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Abstract Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs. Graphical Abstract

Amyloid β (Aβ) is pivotal in the progression of Alzheimer’s disease (AD) by inducing neuron damage. Recent evidences implied that the formation of mitochondrial permeability transition pore (mPTP) was involved in Aβ-mediated mitochondrial dysfunction. Cyclophilin D (CypD), which is the essential component of mPTP, could interact with Aβ and promote mPTP formation, resulting in severe mitochondrial dysfunction and eventually cell death. In this study, we demonstrated that a glycopeptide, FMP-6-S4, purified from the fruit of Fructus Mori bond to CypD and suppressed its expression. Furthermore, FMP-6-S4 markedly inhibited the opening of mPTP, the generation of reactive oxygen species and calcium releasing. Mechanistically study showed that FMP-6-S4 could bind to CypD to disrupt the interaction between CypD and Aβ42. Finally, FMP-6-S4 could bind to Aβ42 directly then attenuate cell damage induced by Aβ42 via p53-puma signaling pathway. Together, our results suggest FMP-6-S4 might be a potential candidate for anti-AD drug development.

Abstract Value‐added conversion of lignocellulose is a sustainable approach. Photo‐refining biomass is in line with current environmental protection strategies. However, photo‐reforming biomass suffers from poor catalyst stability and low conversion efficiency. Here, we designed fructose as a lignocellulosic model. The heterogeneous structure of Prussian blue coating was constructed with a special covalent bond structure of CoCNZn. This structure has a catalytic conversion mechanism that can accelerate electron transfer. Fructose was simultaneously converted to value‐added platform compounds (5‐HMF and formic acid) and gaseous fuels (CO, CH4) with a conversion rate of up to 92.5%, which is more than 1.7 times than that of catalysts without adding Prussian blue. Hydrogen transfer and carbon transfer on the carbon atoms of fructose facilitates the production and accelerates the spillover of CO from formic acid. This work provides new ideas for the development of Prussian blue catalysts and the conversion of pentose.

Abstract Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end‐stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the “gut‐kidney axis,” therefore, although clinical intervention to modulate the “gut‐kidney axis” imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non‐absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD‐triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain‐containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor‐β (TGF‐β) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4‐regulated TGF‐β pathway.

Objectives: This study aimed to explore the relationship between red blood cell distribution width (RDW) and all-cause mortality in critically ill patients undergoing intra-aortic balloon pumping (IABP) in the intensive care unit (ICU). Methods: This study retrospectively analyzed data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary endpoint was the 30-day mortality rate, while the secondary endpoint was the in-hospital mortality rate. Restricted cubic splines were used to assess the dose–response relationship. The receiver operating characteristic (ROC) curve and Kaplan-Meier curve analysis were carried out to evaluate the predictive performance of RDW. Moreover, multiple logistic regression analyses and subgroup analyses were conducted to investigate the relationship between RDW and 30-day mortality. Finally, propensity score matching (PSM) was performed to adjust for the imbalance of covariates. Results: In total, 732 patients were finally identified from the MIMIC-IV database in this study. The RDW of patients in the non-survivor group was significantly higher compared with those in the survivor group (P

Background: The potential effect of removing danger-associated molecular patterns (DAMPs) from gut lymph on reducing acute lung injury (ALI) induced by gut ischemia-reperfusion injury (GIRI) is uncertain. This study aimed to investigate whether gut lymph purification (GLP) could improve GIRI-induced acute lung injury in rats by clearing danger-associated molecular patterns. Materials and methods: Rats were divided into four groups: Sham, GIRI, GIRI + gut lymph drainage (GLD), and GIRI + GLP. After successful modeling, lung tissue samples were collected from rats for hematoxylin-eosin (HE) staining and detection of apoptotic indexes. We detected the DAMPs levels in blood and lymph samples. We observed the microstructure of AEC Ⅱ and measured the expression levels of apoptosis indexes. Results: The GIRI group showed destruction of alveolar structure, thickened alveolar walls, and inflammatory cell infiltration. This was accompanied by significantly increased levels of high mobility group protein-1 (HMGB-1) and Interleukin-6 (IL-6), while reduced levels of heat shock protein 70 (HSP 70) and Interleukin-10 (IL-10) in both lymph and serum. In contrast, the lung tissue damage in the GIRI + GLP group was significantly improved compared to the GIRI group. This was evidenced by a reduction in the expression levels of HMGB-1 and IL-6 in both lymph and serum and an increase in HSP 70 and IL-10 levels. Additionally, organelle structure of AEC II was significantly improved in the GIRI + GLP group compared to the GIRI group. Conclusions: GLP inhibits inflammation and cell apoptosis in GIRI-induced ALI by blocking the link between DAMPs and mononuclear phagocytes, reducing the severity of ALI.

