Spinal cord injury (SCI) is a severe traumatic disease of the central nervous system, with a global prevalence of 236-4187 per million people. This meta-analysis aimed to evaluate the safety and ...efficacy of mesenchymal stem cells (MSCs) in treating patients with SCI as well as the optimal source and transplantation method of MSCs. PubMed, OVID, Cochrane, Web of Science, and China Biomedical Database were searched up until April 01, 2021. The study was conducted for five endpoints: American Spinal Injury Association (ASIA) motor and sensory score, ASIA grade improvement, Barthel Index (BI), and adverse reactions. Standard meta-analysis and network meta-analysis were performed using Stata 14.0. Eighteen studies with a total of 949 patients, were included in the meta-analysis. Standard meta-analysis showed that MSCs significantly improved ASIA motor score (P < 0.001), sensory score (P < 0.001), ASIA grade (P < 0.001), and BI (P < 0.001) compared to rehabilitation. In addition, in the network meta-analysis, autologous MSCs significantly improved the ASIA motor MD = 8.01, 95% CI (4.27, 11.76), sensory score MD = 17.98, 95% CI (10.04, 25.91), and BI MD = 7.69, 95% CI (2.10, 13.29) compared to rehabilitation. Similarly, compared to rehabilitation, intrathecal injection (IT) of MSCs significantly improved the ASIA motor MD = 7.97, 95% CI (4.40, 11.53) and sensory score MD = 19.60, 95% CI (9.74, 29.46). Compared to rehabilitation, however, only the IL of MSCs was associated with more adverse reactions OR = 17.82, 95% CI (2.48, 128.22). According to the results of SUCRA, both autologous MSCs and IT transplantation approaches most improved the neurological function in SCI patients. Cell transplantation using MSCs is effective in patients with SCI and IT of autologous MSCs may be more beneficial.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes of gut microbiota and metabolites in ...intestinal I/R and the role of gut microbiota metabolites on ferroptosis-induced intestinal I/R injury. This study aimed to establish a mouse intestinal I/R model and ileum organoid hypoxia/reoxygenation (H/R) model to explore the changes of the gut microbiota and metabolites during intestinal I/R and protective ability of capsiate (CAT) against ferroptosis-dependent intestinal I/R injury. Intestinal I/R induced disturbance of gut microbiota and significant changes in metabolites. We found that CAT is a metabolite of the gut microbiota and that CAT levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with intestinal I/R injury. Furthermore, CAT reduced ferroptosis-dependent intestinal I/R injury in vivo and in vitro. However, the protective effects of CAT against ferroptosis-dependent intestinal I/R injury were abolished by RSL3, an inhibitor of glutathione peroxidase 4 (Gpx4), which is a negative regulator of ferroptosis. We also found that the ability of CAT to promote Gpx4 expression and inhibit ferroptosis-dependent intestinal I/R injury was abrogated by JNJ-17203212, an antagonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). This study suggests that the gut microbiota metabolite CAT enhances Gpx4 expression and inhibits ferroptosis by activating TRPV1 in intestinal I/R injury, providing a potential avenue for the management of intestinal I/R injury.
Neuropeptide Y (NPY), which is widely distributed in the nervous system, is involved in regulating a variety of biological processes, including food intake, energy metabolism, and emotional ...expression. However, emerging evidence points to NPY also as a critical transmitter between the nervous system and immune system, as well as a mediator produced and released by immune cells.
and
studies based on gene-editing techniques and specific NPY receptor agonists and antagonists have demonstrated that NPY is responsible for multifarious direct modulations on immune cells by acting on NPY receptors. Moreover, via the central or peripheral nervous system, NPY is closely connected to body temperature regulation, obesity development, glucose metabolism, and emotional expression, which are all immunomodulatory factors for the immune system. In this review, we focus on the direct role of NPY in immune cells and particularly discuss its indirect impact on the immune response.
Background
Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis‐induced cardiomyopathy ...(SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM.
Methods
A case‒control and single‐center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis‐uninduced cardiomyopathy patients (SNICM, n = 16).
Results
Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28‐day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM.
