3D color multimodality fusion imaging as an augmented reality educational and surgical planning tool for extracerebral tumors.

Extracerebral tumors often occur on the surface of the brain or at the skull base. It is important to identify the peritumoral sulci, gyri, and nerve fibers. Preoperative visualization of three-dimensional (3D) multimodal fusion imaging (MFI) is crucial for surgery. However, the traditional 3D-MFI brain models are homochromatic and do not allow easy identification of anatomical functional areas. In this study, 33 patients with extracerebral tumors without peritumoral edema were retrospectively recruited. They underwent 3D T1-weighted MRI, diffusion tensor imaging (DTI), and CT angiography (CTA) sequence scans. 3DSlicer, Freesurfer, and BrainSuite were used to explore 3D-color-MFI and preoperative planning. To determine the effectiveness of 3D-color-MFI as an augmented reality (AR) teaching tool for neurosurgeons and as a patient education and communication tool, questionnaires were administered to 15 neurosurgery residents and all patients, respectively. For neurosurgical residents, 3D-color-MFI provided a better understanding of surgical anatomy and more efficient techniques for removing extracerebral tumors than traditional 3D-MFI (P < 0.001). For patients, the use of 3D-color MFI can significantly improve their understanding of the surgical approach and risks (P < 0.005). 3D-color-MFI is a promising AR tool for extracerebral tumors and is more useful for learning surgical anatomy, developing surgical strategies, and improving communication with patients.

[Clinical Features and Surgical Outcomes of 15 Cases of Intracranial Alveolar Echinococcosis]. / 15ä¾‹é¢ å† æ³¡åž‹æ£˜çƒèš´ç— çš„ä¸´åºŠç‰¹ç‚¹åŠæ‰‹æœ¯ç–—æ•ˆåˆ†æž.

Objective: To investigate the surgical treatment strategy of intracranial alveolar echinococcosis (AE) and the clinical outcomes. Methods: The clinical and follow-up data of 15 intracranial AE patients who underwent surgical treatment in the Departments of Neurosurgery of Sichuan Provincial People's Hospital (SPPH) and People's Hospital of Aba Tibetan and Qiang Autonomous Prefecture (a branch hospital of SPPH) between March 2017 and January 2021 were retrospectively analyzed. Full follow-up data were available for each of the 15 cases. The clinical and imaging characteristics, general surgical information, and surgical outcomes were analyzed. Results: In the 15 patients, there were a total of 50 intracranial lesions, with an average of (3.3±3.1)/case. Four cases had solitary intracranial lesions, while 11 cases had multiple lesions, with the number of intracranial lesions per case ranging from 2 to 13. All patients with solitary intracranial lesions received total resection. In 6 patients with multiple intracranial lesions, only the largest lesion was surgically removed, and in 5 patients, 2 to 3 adjacent lesions were surgically removed. All but one patient had extracranial lesions in their liver, lungs, kidneys, adrenal glands, and thoracic vertebrae. The patients were followed up for 12 to 58 months after surgery, with the mean follow-up time being (28.1±13.4) months. Among the 15 cases, 13 showed stable intracranial condition during postoperative follow-up. Intracranial lesions recurred in 2 patients who had deep lesions accompanied by dissemination to the subarachnoid space. Two patients died during follow-up. Conclusion: Microsurgical treatment of intracranial AE is effective, but total surgical resection is difficult to accomplish when patients have echinococcosis lesions located at a depth, especially when the lesions are spreading to the subarachnoid space. The prognosis of patients is closely associated with the extent of lesion invasion and the control of systemic hydatid lesions, especially those in the liver.

miR-1297 sensitizes glioma cells to temozolomide (TMZ) treatment through targeting adrenomedullin (ADM).