Daedaleopsis sinensis is a fungus that grows on wood and secretes a series of enzymes to degrade cellulose, hemicellulose, and lignin and cause wood rot decay. Wood-decaying fungi have ecological, economic, edible, and medicinal functions. Furthermore, the use of microorganisms to biodegrade lignocellulose has high application value. Genome sequencing has allowed microorganisms to be analyzed from the aspects of genome characteristics, genome function annotation, metabolic pathways, and comparative genomics. Subsequently, the relevant information regarding lignocellulosic degradation has been mined by bioinformatics. Here, we sequenced and analyzed the genome of D. sinensis for the first time. A 51.67-Mb genome sequence was assembled to 24 contigs, which led to the prediction of 12,153 protein-coding genes. Kyoto Encyclopedia of Genes and Genomes database analysis of the D. sinensis data revealed that 3,831 genes are involved in almost 120 metabolic pathways. According to the Carbohydrate-Active Enzyme database, 481 enzymes are found in D. sinensis, of which glycoside hydrolases are the most abundant. The genome sequence of D. sinensis provides insights into its lignocellulosic degradation and subsequent applications.

Salvia yunnanensis is a traditional Chinese medicine for promoting blood circulation and eliminating blood stasis. Previous researches reported that Tanshinone IIA from Salvia yunnanensis had anti-angiogenic effect, however, whether its carbohydrates with similar effect is unknown. Here, we showed that a stachyose (Sta) from Salvia yunnanensis was purified by DEAE SepharoseTM Fast Flow anion-exchange chromatography and Bio-Gel P-2 gel permeation chromatography. Structure analyses suggested that Sta was tetrasaccharide as α-Gal-(1 → 6)-α-Gal-(1 → 6)-α-Glc-(1 → 2)-β-Fru. Further sulfated Sta was made and the degree of sulfate substitution was measured as 0.98. Bioactivity studies showed that Sta might block human microvascular endothelial cells tube formation in vitro and in vivo without significant cytotoxicity. Mechanism study suggested that Sta might bind to Galectin-3 (KD: 5.777E−6) and inhibit its expression to block angiogenesis linked to VEGFR/FAK and PDGFR/AKT/ERK signaling. Evidence also supported that Sta might be a potential compound for developing stachyose as an anti-angiogenesis functional food.

Sanghuangporus, also known as “Sanghuang” in China, is a well-known genus of traditional Chinese medicinal macrofungi. To make more effective use of Sanghuangporus resources, we completed the first genome assembly and annotation of a monokaryon strain of S. weigelae in the present study. A 33.96-Mb genome sequence was assembled as 13 contigs, leading to prediction of 9377 protein-coding genes. Phylogenetic and average nucleotide identity analyses indicated that the S. weigelae genome is closely related to those of other Sanghuangporus species in evolutionary tree, which clustered in one clade. Collinearity analysis revealed a high level of collinearity of S. weigelae with S. baumii, S. vaninii, and S. sanghuang. Biosynthesis pathways potentially involved in medicinal properties, including terpenoid and polysaccharide synthesis, were identified in S. weigelae, while polysaccharides were identified as the main medicinal metabolites in S. weigelae, with flavonoids more important in Sanghuangporus than other medicinal mushroom groups. Genes encoding 332 carbohydrate-active enzymes were identified in the S. weigelae genome, including major glycoside hydrolases and glycosyltransferases predicted, revealing the robust lignocellulose degradation capacity of S. weigelae. Further, 130 genes, clustered in seven classes were annotated to encode cytochromes P450 in the S. weigelae genome. Overall, our results reveal the remarkably medicinal capacity of S. weigelae and provide new insights that will inform the study of evolution and medicinal application of S. weigelae. The data are a reference resource for the formulation of scientific and rational ecological protection policies for Sanghuangporus species.

Abstract In this study, calcium carbonate, sepiolite, and commonly used diatomite (DE) carriers were mixed to prepare calcium carbonate or sepiolite mixed DE/nano-titanium dioxide (TiO2). The analyses of X-ray diffraction and scanning electron microscope confirmed that the particle size of nano-TiO2 was about 20–24 nm in DE/nano-TiO2, and the particles were relatively uniform. When (calcium carbonate and sepiolite + DE)/nano-TiO2 was used, the Ti content in the composite remained unchanged, while the particle size of nano-TiO2 increased to a certain extent. Among them, the use of (calcium carbonate + DE)/nano-TiO2 increased the Ti content in the composite material significantly. Therefore, the findings demonstrated the feasibility of nano-TiO2 supported by the mixed carrier.

Understanding of sedimentary environment is the basis of oil exploration and development. Previous research on the characteristics and distinguishing of single sedimentary system by using logging curves and seismic data was mostly carried out on the determined sedimentary system. However, for the river-tide controlled cases, when the main bodies of fluvial and tidal actions are unclear, sedimentary systems are rarely studied. Based on the difference of the oscillation frequency of tide and river water bodies, combined with the correlation between the logging curves of gamma ray and the mud content as well as the influence on seismic facies by hydrodynamic strength and the difference of the size and scale of river-tide controlled delta, a geophysical method on the basis of natural gamma log difference (ΔGR) and seismic facies wave length/height ratio is proposed to distinguish river-tide controlled delta sedimentary systems. A case study was carried out with the sedimentary system of the Pinghu Formation in Pingbei area of the Xihu Sag, East China Sea Shelf Basin, and it was concluded that this method can effectively distinguish river-tide controlled delta system. At the side edge of the underwater low uplift, Baoyunting low uplift, relevant parameters have been effectively picked up to distinguish the river-tide controlled delta system, and to identify the tidal channel development zone and potential targets for channel filling. It is clear that the identification of river-tide controlled system has an indicative significance for the prediction of lithologic traps and favorable reservoir units.

