Lyophilizable Stem Cell-Hybrid Liposome with Long-Term Stability and High Targeting Capacity.

The hybridization of liposome with stem cell membrane is an emerging technology to prepare the nanovehicle with the capacity of disease-responsive targeting. However, the long-term storage of this hybrid liposome has received limited attention in the literature, which is essential for their potential applicability in the clinic. Therefore, the preservation of long-term activity of stem cell-hybrid liposome using freeze-drying is investigated in the present study. Mesenchymal stem cell-hybrid liposome is synthesized and its feasibility for freeze-drying under different conditions is examined. Results revealed that pre-freezing the hybrid liposome at -20 °C in Tris buffer solution (pH 7.4) containing 10% trehalose could well preserve the liposomal structure for at least 3 months. Notably, major membrane proteins on the hybrid liposome are protected in this formulation and CXCR4-associated targeting capacity is maintained both in vitro and in vivo. Consequently, the hybrid liposome stored for 3 months demonstrate a comparable tumor inhibition as the fresh-prepared ones. The present study provides the first insights into the long-term storage of stem cell hybrid liposome using lyophilization, which may make an important step forward in enhancing the long-term stability of these promising biomimetic nanovehicle and ease the logistics and the freeze-storage in the potential clinical applications. This article is protected by copyright. All rights reserved.

Partial root-zone drying subsurface drip irrigation increased the alfalfa quality yield but decreased the alfalfa quality content.

Water shortage seriously restricts the development of grassland agriculture in arid land and dramatically impacts alfalfa (Medicago sativa L.) quality content and hay yield. Reasonable irrigation methods have the potential to enhance the alfalfa quality content, hay yield, and thus quality yield. Whether partial root-zone drying subsurface drip irrigation (PRDSDI) improves the alfalfa quality yield, quality content, and hay yield is still unknown compared with conventional subsurface drip irrigation (CSDI). The effects of PRDSDI compared with that of CSDI and the interaction with irrigation volume (10 mm/week, 20 mm/week, and 30 mm/week) on the alfalfa quality yield were investigated in 2017-2018 and explained the change in quality yield with the alfalfa quality content and hay yield. Here, the results showed that PRDSDI did not increase the alfalfa quality yield in 2 years. PRDSDI significantly increased acid detergent fiber by 13.3% and 12.2% in 2018 with 10-mm and 20-mm irrigation volumes and neutral detergent fiber by 16.2%, 13.2%, and 12.6% in 2017 with 10-mm, 20-mm, and 30-mm irrigation volumes, respectively. PRDSDI significantly decreased the crude protein by 5.4% and 8.4% in 2018 with 10-mm and 20-mm irrigation volumes and relative feed value by 15.0% with 20-mm irrigation volume in 2017 and 9.8% with 10-mm irrigation volume in 2018, respectively. In addition, PRDSDI significantly increased the alfalfa average hay yield by 49.5% and 59.6% with 10-mm and 20-mm irrigation volumes in 2018, respectively. Our results provide a counterexample for PRDSDI to improve crop quality. Although there was no significant improvement in average quality yield by PRDSDI, the positive impact of average hay yield on quality yield outweighed the negative impact of quality content. Thus, it has the potential to improve quality yields. The novel findings regarding the effects of PRDSDI on quality yield are potentially favorable for the forage feed value in water-limited areas.

Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance.