Conclusions
SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Blocking effects of Pisha sandstone on water leakage in sandy land were examined.•Inserted Pisha sandstone in sandy land changed the vertical distribution of soil water.•Inserted Pisha sandstone at ...10–15 cm depth caused high permeability resistance.•Inserted Pisha sandstone effectively hindered the downward leakage of sandy soil water.
Quick water seepage in sandy soils results in a serious restriction for ecological restoration, becoming a worldwide urgent research issue in arid areas. Search for practical solutions are focused on reserving the limited rainfall into topsoil layer to meet plant water demand. Based on fieldwork, this study evaluates the blocking effects of Pisha sandstone on soil water leakage, by inserting sandstone layers in the different soil depths (10–15 cm, 20–25 cm, 30–35 cm), which act as isolation layers within the sandy soil. Results showed that the inserted Pisha sandstone layers significantly decreased the soil water infiltration rates at the different stages and cumulative infiltration. The inserted sandstone layer at the depth of 10–15 cm presented the highest permeability resistance, and its initial infiltration rate, stable infiltration rate and average infiltration rate decreased by 102.42 mm h−1, 144.30 mm h−1 and 132.79 mm h−1, respectively. Meanwhile, the soil water content in the 5–10, 20–25, and 30–35 cm soil layers increased by 2.17%, 2.20%, and 1.37%, respectively, due to the inserted Pisha sandstones. This experimental study proves that the insertion of Pisha sandstones effectively hinders the downward penetration of soil water in sandy soil. These findings provide a new alternative for an effective solution of the fast water leakage problem of sandy land.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Intestinal ischemia/reperfusion is a grave condition with high morbidity and mortality in perioperative and critical care settings and causes multiple organ injuries beyond the intestine, including ...brain injury. Exosomes act as intercellular communication carriers by the transmission of their cargo to recipient cells. Here, we investigate whether exosomes derived from the intestine contribute to brain injury after intestinal ischemia/reperfusion via interacting with microglia in the brain. Intestinal ischemia/reperfusion was established in male C57/BL mice by clamping the superior mesenteric artery for 30 min followed by reperfusion. The sham surgery including laparotomy and isolation of the superior mesenteric artery without occlusion was performed as control. Male C57 mouse was intracerebral ventricular injected with intestinal exosomes from mice of intestinal ischemia/reperfusion or sham surgery. Primary microglia were cocultured with intestinal exosomes; HT-22 cells were treated with intestinal exosomes or microglia conditioned media. Intestinal ischemia/reperfusion-induced microglial activation, neuronal loss, synaptic stability decline, and cognitive deficit. Intracerebral ventricular injection of intestinal exosomes from intestinal ischemia/reperfusion mice causes microglial activation, neuronal loss, synaptic stability decline, and cognitive impairment. Microglia can incorporate intestinal exosomes both in vivo and in vitro. Microglia activated by intestinal exosomes increases neuron apoptotic rate and decreases synaptic stability. This study indicates that intestinal exosomes mediate memory impairment after intestinal ischemia/reperfusion via activating microglia. Inhibiting exosome secretion or suppressing microglial activation can be a therapeutic target to prevent memorial impairment after intestinal ischemia/reperfusion.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
Recently, a novel group of CD34 and S100 co-expression spindle cell tumors with distinctive stromal and perivascular hyalinization harboring recurrent gene fusions involving
RET
,
...RAF1
,
BRAF
, and
NTRK1/2
gene has been identified.
Case presentation
In this study, we reported two Chinese male patients with soft tissue tumors presenting in the right knee joint and the left thigh, respectively. For both patients, the tumors were completely excised with clear margin. Microscopically, case 1showed morphological overlap with neurofibroma, and case 2 showed overlap with lipomatous solitary fibrous tumor. Both tumors showed co-expression of S100 and CD34, and absence of SOX10. Genomic profiling with DNA-based next-generation sequencing (NGS) assay was performed and revealed
KIF5B-RAF1
(K16:R8) and
TLN2-RAF1
(T54:R8) rearrangements. RNA-based NGS and RT-PCR were performed to confirm the gene fusion.