Phylogenetic and morphological analyses on Rigidoporus were carried out. The genus Rigidoporus (Hymenochaetales, Basidiomycota), typified by R. microporus (Fr.) Overeem. (synonym Polyporus micromegas Mont.), was established by Murrill in 1905. The genus is mainly characterized by annual to perennial, resupinate, effused-reflexed to pileate or stipitate basidiomata with azonate or concentrically zonate and sulcate upper surface, a monomitic to pseudo-dimitic hyphal structure, simple-septate generative hyphae, and ellipsoid to globose basidiospores. Phylogeny on species of the genus is reconstructed with two loci DNA sequences including the internal transcribed spacer regions and the large subunit. Three new species in Rigidoporus are described and illustrated from Asia, and one new combination in the genus is proposed. The main morphological characteristics of the currently accepted species of Rigidoporus are provided.

Cortinarius is a globally distributed agaricoid genus that has been well studied in Europe and America with over 1,000 described species. However, as part of an ongoing effort to investigate the diversity of Cortinarius section Anomali in China, the resource investigation and classification research are still limited, and the species diversity has not been clarified by far. During the re-examination of the Chinese Cortinarius specimens, C. cinnamomeolilacinus, C. subclackamasensis, and C. tropicus, belonging to the sect. Anomali, were described in China as new to science based on morphological examination and phylogenetic analysis. The three new species are described and illustrated in detail according to the Chinese materials. The phylogenetic analysis based on internal transcribed spacer sequences confirmed the placement of the three species in the Cortinarius sect. Anomali clade. Phylogenetically related and morphologically similar species to these three new species are discussed.

Abstract Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEVs) have been demonstrated as a therapeutic agent to prevent and treat cisplatin-induced acute kidney injury (AKI). However, hucMSC-sEVs still face many problems and challenges in the repair and treatment of tissue injury, including short circulation time, insufficient targeting, and low therapeutic efficacy. Therefore, we constructed engineered hybrid vesicles fused with nanovesicles derived from human neutrophil membranes and hucMSC-sEVs, named neutrophil membrane engineered hucMSC-sEVs (NEX). NEX significantly enhanced the targeting of hucMSC-sEVs to injured kidney tissues, improved the impaired renal function via reducing pro-inflammatory cytokines expression, promoted the proliferation of renal tissue cells, and inhibited renal cell apoptosis in vivo. In addition, NEX enhanced hucMSC-sEVs uptake by NRK52E cells, but inhibited its uptake by RAW264.7 cells. Moreover, administration of NEX reduced cellular oxidative stress and promoted proliferation of NRK52E cells treated with cisplatin in vitro. In summary, our findings indicate that this design of a universal approach enhances the targeting and therapeutic efficacy of hucMSC-sEVs in kidney tissue regeneration, and provides new evidence promoting its clinical application.

Mollusk shells are characterized by hierarchical aggregation of calcium carbonate and organic matrix, and matrix protein is considered as a key active ingredient to understand shell biomineralization. In this study, a total of 21 proteins, including a novel matrix protein Hcprismatin-14 were identified in the EDTA-soluble matrix of the prismatic layer of the mussel Hyriopsis cumingii by liquid chromatography tandem mass spectrometry (LC-MS/MS). The full length of Hcprismatin-14 cDNA was cloned from the mantle of H. cumingii. Hcprismatin-14 contains a high proportion of Gly, Tyr, Arg and Asp residues, their concentrated distribution forms three structurally characteristic regions: a Gly/Tyr-rich region, a WDD-repeat region and a C-terminal basic tail. Hcprismatin-14 expression was high in mantle edge tissue in a tissue-specific analysis, and during disordered crystal deposition in a saibo transplantation assay. Knocking down Hcprismatin-14 expression with double-stranded RNA induced subgrains deposition inhibition and lost contact with chitinous scaffold. In addition, the WDD-repeat region polypeptide was involved in morphological regulation of calcite and had dose-dependent inhibitory activity against aragonite deposition in vitro. Based on these results, Hcprismatin-14 appears to be a dual-function prismatic-layer matrix protein, responsible for both framework recognition and crystal deposition. These findings contribute to understanding the relationship between the modular structure of matrix protein and their regulation mechanism during shell biomineralization in mollusks.

Summary: Muscle stem cells, called satellite cells (SCs), are employed to repair and rebuild muscle. SC-based therapeutic strategies are urgently needed. In this study, we showed that Lycium barbarum extract (LBE) improved the number of SCs and enhanced muscle regeneration by promoting SC activation and self-renewal in both adult and aging mice. L. barbarum polysaccharide (LBP), the main component of LBE, also played a similar role. More importantly, LBP1C-2, a homogeneous polysaccharide isolated from LBP, was uncovered to be an active component in regulating SC function. Mechanism study revealed that LBP1C-2 might bind to FGFR1 to activate SCs and promote SC self-renewal through Spry1 upregulation. This might be the first study to show that LBE participated in the regulation of SCs, and the active components and targets of LBE were identified. This study lays a theoretical foundation for the medicinal or auxiliary medicinal use of L. barbarum in skeletal muscle.

