[Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway].

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-ß-galactosidase(SA-ß-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1ß(IL-1ß), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1ß and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1ß and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

First Report of Mucor inaequisporus Dade (Mucorales, Mucoromycota) causing Postharvest rot of Strawberry Fruit in Kunming, China.

Strawberry (Fragaria × ananassa Duch.) is an important and very popular fruit around the world because they have unique taste, special fragrance and rich nutrition (Hashmi et al., 2013; Neri et al., 2015). However, mature fruits have the characteristics of smooth texture, high softening rate and re-breathing rate were easily infected by various pathogens (Lara et al., 2004). In June 2022, a few postharvest strawberry fruits were found to rot, soften and cover with a green or yellow mycelium in Kunming city, Yunnan Province (25°02' N; 102°42' E), southwest China. The symptoms of fruits initially observed a tiny white mycelium and water damage, then the mycelium became yellow, with water-soaked areas extended rapidly. Eventually, the entire fruit was covered with yellow, dense mycelium (Fig. 1A, B). The incidence of this postharvest decay in strawberry fruits ranged from 35 to 45% and caused serious loss. This pathogen was isolated from diseased fruit tissues, transferred to potato dextrose agar (PDA) and malt extract agar (MEA), and incubated in the dark at 25 ± 1 ℃. Then purify and separate again. Four pure strains (BDFM1 to BDMF4) were obtained and stored in 15% glycerol at -80 ℃ in the State Key Laboratory for Conservation and Utilization of Bio-Resources Room 1012, Yunnan Agricultural University. On PDA, the colonies were initially white and the reverse was light yellow, after 5 days, the hyphae became golden yellow, and the diameter of the colony reached 5 cm (Fig. 1C). On MEA, the colonies were initially light yellow, and after 4 days, yellow-orange and the reverse were yellow to dark yellow (Fig. 1D). Unbranched sporangiophores are up to 26.7-30.8 µm diameter with columellae frequently pyriform, oblong or ellipsoid, obovoid (43- 60 × 90-135 µm), colorless or yellowish (Fig. 1E), simple or with long or short sympodial branches. Sporangia yellow, globose or subglobose, 55.3-123.7 µm in diameter, wall echinulate, which are spherical formed at the top of the main sporangiophore and each branch (Fig. 1F), Sporangiospores yellow, which are spherical (5.0-8.5 × 5.5-9 µm), oval (21.5-7 × 11-20 µm), thin and smooth-walled. To further identify the fungus, the total genomic DNA was extracted from four strains using the CATB method (Aboul-Maaty & Oraby, 2019). The partial fragments of internal transcribed spacer (ITS), and partial 28S rRNA gene sequence were amplified with the primers ITS1/ITS4, and LR0R/LR5 respectively. These sequences of strains BDFM1 to BDMF4 were uploaded to NCBI GenBank as accessions ON951610, ON951611, ON951612 and ON951613, OP430532, OP430533 OP430534 and OP430535. Using NCBI's BLASTn tools, the nucleotide sequences of strains showed 96.12 - 99.21 % identity to JN206177 (M. inaequisporus strain CBS 496.66). BDFM1 to BDMF4 isolates were used to MEGA11 construct a phylogenetic tree. Maximum likelihood phylogenetic analyses (Fig. 2) and phylogenetic tree from Bayesian method (Fig. 3) further confirmed the results. Pathogenicity tests were conducted with healthy strawberry fruits. We selected two stains (BDFM1, BDFM2) from four same isolates for this test, cultured on MEA for 4 days, then washed with sterilized water and the spore suspensions were adjusted at 1.0 × 106 spores/ml. Ten fruits were surface-disinfected with 75% alcohol for 15 s, rinsed with sterile water 3 times, then air-dried, and sprayed with the spore suspension on the surface, while the control fruits were sprayed with sterile water. The fruits were incubated at 26 °C with 90% relative humidity in a plastic container. This test was performed in triplicate. After 2 days, the fruits sprayed with the spore suspensions showed light yellow hyphae (Fig. 1H), which covered one-third of the fruit surface (Fig. 1G). After 4 days, yellow-orange mycelia covered the entire fruit, with yellow oil-droplets at the tip of the mycelium (Fig. I). Control fruits remained healthy. The fungus was re-isolated and identified as Mucor inaequisporus thus completing Koch's postulates. Mucor inaequisporus was identified by symptoms, morphology (de Freitas et al., 2021), rDNA-ITS sequence analysis, and pathogenicity test. As we know, this is the first report of M. inaequisporus on strawberry fruits in China.