BACKGROUND: Gliomas account for about 80% of all malignant brain and other central nervous system (CNS) tumors. Temozolomide (TMZ) resistance represents a major treatment hurdle. Adrenomedullin (ADM) has been reported to induce glioblastoma cell growth. METHODS: Cell viability was measured using the CCK-8 assay. The apoptosis analysis was performed using the Annexin V-FITC Apoptosis Detection Kit. The mitochondrial membrane potential was determined by JC-1 staining. A nude mouse tumor assay was used to detect tumor formation. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were performed in tissue sections. Activation of Akt and Erk and expression of apoptosis-related proteins were determined by immunoblotting. RESULTS: ADM expression has been found upregulated in TMZ -resistant glioma samples based on bioinformatics and experimental analyses. Knocking down ADM in glioma cells enhanced the suppressive effects of TMZ on glioma cell viability, promotive effects on cell apoptosis, and inhibitory effects on mitochondrial membrane potential. Moreover, ADM knockdown also enhanced TMZ effects on Bax/Bcl-2, Akt phosphorylation, and Erk1/2 phosphorylation. Bioinformatics and experimental investigation indicated that miR-1297 directly targeted ADM and inhibited ADM expression. miR-1297 overexpression exerted similar effects to ADM knockdown on TMZ-treated glioma cells. More importantly, under TMZ treatment, inhibition of miR-1297 attenuated TMZ treatment on glioma cells; ADM knockdown partially attenuated the effects of miR-1297 inhibition on TMZ-treated glioma cells. CONCLUSIONS: miR-1297 sensitizes glioma cells to TMZ treatment through targeting ADM. The Bax/Bcl-2, Akt, and Erk1/2 signaling pathways, as well as mitochondrial functions might be involved.

Downregulation of GTSE1 leads to the inhibition of proliferation, migration, and Warburg effect in cervical cancer by blocking LHDA expression.

AIM: G2 and S phase-expressed-1 (GTSE1) has been identified to play a vital role in several kinds of cancers, but its role in cervical cancer development remains unknown. Herein, we aimed to reveal the role and underlying mechanism of GTSE1 in cervical cancer cell growth, migration, and aerobic glycolysis. METHODS: GTSE1 expression levels in cervical cancer tissues and normal cervical tissues were determined by real time PCR and immunohistochemistry. Human short hairpin RNA was used to downregulate GTSE1 level in cervical cancer cells SiHa and HeLa cells. Colony formation, cell counting kit-8, and wound-healing assays were used for cell function evaluation. Lactate production, lactate dehydrogenase activity, and glucose concentration were tested to assess the Warburg effect. RESULTS: GTSE1 expressions at both mRNA and protein levels were significantly elevated in cervical cancer tissues compared with normal tissues. Downregulation of GTSE1 induced significant repressions in cell colony formation, viability and migration, and Warburg effect, as well as reduced expression of lactate dehydrogenase isoform A (LDHA) at mRNA and protein levels. Additionally, downregulation of GTSE1 weakened the tumorigenesis of HeLa and SiHa cells in vivo. CONCLUSION: This study demonstrated that downregulation of GTSE1 led to significant inhibitions in cell proliferation, migration, tumorigenesis, and Warburg effect in cervical cancer by blocking the expression of LHDA.

Next-generation sequencing of microRNAs reveals a unique expression pattern in different types of pituitary adenomas.

Pituitary adenomas (PAs) are considered the most common intracranial tumor to cause serious morbidity because of dysregulated pituitary hormone secretions. Aberrant expression of microRNAs (miRNAs) is correlated with the development and function of the pituitary gland as well as the tumorigenesis of hypothalamic-pituitary axis-related pituitary tumors. In this study, we showed the differential expression patterns of miRNAs in NFPAs (nonfunctioning pituitary adenomas), GHPAs (growth hormone-secreting pituitary adenomas) and PRLPAs (prolactin-secreting pituitary adenomas) compared to those in three normal pituitary glands using the HiSeq 2000 sequencing system (Illumina). We validated miRNA expression using real-time quantitative polymerase chain reaction (RT-qPCR) analyses of samples from 73 patients (13 GHPAs, 42 NFPAs, and 18 PRLPAs) and 6 normal pituitary gland. We observed that miR-34c-3p was significantly downregulated in our PRLPA samples (p < 0.01), along with miR-34b-5p, miR-378 and miR-338-5p (all p < 0.05). In NFPAs, miR-493-5p was downregulated, and miR-181b-5p was significantly upregulated (p < 0.01). In GHPAs, miR-184 was significantly upregulated (p < 0.05). We observed that the tumor suppressive miR-124-3p was downregulated in both NFPAs and GHPAs. Taken together, we showed distinctive miRNA expression patterns in these three PAs, and these miRNA signatures in PA may have therapeutic potential as novel biomarkers for each type of PA.

MicroRNA-186 targets SKP2 to induce p27Kip1-mediated pituitary tumor cell cycle deregulation and modulate cell proliferation.