Shale gas production is obviously higher within the Silurian Longmaxi Formation than that of the Cambrian Niutitang Formation according to the drilling test results in the northwest Hunan area. To clarify the reasons behind this variation, core samples from the two sets of shales were studied for a comprehensive comparison and analysis of their organic matter (OM) pore structure. Methods were used, including the total organic carbon content test, the vitrinite reflectance test, X-ray diffraction, and focused ion-beam scanning electron microscopy (FIB-SEM). The results show that these two shales have similar reservoir characteristics, both with abundant organic matter and high content of brittle minerals. However, the Longmaxi shale with 2.3% to 3.0%Ro presents lower thermal maturity than the Niutitang shale with over 3.0%Ro. In the case of pore structure associated with OM, a huge difference exists between the two shales. The OM pore shape of the Longmaxi shale is very regular, being mostly round and oval, while the OM pore shape of the Niutitang shale is irregular, being flat with a thin middle and thick and elongated ends. An important factor affecting OM pore evolution is thermal maturity. In turn, the thermal maturity is controlled by the tectonic evolution process, especially the maximum paleo-burial depth. In conclusion, the paleo-burial depth of the Lower Cambrian Niutitang shale in northwest Hunan is too large, which leads to the excessive evolution of organic matter in the shale, and the physical and chemical properties are similar to graphite, which leads to the disappearance of OM pores. Shale gas has no effective reservoir space and is largely dispersed in geological history. At the same time, due to the insufficient hydrocarbon-generation evolution time of the Lower Silurian Longmaxi Formation shale in this area, the shale could not form enough gaseous hydrocarbons and a large amount of effective reservoir space (OM pores with regular shape and large pore size), and finally failed to become a gas reservoir. Therefore, the exploration and development potential of the marine shale gas of the Lower Cambrian Niutitang Formation and the Lower Silurian Longmaxi Formation in northwest Hunan is poor.

Crystallization selectivity is an important principle in polymorph control. Ribavirin Form I, Form II, DMSO solvate, and amorphous ribavirin are prepared, and the short-range order similarities between these solid forms and ribavirin aqueous solution and DMSO solution are compared via mid-frequency Raman difference spectra (MFRDS). The crystallization process from amorphous ribavirin to Form I and from solution to amorphous phase is explained. Reasons for the difficulty in preparing the DMSO solvate are proposed. The rationale provided for the crystallization selectivity provides a foundation for the synthesis of metastable phases with a robust and convenient method.

Abstract. This review attempts to unveil the possible mechanisms underlying how gut lymph affects lung and further gives rise to acute respiratory distress syndrome, as well as potential interventional targets under the condition of ischemia-reperfusion injury. We searched electronic databases including PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, and Embase to identify relevant literatures published up to December 2019. We enrolled the literatures including the Mesh Terms of “gut lymph or intestinal lymph and acute lung injury or acute respiratory distress syndrome.” Gut is considered to be the origin of systemic inflammation and the engine of multiple organ distress syndrome in the field of critical care medicine, whereas gut lymph plays a pivotal role in initiation of ischemia-reperfusion injury-induced acute respiratory distress syndrome. In fact, in the having been established pathologic model of sepsis leading to multiple organ dysfunction named by Gut Lymph theory, a variety of literatures showed the position and role of changes in gut lymph components in the initiation of systemic inflammatory response, which allows us to screen out potential intervention targets to pave the way for future clinic and basic research.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors in the digestive system. A greater understanding of the pathogenesis of PDAC may facilitate the search for new therapeutic targets. Guanine nucleotide‐binding protein subunit gamma‐12 (GNG12) belongs to the G protein family and participates in the modulation of the inflammatory signaling cascade. However, the cancer‐related function and clinical relevance of GNG12 in PDAC have not previously been reported. Here, we investigated the clinical significance of GNG12 in PDAC using the Oncomine web tool, the gene expression profiling interactive analysis tool and tissue microarray (TMA). GNG12 expression was observed to be higher in PDAC patient specimens than in nontumor pancreatic tissues, and high expression of GNG12 was associated with poor prognosis. We subsequently show that GNG12 promotes pancreatic cancer cell growth in vivo and in vitro, as evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium, inner salt assays, colony formation assays and a xenograft mouse model. Furthermore, our results suggest that GNG12 activates nuclear factor‐κB signaling and modulates the immune response. Collectively, our findings suggest that GNG12 may be suitable as a new prognosis‐related biomarker and a promising target for treatment of pancreatic cancer.

