The role of γδT lymphocytes in atherosclerosis.

Atherosclerosis poses a significant threat to human health, impacting overall well-being and imposing substantial financial burdens. Current treatment strategies mainly focus on managing low-density lipids (LDL) and optimizing liver functions. However, it's crucial to recognize that Atherosclerosis involves more than just lipid accumulation; it entails a complex interplay of immune responses. Research highlights the pivotal role of lipid-laden macrophages in the formation of atherosclerotic plaques. These macrophages attract lymphocytes like CD4 and CD8 to the inflamed site, potentially intensifying the inflammatory response. γδ T lymphocytes, with their diverse functions in innate and adaptive immune responses, pathogen defense, antigen presentation, and inflammation regulation, have been implicated in the early stages of Atherosclerosis. However, our understanding of the roles of γδ T cells in Atherosclerosis remains limited. This mini-review aims to shed light on the characteristics and functions of γδ T cells in Atherosclerosis. By gaining insights into the roles of γδ T cells, we may uncover a promising strategy to mitigate plaque buildup and dampen the inflammatory response, thereby opening new avenues for effectively managing this condition.

Development and external validation of a novel score for predicting postoperative 30­day mortality in tumor craniotomy patients: A cross­sectional diagnostic study.

The identification of patients with craniotomy at high risk for postoperative 30-day mortality may contribute to achieving targeted delivery of interventions. The present study aimed to develop a personalized nomogram and scoring system for predicting the risk of postoperative 30-day mortality in such patients. In this retrospective cross-sectional study, 18,642 patients with craniotomy were stratified into a training cohort (n=7,800; year of surgery, 2012-2013) and an external validation cohort (n=10,842; year of surgery, 2014-2015). The least absolute shrinkage and selection operator (LASSO) model was used to select the most important variables among the candidate variables. Furthermore, a stepwise logistic regression model was established to screen out the risk factors based on the predictors chosen by the LASSO model. The model and a nomogram were constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and calibration plot analysis were used to assess the model's discrimination ability and accuracy. The associated risk factors were categorized according to clinical cutoff points to create a scoring model for postoperative 30-day mortality. The total score was divided into four risk categories: Extremely high, high, intermediate and low risk. The postoperative 30-day mortality rates were 2.43 and 2.58% in the training and validation cohort, respectively. A simple nomogram and scoring system were developed for predicting the risk of postoperative 30-day mortality according to the white blood cell count; hematocrit and blood urea nitrogen levels; age range; functional health status; and incidence of disseminated cancer cells. The ROC AUC of the nomogram was 0.795 (95% CI: 0.764 to 0.826) in the training cohort and it was 0.738 (95% CI: 0.7091 to 0.7674) in the validation cohort. The calibration demonstrated a perfect fit between the predicted 30-day mortality risk and the observed 30-day mortality risk. Low, intermediate, high and extremely high risk statuses for 30-day mortality were associated with total scores of (-1.5 to -1), (-0.5 to 0.5), (1 to 2) and (2.5 to 9), respectively. A personalized nomogram and scoring system for predicting postoperative 30-day mortality in adult patients who underwent craniotomy were developed and validated, and individuals at high risk of 30-day mortality were able to be identified.

Diterpenoid honatisine overcomes temozolomide resistance in glioblastoma by inducing mitonuclear protein imbalance through disruption of TFAM-mediated mtDNA transcription.

