Therapeutic potential and pharmacological significance of extracellular vesicles derived from traditional medicinal plants

Medicinal plants are the primary sources for the discovery of novel medicines and the basis of ethnopharmacological research. While existing studies mainly focus on the chemical compounds, there is little research about the functions of other contents in medicinal plants. Extracellular vesicles (EVs) are functionally active, nanoscale, membrane-bound vesicles secreted by almost all eukaryotic cells. Intriguingly, plant-derived extracellular vesicles (PDEVs) also have been implicated to play an important role in therapeutic application. PDEVs were reported to have physical and chemical properties similar to mammalian EVs, which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. Besides these properties, PDEVs also exhibit unique advantages, especially intrinsic bioactivity, high stability, and easy absorption. PDEVs were found to be transferred into recipient cells and significantly affect their biological process involved in many diseases, such as inflammation and tumors. PDEVs also could offer unique morphological and compositional characteristics as natural nanocarriers by innately shuttling bioactive lipids, RNA, proteins, and other pharmacologically active substances. In addition, PDEVs could effectively encapsulate hydrophobic and hydrophilic chemicals, remain stable, and cross stringent biological barriers. Thus, this study focuses on the pharmacological action and mechanisms of PDEVs in therapeutic applications. We also systemically deal with facets of PDEVs, ranging from their isolation to composition, biological functions, and biotherapeutic roles. Efforts are also made to elucidate recent advances in re-engineering PDEVs applied as stable, effective, and non-immunogenic therapeutic applications to meet the ever-stringent demands. Considering its unique advantages, these studies not only provide relevant scientific evidence on therapeutic applications but could also replenish and inherit precious cultural heritage

Comparative adaptability of 307 Saccharomyces cerevisiae strains from winemaking and Mantou fermentation

Domesticated Saccharomyces cerevisiae is one of the most significant microbial populations in human civilization due to its remarkable diversity and high adaptability to human environments. However, the adaptability mechanisms underlying this population ecological behavior remain unclear. This study explored the adaptive behaviors of S. cerevisiae strains from the Wine and Mantou genetic lineages under both artificial stress conditions and natural or near-natural environments. A total of 307 diploid S. cerevisiae strains were analyzed, including 169 strains derived from grape sources and 138 from sourdough sources. Various stress factors, including sodium chloride, tannins, ethanol, pH, temperature, and sulfur dioxide (SO2), as well as different substrates (natural grape juice, simulated grape juice, and simulated dough), were applied to evaluate adaptability. The results demonstrated that Wine population exhibited superior performance in grape juice environments, characterized by higher CO2 production. The biomass of both the Wine and Mantou populations in the simulated dough was significantly higher than that in the simulated grape juice. In the simulated grape juice environment, the adaptability of the Wine population was significantly superior to that of the Mantou population. In contrast, in the simulated dough environment, the Mantou population exhibited better adaptability than the Wine population. Furthermore, Wine population displayed higher tolerance to ethanol, extreme temperatures, tannins, and sodium chloride in YPD medium compared to Mantou population. Diploid strains also exhibited greater stress tolerance than haploid strains. These findings offer valuable insights into the distinct adaptive mechanisms of domesticated S. cerevisiae lineages

The anti-cholestatic effects of Coptis chinensis Franch. alone and combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley: dual effects on fecal metabolism and microbial diversity

Introduction: Drug dosages and combinations are the main factors that affect the efficacy of pleiotropic traditional Chinese medicine (TCM). Coptis chinensis Franch. (CF) is a representative TCM with multiple effects and is often combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley (TR) to treat cholestasis. The present study assessed the influence of CF dose and its combination with TR on the efficacy of CF in cholestasis treatment, including their effects on fecal metabolism and fecal microorganisms.Methods: Rats with α-naphthylisothiocyanate (ANIT, 50 mg/kg)-induced cholestasis were administered low (0.3 g/kg) and high (0.6 g/kg) doses of CF, as well as CF combined with TR at doses of 0.6 g/kg and 0.9 g/kg, respectively. The anti-cholestatic effects of these treatments were assessed by determining their anti-inflammatory, hypolipidemic, and anti-oxidative stress properties. Additionally, fecal metabolomics and fecal microorganisms were analyzed.Results: Low dose CF had a more potent hypolipidemic effect than high dose CF, whereas high dose CF had more potent anti-inflammatory and anti-oxidative stress effects. Combination with TR enhanced the hypolipidemic effect, but antagonized the anti-inflammatory effect, of CF. Analyses of fecal metabolomics and fecal microorganisms showed differences in the regulation of lipid- and amino acid metabolism-related pathways, including pathways of linoleic acid, tyrosine, and arachidonic acid metabolism, and amino acid biosynthesis between different doses of CF as well as between different doses of CF in combination with TR. These differences may contribute to differences in the anti-cholestatic effects of these preparations.Conclusion: CF dose influences its anti-cholestatic efficacy. The combination with TR had synergistic or antagonistic effects on the properties of CF, perhaps by altering fecal metabolism and fecal microbial homeostasis