The exploration and development of the shale in the Lower Silurian Longmaxi Formation in the Chongqing area has shown that gas production here is commercially viable. In contrast, the Longmaxi Formation shale in Hunan shows that gas production is not commercial. Why is there such a difference between the Chongqing and Hunan areas for the same formation. A mount of previous studies showed that gas is stored primarily in the organic matter (OM) pores in shale. This study has investigated the Longmaxi shale from two well locations in Chongqing and Hunan in order to understand whether differences in pore structure are the cause of the difference in commerciality in the two areas. The formation burial histories were established, analyzing samples for mineral composition, total organic carbon (TOC) content, thermal maturity (Ro), and OM pore structures. The results show that the Longmaxi shale in Chongqing and Hunan has similar TOC content and Ro. The average TOC content is above 3.0% for samples from both areas, and the thermal maturity was all between 2.4 and 2.9%. OM pores of the Longmaxi shale in Chongqing are abundant in number and relatively large sized, with mostly circular and oval shapes. In contrast, the number and size of the OM pores in the Longmaxi shale in Hunan are small, and the shape is irregular. OM pore structure of the Longmaxi shale in Chongqing is therefore favorable for preservation of gas. The poor pore structure of the Longmaxi shale in Hunan is not conducive to gas preservation. The OM pore structure difference of the Longmaxi shale in Chongqing and Hunan is determined by the formation burial history. The Longmaxi shale in the Chongqing area experienced rapid burial in the Early Jurassic and rapid uplift in the Late Cretaceous. The Longmaxi Formation in Hunan experienced rapid burial in the Early Triassic and rapid uplift in the Early Jurassic. The long evolution time (100 Ma) of the Longmaxi shale in Chongqing produced a large amount of gas supply and enough storage space (OM pores) for the gas occurrence, which makes the amount of gas be preserved in geological history. The short evolution time (50 Ma) of the Longmaxi shale in Hunan produced insufficient gas supply and not enough OM pores in reservoir, which leads to gas loss in geological history, resulting in low gas content. Therefore, to evaluate the potential of shale gas, the evolution time of organic matter must be considered. In other words, the time interval between rapid subsidence and uplift of formation during geological history must be considered.

Mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) serving as delivery system have attracted extensive research interest, especially in cancer therapy. In our previous study, lipocalin-type prostaglandin D2 synthase (L-PGDS) showed inhibitory effects on gastric cancer growth. In this study, we aimed to explore whether MSC-EV-delivered L-PGDS (EVs-L-PGDS) could inhibit gastric cancer progression. EVs-L-PGDS were generated from MSCs transfected with adenovirus encoding L-PGDS. Cell colony-forming, migration, invasion, and flow cytometry assays were used to show the inhibitory effects of EVs on tumor cells in vitro, and the nude mouse subcutaneous tumor model was performed to show the inhibitory effect of EVs on tumor progression in vivo. In vitro, EVs-L-PGDS could be internalized and inhibit the colony-forming, migration, and invasion ability of gastric cancer cell SGC-7901 and promote cell apoptosis. In vivo, EVs-L-PGDS inhibited the tumor growth in nude mouse subcutaneous tumor-bearing model. Compared with the PBS and EVs containing empty vector (EVs-Vector) group, more apoptotic cells and higher L-PGDS expression were detected in tumor tissue of the EVs-L-PGDS treatment group. And these differences are significant. Mechanistically, EVs-L-PGDS reduced the expression of stem cell markers including Oct4, Nanog, and Sox2 and inhibited STAT3 phosphorylation in gastric cancer cell SGC-7901. In conclusion, our results imply that MSC-derived EVs could be utilized as an effective nanovehicle to deliver L-PGDS for gastric cancer treatment, which provides a novel idea for the EV-based cancer therapy.

In this work, Gd2O3 bulks were sintered at temperatures ranging from 1400 °C to 1600 °C for times from 6 h to 24 h, and their microstructure and properties were studied for a wider application of materials in thermal barrier coatings. The densification of the Gd2O3 bulk reached 96.16% when it was sintered at 1600 °C for 24 h. The elastic modulus, hardness, fracture toughness and thermal conductivity of the bulks all increased with the rise in sintering temperature and extension of sintering time, while the coefficient of thermal expansion decreased. When the Gd2O3 bulk was sintered at 1600 °C for 24 h, it had the greatest elastic modulus, hardness, fracture toughness and thermal conductivity of 201.15 GPa, 9.13 GPa, 15.03 MPa·m0.5 and 2.75 W/(m·k) (at 1100 °C), respectively, as well as the smallest thermal expansion coefficients of 6.69 × 10−6/°C (at 1100 °C).

Based on Particle Swarm Optimization (PSO) and Second-Order Cone Programming (SOCP) algorithm, this paper proposes a hybrid optimization method to suppress the grating lobes of sparse arrays and improve the robustness of array layout. With the peak side-lobe level (PSLL) as the objective function, the paper adopts the particle swarm optimization as a global optimization algorithm to optimize the elements’ positions, the convex optimization as a local optimization algorithm to optimize the elements’ weights. The effectiveness of the grating lobes suppression (as low as -32.13 dB) by this method is illustrated through its application to the sparse linear array when the actual steering vector is known. To enhance the robustness of the optimized array, a rebuilt robust convex optimization model is adopted in the optimization of both array excitations and layout. When the array manifold mismatch error is 1cm, the PSLL by the robust algorithm can be compressed to -27dB, compared to that of -24dB by the ordinary optimization. Results of a set of representative numerical experiments show that the algorithm proposed in this paper can obtain a more robust array layout and matched elements’ weight coefficients to avoid the huge degradation of the array pattern performance in the presence of array manifold mismatch errors. The good performance of pattern synthesis demonstrates the effectiveness of the proposed robust algorithm.