Accumulating evidence suggests that cancer-associated fibroblast (CAF) macroautophagy/autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAF autophagy during immune surveillance and cancer immunotherapy is unclear. The present study revealed that the inhibition of CAF autophagy suppresses in vivo tumor development in immune-deficient xenografts. This deletion compromises anti-tumor immunity and anti-tumor efficacy both in vitro and in vivo by upregulating CD274/PDL1 levels in an immune-competent mouse model. A block in CAF autophagy reduced the production of IL6 (interleukin 6), disrupting high desmoplastic TME and decreasing USP14 expression at the transcription level in pancreatic cancer cells. We further identify USP14 as the post-translational factor responsible for downregulating CD274 expression by removing K63 linked-ubiquitination at the K280 residue. Finally, chloroquine diphosphate-loaded mesenchymal stem cell (MSC)-liposomes, by accurately targeting CAFs, inhibited CAF autophagy, improving the efficacy of immunochemotherapy to combat pancreatic cancer.Abbreviation: AIR: adaptive immune resistance; ATRA: all-trans-retinoicacid; CAF: cancer-associated fibroblast; CD274/PDL1: CD274 molecule; CM: conditioned medium; CQ: chloroquine diphosphate; CyTOF: Mass cytometry; FGF2/bFGF: fibroblast growth factor 2; ICB: immune checkpoint blockade; IF: immunofluorescence; IHC: immunohistochemistry; IP: immunoprecipitation; MS: mass spectrometer; MSC: mesenchymal stem cell; PDAC: pancreatic ductal adenocarcinoma; TEM: transmission electron microscopy; TILs: tumor infiltrating lymphocytes; TME: tumor microenvironment; USP14: ubiquitin specific peptidase 14.

Correlation between ovarian follicular development and Hippo pathway in polycystic ovary syndrome.

BACKGROUND: For women of childbearing age, the biggest problem caused by polycystic ovary syndrome (PCOS) is infertility, which is mainly caused by anovulation, abnormal follicular development, proliferation of small antral follicles, and cystic follicles. The mechanism underlying its occurrence is not clear. The abnormal proliferation and development of follicles in PCOS patients is a complex process, which is affected by many factors. The objective of this study was to investigate the relationship between the Hippo pathway and follicular development in PCOS, and to further explore this relationship by using the YAP inhibitor verteporfin (VP). METHOD: 30 3-week-old BALB/C female rats were randomly divided into control group (n = 10), DHEA group (n = 10) and DHEA + VP group (n = 10). The morphology of ovary and the degree of follicular development were observed by HE staining, and the expression and location of AMH in ovarian follicles were observed by immunofluorescence. The ovarian reserve function index AMH, cell proliferation index PCNA and the ratio of Hippo pathway related proteins MST, LATS, YAP, P-YAP and P-YAP/YAP were detected by Western blot. RESULTS: After dividing 30 3-week-old female mice into control, dehydroepiandrosterone (DHEA; model of PCOS), and DHEA + VP groups, we found that the number of small follicles increased in the DHEA group compared to the control group. Additionally, in the DHEA group compared to the control group, anti-müllerian hormone (AMH; ovarian reserve index) increased, proliferating cell nuclear antigen (PCNA; cell proliferation index) decreased, and upstream (MST and LATS) and downstream (YAP and p-YAP) proteins in the Hippo pathway increased, though the p-YAP/YAP ratio decreased. VP ameliorated the increases in AMH, MST, LATS, YAP and p-YAP, but did not ameliorate the decrease in the p-YAP/YAP ratio. CONCLUSIONS: This study indicates that the increased small follicles in the ovaries and changes in ovarian reserve and cell proliferation may be closely related to Hippo pathway activation. This suggests that the Hippo pathway may be an important pathway affecting the proliferation and development of follicles and the occurrence of PCOS.

Single-cell characterization of deformation and dynamics of mesenchymal stem cells in microfluidic systems: A computational study.

Understanding the homing dynamics of individual mesenchymal stem cells (MSCs) in physiologically relevant microenvironments is crucial for improving the efficacy of MSC-based therapies for therapeutic and targeting purposes. This study investigates the passive homing behavior of individual MSCs in micropores that mimic interendothelial clefts through predictive computational simulations informed by previous microfluidic experiments. Initially, we quantified the size-dependent behavior of MSCs in micropores and elucidated the underlying mechanisms. Subsequently, we analyzed the shape deformation and traversal dynamics of each MSC. In addition, we conducted a systematic investigation to understand how the mechanical properties of MSCs impact their traversal process. We considered geometric and mechanical parameters, such as reduced cell volume, cell-to-nucleus diameter ratio, and cytoskeletal prestress states. Furthermore, we quantified the changes in the MSC traversal process and identified the quantitative limits in their response to variations in micropore length. Taken together, the computational results indicate the complex dynamic behavior of individual MSCs in the confined microflow. This finding offers an objective way to evaluate the homing ability of MSCs in an interendothelial-slit-like microenvironment.

