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 0.9, 95% CI: (0.85-0.95)] and the 1-week tegoprazan-based triple regimen [T-Tri-1w, RR = 0.79, 95% CI: (0.64-0.97)]; the 2-week tegoprazan-based quadruple regimen (T-Qua-2w) was superior to the 1-week PPI-based triple regimen [P-Tri-1w, RR = 0.82, 95% CI: (0.67-0.99)], and there was no difference between the remaining tegoprazan-based regimens and the PPI-based or vonoprazan-based regimens. In terms of the incidence of adverse reactions, the 2-week vonoprazan-based binary regimen (V-Bi-2w) was lower than that of the 2-week PPI-based quadruple regimen [P-Qua-2w, RR = 1.98, 95% CI: (1.57-2.52)]; there was no significant difference between 1 and 2 weeks for each regimen, such as the vonoprazan-based triple regimen [RR = 1.11, 95% CI: (0.82-1.52)]. Conclusion: In the eradication treatment of Hp, the efficacy and safety of vonoprazan-based regimens are generally better than those of PPI-based regimens. Among them, the V-Tri-2w regimen has the highest eradication rate and may be the preferred choice for Hp eradication.

Non-invasive imaging for predicting labial salivary gland biopsy outcomes in patients with suspected primary Sjögren syndrome.

To identify the value of salivary gland ultrasound (SGUS) combined with magnetic resonance imaging (MRI) and magnetic resonance sialography (MRS) in predicting the results of labial salivary gland biopsy (LSGB) in patients with suspected primary Sjögren syndrome (pSS), and construct a nomogram model to predict LSGB results. A total of 181 patients who were admitted with suspected pSS from December 2018 to April 2023 were examined and divided into a training set (n = 120) and a validation set (n = 61). Baseline data of the two groups were examined, and the value of SGUS, MRI, and MRS in predicting LSGB was analyzed. Multivariate logistic analysis was used to screen for risk factors, and nomogram prediction models were constructed using these results. In the training set, the SGUS, MRI, and MRS scores of patients in the LSGB + group were higher than those in the LSGB - group (all P < 0.001). The positive prediction value (PPV) was 91% for an SGUS score of 3, and 82% for MRI and MRS scores of 2 or more. We developed a nomogram prediction model based on SGUS, MRI, and MRS data, and it had a concordance index (C-index) of 0.94. The Hosmer-Lemeshow test (χ2 = 3.17, P = 0.92) also indicated the nomogram prediction model had good accuracy and calibration for prediction of LSGB results. A nomogram model based on SGUS, MRI, and MRS results can help rheumatologists decide whether LSGB should be performed in patients with suspected pSS.

Fibroblast-like synoviocytes-derived exosomal circFTO deteriorates rheumatoid arthritis by enhancing N6-methyladenosine modification of SOX9 in chondrocytes.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes disability worldwide. Exosomes released by fibroblast-like synoviocytes in RA (RA-FLSs-Exos) play a role in the development of RA, and circular RNAs (circRNAs) are important for RA progression. This study aimed to investigate the molecular mechanisms underlying the effects of RA-FLSs-Exos in RA and identify the potential pathway responsible for these effects. METHODS: We initially conducted microarray analysis to identify dysregulated circRNAs in exosomes associated with RA. We then co-cultured isolated RA-FLSs-Exos with chondrocytes to examine their role in RA. In vivo experiments were performed using collagen-induced arthritis mouse models, and circFTO knockdown was achieved through intra-articular injection of AAV5 vectors. RESULTS: Our findings revealed increased expression of circFTO in both RA-FLSs-Exos and synovial tissues from patients with RA. Exosomal circFTO hindered chondrocyte proliferation, migration, and anabolism while promoting apoptosis and catabolism. Mechanistically, we discovered that circFTO facilitates the formation of methyltransferases complex to suppress SRY-related high-mobility group box 9 (SOX9) expression with assistance from YTH domain family 2 (YTHDF2) through an m6A-dependent mechanism. Furthermore, inhibition of circFTO improved symptoms of RA in vivo. CONCLUSION: Taken together, our study demonstrates that exosomal circFTO derived from FLSs contributes to the progression of RA by targeting SOX9. These findings highlight a promising target for treating RA.

Whole-genome sequencing and comparative genomic analyses of the medicinal fungus Sanguinoderma infundibulare in Ganodermataceae.