Pituitary tumors are usually benign but can occasionally exhibit hormonal and proliferative behaviors. Dysregulation of the G1/S restriction point largely contributes to the over-proliferation of pituitary tumor cells. F-box protein S-phase kinase-interacting protein-2 (SKP2) reportedly targets and inhibits the expression of p27Kip1, a well-known negative regulator of G1 cell cycle progression. In this study, SKP2 expression was found to be upregulated while p27Kip1 expression was determined to be downregulated in rat and human pituitary tumor cells. Furthermore, SKP2 knockdown induced upregulation of p27Kip1 and cell growth inhibition in rat and human pituitary tumor cells, while SKP2overexpression elicited opposite effects on p27Kip1 expression and cell growth. The expression of microRNA-186 (miR-186) was reported to be reduced in pituitary tumors. Online tools predicted SKP2 to be a direct downstream target of miR-186, which was further confirmed by luciferase reporter gene assays. Moreover, miR-186 could modulate the cell proliferation and p27Kip1-mediated cell cycle alternation of rat and human pituitary tumor cells through SKP2. As further confirmation of these findings, miR-186 and p27Kip1 expression were downregulated, while SKP2 expression was upregulated in human pituitary tumor tissue samples; thus, SKP2 expression negatively correlated with miR-186 and p27Kip1 expression. In contrast, miR-186 expression positively associated with p27Kip1 expression. Taken together, we discovered a novel mechanism by which miR-186/SKP2 axis modulates pituitary tumor cell proliferation through p27Kip1-mediated cell cycle alternation.

Fluorescent Nanobiosensors for Sensing Glucose.

Glucose sensing in diabetes diagnosis and therapy is of great importance due to the prevalence of diabetes in the world. Furthermore, glucose sensing is also critical in the food and drug industries. Sensing glucose has been accomplished through various strategies, such as electrochemical or optical methods. Novel transducers made with nanomaterials that integrate fluorescent techniques have allowed for the development of advanced glucose sensors with superior sensitivity and convenience. In this review, glucose sensing by fluorescent nanobiosensor systems is discussed. Firstly, typical fluorescence emitting/interacting nanomaterials utilized in various glucose assays are discussed. Secondly, strategies for integrating fluorescent nanomaterials and biological sensing elements are reviewed and discussed. In summary, this review highlights the applicability of fluorescent nanomaterials, which makes them ideal for glucose sensing. Insight on the future direction of fluorescent nanobiosensor systems is also provided.

The diagnostic, prediction of postoperative recurrence and prognostic value of HE4 in epithelial ovarian cancer.

PURPOSE: To explore the clinical value of the level of human epididymis protein 4 (HE4) in serum in the diagnosis, prediction of postoperative recurrence and prognosis of epithelial ovarian cancer (EOC). METHODS: A total of 103 EOC patients and 121 individuals with benign ovarian lesions were selected. All of them were admitted to our hospital between January 2013 and January 2014 as group A (EOC, n=103) and group B (benign ovarian lesions, n=121), respectively. Additionally, 106 serum samples collected from healthy people who underwent physical examination were selected as group C. The serum levels of HE4 were assessed one day before and one day after the operation to reveal differences among the three groups. In addition, we analyzed the clinical value of HE4 in the diagnosis, prediction of recurrence and progression-free survival (PFS) of EOC patients. RESULTS: In group A, the level of HE4 was significantly higher than in groups B and C (p<0.05), while comparison between the group B and C revealed no statistically significant difference (p>0.05). The sensitivity, specificity, positive predictive value and negative predictive value of HE4 in the diagnosis of EOC were 82.52, 84.46, 83.47 and 92.34%, respectively. In the prediction of recurrence of EOC, the sensitivity and specificity of HE4 alone were 87.57 and 92.45%, respectively, while the sensitivity and specificity of HE4 combined with CA-125 were 93.45 and 94.24%, respectively. In addition, the level of HE4 showed a significant negative effect on PFS (p<0.05). CONCLUSIONS: Detection of HE4 is conducive to the diagnosis and prediction of recurrence of EOC, and HE4 in high concentration suggests poor prognosis.

The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation and migration by targeting iASPP.