Hyperandrogenism drives ovarian inflammation and pyroptosis: A possible pathogenesis of PCOS follicular dysplasia.

Hyperandrogenemia and persistent chronic inflammation, two main striking features of polycystic ovary syndrome (PCOS), have been proven involved in follicular dysgenesis in PCOS. However, the association between hyperandrogenism and inflammation activation in PCOS is not fully understood. Excess testosterone（T） induces inflammation and pyroptosis activation in a mouse model of PCOS, leading to ovarian dysfunction and fibrosis. Excessive endoplasmic reticulum (ER) stress is present in ovarian granulosa cells (GCs), testosterone-induced PCOS mouse and cellular models. This study found higher levels of interleukin (IL)-1ß, IL-8, IL-17, and IL-18 in the follicular fluid of PCOS patients with hyperandrogenemia undergoing IVF treatment. In addition, pyroptosis in GCs was demonstrated, which was significantly elevated in PCOS patients. To clarify the association of hyperandrogenism, inflammation, and pyroptosis activation in PCOS, dehydroepiandrosterone(DHEA)-treated mouse PCOS model and T-treated KGN cell line were explored for PCOS mechanism. Markers of inflammatory activation and pyroptosis were significantly increased after DHEA treatment in mice and T treatment in KGN cells. In addition, ER stress sensor proteins were increased simultaneously. However, suppression of inflammation by genipin(GP) led to decreased pyroptosis in KGN cells but no variation in ER stress sensor proteins. In contrast, when treated with tauroursodeoxycholic acid(TUDCA) to attenuate ER stress, the markers of inflammatory factors were significantly reduced, accompanied by a reduction in pyroptosis. Our results suggest that persistent hyperandrogenemia of PCOS promotes local inflammatory activation of the ovary, and the imbalanced inflammatory microenvironment leads to pyroptosis of GCs, which is mediated by ER stress activation.

Machine Learning-Assisted Low-Dimensional Electrocatalysts Design for Hydrogen Evolution Reaction.

Efficient electrocatalysts are crucial for hydrogen generation from electrolyzing water. Nevertheless, the conventional "trial and error" method for producing advanced electrocatalysts is not only cost-ineffective but also time-consuming and labor-intensive. Fortunately, the advancement of machine learning brings new opportunities for electrocatalysts discovery and design. By analyzing experimental and theoretical data, machine learning can effectively predict their hydrogen evolution reaction (HER) performance. This review summarizes recent developments in machine learning for low-dimensional electrocatalysts, including zero-dimension nanoparticles and nanoclusters, one-dimensional nanotubes and nanowires, two-dimensional nanosheets, as well as other electrocatalysts. In particular, the effects of descriptors and algorithms on screening low-dimensional electrocatalysts and investigating their HER performance are highlighted. Finally, the future directions and perspectives for machine learning in electrocatalysis are discussed, emphasizing the potential for machine learning to accelerate electrocatalyst discovery, optimize their performance, and provide new insights into electrocatalytic mechanisms. Overall, this work offers an in-depth understanding of the current state of machine learning in electrocatalysis and its potential for future research.

Unraveling the Atomic Shuffles of Twinning Nucleation in Hexagonal Close-Packed Rhenium Nanocrystals.

Reining in deformation twinning is crucial for the mechanical properties of hexagonal close-packed (HCP) metals and hinges on an explicit understanding of the twinning nucleation mechanism. Unfortunately, it is often suggested rather than conclusively demonstrated that twinning nucleation can be mediated by pure atomic shuffles. Herein, by utilizing in situ high-resolution transmission electron microscopy, we have dissected the atomic shuffling mechanism during the {101̅2} twinning nucleation in rhenium nanocrystals, which revealed the emergence of an intermediate body-centered tetragonal (BCT) structure. Specifically, the double-layered prismatic planes initially shuffle into single-layered {11̅0}BCT planes; subsequently, adjacent {22̅0}BCT planes shuffle in opposite directions to form the basal planes of the twin embryo. This shuffling mechanism is further corroborated by molecular dynamic simulations. The finding provides direct evidence of shuffle-dominated twinning nucleation with atomic details that may lead to better control of this critical twinning mode in HCP metals.