BACKGROUND: Glioblastoma (GBM) represents as the most formidable intracranial malignancy. The systematic exploration of natural compounds for their potential applications in GBM therapy has emerged as a pivotal and fruitful avenue of research. PURPOSE: In the present study, a panel of 96 diterpenoids was systematically evaluated as a repository of potential antitumour agents. The primary objective was to discern their potency in overcoming resistance to temozolomide (TMZ). Through an extensive screening process, honatisine, a heptacyclic diterpenoid alkaloid, emerged as the most robust candidate. Notably, honatisine exhibited remarkable efficacy in patient-derived primary and recurrent GBM strains. Subsequently, we subjected this compound to comprehensive scrutiny, encompassing GBM cultured spheres, GBM organoids (GBOs), TMZ-resistant GBM cell lines, and orthotopic xenograft mouse models of GBM cells. RESULTS: Our investigative efforts delved into the mechanistic underpinnings of honatisine's impact. It was discerned that honatisine prompted mitonuclear protein imbalance and elicited the mitochondrial unfolded protein response (UPRmt). This effect was mediated through the selective depletion of mitochondrial DNA (mtDNA)-encoded subunits, with a particular emphasis on the diminution of mitochondrial transcription factor A (TFAM). The ultimate outcome was the instigation of deleterious mitochondrial dysfunction, culminating in apoptosis. Molecular docking and surface plasmon resonance (SPR) experiments validated honatisine's binding affinity to TFAM within its HMG-box B domain. This binding may promote phosphorylation of TFAM and obstruct the interaction of TFAM bound to heavy strand promoter 1 (HSP1), thereby enhancing Lon-mediated TFAM degradation. Finally, in vivo experiments confirmed honatisine's antiglioma properties. Our comprehensive toxicological assessments underscored its mild toxicity profile, emphasizing the necessity for a thorough evaluation of honatisine as a novel antiglioma agent. CONCLUSION: In summary, our data provide new insights into the therapeutic mechanisms underlying honatisine's selective inducetion of apoptosis and its ability to overcome chemotherapy resistance in GBM. These actions are mediated through the disruption of mitochondrial proteostasis and function, achieved by the inhibition of TFAM-mediated mtDNA transcription. This study highlights honatisine's potential as a promising agent for glioblastoma therapy, underscoring the need for further exploration and investigation.

Shared and malignancy-specific functional plasticity of dynamic brain properties for patients with left frontal glioma.

The time-varying brain activity may parallel the disease progression of cerebral glioma. Assessment of brain dynamics would better characterize the pathological profile of glioma and the relevant functional remodeling. This study aims to investigate the dynamic properties of functional networks based on sliding-window approach for patients with left frontal glioma. The generalized functional plasticity due to glioma was characterized by reduced dynamic amplitude of low-frequency fluctuation of somatosensory networks, reduced dynamic functional connectivity between homotopic regions mainly involving dorsal attention network and subcortical nuclei, and enhanced subcortical dynamic functional connectivity. Malignancy-specific functional remodeling featured a chaotic modification of dynamic amplitude of low-frequency fluctuation and dynamic functional connectivity for low-grade gliomas, and attenuated dynamic functional connectivity of the intrahemispheric cortico-subcortical connections and reduced dynamic amplitude of low-frequency fluctuation of the bilateral caudate for high-grade gliomas. Network dynamic activity was clustered into four distinct configuration states. The occurrence and dwell time of the weakly connected state were reduced in patients' brains. Support vector machine model combined with predictive dynamic features achieved an averaged accuracy of 87.9% in distinguishing low- and high-grade gliomas. In conclusion, dynamic network properties are highly predictive of the malignant grade of gliomas, thus could serve as new biomarkers for disease characterization.

Toxicity study of rats treated by plasma-activated solution.

Background: Cold atmospheric plasma (CAP) is an effective treatment for various skin diseases. Plasma-activated solution (PAS) is an indirect method of CAP treatment that produces biological effects similar to those of direct treatment with plasma devices. The anticancer and bacteriostatic effects of PAS have been demonstrated in vitro experiments; however, on the basis of the lack of toxicological studies on PAS, its effects on living mammals when administered by subcutaneous injection is poorly known. Purpose: The purpose of this study was to evaluate the effects of PAS on local skin tissue cells, blood system, heart, liver, lungs, kidneys and other vital organs of the rat when injected subcutaneously. Methods: PAS was prepared by CAP irradiation of phosphate-buffered saline (PBS). PBS and different PBS groups (CAP irradiation for 1, 3, or 5 min) were injected subcutaneously once every 48 h. The rats were euthanized immediately after 10 cycles of therapy. Results: No adverse effects were observed during the entire period of the experiment. Histopathological examination of organs and tissues revealed no structural changes. Moreover, no obvious structural changes were observed in skin tissue. DNA damage and cancerous proliferative changes were not detected in skin tissue treated with PAS. Subsequently, RNA sequencing and western blotting were performed. The results showed that PAS increased the expression of growth factors like transforming growth factor beta (TGF-ß) and vascular endothelial growth factor A (VEGFA). These results might be directly linked to the role of PAS in stimulating TGF-ß receptor signaling pathway and angiogenesis. Conclusion: The results showed that multiple subcutaneous injections of PAS did not show significant toxic side effects on local skin tissues and some vital organs in rats, providing a scientific basis to support the future treatment of skin diseases with PAS.