Summary: Intracranial aneurysm (IA) is an enormous threat to human health, which often results in nontraumatic subarachnoid hemorrhage or dismal prognosis. Diagnosing IAs on commonly used computed tomographic angiography (CTA) examinations remains laborious and time consuming, leading to error-prone results in clinical practice, especially for small targets. In this study, we propose a fully automatic deep-learning model for IA segmentation that can be applied to CTA images. Our model, called Global Localization-based IA Network (GLIA-Net), can incorporate the global localization prior and generates the fine-grain three-dimensional segmentation. GLIA-Net is trained and evaluated on a big internal dataset (1,338 scans from six institutions) and two external datasets. Evaluations show that our model exhibits good tolerance to different settings and achieves superior performance to other models. A clinical experiment further demonstrates the clinical utility of our technique, which helps radiologists in the diagnosis of IAs. The bigger picture: Intracranial aneurysms (IAs) are enormous threats to human health with a prevalence of approximately 4%. The rupture of IAs usually causes death or severe damage to the patients. To enhance the clinical diagnosis of IAs, we present a deep learning model (GLIA-Net) for IA detection and segmentation without laborious human intervention, which achieves superior diagnostic performance validated by quantitative evaluations as well as a sophisticated clinical study. We anticipate that the publicly released data and the artificial intelligence technique would help to transform the clinical diagnostics and precision treatments of cerebrovascular diseases. They may also revolutionize the landscape of healthcare and biomedical research in the future.

Exosomes are nanometer-sized small EVs coated with bilayer structure, which are released by prokaryotic and eukaryotic cells. Exosomes are rich in a variety of biologically active substances, such as proteins, nucleotides, and lipids. Exosomes are widely present in various body fluids and cell culture supernatants, and it mediates the physiological and pathological processes of the body through the shuttle of these active ingredients to target cells. In recent years, studies have shown that exosomes from a variety of cell sources can play a beneficial role in acute and chronic kidney disease. In particular, exosomes derived from mesenchymal stem cells have significant curative effects on the prevention and treatment of kidney disease in preclinical trials. Besides, some encapsulated substances are demonstrated to exert beneficial effects on various diseases, so they have attracted much attention. In addition, exosomes have extensive sources, stable biological activity, and good biocompatibility and are easy to store and transport; these advantages endow exosomes with superior diagnostic value. With the rapid development of liquid biopsy technology related to exosomes, the application of exosomes in the rapid diagnosis of kidney disease has become more prominent. In this review, the latest development of exosomes, including the biosynthesis process, the isolation and identification methods of exosomes are systematically summarized. The utilization of exosomes in diagnosis and their positive effects in the repair of kidney dysfunction are discussed, along with the specific mechanisms. This review is expected to be helpful for relevant studies and to provide insight into future applications in clinical practice.

Shell biomineralization is a process in which inorganic minerals assemble under accuracy control of macromolecule, mainly the matrix proteins. A shell-notching assay was used in Hyriopsis cumingii and CaCO3 deposition during shell regeneration and the expression pattern of five shell matrix protein encoding genes, HcTyp-1, hic31, hic52, silkmapin and Hcperlucin were analyzed. Macro- and microscopic observation revealed that shell regeneration can be broadly separated into three stages. (1) The formative period of the periostracum (from 0th day to 6thday), the pellicle formed and covered the gap creating a sealed space for mineralized layer origin. (2) The period of prismatic layer mineralization (from 14 to 21 days), the periostracum continued to grow, and aragonite seeds originated from the organic membrane accumulated and grew laterally to cover the whole periostracum. (3) The growth period of the nacreous layer (from 29 to 39 days), the initial nacreous layer formed, and regular aragonite crystals deposited, nucleated and eventually grew to form a distinctive brick wall structure. Furthermore, the periodic high-expression of five shell matrix protein genes during periostracum formation and prismatic or nacreous layer mineralization suggested they had a dominant role in the programmed reparative process. These observations contribute to understanding the molecular mechanism of shell formation. Keywords: Matrix protein, Shell, Biomineralization, Hyriopsis cumingii

Large-scale exploration and development of shale gas in Lower Cambrian Niutitang Formation of South China has been carried out in recent years, but the result is not good, only except some drilling wells in Jingyan-Qianwei area of Sichuan Basin and Yichang of Hubei obtain some commercial gas flows. In order to clarify reasons for failure of shale gas exploration and development in Niutitang Formation around Sichuan Basin and to provide reservoir geological parameters for subsequent efficient exploration and development, taking a case of shale gas reservoirs in Lower Cambrian Niutitang Formation in northeast Chongqing around Sichuan Basin, some experimental methods, such as analysis of organic carbon pyrolysis, determination of equivalent vitrinite reflectance, focused ion beam scanning electron microscope (FIB-SEM) and other are adopted in this study. The results show that the average TOC of shale samples in Niutitang Formation in northeast Chongqing is 3.1%, the equivalent vitrinite reflectance ranges from 3.0% to 4.0%, and the degree of thermal evolution reaches the post-mature–metamorphic stage. Due to excessively high degree of the thermal evolution, organic pores in shale samples are not developed in Lower Cambrian Niutitang Formation in the study area, instead, micro-nano pores dominated by intergranular pores and intragranular pores are developed in the shale. The degree of the thermal evolution controls the sustaining gas generation of kerogen and retained liquid hydrocarbons in the shale, it also controls the development of organic pores of the shale. The evolution of organic pores and hydrocarbon generation in the shale of Niutitang Formation in northeast Chongqing around Sichuan Basin do not match best with each other, that is, during development period of a large number of organic pores, thermal evolution degree of reservoirs is further enhanced because the strata are not uplifted in time, therefore, the quantity of organic pores is decreased sharply, the shale gas would be escaped due to the absence of organic pores as effective storage space after the shale gas generation. Therefore, the efficient exploration and development of the shale gas in Lower Cambrian Niutitang Formation in South China should be focused on the shale development area where the shale is characterized by moderate thermal evolution degree (2.0%