Sanguinoderma infundibulare is a newly discovered species of Ganodermataceae known to have high medicinal and ecological values. In this study, the whole-genome sequencing and comparative genomic analyses were conducted to further understand Ganodermataceae's genomic structural and functional characteristics. Using the Illumina NovaSeq and PacBio Sequel platforms, 88 scaffolds were assembled to obtain a 48.99-Mb high-quality genome of S. infundibulare. A total of 14,146 protein-coding genes were annotated in the whole genome, with 98.6% of complete benchmarking universal single-copy orthologs (BUSCO) scores. Comparative genomic analyses were conducted among S. infundibulare, Sanguinoderma rugosum, Ganoderma lucidum, and Ganoderma sinense to determine their intergeneric differences. The 4 species were found to share 4,011 orthogroups, and 24 specific gene families were detected in the genus Sanguinoderma. The gene families associated with carbohydrate esterase in S. infundibulare were significantly abundant, which was reported to be involved in hemicellulose degradation. One specific gene family in Sanguinoderma was annotated with siroheme synthase, which may be related to the typical characteristics of fresh pore surface changing to blood red when bruised. This study enriched the available genome data for the genus Sanguinoderma, elucidated the differences between Ganoderma and Sanguinoderma, and provided insights into the characteristics of the genome structure and function of S. infundibulare.

Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis.

OBJECTIVE: To evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical decision-making. METHODS: Randomized controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation results. RESULTS: A total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (-0.86, 17.75), 5 (-5.01, 11.09), and 6 (-1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, respectively. CONCLUSION: Based on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

Two-Second-Annealed 2D/3D Perovskite Films with Graded Energy Funnels and Toughened Heterointerfaces for Efficient and Durable Solar Cells.

The 2D/3D perovskite heterostructures have been widely investigated to enhance the efficiency and stability of perovskite solar cells (PSCs). However, rational manipulation of phase distribution and energy level alignment in such 2D/3D perovskite hybrids are still of great challenge. Herein, we successfully achieved spontaneous phase alignment of 2D/3D perovskite heterostructures by concurrently introducing both 2D perovskite component and organic halide additive. The graded phase distribution of 2D perovskites with different n values and 3D perovskites induced favorable energy band alignment across the perovskite film and boosted the charge transfer at the relevant heterointerfaces. Moreover, the 2D perovskite component also acted as a "band-aid" to simultaneously passivate the defects and release the residual tensile stress of perovskite films. Encouragingly, the blade-coated PSCs based on only ≈2 s in-situ fast annealed 2D/3D perovskite films with favorable energy funnels and toughened heterointerfaces achieved promising efficiencies of 22.5 %, accompanied by extended lifespan. To our knowledge, this is the highest reported efficiency for the PSCs fabricated with energy-saved thermal treatment just within a few seconds, which also outperformed those state-of-the-art annealing-free analogues. Such a two-second-in-situ-annealing technique could save the energy cost by up to 99.6 % during device fabrication, which will grant its low-coast implementation.

Durable organic nonlinear optical membranes for thermotolerant lightings and in vivo bioimaging.

Organic nonlinear optical materials have potential in applications such as lightings and bioimaging, but tend to have low photoluminescent quantum yields and are prone to lose the nonlinear optical activity. Herein, we demonstrate to weave large-area, flexible organic nonlinear optical membranes composed of 4-N,N-dimethylamino-4'-N'-methyl-stilbazolium tosylate@cyclodextrin host-guest supramolecular complex. These membranes exhibited a record high photoluminescence quantum yield of 73.5%, and could continuously emit orange luminescence even being heated at 300 °C, thus enabling the fabrication of thermotolerant light-emitting diodes. The nonlinear optical property of these membranes can be well-preserved even in polar environment. The supramolecular assemblies with multiphoton absorption characteristics were used for in vivo real-time imaging of Escherichia coli at 1000 nm excitation. These findings demonstrate to achieve scalable fabrication of organic nonlinear optical materials with high photoluminescence quantum yields, and good stability against thermal stress and polar environment for high-performance, durable optoelectronic devices and humanized multiphoton bio-probes.

The causal effects of age at menarche, age at first live birth, and estradiol levels on systemic lupus erythematosus: A two-sample Mendelian randomization analysis.