Myeloid cell ACE shapes cellular metabolism and function in PCSK-9 induced atherosclerosis.

The pathogenesis of atherosclerosis is defined by impaired lipid handling by macrophages which increases intracellular lipid accumulation. This dysregulation of macrophages triggers the accumulation of apoptotic cells and chronic inflammation which contributes to disease progression. We previously reported that mice with increased macrophage-specific angiotensin-converting enzyme, termed ACE10/10 mice, resist atherosclerosis in an adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-induced model. This is due to increased lipid metabolism by macrophages which contributes to plaque resolution. However, the importance of ACE in peripheral blood monocytes, which are the primary precursors of lesional-infiltrating macrophages, is still unknown in atherosclerosis. Here, we show that the ACE-mediated metabolic phenotype is already triggered in peripheral blood circulating monocytes and that this functional modification is directly transferred to differentiated macrophages in ACE10/10 mice. We found that Ly-6Clo monocytes were increased in atherosclerotic ACE10/10 mice. The monocytes isolated from atherosclerotic ACE10/10 mice showed enhanced lipid metabolism, elevated mitochondrial activity, and increased adenosine triphosphate (ATP) levels which implies that ACE overexpression is already altered in atherosclerosis. Furthermore, we observed increased oxygen consumption (VO2), respiratory exchange ratio (RER), and spontaneous physical activity in ACE10/10 mice compared to WT mice in atherosclerotic conditions, indicating enhanced systemic energy consumption. Thus, ACE overexpression in myeloid lineage cells modifies the metabolic function of peripheral blood circulating monocytes which differentiate to macrophages and protect against atherosclerotic lesion progression due to better lipid metabolism.

Association between preoperative serum sodium and postoperative 30-day mortality in adult patients with tumor craniotomy.

BACKGROUND: Limited data exist regarding preoperative serum sodium (Na) and 30-day mortality in adult patients with tumor craniotomy. Therefore, this study investigates their relationship. METHODS: A secondary retrospective analysis was performed using data from the ACS NSQIP database (2012-2015). The principal exposure was preoperative Na. The outcome measure was 30-day postoperative mortality. Binary logistic regression modeling was conducted to explore the link between them, and a generalized additive model and smooth curve fitting were applied to evaluate the potential association and its explicit curve shape. We also conducted sensitivity analyses and subgroup analyses. RESULTS: A total of 17,844 patients (47.59% male) were included in our analysis. The mean preoperative Na was 138.63 ± 3.23 mmol/L. The 30-day mortality was 2.54% (455/17,844). After adjusting for covariates, we found that preoperative Na was negative associated with 30-day mortality. (OR = 0.967, 95% CI:0.941, 0.994). For patients with Na ≤ 140, each increase Na was related to a 7.1% decreased 30-day mortality (OR = 0.929, 95% CI:0.898, 0.961); for cases with Na > 140, each increased Na unit was related to a 8.8% increase 30-day mortality (OR = 1.088, 95% CI:1.019, 1.162). The sensitivity analysis and subgroup analysis indicated that the results were robust. CONCLUSIONS: This study shows a positive and nonlinear association between preoperative Na and postoperative 30-day mortality in adult patients with tumor craniotomy. Appropriate preoperative Na management and maintenance of serum Na near the inflection point (140) may reduce 30-day mortality.

Role of dendritic cells in MYD88-mediated immune recognition and osteoinduction initiated by the implantation of biomaterials.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.

MoS2 nanopore identifies single amino acids with sub-1 Dalton resolution.

The sequencing of single protein molecules using nanopores is faced with a huge challenge due to the lack of resolution needed to resolve single amino acids. Here we report the direct experimental identification of single amino acids in nanopores. With atomically engineered regions of sensitivity comparable to the size of single amino acids, MoS2 nanopores provide a sub-1 Dalton resolution for discriminating the chemical group difference of single amino acids, including recognizing the amino acid isomers. This ultra-confined nanopore system is further used to detect the phosphorylation of individual amino acids, demonstrating its capability for reading post-translational modifications. Our study suggests that a sub-nanometer engineered pore has the potential to be applied in future chemical recognition and de novo protein sequencing at the single-molecule level.