Long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) has been reported to be involved in the development and progression of many types of tumors including breast cancer, gastric cancer, and bladder cancer. However, the exact effects and molecular mechanisms of UCA1 in glioma progression remain unclear up to now. In this study, we firstly found that UCA1 was upregulated in glioma tumor samples and negatively correlated with survival time. Then, we investigated the role of UCA1 in human glioma cell lines. Our results showed that upregulation of lncRNA-UCA1 in glioma tissues and cell lines could promote glioma cell proliferation and migration through interaction with miR-182, and knockdown of UCA1 inhibited the proliferation and migration of human glioma cell. In addition, miR-182 dependent inhibitor of apoptosis-stimulating protein of p53 (iASPP) was required in the regulation of UCA1 induced glioma cell proliferation. Taken together, UCA1 might promote proliferation and migration of glioma, to regulate the tumor growth and metastasis via miR-182 dependent iASPP regulation. Therefore, lncRNA-UCA1 could be regarded as a therapeutic target in human glioma.

Nanostructured biosensor using bioluminescence quenching technique for glucose detection.

BACKGROUND: Most methods for monitoring glucose level require an external energy source which may limit their application, particularly in vivo test. Bioluminescence technique offers an alternative way to provide emission light without external energy source by using bioluminescent proteins found from firefly or marine vertebrates and invertebrates. For quick and non-invasive detection of glucose, we herein developed a nanostructured biosensor by applying the bioluminescence technique. RESULTS: Luciferase bioluminescence protein (Rluc) is conjugated with ß-cyclodextrin (ß-CD). The bioluminescence intensity of Rluc can be quenched by 8 ± 3 nm gold nanoparticles (Au NPs) when Au NPs covalently bind to ß-CD. In the presence of glucose, Au NPs are replaced and leave far from Rluc through a competitive reaction, which results in the restored bioluminescence intensity of Rluc. A linear relationship is observed between the restored bioluminescence intensity and the logarithmic glucose concentration in the range of 1-100 µM. In addition, the selectivity of this designed sensor has been evaluated. The performance of the senor for determination of the concentration of glucose in the blood of diabetic rats is studied for comparison with that of the concentration of glucose in aqueous. CONCLUSIONS: This study demonstrates the design of a bioluminescence sensor for quickly detecting the concentration of glucose sensitively.

TREM2 gene induces differentiation of induced pluripotent stem cells into dopaminergic neurons and promotes neuronal repair via TGF-ß activation in 6-OHDA-lesioned mouse model of Parkinson's disease.

OBJECTIVE: Induced pluripotent stem cells (iPSCs) hold a promising potential for rescuing dopaminergic neurons in therapy for Parkinson's disease (PD). This study clarifies a TREM2-dependent mechanism explaining the function of iPSC differentiation in neuronal repair of PD. METHODS: PD-related differentially expressed genes were screened by bioinformatics analyses and their expression was verified using RT-qPCR in nigral tissues of 6-OHDA-lesioned mice. Following ectopic expression and depletion experiments in iPSCs, cell differentiation into dopaminergic neurons as well as the expression of dopaminergic neuronal markers TH and DAT was measured. Stereotaxic injection of 6-OHDA was used to develop a mouse model of PD, which was injected with iPSC suspension overexpressing TREM2 to verify the effect of TREM2 on neuronal repair. RESULTS: TREM2 was poorly expressed in the nigral tissues of 6-OHDA-lesioned mice. In the presence of TREM2 overexpression, the iPSCs showed increased expression of dopaminergic neuronal markers TH and DAT, which facilitated the differentiation of iPSCs into dopaminergic neurons. Mechanistic investigations indicated that TREM2 activated the TGF-ß pathway and induced iPSC differentiation into dopaminergic neurons. In vivo data showed that iPSCs overexpressing TREM2 enhanced neuronal repair in 6-OHDA-lesioned mice. CONCLUSION: This work identifies a mechanistic insight for TREM2-mediated TGF-ß activation in the regulation of neuronal repair in PD and suggests novel strategies for neurodegenerative disorders.

Transcriptomic analysis identifies the neuropeptide cortistatin (CORT) as an inhibitor of temozolomide (TMZ) resistance by suppressing the NF-κB-MGMT signaling axis in human glioma.