OBJECTIVES: To determine whether age at menarche (AAM), age at first live birth (AFB), and estradiol levels are causally correlated with the development of systemic lupus erythematosus (SLE). METHODS: A two-sample Mendelian randomization (MR) analysis was performed after data was collected from a dataset of genome-wide association studies (GWASs) related to SLE (as outcome), and from open access databases to find statistics related to AAM, AFB, and estradiol levels (as exposure). RESULT: In our study, a negative causal correlation between AAM and SLE was confirmed by MR analysis (MR egger: beta = 0.116, SE = 0.948, p = 0.909; weighted median: beta = -0.416, SE = 0.192, p = 0.030; and IVW: beta = -0.395, SE = 0.165, p = 0.016). However, there were no genetic causal effects of AFB and the estradiol levels on SLE, based on the results of MR analysis as follows: AFB (MR egger: beta = - 2.815, SE = 1.469, p = 0.065; Weighted median: beta = 0.334, SE = 0.378, p = 0.377; and IVW: beta = 0.188, SE = 0.282, p = 0.505) and the estradiol levels (MR egger: beta = 0.139, SE = 0.294, p = 0.651; weighted median: beta = 0.063, SE = 0.108, p = 0.559; IVW: beta = 0.126, SE = 0.097, p = 0.192). CONCLUSIONS: Our findings revealed that AAM may be associated with increased risk of the development of SLE, while there were no such causal effects from AFB and estradiol levels.

Piecewise-potential-field-based path planning method for fixed-wing UAV formation.

The multi-UAV path planning method based on artificial potential field (APF) has the advantage of rapid processing speed and the ability to deal with dynamic obstacles, though some problems remain-such as a lack of consideration of the initial heading constraint of the UAVs, making it easy to fall into a local minimum trap, and the path not being sufficiently smooth. Consequently, a fixed-wing UAV formation path planning method based on piecewise potential field (PPF) is proposed, where the problem of UAV formation flight path planning in different states can be solved by suitable design of the PPF function. Firstly, the potential field vector can be used to represent the potential field functions of obstacles and target points to meet the kinematic constraints of the UAV. Secondly, the local minimum region can be detected, the additional potential field vector being set to break away from this region. Finally, the change rules of the potential field vector of a UAV in the formation reconstruction scene can be designed, a smooth formation flight track being assured by adjusting the corresponding speed of each UAV track point. Considering the path planning of a five-UAV formation as an example, we conducted simulation experiments. The results showed that-compared with the existing methods based on APF-the results obtained using the PPF-based method considered the initial heading limits of the UAVs, the planned path being considerably smoother. Moreover, the proposed method could plan multiple UAV tracks, satisfying the known constraints without conflict in complex scenarios.

Near-Stoichiometric and Homogenized Perovskite Films for Solar Cells with Minimized Performance Variation.

Mixed-cation, small band-gap perovskites via rationally alloying formamidinium (FA) and methylammonium (MA) together have been widely employed for blade-coated perovskite solar cells with satisfied efficiencies. One of the stringent challenges lies in difficult control of the nucleation and crystallization kinetics of the perovskites with mixed ingredients. Herein, a pre-seeding strategy by mixing FAPbI3 solution with pre-synthesized MAPbI3 microcrystals has been developed to smartly decouple the nucleation and crystallization process. As a result, the time window of initialized crystallization has been greatly extended by 3 folds (i.e. from 5 s to 20 s), which enables the formation of uniform and homogeneous alloyed-FAMA perovskite films with designated stoichiometric ratios. The resultant blade-coated solar cells achieved a champion efficiency of 24.31 % accompanied by outstanding reproducibility with more than 87 % of the devices showing efficiencies higher than 23 %.

Large-area waterproof and durable perovskite luminescent textiles.

Lead halide perovskites show great potential to be used in wearable optoelectronics. However, obstacles for real applications lie in their instability under light, moisture and temperature stress, noxious lead ions leakage and difficulties in fabricating uniform luminescent textiles at large scale and high production rates. Overcoming these obstacles, we report simple, high-throughput electrospinning of large-area (> 375 cm2) flexible perovskite luminescent textiles woven by ultra-stable polymer@perovskite@cyclodextrin@silane composite fibers. These textiles exhibit bright and narrow-band photoluminescence (a photoluminescence quantum yield of 49.7%, full-width at half-maximum <17 nm) and the time to reach 50% photoluminescence of 14,193 h under ambient conditions, showcasing good stability against water immersion (> 3300 h), ultraviolet irradiation, high temperatures (up to 250 °C) and pressure surge (up to 30 MPa). The waterproof PLTs withstood fierce water scouring without any detectable leaching of lead ions. These low-cost and scalable woven PLTs enable breakthrough application in marine rescue.