Inducing Electric Current in Graphene Using Ionic Flow.

Classical nanofluidic frameworks account for the confined fluid and ion transport under an electrostatic field at the solid-liquid interface, but the electronic property of the solid is often overlooked. Harvesting the interaction of the nanofluidic transport with the electron transport in solid requires a route effectively coupling ion and electron dynamics. Here we report a nanofluidic analogy of Coulomb drag for exploring the dynamic ion-electron interactions at the liquid-graphene interface. An induced electric current in graphene by ionic flow with no bias directly applied to the graphene channel is observed experimentally, featuring an opposite electron current direction to the ion current. Our experiments and ab initio calculations show that the current generation stems from the confined ion-electron interactions via a nanofluidic Coulomb drag mechanism. Our findings may open up a new dimension for nanofluidics and transport control by ion-electron coupling.

Association between preoperative hematocrit and postoperative 30-day mortality in adult patients with tumor craniotomy.

Background: The purpose of this research was to synthesize the American College of Surgeons National Surgical Quality Improvement Program database to investigate the link between preoperative hematocrit and postoperative 30-day mortality in patients with tumor craniotomy. Methods: A secondary retrospective analysis of electronic medical records of 18,642 patients with tumor craniotomy between 2012 and 2015 was performed. The principal exposure was preoperative hematocrit. The outcome measure was postoperative 30-day mortality. We used the binary logistic regression model to explore the link between them and conducted a generalized additive model and smooth curve fitting to investigate the link and its explicit curve shape. We conducted sensitivity analyses by converting a continuous HCT into a categorical variable and calculated an E-value. Results: A total of 18,202 patients (47.37% male participants) were included in our analysis. The postoperative 30-day mortality was 2.5% (455/18,202). After adjusting for covariates, we found that preoperative hematocrit was positively associated with postoperative 30-day mortality (OR = 0.945, 95% CI: 0.928, 0.963). A non-linear relationship was also discovered between them, with an inflection point at a hematocrit of 41.6. The effect sizes (OR) on the left and right sides of the inflection point were 0.918 (0.897, 0.939) and 1.045 (0.993, 1.099), respectively. The sensitivity analysis proved that our findings were robust. The subgroup analysis demonstrated that a weaker association between preoperative hematocrit and postoperative 30-day mortality was found for patients who did not use steroids for chronic conditions (OR = 0.963, 95% CI: 0.941-0.986), and a stronger association was discovered in participants who used steroids (OR = 0.914, 95% CI: 0.883-0.946). In addition, there were 3,841 (21.1%) cases in the anemic group (anemia is defined as a hematocrit (HCT) <36% in female participants and <39% in male participants). In the fully adjusted model, compared with the non-anemic group, patients in the anemic group had a 57.6% increased risk of postoperative 30-day mortality (OR = 1.576; 95% CI: 1.266, 1.961). Conclusion: This study confirms that a positive and nonlinear association exists between preoperative hematocrit and postoperative 30-day mortality in adult patients undergoing tumor craniotomy. Preoperative hematocrit was significantly associated with postoperative 30-day mortality when the preoperative hematocrit was <41.6.

Light-Driven Ion Transport through Single-Heterojunction Nanopores.

Inspired by natural photosynthesis, light has become an emerging ionic behavior regulator and ion-pumping source. Nanoprocessing technology has allowed the bridge between the light-regulated nanofluids and the optoelectronic properties of two-dimensional (2D) materials, which inspires applications like energy harvesting and enhances fundamental understandings in nanofluidics. However, unlike light-induced ion pumping based on densely layered membranes with multiple nanochannels, experimental implementation on atomically thin materials featuring only a single nanochannel remains challenging. Here, we report light-induced ion pumping based on a single artificial heterojunction nanopore. Under light illumination, the induced current through a single nanopore reaches tens of picoamperes. The hole-electron separation originating from the optoelectrical property of a van der Waals PN junction is proposed to capture the light-driven ion transport. Further, different methods are adopted to modify the ion behavior and response time, presenting potential applications in fluidic photoenergy harvesting, photoelectric ion transport control, and bionic artificial neurons.