Gd and Yb elements have high chemical stability, which can stabilize the solid solution in ZrO2. Gd2O3 and Yb2O3 have high melting points, and good oxidation resistance in extreme environments, stable chemical properties. Therefore, Gd2O3 and Yb2O3 were added to ZrO2 to stabilize oxides, improve the high temperature stability, and effectively decrease the thermal conductivity at high temperature. In this work, 5 wt% Yb2O3 and 5 wt%, 10 wt%, 15 wt% Gd2O3 were doped into 8 wt% Y2O3 stabilized ZrO2 (8YSZ) powders as thermal barrier coating materials, and sintered at 1650 °C for 6 h, 12 h, 24 h. The effects of Gd2O3 addition on the microstructure, density, thermal conductivity, hardness, and fracture toughness of Gd2O3-Yb2O3-Y2O3-ZrO2 (GYYZO) bulk composite ceramics were investigated. It was found that the densification of the 8YSZ bulk and GYYZO bulk with 15 wt% Gd2O3 reached 96.89% and 96.22% sintered at 1650 °C for 24 h. With the increase of Gd2O3 addition, the hardness, elastic modulus and fracture toughness of the GYYZO bulk increased and the thermal conductivity and thermal expansion coefficient of the GYYZO bulk decreased. GYYZO bulk with 15 wt% Gd2O3 sintered at 1650 °C for 24h had the highest hardness, elastic modulus and fracture toughness of 15.61 GPa, 306.88 GPa, 7.822 MPa·m0.5, and the lowest thermal conductivity and thermal expansion coefficient of 1.04 W/(m·k) and 7.89 × 10−6/°C at 1100 °C, respectively. The addition of Gd2O3 into YSZ could not only effectively reduce the thermal conductivity but also improve the mechanical properties, which would improve the thermal barrier coatings’ performances further.

Organic matrix proteins play an important role in the biomineralization of mollusc shells. We have identified and characterized a novel matrix protein, namely hic74, isolated from the mantle of the freshwater mussel Hyriopsis cumingii. The hic74 gene encodes a 850 amino acid protein that is rich in alanine (ala, 30.8%), glycine (gly, 25.8%) and serine (ser, 10.6%), with ala mainly existing in poly-ala forms within the ala/gly-rich regions. Quantitative PCR expression analysis demonstrated that hic74 was specifically amplified from the mantle and in situ hybridization showed a strong signal in the epithelial cells in the pallial region of the mantle. Lower levels of expression were detected during the early stages of pearl sac formation but increased and remained constant during nacreous layer formation suggesting that hic74 might be involved in this process.

Eight phenyl imidazolinone derivatives were synthesized from N2-(2,4-dimethylphenyl)-N1-methyformamidine (DPMF) via scaffold-hopping method using the ring-closure approach. The prepared compounds were verified using 1H and 13C NMR and HRMS spectroscopies. The structure of compound 3c was confirmed by single-crystal X-ray diffraction analysis. The mean plane of the phenyl and imidazolinone moieties was almost coplanar with an angle of 8.85(4)°. In the crystal, molecules were interlinked with intermolecular hydrogen bonds (N–H···O and C–H···O), generating a network structure. Additionally, compound 3f displayed the highest insecticidal activity (86.7%) against Plutella xylostella at 600 mg/L, which was significantly higher than the insecticidal activity (23.0%) of DPMF. Also, compound 3d displayed good fungicidal activities against Phytophthora capsici, Phytophthora sojae, and Phytophthora infestans. Density functional theory (DFT) calculations were performed to explain the insecticidal and fungicidal activities of phenyl imidazolidin-2-one derivatives, especially potent compounds 3f and 3d. Moreover, the binding modes of compounds 3a–h and DPMF against octopamine receptor of Plutella xylostella were studied by homology modeling and molecular docking. Therefore, a preliminary structure–activity relationship (SAR) was derived and discussed. These results encourage the exploration of novel insecticides and fungicides based on DPMF.