Transcription factor EB attenuates neuronal damage following cerebral ischemia via regulating autophagy-lysosomal pathway / 国际脑血管病杂志

The disorder of autophagy lysosomal pathway (ALP) is an important pathogenesis of neuronal damage after cerebral ischemia, and the restoration of ALP may alleviate neuronal damage after cerebral ischemia. As the main transcription factor regulating ALP, transcription factor EB (TFEB) can directly regulate autophagosome generation, autophagosome-lysosome fusion, and autophagic flux by regulating the expression of autophagic genes and lysosomal genes. Therefore, regulating TFEB can alleviate ALP dysfunction and thereby reduce cerebral ischemic damage. This article reviews the structure, biological function of TFEB and its role in regulating ALP to alleviate neuronal damage after cerebral ischemia.

Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway / 中国中药杂志

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-β-galactosidase(SA-β-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1β(IL-1β), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1β and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1β and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Multicenter epidemiological characteristics of Mycoplasma pneumoniae infection in children in Hainan Province, 2012-2020 / 中国热带医学

@#Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.

Role of CCAAT/enhancer binding protein β in acute cerebral ischemia / 国际脑血管病杂志

CCAAT/enhancer binding protein β (C/EBPβ), a transcriptional factor of the basic-leucine zipper family, can regulate the transcription activity of downstream target genes. After acute cerebral ischemia, the activity of C/EBPβ changes, and participates in the process of cerebral ischemia injury by regulating neuronal apoptosis and inflammation. This article reviews the molecular biological characteristics of C/EBPβ and its expression changes and role in acute cerebral ischemia, providing a basis for developing new neuroprotective drugs for acute cerebral ischemia using C/EBPβ as therapeutic target.

Role and mechanism of mixed lineage kinase domain-like protein in cerebral ischemia / 国际脑血管病杂志

Mixed lineage kinase domain-like protein (MLKL) is a pseudokinase with a kinase domain, which plays an important role in the regulation of necroptosis. After cerebral ischemia, MLKL, as the substrate protein of the receptor-interacting protein 3, undergoes oligomerization and phosphorylation, and then translocates from the cytoplasm to the plasmalemma, causing mitochondrial division and cell membrane rupture. MLKL can also mediate the inflammatory response after cerebral ischemia by inducing necroptosis and directly activating inflammasomes, thereby aggravating brain injury. Therefore, to clarify the biological characteristics of MLKL and its role and mechanism in cerebral ischemia is very important for the treatment of cerebral ischemia.

Role of exosomes in neuroinflammation after cerebral ischemia / 国际脑血管病杂志

Exosomes are extracellular small molecular vesicles with lipid bilayers, which contain biologically active substances such as RNA and proteins. Exosomes can conduct material transport and information transmission between cells. After cerebral ischemia, neuron-derived exosomes affect the occurrence and development of neuroinflammation by regulating the activation of glial cells, and the activated glial cells secrete exosomes containing inflammatory factors or inflammation related microRNAs to regulate the survival or death of neurons. Studies have shown that exosomes can be used as biomarkers and therapeutic targets for inflammatory injury after cerebral ischemia. This article describes the composition and function of exosomes, as well as their role and possible mechanism in neuroinflammation after cerebral ischemia.