Association between preoperative platelet and 30-day postoperative mortality of adult patients undergoing craniotomy for brain tumors: data from the American College of Surgeons National Surgical Quality Improvement Program database.

BACKGROUND: Evidence regarding the relationship between preoperative platelet and 30-day postoperative mortality of intracranial tumor patients undergoing craniotomy is still limited. Therefore, the present research was conducted to explore the link of the platelet and 30-day postoperative mortality. METHODS: Electronic medical records of 18,642 adult patients undergoing craniotomy for brain tumors from 2012 to 2015 in the American College of Surgeons National Surgical Quality Improvement Program, were subject to secondary retrospective analysis. A binary logistic regression model evaluated the independent association between preoperative platelet and 30-day postoperative mortality. A generalized additive model and smooth curve fitting was conducted to explore the exact shape of the curve between them. Additionally, We also conducted sensitivity analyses to test the robustness of the results, and performed subgroup analyses. RESULTS: Eighteen thousand sixty-three patients were included in this study analysis. Of these, 47.49% were male. The mean preoperative platelet value was (244.12 ± 76.77) × 109/L. The 30-day postoperative mortality of included participants was 2.5% (452/18,063). After adjusting covariates, the results showed that preoperative platelet was positively associated with 30-day postoperative mortality (OR = 0.999, 95%CI: 0.997, 1.000). There was also a nonlinear relationship between preoperative platelet and 30-day postoperative mortality, and the inflection point of the platelet was 236. The effect sizes (OR) on the right and left sides of the inflection point were 1.002 (1.000, 1.004) and 0.993 (0.990, 0.995), respectively. And sensitive analysis demonstrated the robustness of the results. Subgroup analysis showed a stronger association between preoperative platelet and 30-day postoperative mortality in non-emergency surgery patients when preoperative platelet value is less than 235 × 109/L. CONCLUSIONS: This research demonstrates a positive and non-linear relationship between preoperative platelet and 30-day postoperative mortality in U.S. adult brain tumor patients undergoing craniotomy. Preoperative platelet is strongly related to 30-day postoperative mortality when the platelet is less than 235 × 109/L. Proper preoperative management of platelet and maintenance of platelet near inflection point (235) could reduce risk of 30-day postoperative mortality in these cases.

Association Between Pre-operative BUN and Post-operative 30-Day Mortality in Patients Undergoing Craniotomy for Tumors: Data From the ACS NSQIP Database.

Objective: There is limited evidence to clarify the specific relationship between pre-operative blood urea nitrogen (BUN) and post-operative 30-day mortality in patients undergoing craniotomy for tumors. Therefore, we aimed to investigate this relationship in detail. Methods: Electronic medical records of 18,642 patients undergoing craniotomy for tumors in the ACS NSQIP from 2012 to 2015 were subjected to secondary retrospective analysis. The principal exposure was pre-operative BUN. Outcome measures were post-operative 30-day mortality. We used binary logistic regression modeling to evaluate the association between them and conducted a generalized additive model and smooth curve fitting (penalized spline method) to explore the potential relationship and its explicit curve shape. We also conducted sensitivity analyses to ensure the robustness of the results and performed subgroup analyses. Results: A total of 16,876 patients were included in this analysis. Of these, 47.48% of patients were men. The post-operative 30-day mortality of the included cases was 2.49% (420/16,876), and the mean BUN was 16.874 ± 6.648 mg/dl. After adjusting covariates, the results showed that pre-operative BUN was positively associated with post-operative 30-day mortality (OR = 1.020, 95% CI: 1.004, 1.036). There was also a non-linear relationship between BUN and post-operative 30-day mortality, and the inflection point of the BUN was 9.804. For patients with BUN < 9.804 mg/dl, a 1 unit decrease in BUN was related to a 16.8% increase in the risk of post-operative 30-day mortality (OR = 0.832, 95% CI: 0.737, 0.941); for patients with BUN > 9.804 mg/dl, a 1 unit increase in BUN was related to a 2.8% increase in the risk of post-operative 30-day mortality (OR = 1.028, 95% CI: 1.011, 1.045). The sensitivity analysis proved that the results were robust. The subgroup analysis revealed that all listed subgroups did not affect the relationship between pre-operative BUN and post-operative 30-day mortality (P > 0.05). Conclusion: Our study demonstrated that pre-operative BUN (mg/dl) has specific linear and non-linear relationships with post-operative 30-day mortality in patients over 18 years of age who underwent craniotomy for tumors. Proper pre-operative management of BUN and maintenance of BUN near the inflection point (9.804 mg/dl) could reduce the risk of post-operative 30-day mortality in these cases.