Direct conversion of methane to formaldehyde and CO on B2O3 catalysts

甲烷作为天然气的主要成分，是非常重要的碳基资源。不过，甲烷分子的化学惰性使得其转化通常需要在高温条件下进行，反应选择性难于控制。如何实现甲烷的高选择性定向转化一直是化学研究中的重要挑战，甚至被誉为化学领域的“圣杯”。化学化工学院王帅教授与华盛顿州立大学王勇教授合作在甲烷选择氧化反应非金属硼基催化剂的研究中取得重要进展，本研究中发现负载型氧化硼催化剂在甲烷直接氧化反应中表现出优异的抗深度氧化能力。本研究工作是在王帅教授和王勇教授的共同指导下完成。2015级博士生田金树（已毕业）、硕士生谈江乔（已毕业）以及醇醚酯清洁生产国家工程实验室张朝霞工程师为共同第一作者，林敬东副教授和万绍隆副教授等参与了部分研究和讨论。【Abstract】Direct oxidation of methane to value-added C1 chemicals (e.g. HCHO and CO) provides a promising way to utilize natural gas sources under relatively mild conditions. Such conversions remain, however, a key selectivity challenge, resulting from the facile formation of undesired fully-oxidized CO2. Here we show that B2O3-based catalysts are selective in the direct conversion of methane to HCHO and CO (~94% selectivity with a HCHO/CO ratio of ~1 at 6% conversion) and highly stable (over 100 hour time-on-stream operation) conducted in a fixed-bed reactor (550 °C, 100 kPa, space velocity 4650 mL gcat−1 h−1 ). Combined catalyst characterization, kinetic studies, and isotopic labeling experiments unveil that molecular O2 bonded to tri-coordinated BO3 centers on B2O3 surfaces acts as a judicious oxidant for methane activation with mitigated CO2 formation, even at high O2/CH4 ratios of the feed. These findings shed light on the great potential of designing innovative catalytic processes for the direct conversion of alkanes to fuels/chemicals.This work was supported by the National Natural Science Foundation of China (No. 21922201, 21872113, 91945301, 21673189, and 91545114) and the Fundamental Research Funds for the Central Universities (No. 20720190036 and 20720160032).研究工作得到了国家自然科学基金（21922201、21872113、91945301、21673189、91545114）和中央高校基本科研业务费专项资金（20720190036、20720160032）的资助与支持

Critical Role of Al Pair Sites in Methane Oxidation to Methanol on Cu-Exchanged Mordenite Zeolites

Cu-exchanged aluminosilicate zeolites have been intensively studied for the selective oxidation of methane to methanol via a chemical looping manner, while the nature of active Cu-oxo species for these catalysts is still under debate. This study inquired into the effects of Al distribution on methane oxidation over Cu-exchanged aluminosilicate zeolites, which provided an effective way to discern the activity difference between mononuclear and polynuclear Cu-oxo species. Specifically, conventional Na+/Co2+ ion-exchange methods were applied to quantify isolated Al and Al pair (i.e., Al−OH−(Si−O)1–3−Al−OH) sites for three mordenite (MOR) zeolites, and a correlation was established between the reactivity of the resultant Cu-MOR catalysts and the portions of the accessible framework Al sites. These results indicated that the Cu-oxo clusters derived from the Al pair sites were more reactive than the CuOH species grafted at the isolated Al sites, which is consistent with in situ ultraviolet-visible spectroscopic characterization and density functional theory calculations. Further theoretical analysis of the first C–H bond cleavage in methane on these Cu-oxo species unveiled that stabilization of the formed methyl group was the predominant factor in determining the reactivity of methane oxidation

Microbiological and Physicochemical Dynamics in Traditional and Industrial Fermentation Processes of Koumiss

Koumiss, a traditional fermented beverage made from mare’s milk, is typically consumed by nomads. Industrialized production of koumiss has been increasingly applied recently due to the increased demand for the beverage and awareness of its potential health benefits. However, it is unknown whether industrial koumiss is comparable to the traditional koumiss in terms of quality. In this study, we compared the microbiological and physicochemical properties in the industrial and traditional koumiss fermentation processes synchronously using culture-dependent and culture-independent approaches. Although Lactobacillus and Kazachstania species were similarly dominant in the bacterial and fungal communities, respectively, in both processes, the microbial counts and diversity in the traditional koumiss were significantly higher than those in the industrial koumiss. Furthermore, the traditional koumiss fermentation consumed more lactose, produced more flavor substances including acetic acid, lactic acid, ethanol, and free amino acids, and reached a lower pH value at the final stage. The physicochemical characters of traditional koumiss were mainly associated with Lactobacillus and Kazachstania species, which, in turn, were positively correlated with each other but negatively correlated with other non-dominant microbes. The starter was the major source of the microbial community of industrial koumiss, whereas both the starter and environment were the major sources of traditional koumiss. Random forest analysis recognized 11 significantly important genera as microbial indicators to distinguish industrial from traditional koumiss. Overall, this study shows that the microbial and physicochemical dynamics during the traditional and industrial fermentation of koumiss differ significantly, and the results obtained are valuable for improving the quality of industrial koumiss

Nanoparticle-Based Drug Delivery Systems Targeting Tumor Microenvironment for Cancer Immunotherapy Resistance: Current Advances and Applications

Cancer immunotherapy has shown impressive anti-tumor activity in patients with advanced and early-stage malignant tumors, thus improving long-term survival. However, current cancer immunotherapy is limited by barriers such as low tumor specificity, poor response rate, and systemic toxicities, which result in the development of primary, adaptive, or acquired resistance. Immunotherapy resistance has complex mechanisms that depend on the interaction between tumor cells and the tumor microenvironment (TME). Therefore, targeting TME has recently received attention as a feasibility strategy for re-sensitizing resistant neoplastic niches to existing cancer immunotherapy. With the development of nanotechnology, nanoplatforms possess outstanding features, including high loading capacity, tunable porosity, and specific targeting to the desired locus. Therefore, nanoplatforms can significantly improve the effectiveness of immunotherapy while reducing its toxic and side effects on non-target cells that receive intense attention in cancer immunotherapy. This review explores the mechanisms of tumor microenvironment reprogramming in immunotherapy resistance, including TAMs, CAFs, vasculature, and hypoxia. We also examined whether the application of nano-drugs combined with current regimens is improving immunotherapy clinical outcomes in solid tumors