Role of p75 neurotrophin receptor in neuronal apoptosis after cerebral ischemia / 国际脑血管病杂志

p75 neurotrophin receptor (p75 NTR) is a member of the tumor necrosis factor receptor superfamily, which interacts with tropomyosin receptor kinase (Trk) receptor or binds neurotrophic factors. It mediates a variety of complex signal transduction pathways, induces synaptic growth and affects cell survival. After acute cerebral ischemia, p75 NTR binds effector factors such as pro-nerve growth factor (proNGF) and sortilin, activating downstream apoptotic signal molecules and leading to neuronal death. Therefore, elucidating the pathways and molecular mechanisms of p75 NTR that mediate neuronal apoptosis in acute cerebral ischemia is of great significance for the development of new therapeutic drugs for acute cerebral ischemia.

Impact of inflammatory reaction levels and culprit plaque characteristics on preprocedural thrombolysis in myocardial infarction flow grade in patients with ST-segment elevation myocardial infarction / 中华心血管病杂志

Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm2 vs. 1.4(1.1-1.9)mm2, all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.

Role and mechanism of activating transcription factor 4 in cerebral ischemia / 国际脑血管病杂志

Activating transcription factor 4 (ATF4) is a stress response factor containing a basic region-leucine zipper. When the body is under stress, the increased expression of ATF4 binds to cellular transcription factors, which in turn regulates the corresponding downstream target genes, thereby initiating cellular responses. After cerebral ischemia, ATF4 plays a neuroprotective role by participating in various pathophysiological processes such as regulating endoplasmic reticulum stress, oxidative stress, mitochondrial autophagy, inflammatory response, vascular regeneration, and synaptic plasticity. Therefore, ATF4 is expected to become a new target for the treatment of ischemic brain injury.

Research on sintering process of tricalcium phosphate bone tissue engineering scaffold based on three-dimensional printing / 生物医学工程学杂志

Tricalcium phosphate (TCP) is one of the most widely used bioceramics for constructing bone tissue engineering scaffold. The three-dimensional (3D) printed TCP scaffold has precise and controllable pore structure, while with the limitation of insufficient mechanical properties. In this study, we investigated the effect of sintering temperature on the mechanical properties of 3D-printed TCP scaffolds in detail, due to the important role of the sintering process on the mechanical properties of bioceramic scaffolds. The morphology, mass and volume shrinkage, porosity, mechanical properties and degradation property of the scaffold was studied. The results showed that the scaffold sintered at 1 150℃ had the maximum volume shrinkage, the minimum porosity and optimal mechanical strength, with the compressive strength of (6.52 ± 0.84) MPa and the compressive modulus of (100.08 ± 18.6) MPa, which could meet the requirements of human cancellous bone. In addition, the 1 150℃ sintered scaffold degraded most slowly in the acidic environment compared to the scaffolds sintered at the other temperatures, demonstrating its optimal mechanical stability over long-term implantation. The scaffold can support bone mesenchymal stem cells (BMSCs) adherence and rapid proliferation and has good biocompatibility. In summary, this paper optimizes the sintering process of 3D printed TCP scaffold and improves its mechanical properties, which lays a foundation for its application as a load-bearing bone.

MiR-96-5p inhibition induces cell apoptosis in gastric adenocarcinoma.