Ionic Liquid Decelerates Single-Stranded DNA Transport through Molybdenum Disulfide Nanopores.

Nanopores in two-dimensional (2D) materials have emerged to offer in principle necessary spatial resolution for high-throughput DNA sequencing. However, their fidelity is severely limited by the fast DNA translocation. A recent experiment indicates that introducing ionic liquids could slow down DNA translocation in a MoS2 nanopore. However, the corresponding in-depth molecular mechanism underlying the experimental findings is not fully understood, which is crucial for the future improvement of rational DNA translocation control. Here, we computationally investigate and then experimentally identify the effect of BmimCl ionic liquid on the retardation of ssDNA translocation through a single-layer MoS2 nanopore. Our all-atom molecular dynamics simulations demonstrate that the strong interaction between Bmim+ and ssDNA offers a considerable dragging force to decelerate the electrophoretic motion of ssDNA in the BmimCl solution. Moreover, we show that Bmim+ ions exhibit preferential binding on the sulfur edges of the nanopore. These Bmim+ in the pore region can not only act as a steric blockage but also form π-π stackings with nucleobases, which provide a further restriction on the ssDNA motion. Therefore, our molecular dynamics simulation investigations deepen the understanding of the critical role of ionic liquid in DNA translocation through a nanopore from a molecular landscape, which may benefit practical implementations of ionic liquids in nanopore sequencing.

Cucurbitane triterpenoid entities derived from Hemsleya penxianensis triggered glioma cell apoptosis via ER stress and MAPK signalling cross-talk.

In the present study, six new cucurbitane type compounds, including three triterpenoids hemsleyacins P-R (6-7, 13) and three cucurbitane-type triterpenoid glycosides hemsleyaosides L-N (15-17), along with seventeen known cucurbitacin analogues were separated from the root tuber of Hemsleya penxianensis and elucidated based on NMR and HRESIMS. Then, 23 analogues of three types, namely, polyhydroxy-type (I) (1-7), monohydroxy-type (II) (8-13), and glycosides-type (III) (14-23), were assessed for their antitumor activity and structure-activity relationship analysis (SAR). We determined temozolomide (TMZ)-resistant GBM cell was the most sensitive to the tested compounds, and found hemsleyaoside N (HDN) displayed the best antineoplastic potency. Furthermore, we confirmed the anti-glioma activity of HDN in patient-derived recurrent GBM strains, GBM organoid (GBO) and orthotopic nude mouse models. Investigations exploring the mechanism made clear that HDN induced synchronous activation of UPR and MAPK signaling, which triggered deadly ER stress and apoptosis. Taken together, the potent antitumor activity of HDN warrants further comprehensive evaluation as a novel anti-glioma agent.

PTPRN Serves as a Prognostic Biomarker and Correlated with Immune Infiltrates in Low Grade Glioma.