Value of magnetic resonance imaging and sialography of the parotid gland for diagnosis of primary Sjögren syndrome.

AIM: To evaluate the utility of magnetic resonance imaging (MRI) and magnetic resonance sialography (MRS) for diagnosis of primary Sjögren syndrome (pSS) singly or integrated with 2016 American College of Rheumatology (ACR)/European League Against Rheumatic Diseases (EULAR) classification criteria. METHODS: The diagnostic efficiencies of MRI, MRS, and labial salivary gland biopsy (LSGB) were evaluated. The prediction model was established by multivariate analysis. Finally, performance of the ACR/EULAR criteria was evaluated after addition of MRI + MRS or replacement of original items by MRI + MRS. RESULTS: The combined use of LSGB + MRI + MRS provided the greatest diagnostic value. MRI and MRS grade had positive correlations with disease duration and pathological grade of the labial gland (both P < 0.001). MRI and MRS grade had positive correlations with xerostomia severity and negative correlations with unstimulated salivary flow rate (both P < 0.001). The consistency of MRI grade and MRS grade in the diagnosis of parotid gland lesions was poor (κ = 0.253, P < 0.001). The diagnostic efficiency of our prediction model (AUC 0.906) was similar to that of criteria from the ACR/EULAR (AUC 0.930). Adding MRI + MRS to the ACR/EULAR criteria improved the sensitivity (92.3% vs 90.8%), whereas the specificity remained the same (88.9% vs 89.1%). Replacing LSGB by MRI + MRS in the ACR/EULAR criteria decreased both sensitivity and specificity (88.1% vs 90.8% and 86.4% vs 89.1%, respectively). CONCLUSION: The combined application of MRI and MRS has ideal clinical application value in the diagnosis of early-stage pSS. Validity of the ACR/EULAR criteria remains high after incorporation of MRI + MRS.

Phylogenomics and Comparative Genomics Highlight Specific Genetic Features in Ganoderma Species.

The Ganoderma species in Polyporales are ecologically and economically relevant wood decayers used in traditional medicine, but their genomic traits are still poorly documented. In the present study, we carried out a phylogenomic and comparative genomic analyses to better understand the genetic blueprint of this fungal lineage. We investigated seven Ganoderma genomes, including three new genomes, G. australe, G. leucocontextum, and G. lingzhi. The size of the newly sequenced genomes ranged from 60.34 to 84.27 Mb and they encoded 15,007 to 20,460 genes. A total of 58 species, including 40 white-rot fungi, 11 brown-rot fungi, four ectomycorrhizal fungi, one endophyte fungus, and two pathogens in Basidiomycota, were used for phylogenomic analyses based on 143 single-copy genes. It confirmed that Ganoderma species belong to the core polyporoid clade. Comparing to the other selected species, the genomes of the Ganoderma species encoded a larger set of genes involved in terpene metabolism and coding for secreted proteins (CAZymes, lipases, proteases and SSPs). Of note, G. australe has the largest genome size with no obvious genome wide duplication, but showed transposable elements (TEs) expansion and the largest set of terpene gene clusters, suggesting a high ability to produce terpenoids for medicinal treatment. G. australe also encoded the largest set of proteins containing domains for cytochrome P450s, heterokaryon incompatibility and major facilitator families. Besides, the size of G. australe secretome is the largest, including CAZymes (AA9, GH18, A01A), proteases G01, and lipases GGGX, which may enhance the catabolism of cell wall carbohydrates, proteins, and fats during hosts colonization. The current genomic resource will be used to develop further biotechnology and medicinal applications, together with ecological studies of the Ganoderma species.

Taxonomy and phylogeny of Sanguinoderma rugosum complex with descriptions of a new species and a new combination.