Cell membrane-based biomimetic vehicles for effective central nervous system target delivery: Insights and challenges.

Central nervous system (CNS) disorders, including brain tumor, ischemic stroke, Alzheimer's disease, and Parkinson's disease, threaten human health. And the existence of the blood-brain barrier (BBB) hinders the delivery of drugs and the design of drug targeting delivery vehicles. Over the past decades, great interest has been given to cell membrane-based biomimetic vehicles since the rise of targeting drug delivery systems and biomimetic nanotechnology. Cell membranes are regarded as natural multifunction biomaterials, and provide potential for targeting delivery design and modification. Cell membrane-based biomimetic vehicles appear timely with the participation of cell membranes and nanoparticles, and raises new lights for BBB recognition and transport, and effective therapy with its biological multifunction and high biocompatibility. This review summarizes existing challenges in CNS target delivery and recent advances of different kinds of cell membrane-based biomimetic vehicles for effective CNS target delivery, and deliberates the BBB targeting mechanism. It also discusses the challenges and possibility of clinical translation, and presents new insights for development.

Plastic bottles for chilled carbonated beverages as a source of microplastics and nanoplastics.

Carbonated beverages are characterized by low temperatures, multiple microbubbles, high pressure, and an acidic environment, creating ideal conditions for releasing contaminants from plastic bottles. However, the release patterns of microplastics (MPs) and nanoplastics (NPs) are poorly understood. We investigated the effects of plastic type, CO2 filling volume, temperature, sugar content, and additive on the leakage of MPs/NPs and heavy metals. Our results showed that polypropylene bottles released greater MPs (234±9.66 particles/L) and NPs (9.21±0.73 × 107 particles/L) than polyethylene and polyethylene terephthalate bottles. However, subjecting the plastic bottles to 3 repeated inflation treatments resulted in 91.65-93.18% removal of MPs/NPs. The release of MPs/NPs increased with increasing CO2 filling volume, driven by the synergistic effect of CO2 bubbles and pressure. After 4 freeze-thaw cycles, the release of MPs and NPs significantly increased, reaching 450±38.65 MPs and 2.91±0.10 × 108 NPs per liter, respectively. The presence of sugar leads to an elevation in MPs release compared to sucrose-free carbonated water, while the addition of additives to carbonated water exhibits negligible effects on MPs release. Interestingly, actual carbonated beverages demonstrated higher MPs concentrations (260.52±27.18-281.38±61.33 particles/L) than those observed in our well-controlled experimental setup. Our study highlights the non-negligible risk of MPs/NPs in carbonated beverages at low temperatures and suggests strategies to mitigate human ingestion of MPs/NPs, such as selecting appropriate plastic materials, high-pressure carbonated water pretreatment, and minimizing freeze-thaw cycles. Our findings provide insights for further study of the release patterns of the contaminants in natural environments with bubbles, pressure, low temperature, and freeze-thaw conditions.

High Targeting Specificity toward Pulmonary Inflammation Using Mesenchymal Stem Cell-Hybrid Nanovehicle for an Efficient Inflammation Intervention.

Pulmonary inflammation is one of the most reported tissue inflammations in clinic. Successful suppression of inflammation is vital to prevent further inevitably fatal lung degeneration. Glucocorticoid hormone, such as methylprednisolone (MP), is the most applied strategy to control the inflammatory progression yet faces the challenge of systemic side effects caused by the requirement of large-dosage and frequent administration. Highly efficient delivery of MP specifically targeted to inflammatory lung sites may overcome this challenge. Therefore, the present study develops an inflammation-targeted biomimetic nanovehicle, which hybridizes the cell membrane of mesenchymal stem cell with liposome, named as MSCsome. This hybrid nanovehicle shows the ability of high targeting specificity toward inflamed lung cells, due to both the good lung endothelium penetration and the high uptake by inflamed lung cells. Consequently, a single-dose administration of this MP-loaded hybrid nanovehicle achieves a prominent treatment of lipopolysaccharide-induced lung inflammation, and negligible treatment-induced side effects are observed. The present study provides a powerful inflammation-targeted nanovehicle using biomimetic strategy to solve the current challenges of targeted inflammation intervention.