BACKGROUND: Gastric adenocarcinoma (GAC) mortality rates have remained relatively changed over the past 30 years, and it continues to be one of the leading causes of cancer-related death. AIM: To search for novel miRNAs related to GAC prognosis and further investigate the effect of miR-96-5p on MGC-803 cells. METHODS: The miRNA expression profile data of GAC based on The Cancer Genome Atlas were obtained and used to screen differently expressed miRNAs (DEMs) and DEMs related to GAC prognosis. Then, the expression of DEMs related to GAC prognosis was identified in GAC tumor samples and adjacent normal samples by qRT-PCR. The target gene, ZDHHC5, of miR-96-5p was predicted using TargetScan, miRTarBase, and miRDB databases and confirmed by luciferase reporter assay. Furthermore, MGC-803 cells were transfected with inhibitor NC, miR-96-5p inhibitor, si-ZDHHC5, or miR-96-5p inhibitor + si-ZDHHC5, and then cell apoptosis was detected by flow cytometry. The expression of ZDHHC5, Bcl-2, and COX-2 was detected using western blotting. RESULTS: A total of 299 DEMs and 35 DEMs related to GAC prognosis were screened based on The Cancer Genome Atlas. Then compared with adjacent normal samples, the levels of miR-96-5p, miR-222-5p, and miR-652-5p were remarkably increased, while miR-125-5p, miR-145-3p, and miR-379-3p levels were reduced in GAC tumor samples (P < 0.01), which were consistent with bioinformatics analysis. Furthermore, ZDHHC5 was defined as a direct target gene of miR-96-5p. miR-96-5p inhibition increased the number of apoptotic cells as well as promoted the expression of ZDHHC5, Bcl-2, and COX-2 in MGC-803 cells (P < 0.01). After ZDHHC5 inhibition, the number of apoptotic cells and the expression of ZDHHC5, Bcl-2, and COX-2 were reduced. The addition of an miR-96-5p inhibitor partly reversed these effects (P < 0.01). CONCLUSION: Our findings identified six miRNAs related to GAC prognosis and suggested that downregulated miR-96-5p might induce cell apoptosis via upregulating ZDHHC5 expression in MGC-803 cells.

Synthetic cell-cell communication in a three-species consortium for one-step vitamin C fermentation.

OBJECTIVES: A three-species consortium for one-step fermentation of 2-keto-L-gulonic acid (2-KGA) was constructed to better strengthen the cell-cell communication. And the programmed cell death module based on the LuxI/LuxR quorum-sensing (QS) system was established in Gluconobacter oxydans to reduce the competition that between G. oxydans and Ketogulonicigenium vulgare. RESULTS: By constructing and optimizing the core region of the promoter, which directly regulated the expression of lethal ccdB genes in QS system, IR3C achieved the best lethal effect. The consortium of IR3C- K. vulgare-Bacillus megaterium (abbreviated as 3C) achieved the highest 2-KGA titer (68.80 ± 4.18 g/l), and the molar conversion rate was 80.7% within 36 h in 5 l fermenter. Metabolomic analysis on intracellular small molecules of consortia 3C and 1C showed that most amino acids (such as glycine, leucine, methionine and proline) and TCA cycle intermediates (such as succinic acid, fumaric acid and malic acid) were significantly affected. These results further validated that the programmed cell death module based on the LuxI/LuxR QS system in G. oxydans could also faciliate better growth and higher production of consortium 3C for one-step fermentation. CONCLUSIONS: We successfully constructed a novel three-species consortia for one-step vitamin C fermentation by strengthening the cell-cell communication. This will be very useful for probing the rational design principles of more complex multi-microbial consortia.

Integrated proteomic and metabolomic analysis of a reconstructed three-species microbial consortium for one-step fermentation of 2-keto-L-gulonic acid, the precursor of vitamin C.

Microbial consortia, with the merits of strong stability, robustness, and multi-function, played critical roles in human health, bioenergy, and food manufacture, etc. On the basis of 'build a consortium to understand it', a novel microbial consortium consisted of Gluconobacter oxydans, Ketogulonicigenium vulgare and Bacillus endophyticus was reconstructed to produce 2-keto-L-gulonic acid (2-KGA), the precursor of vitamin C. With this synthetic consortium, 73.7 g/L 2-KGA was obtained within 30 h, which is comparable to the conventional industrial method. A combined time-series proteomic and metabolomic analysis of the fermentation process was conducted to further investigate the cell-cell interaction. The results suggested that the existence of B. endophyticus and G. oxydans together promoted the growth of K. vulgare by supplying additional nutrients, and promoted the 2-KGA production by supplying more substrate. Meanwhile, the growth of B. endophyticus and G. oxydans was compromised from the competition of the nutrients by K. vulgare, enabling the efficient production of 2-KGA. This study provides valuable guidance for further study of synthetic microbial consortia.