Sanguinoderma is distributed in tropical and subtropical areas as a member of Amauroderma s. lat., and the economic values of Sanguinoderma led to high attention in the taxonomic studies. Previously, 16 species have been developed into Sanguinoderma. In this study, the taxonomic system of Sanguinoderma was reconducted based on morphological and multi-gene phylogenetic analyses, especially making a distinction for Sanguinoderma rugosum complex. Morphological analysis was based on the notes of macro- and micro morphological observations. Multi-gene phylogenetic analyses were used maximum likelihood (ML) and Bayesian inference (BI) analyses inferred from combined dataset of ITS, nLSU, rpb2, tef1, mtSSU, and nSSU. Combined with morphological characters and phylogenetic evidence, the results demonstrated that S. rugosum complex consists of five taxa, in which Sanguinoderma leucomarginatum was described as a new species, and it is characterized by the orbicular pilei with white to buff margin when fresh and clavate apical cells of pileipellis with septa. In addition, Amauroderma preussii was transferred to Sanguinoderma as a new combination due to its blood-red color-changed pore surface; it is characterized by the funnel-shaped, greyish brown, and glabrous pilei with strongly incurved margin. Detailed descriptions and photographs of the two species were provided. With the extension of this study, 18 species were accepted in Sanguinoderma, and 12 species among them were distributed in China. A key to accepted species of Sanguinoderma was also provided.

MicroRNA-21 from bone marrow mesenchymal stem cell-derived extracellular vesicles targets TET1 to suppress KLF4 and alleviate rheumatoid arthritis.

BACKGROUND: Accumulating evidence has demonstrated that bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) can be used effectively to transfer drugs and biomolecules to target lesions. Meanwhile, BMSCs have been reported to be beneficial in the treatment of rheumatoid arthritis (RA). In this study, we employ gain- and loss-of-function experiments to determine how BMSCs-derived EVs alleviate RA in vitro and in vivo. METHODS: We isolated EVs from BMSCs and characterized them by transmission electron microscopy and western blot analysis. The regulatory relationship between miR-21 and TET1 was predicted by bioinformatics analysis and validated by dual luciferase assay. Next, we utilized bisulfite sequencing PCR to decipher how TET1 promoted KLF4 transcription. Then, we established an RA mouse model and determined the role of miR-21 in RA progression. Functional assays were used to validate the role the miR-21-TET1-KLF4 regulatory axis in controlling mouse fibroblast-like synoviocytes (mFLS) cell proliferation and inflammatory cytokines secretion in vitro. RESULTS: RT-qPCR results revealed that miR-21 was highly expressed in BMSCs-derived EVs, and confirmed that BMSCs-derived EVs transferred miR-21 into mFLS cells. Bioinformatic analysis predicted that TET1 was the directly downstream target of miR-21, which was further validated by dual luciferase assay. TET1 promoted KLF4 promoter methylation to increase its expression. Collectively, BMSCs-derived EVs relieved RA by delivering miR-21, while the exosomal miR-21 alleviated RA through targeting the TET1/KLF4 regulatory axis. CONCLUSION: miR-21 from BMSCs-derived EVs suppresses KLF4 to relive RA by targeting TET1.

Delivery of Long Non-coding RNA NEAT1 by Peripheral Blood Monouclear Cells-Derived Exosomes Promotes the Occurrence of Rheumatoid Arthritis via the MicroRNA-23a/MDM2/SIRT6 Axis.

Emerging evidence has pointed out the importance of long non-coding RNAs (lncRNAs) in multiple diseases, the knowledge of rheumatoid arthritis (RA)-associated lncRNAs remains limited. In this present study, we aimed to elucidate the mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) from peripheral blood monouclear cell (PBMC)-derived exosomes (exos) on RA development by modulating the microRNA-23a (miR-23a)/murine double minute-2 (MDM2)/Sirtuin 6 (SIRT6) axis. RA was modeled in vivo by collagen induction in mice and in vitro by exposing fibroblast-like synoviocytes (FLSs) to lipopolysaccharide. Exos were isolated from human or mouse PBMCs, which were then were co-cultured with FLSs. Based on gain- and loss-of-function experiments, the cell proliferation and secretion of inflammatory factors were measured. LncRNA NEAT1 was found to be highly expressed in RA, and PBMCs-derived exos contributed to RA development by delivering lncRNA NEAT1. In lipopolysaccharide-induced FLSs, miR-23a inhibited the expression of MDM2, and overexpression of MDM2 partially rescued the inhibitory effect of miR-23a on FLS proliferation and inflammatory response. Mechanistically, MDM2 ubiquitination degraded SIRT6 in RA. LncRNA NEAT1 shuttled by PBMC-derived exos promoted FLS proliferation and inflammation through regulating the MDM2/SIRT6 axis. Furthermore, in vivo experiments suggested that downregulated lncRNA NEAT1 shuttled by PBMC-derived exos or upregulated miR-23a impeded RA deterioration in mice. This study highlights that lncRNA NEAT1 shuttled by PBMC-derived exos contributes to RA development with the involvement of the miR-23a/MDM2/SIRT6 axis.