BACKGROUND: Glioma is one of the most common malignant tumors of the central nervous system. Immune infiltration of tumor microenvironment was associated with overall survival in low grade glioma (LGG). However, effects of Tyrosine phosphatase receptor type N (PTPRN) on the progress of LGG and its correlation with tumor infiltration are unclear. METHODS: Here, datasets of LGG were from The Cancer Genome Atlas (TCGA) and normal samples were from GTEx dataset. Gepia website and Human Protein Atlas (HPA) Database were used to analyze the mRNA and protein expression of PTPRN. We evaluated the influence of PTPRN on survival of LGG patients. MethSurv was used to explore the expression and prognostic patterns of single CpG methylation of PTPRN gene in LGG. The correlations between the clinical information and PTPRN expression were analyzed using logistic regression and Multivariate Cox regression. We also explored the correlation between PTPRN expression and cancer immune infiltration by TIMER. Gene set enrichment analysis (GSEA) was formed using TCGA RNA-seq datasets. RESULTS: PTPRN mRNA and protein expression decreased in LGG compared to normal brain tissue in TCGA and HPA database. Kaplan-Meier analysis showed that the high expression level of PTPRN correlated with a good overall survival (OS) of patients with LGG. The Multivariate Cox analysis demonstrated that PTPRN expression and other clinical-pathological factors (age, WHO grade, IDH status, and primary therapy outcome) significantly correlated with OS of LGG patients. The DNA methylation pattern of PTPRN with significant prognostic value were confirmed, including cg00672332, cg06971096, cg01382864, cg03970036, cg10140638, cg16166796, cg03545227, and cg25569248. Interestingly, PTPRN expression level significantly negatively correlated with infiltrating level of B cell, CD4+ T cells, Macrophages, Neutrophils, and DCs in LGG. Finally, GSEA showed that signaling pathways, mainly associated with tumor microenvironment and immune cells, were significantly enriched in PTPRN high expression. CONCLUSION: PTPRN is a potential biomarker and correlates with tumor immune infiltration in LGG.

Prognostic data analysis of surgical treatments for intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a commonly occurring disease in neurosurgery, yet its surgical treatment is controversial. This paper pertains to the study of the effects of different treatment regimens on the outcome of ICH population. Based on a globally shared third-party MIMIC-III database, the researchers firstly described the dissimilarities in survival probability, mortality, and neurological recovery among mainstream treatments for ICH; secondly, patient classification was determined by important clinical features; and outcome variations among treatment groups were compared. The 28-day, 90-day, and in-hospital mortality in the craniotomy group were significantly lower than minimally invasive surgery (MIS) and non-surgical group patients; and, the medium/long-term mortality in MIS group was significantly lower than the non-surgical group. The craniotomy group positively correlated with short-term GCS recovery compared with the MIS group; no difference existed between the non-surgical and MIS groups. The craniotomy group 90-day survival probability and short-term GCS recovery were superior to the other two treatments in the subgroups of first GCS 3-12; this tendency also presented in the MIS group over non-surgical group. For milder patients (first GCS > 12), the three treatment regimens had a minimal effect on patient survival, but the non-surgical group showed an advantage in short-term GCS recovery. Craniotomy patients have a lower mortality and a better short-term neurological recovery in an ICH population, especially in short-to-medium term mortality and short-term neurological recovery over MIS patients. In addition, surgical treatment is recommendable for patients with a GCS ≤ 12.

Ion Density-Dependent Dynamic Conductance Switching in Biomimetic Graphene Nanopores.

Gating in ion transport is at the center of many vital living-substance transmission processes, and understanding how gating works at an atomic level is essential but intricate. However, our understanding and finite experimental findings of subcontinuum ion transport in subnanometer nanopores are still limited, which is out of reach of the classical continuum nanofluidics. Moreover, the influence of ion density on subcontinuum ion transport is poorly understood. Here we report the ion density-dependent dynamic conductance switching process in biomimetic graphene nanopores and explain the phenomenon by a reversible ion absorption mechanism. Our molecular dynamics simulations demonstrate that the cations near the graphene nanopore can interact with the surface charges on the nanopore, thereby realizing the switching of high- and low-conductance states. This work has deepened the understanding of gating in ion transport.

Nonlinear electrohydrodynamic ion transport in graphene nanopores.

Mechanosensitivity is one of the essential functionalities of biological ion channels. Synthesizing an artificial nanofluidic system to mimic such sensations will not only improve our understanding of these fluidic systems but also inspire applications. In contrast to the electrohydrodynamic ion transport in long nanoslits and nanotubes, coupling hydrodynamical and ion transport at the single-atom thickness remains challenging. Here, we report the pressure-modulated ion conduction in graphene nanopores featuring nonlinear electrohydrodynamic coupling. Increase of ionic conductance, ranging from a few percent to 204.5% induced by the pressure­an effect that was not predicted by the classical linear coupling of molecular streaming to voltage-driven ion transport­was observed experimentally. Computational and theoretical studies reveal that the pressure sensitivity of graphene nanopores arises from the transport of capacitively accumulated ions near the graphene surface. Our findings may help understand the electrohydrodynamic ion transport in nanopores and offer a new ion transport controlling methodology.