In this study, we clone and characterize a novel matrix protein, hic31, from the mantle of Hyriopsis cumingii. The amino acid composition of hic31 consists of a high proportion of Glycine residues (26.67%). Tissue expression detection by RT-PCR indicates that hic31 is expressed specifically at the mantle edge. In situ hybridization results reveals strong signals from the dorsal epithelial cells of the outer fold at the mantle edge, and weak signals from inner epithelial cells of the same fold, indicating that hic31 is a prismatic-layer matrix protein. Although BLASTP results identify no shared homology with other shell-matrix proteins or any other known proteins, the hic31 tertiary structure is similar to that of collagen I, alpha 1 and alpha 2. It has been well proved that collagen forms the basic organic frameworks in way of collagen fibrils and minerals present within or outside of these fibrils. Therefore, hic31 might be a framework-matrix protein involved in the prismatic-layer biomineralization. Besides, the gene expression of hic31 increase in the early stages of pearl sac development, indicating that hic31 may play important roles in biomineralization of the pearl prismatic layer.

A water-soluble polysaccharide (JCS1) was isolated from the stems of Dendrobium nobile Lindl. JCS1 was structurally characterized using a combination of chemical and spectral analysis, including methylation analysis, partial acid hydrolysis, Fourier-transform infrared (FTIR) spectroscopy, gas chromatography (GC), GC-mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. The molecular weight was estimated to be 2.3 × 104 Da using high-performance gel permeation chromatography (HPGPC). The sugar composition analysis indicated it was composed of glucose, mannose, xylose, and arabinose in a 40.2:2.3:1.7:1.0 molar ratio. The structure analysis showed that JCS1 was a mannoglucan with a backbone consisting of (1→4)-linked β-Manp and (1→4)-linked α-Glcp with branches at C-6 of (1→4)-linked α-Glcp residues. The branches were composed of T-α-Glcp, 1,4-α-Xylp, and T-α-Araf. In vitro bioactivity tests revealed that the acetylated derivative of JCS1, YJCS1, induced neuritogenesis of PC-12 cells. These results demonstrate that YJCS1 might be a promising bioactive polysaccharide for development as a drug candidate for the possible prevention and treatment of neurodegeneration diseases.

The photochemistry of EDA complexes is initiated from a groundstate associate with a biomolecule capable of intermolecular electron transfer by channelling chemical synthesis via a specific radical-based mechanistic pathway. Herein, we activate the innovative cascade mode of EDA complex photoexcitation for nitroreduction in aqueous media using charge transfer interactions between a sole donor and multiple acceptors (ArNO2, ArNO, and ArNHOH·glycine adduct). A triplet-state quenching experiment, UV-vis analysis, NMR titration, and preliminary kinetic investigation verified the rationality and feasibility of the mechanism. With successful applications of this cascaded system in arylamine compounds and commercially available drug synthesis (61 examples), these achievements highlight the attractiveness, usefulness, and effectiveness of this protocol. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an intervention for schizophrenia remain unclear. This systematic review examined the efficacy and safety of dTMS for schizophrenia. Methods: A systematic search of Chinese (WanFang and Chinese Journal Net) and English databases (PubMed, EMBASE, PsycINFO, and Cochrane Library) were conducted. Results: Three randomized clinical trials (RCTs) comprising 80 patients were included in the analyses. Active dTMS was comparable to the sham treatment in improving total psychopathology, positive symptoms, negative symptoms, and auditory hallucinations measured by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Auditory Hallucinations Rating Scale (AHRS), respectively. Only one RCT reported the effects on neurocognitive function measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB), suggesting that dTMS may only improve one Stockings of Cambridge measure (i.e., subsequent times for five move problems). All three studies reported overall discontinuation rates, which ranged from 16.7% to 44.4%. Adverse events were reported in only one RCT, the most common being tingling/twitching (30.0%, 3/10), head/facial discomfort (30.0%, 3/10), and back pain (20.0%, 2/10). Conclusion: This systematic review suggests that dTMS does not reduce psychotic symptoms in schizophrenia, but it shows potential for improving executive functions. Future RCTs with larger sample sizes focusing on the effects of dTMS on psychotic symptoms and neurocognitive function in schizophrenia are warranted to further explore these findings. [ABSTRACT FROM AUTHOR]

Aqueous zinc-ion batteries (AZIBs) are promising contenders for large-scale energy storage systems (ESSs) due to their high security, high capacity, low cost, and ecological friendliness. Polyanionic materials have been extensively investigated as promising cathodes for AZIBs by virtue of their high operating voltages and robust structures in recent years. Nevertheless, their poor intrinsic electronic conductivity, relatively low specific capacity, and complex and controversial energy storage mechanisms still hinder their development. Herein, aiming at tackling these challenging issues, we comprehensively review the latest research progress in polyanionic cathode materials for AZIBs. First, we summarize the three typical crystal structures of polyanionic compounds, including Na superionic conductor (NASICON)-type, layered, and olivine-type structures. Next, we discuss the three mainstream fundamental reaction mechanisms of Zn2+ insertion/extraction, ion/molecule co-insertion/extraction, and anionic redox chemistry. Then, we expound four feasible design strategies: intercalation engineering, defect/doping engineering, morphology control, and surface coating. Finally, the critical remaining challenges and future perspectives on advanced polyanionic cathode materials for aqueous Zn-storage are elaborated. We believe that this review can provide novel insights into the development of high-performance polyanionic cathode materials for AZIBs. [ABSTRACT FROM AUTHOR]