Multi-Scale Microstructural Tailoring and Associated Properties of Press-Hardened Steels: A Review.

High-strength press-hardened steels (PHS) are highly desired in the automotive industry to meet the requirement of carbon neutrality. This review aims to provide a systematic study of the relationship between multi-scale microstructural tailoring and the mechanical behavior and other service performance of PHS. It begins with a brief introduction to the background of PHS, followed by an in-depth description of the strategies used to enhance their properties. These strategies are categorized into traditional Mn-B steels and novel PHS. For traditional Mn-B steels, extensive research has verified that the addition of microalloying elements can refine the microstructure of PHS, resulting in improved mechanical properties, hydrogen embrittlement resistance, and other service performance. In the case of novel PHS, recent progress has principally demonstrated that the novel composition of steels coupling with innovative thermomechanical processing can obtain multi-phase structure and superior mechanical properties compared with traditional Mn-B steels, and their effect on oxidation resistance is highlighted. Finally, the review offers an outlook on the future development of PHS from the perspective of academic research and industrial applications.

The Characteristic Microstructures and Properties of Steel-Based Alloy via Additive Manufacturing.

Differing from metal alloys produced by conventional techniques, metallic products prepared by additive manufacturing experience distinct solidification thermal histories and solid-state phase transformation processes, resulting in unique microstructures and superior performance. This review starts with commonly used additive manufacturing techniques in steel-based alloy and then some typical microstructures produced by metal additive manufacturing technologies with different components and processes are summarized, including porosity, dislocation cells, dendrite structures, residual stress, element segregation, etc. The characteristic microstructures may exert a significant influence on the properties of additively manufactured products, and thus it is important to tune the components and additive manufacturing process parameters to achieve the desired microstructures. Finally, the future development and prospects of additive manufacturing technology in steel are discussed.

Study on Corrosion Behavior and Mechanism of Ultrahigh-Strength Hot-Stamping Steel Based on Traditional and Compact Strip-Production Processes.

Hot-stamping steel is a type of high-strength steel that is mainly used in key safety components such as the front and rear bumpers, A-pillars, and B-pillars of vehicles. There are two methods of producing hot-stamping steel, i.e., the traditional process and the near net shape of compact strip production (CSP) process. To assess the potential risks of producing hot-stamping steel using CSP, the microstructure and mechanical properties, and especially the corrosion behavior were focused on between the traditional and CSP processes. The original microstructure of hot-stamping steel produced by the traditional process and the CSP process is different. After quenching, the microstructures transform into full martensite, and their mechanical properties meet the 1500 MPa grade. Corrosion tests showed that the faster the quenching speeds, the smaller the corrosion rate of the steel. The corrosion current density changes from 15 to 8.6 µA·cm-2. The corrosion resistance of hot-stamping steel produced by the CSP process is slightly better than that of traditional processes, mainly since the inclusion size and distribution density of CSP-produced steel were both smaller than those of the traditional process. The reduction of inclusions reduces the number of corrosion sites and improves the corrosion resistance of steel.

Phase Transformation Behaviors of Medium Carbon Steels Produced by Twin Roll Casting and Compact Strip Production Processes.

Medium carbon steels have been widely used in the fields of tool and die manufacturing due to their outstanding hardness and wear resistance. In this study, microstructures of 50# steel strips fabricated by twin roll casting (TRC) and compact strip production (CSP) processes were analyzed to investigate the influences of solidification cooling rate, rolling reduction, and coiling temperature on composition segregation, decarburization, and pearlitic phase transformation. The results show that a partial decarburization layer with a thickness of 13.3 µm and banded C-Mn segregation were observed in the 50# steel produced by CSP, leading to the banded distributions of ferrite and pearlite in the C-Mn poor regions and C-Mn rich regions, respectively. For the steel fabricated by TRC, owing to the sub-rapid solidification cooling rate and short processing time at high temperatures, neither apparent C-Mn segregation nor decarburization was observed. In addition, the steel strip fabricated by TRC has higher pearlite volume fractions, larger pearlite nodule sizes, smaller pearlite colony sizes and interlamellar spacings due to the co-influence of larger prior austenite grain size and lower coiling temperatures. The alleviated segregation, eliminated decarburization and large volume fraction of pearlite render TRC a promising process for medium carbon steel production.