Conclusions
Though systemic therapy was not indicated in these two patients, identification of targetable kinase fusions may help to refine tumors with an ambiguous immunoprofile, and provides suggestions for targeted therapy in rare aggressive cases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Trichoderma spp. are main producers of peptide antibiotics known as peptaibols. While peptaibols have been shown to possess a range of biological activities, molecular understanding of the regulation ...of their production is largely unclear, which hampers the production improvement through genetic engineering. Here, we demonstrated that the orthologue of glucose sensors in the outstanding biocontrol fungus
Trichoderma longibrachiatum SMF2,
TlSTP1, participates in the regulation of peptaibols production. Deletion of
Tlstp1 markedly impaired hyphal growth and conidiation, but significantly increased peptaibols yield by 5‐fold for Trichokonins A and 2.6‐fold for Trichokonins B. Quantitative real‐time polymerase chain reaction analyses showed that the increased peptaibols production occurs at the transcriptional levels of the two nonribosomal peptide synthetase encoding genes,
tlx1 and
tlx2. Transcriptome analyses of the wild type and the
Tlstp1 mutant strains indicated that
TlSTP1 exerts a regulatory effect on a set of genes that are involved in a number of metabolic and cellular processes, including synthesis of several other secondary metabolites. These results suggest an important role of
TlSTP1 in the regulation of vegetative growth and peptaibols production in
T. longibrachiatum SMF2 and provide insights into construction of peptaibol‐hyperproducing strains through genetic engineering.
Trichoderma spp. are main producers of peptide antibiotics known as peptaibols. While peptaibols have been shown to possess a range of biological activities, molecular understanding of the regulation of their production is largely unclear, which hampers the production improvement through genetic engineering.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To determine the sex-specific associations between postoperative haemoglobin and mortality or complications reflecting ischaemia or inadequate oxygen supply after major noncardiac surgery.
A ...retrospective cohort study with prospective validation.
A large university hospital health system in China.
Men and women undergoing elective major noncardiac surgery.
The primary exposure was nadir haemoglobin within 48 h after surgery. The outcome of interest was a composite of postoperative mortality or ischaemic events including myocardial injury, acute kidney injury and stroke within hospitalisation.
The study included 26,049 patients (15,757 men and 10,292 women). Low postoperative haemoglobin was a strong predictor of the composite outcome in both sexes, with the risk progressively increasing as the nadir haemoglobin concentration dropped below 130 g l−1 in men and 120 g l−1 in women (adjusted odds ratio OR 1.43, 95% CI 1.37–1.50 in men, and OR 1.45, 95% CI 1.35–1.55 in women, per 10 g l−1 decrease in postoperative nadir haemoglobin). Above these sex-specific thresholds, the change of nadir haemoglobin was no longer associated with odds of the composite outcome in either men or women. There was no significant interaction between patient sex and the association between postoperative haemoglobin and the composite outcome (Pinteraction = 0.673). Validation in an external prospective cohort (n = 2120) with systematic postoperative troponin and creatinine measurement confirmed our findings.
Postoperative haemoglobin levels following major noncardiac surgery were nonlinearly associated with ischaemic complications or mortality, without any clinically important interaction with patient sex.
•Low postoperative haemoglobin was a strong predictor for ischaemic organ injury.•The association between postoperative haemoglobin and outcomes was nonlinear.•Sex did not modify the association between postoperative haemoglobin and outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•The phase-field model is combined with flow and compression.•Wetting was found to play a significant role in the non-dendritic structure.•No direct association was found between the ...ripening and fragmentation.•Evidence showed the semi-solid alloy is capable of plastic deformation.
The semi-solid metal forming process can prevent the formation of unpopular dendritic microstructures but the mechanism remains unclear. To explore the underlying causes, a challenging phase-field simulation was performed, supported by a semi-solid experiment. The simulation managed to couple dendritic growth with melt flow and solid deformation, a process that few existing models or in situ experimental techniques could analyze. This study found that under deformation, grain boundary formation and wetting play a pivotal role in the formation of non-dendritic structures: it is the grain boundary formation and wetting that split the bending side-branch from dendrite trunk; the detached side-branch could then evolve into a non-dendritic morphology. The simulation showed that wetting could finish almost immediately after a moderate bending. This process appears similar to but is essentially distinct from the conventional explanation that describes dendrite fragmentation as mechanical breakage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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