Roles and mechanisms of chemokine CX3CL1 in cerebral ischemia / 国际脑血管病杂志

Chemokine CX3CL1 mainly participates in the physiological and pathological processes of nervous system by activating its receptor CX3CR1. Under physiological conditions, CX3CL1 can inhibit the activation of microglia; when cerebral ischemia and hypoxia, CX3CL1 can affect the expression of multiple downstream target genes involved in activation of adenosine receptor, inhibition of Ca2+ influx, and promotion of blood vessel growth. It is of great significance to improve the energy metabolism disorder and to establish microcirculation around infarcts after cerebral ischemia.

piRNA and cerebral ischemia / 国际脑血管病杂志

Piwi-interacting RNA (piRNA) is a new class of small non-coding RNAs that function by specifically binding to the Piwi subfamily members of the Argonaute protein family. piRNA regulates the expression of target genes at epigenetic and post-transcriptional levels, and participates in the development and progression of cerebral ischemia by mediating pathophysiological processes such as inflammation, angiogenesis, and neuronal synaptic plasticity.

Roles and mechanisms of chemokine CX3CL1 in cerebral ischemia / 国际脑血管病杂志

Chemokine CX3CL1 mainly participates in the physiological and pathological processes of nervous system by activating its receptor CX3CR1.Under physiological conditions,CX3CL1 can inhibit the activation of microglia;when cerebral ischemia and hypoxia,CX3CL1 can affect the expression of multiple downstream target genes involved in activation of adenosine receptor,inhibition of Ca 2+ influx,and promotion of blood vessel growth.It is of great significance to improve the energy metabolism disorder and to establish microcirculation around infarcts after cerebral ischemia.

Roles and mechanisms of connexin 43 in cerebral ischemia-reperfusion / 国际脑血管病杂志

In the central nervous system, gap junctions exist between neurons and glial cells. Among them, connexin 43 (Cx43) is one of the most abundant connexin proteins in the central nervous system,involved in the metabolic coupling of intercellular substance exchange and electrical coupling of electrical signaling. It plays an important role in regulating cell metabolism, homeostasis, and cell differentiation. After cerebral ischemia, the uncoupling of gap junctions and abnormal hemichannel activity cause a steady-state imbalance of the internal and external environment of the cells, eventually leading to brain tissue damage.Therefore, maintaining the normal function of Cx43 is essential for protecting brain tissue from neuronal damage induced by cerebral ischemia-reperfusion.

Risk Factors, Clinical Features and Prognosis for Subtypes of Ischemic Stroke in a Chinese Population / 华中科技大学学报（医学）（英德文版）

It is unanimously accepted that stroke is a highly heterogeneous disorder.Different subtypes of ischemic stroke may have different risk factors,clinical features,and prognoses.The aim of this study was to evaluate the risk factors,clinical characteristics,and prognoses of different subtypes of ischemic stroke defined by the Trial of ORG10172 in Acute Stroke Treatment (TOAST) criteria.We prospectively analyzed the data from 530 consecutive patients who were admitted to our hospital with acute ischemic stroke within 7 days of stroke onset during the study period.Standardized data assessment was used and the cause of ischemic stroke was classified according to the TOAST criteria.Patients were followed up till 30 and 90 days after stroke onset.It was found that large-artery atherosclerosis was the most frequent etiology of stroke (37.4％),and showed the highest male preponderance,the highest prevalence of previous transient ischemic attack,and the longest hospital stay among all subtypes.Small artery disease (36.4％) was associated with higher body mass index,higher plasma triglycerides,and lower plasma high-density lipoprotein cholesterol than cardioembolism.Cardioembolism (7.7％),which was particularly common in the elderly (i.e.,individuals aged 65 years and older),showed the highest female preponderance,the highest prevalence of atrial fibrillation,the earliest presentation to hospital after stroke onset,the most severe symptoms on admission,the maximum complications associated with an adverse outcome,and the highest rate of stroke recurrence and mortality.Our results suggest that ischemic stroke should be regarded as a highly heterogeneous disorder.Studies involving risk factors,clinical features,and prognoses of ischemic stroke should differentiate between etiologic stroke subtypes.