The potential bias of nitrogen deposition effects on primary productivity and biodiversity.

Atmospheric nitrogen (N) deposition is composed of both inorganic nitrogen (IN) and organic nitrogen (ON), and these sources of N may exhibit different impacts on ecosystems. However, our understanding of the impacts of N deposition is largely based on experimental gradients of INs or more rarely ONs. Thus, the effects of N deposition on ecosystem productivity and biodiversity may be biased. We explored the differential impacts of N addition with different IN:ON ratios (0:10, 3:7, 5:5, 7:3, and 10:0) on aboveground net primary productivity (ANPP) of plant community and plant diversity in a typical temperate grassland with a long-term N addition experiment. Soil pH, litter biomass, soil IN concentration, and light penetration were measured to examine the potential mechanisms underlying species loss with N addition. Our results showed that N addition significantly increased plant community ANPP by 68.33%-105.50% and reduced species richness by 16.20%-37.99%. The IN:ON ratios showed no significant effects on plant community ANPP. However, IN-induced species richness loss was about 2.34 times of ON-induced richness loss. Soil pH was positively related to species richness, and they exhibited very similar response patterns to IN:ON ratios. It implies that soil acidification accounts for the different magnitudes of species loss with IN and ON additions. Overall, our study suggests that it might be reasonable to evaluate the effects of N deposition on plant community ANPP with either IN or ON addition. However, the evaluation of N deposition on biodiversity might be overestimated if only IN is added or underestimated if only ON is added.

First Report of Clonostachys rosea Causing rot of Morchella sextelata in Anhui Province, China.

Morel mushroom (Morchella spp.) is a valuable mushroom, which has extremely high nutritional and economic value. In the early March of 2022, a serious rot disease was observed on approximately 30% fruiting bodies at an M. esculenta farm of Suzhou City, Anhui province, China. A white mold-like hyphae was initially present on the pileus, which then gradually spread to the whole fruiting body, eventually resulting in softening of the fruiting body and death. This disease developed rapidly at relatively high temperature (>20°C) and humidity (>85%), resulting in approximately 80% loss of yield. Twenty infected tissues were cut into small pieces (5 × 5 mm) and placed on potato dextrose agar (PDA) and incubated at 25°C for 5 days. Fifteen morphologically similar isolates were obtained and purified using the single spore isolation technique. Colonies of these isolates were yellowish-white, and tomentose with thick aerial hyphae after 7 days at 25°C on PDA plates. Conidiophores were dimorphic: primary conidiophores were Verticillium-like, secondary conidiophores were penicillate. Primary conidiophore stipe length ranged from 68.6 to 180.5 µm, and the base width was 3.2-5.6 µm. Phialides were solitary, straight, generally slightly tapering towards the tip, each producing a small, hyaline drop of conidia. Secondary conidiophores stipe length ranged from 68.4 to 120.5 µm, the base measured 3.3-6.1µm. Phialides were straight to slightly curved, slightly flask-shaped, with widest point below the middle, slightly tapering in the upper part, without visible collarette. Conidia were colorless, smooth, slightly curved, and distally broadly rounded with an average size of 6.3 to 8.2 × 2.4 to 3.7 µm (n=30). These isolates were initially identified as Clonostachys rosea based on morphological features (Schroers et al. 1999). To confirm the identity of C. rosea, primers ITS1/ITS4 (White et al. 1990) and EF1-728F/ EF1-986R (Carbone and Kohn 1999), were used to amplify the internal transcribed spacer (ITS), and translation elongation factor 1-alpha (EF-1α) genes of the representative isolate 5-3-2. These sequences were deposited in GenBank (GenBank accession nos. ON614093 and ON630916) and had 100% and 99.45% nucleotide identity with Clonostachys rosea E5R(17) and Clonostachys rosea KGSJ26 (GenBank accession nos. MK752437 and MT462122), respectively. Single conidium were isolated and multiplied on PDA for pathogenicity testing. To fulfill Koch's postulates, pathogenicity tests were performed using the fruiting bodies. Spores of C. rosea isolates 5-3-2 were collected and diluted with sterile distilled water at a concentration of 1 × 106 conidia/ml. Five healthy fruiting bodies were inoculated with 1 ml of the spore suspension, which were maintained in an artificial climate chamber at 22°C and 85% humidity. Sterile water inoculated on other 10 healthy fruiting bodies served as control. Mycelia grew rapidly and overgrew more than half of the fruiting bodies within 3 days. The fruiting bodies died five days after inoculation. Clonostachys rosea isolates were re-isolated from symptomatic fruiting bodies and identified by the methods described above. The control group showed no symptoms. The experiment was conducted twice. To our knowledge, this is the first identification of Clonostachys rosea as the causal agent of the Morchella sextelata rot.

New idea to promote the clinical applications of stem cells or their extracellular vesicles in central nervous system disorders: Combining with intranasal delivery.

The clinical translation of stem cells and their extracellular vesicles (EVs)-based therapy for central nervous system (CNS) diseases is booming. Nevertheless, the insufficient CNS delivery and retention together with the invasiveness of current administration routes prevent stem cells or EVs from fully exerting their clinical therapeutic potential. Intranasal (IN) delivery is a possible strategy to solve problems as IN route could circumvent the brain‒blood barrier non-invasively and fit repeated dosage regimens. Herein, we gave an overview of studies and clinical trials involved with IN route and discussed the possibility of employing IN delivery to solve problems in stem cells or EVs-based therapy. We reviewed relevant researches that combining stem cells or EVs-based therapy with IN administration and analyzed benefits brought by IN route. Finally, we proposed possible suggestions to facilitate the development of IN delivery of stem cells or EVs.

Forsythoside B attenuates neuro-inflammation and neuronal apoptosis by inhibition of NF-κB and p38-MAPK signaling pathways through activating Nrf2 post spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a ruinous neurological pathology that results in locomotor and sensory impairment. Neuro-inflammation and secondary neuronal apoptosis contribute to SCI, with anti-inflammatory therapies the focus of many SCI studies. Forsythoside B (FTS•B), a phenylethanoid glycoside extracted from the leaves of Lamiophlomis rotata Kudo, has been shown previously to have anti-inflammatory properties. Nevertheless, the therapeutic effect of FTS•B on neuro-inflammation after SCI is unknown. METHODS: Neuro-inflammation was assessed by western blotting (WB), immunofluorescence (IF) staining, and enzyme-linked immunosorbent assay (ELISA) both in vitro and in vivo. Secondary neuronal apoptosis was simulated in a microglia-neuron co-culture model with the degree of apoptosis measured by WB, IF, and TUNEL staining. In vivo, FTS•B (10 mg/kg, 40 mg/kg) were intraperitoneally injected into SCI mice. Morphological changes following SCI were evaluated by Nissl, Hematoxylin-eosin, and Luxol Fast Blue staining. Basso Mouse Scale scores were used to evaluate locomotor function recovery. RESULTS: FTS•B markedly decreased the levels of iNOS, COX-2 and signature mediators of inflammation. Phosphorylated p38 and nuclear factor-kappa B (NF-κB) were markedly decreased by FTS•B. Additionally, FTS•B-induced inhibition of NF-κB and p38-MAPK signaling pathways was reversed by Nrf2 downregulation. Administration of FTS•B also significantly reduced apoptosis-related protein levels indicating that FTS•B ameliorated secondary neuronal apoptosis. FTS•B administration inhibited glial scar formation, decreased neuronal death, tissue deficiency, alleviated demyelination, and promoted locomotor recovery. CONCLUSION: FTS•B effectively attenuates neuro-inflammation and secondary neuronal apoptosis by inhibition of NF-κB and p38-MAPK signaling pathways through activating Nrf2 after SCI. This study demonstrates FTS•B to be a potential therapeutic for SCI.