Glioma is a common tumor originating in the brain that has a high mortality rate. Temozolomide (TMZ) is the first-line treatment for high-grade gliomas. However, a large proportion of gliomas are resistant to TMZ, posing a great challenge to their treatment. In the study, the specific functions and mechanism(s) by which cortistatin (CORT) regulates TMZ resistance and glioma progression were evaluated. The decreased expression of CORT was detected in glioma tissues, and highly expressed CORT was associated with a better survival rate in patients with glioma. CORT overexpression notably decreased the capacity of glioma cells to proliferate and migrate in vitro and to form tumors in vivo. CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT, p21, and Puma expression. Importantly, CORT overexpression reduced the resistance of gliomas to TMZ in vivo. CORT expression was negatively correlated with MGMT expression in both glioma tissues and cells, and it was found that CORT inhibited NF-κB pathway activation in glioma cells, thereby inhibiting MGMT expression. In conclusion, CORT regulates glioma cell growth, migration, apoptosis, and TMZ resistance by weakening the activity of NF-κB/p65 and thereby regulating MGMT expression. The CORT/NF-κB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ. Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells, independent of its effects on TMZ resistance, providing evidence of novel therapeutic targets for glioma that should be evaluated in further studies.

A Wind Bell Inspired Triboelectric Nanogenerator for Extremely Low­Speed and Omnidirectional Wind Energy Harvesting.

As one of the most promising renewable energies, wind energy is abundant in the natural environment. However, it is still challenging to effectively collect wind energy because of its variable wind speed and unpredictable direction. Here, a triboelectric nanogenerator, which is inspired by ancient Chinese wind bells, has been developed to collect energy from variable-speed and multi-directional wind. The wind-bell-inspired triboelectric nanogenerator (W-TENG) has the capability to generate electricity even at a very low wind speed of 0.5 m s-1. Furthermore, it is able to harvest wind energy effectively from all directions (0-360 degrees). The parameter-optimized W-TENG achieves a maximum output voltage of 9.3 V and a maximum current of 0.63 µA. Electronic devices including a digital watch and 40 light-emitting diodes (LEDs) are successfully powered by the designed W-TENG, demonstrating its applicability. In this study, it is believed that a novel and effective strategy is provided to harvest energy from variable-speed and multi-directional wind.

[Application of far lateral craniocervical approach in the microsurgical treatment of the jugular foramen tumors].

OBJECTIVE: To investigate the administration of far lateral craniocervical approach in the jugular foramen (JF) tumors. METHODS: A retrospective analysis was performed in 14 cases of JF tumors (9 neurilemmomas, 3 meningiomas, 1 glomus jugulare tumor, and 1 adenoid cystic carcinoma) surgically treated between January 2009 and January 2012, with focus on the surgical approach. Six patients (6/14) showed hydrocephalus. The tumor type was composed of 5 intracranial and intraforamen tumors with patent or occluded jugular bulb, 1 intracranial tumor with extension into the upper cervical canal, 4 extracranial and intra foramen tumors, 4 intra- and extracranial dumbbell-shaped communicating tumors involving the parapharyngeal space above C2 or extending caudally below C3. Far lateral postcondylar approach (FLPC) was carried out in 2 cases, far lateral tansjugular process approach (FLTJP) in 3 cases, combined FLPC + C1-2 semi-laminectomy approach in 1 case, combined FLTJP + trans-C1 transverse process approach in 7 cases, and combined FLTJP + neck approach with dissection of carotid sheath to the skull base in 1 case. Endovascular embolotherapy prior to surgical resection was performed in 1 glomus jugulare tumor. RESULTS: Total tumor removal was achieved in 12 patients and subtotal removal in 2 patients, with no cerebrospinal fluid leakage or operative mortality. New cranial nerve paresis occurred after surgery in 1 case of facial nerve and 1 case of lower cranial nerve. Transient worsening of preoperative lower cranial nerve deficits was noted in 3 patients. Long-term follow-up study ranging from 5 to 32 months (average 13.7 months) showed 7 patients with lower cranial nerve deficits (6 preexisting and 1 new), with exception of one preoperative lower cranial nerve dysfunction due to the infiltration of an adenoid cystic carcinoma, experienced favorable improvement with recovery of adequate swallowing function, but voice disturbance remained in 4 cases. One patient with new facial nerve deficit presented with partial improvement and the hydrocephalus in 6 patients all spontaneously regressed. There was no tumor recurrence in patients receiving total removal and no tumor progression in patients undergoing subtotal removal. CONCLUSIONS: FLTJP is a basic approach for JF tumors. The combined cranial and cervical approach should be considered in those tumors extending into the upper cervical canal and parapharyngeal space. The associated hydrocephalus seldom requires additional surgical management.

CK2 inhibitor DMAT ameliorates spinal cord injury by increasing autophagy and inducing anti-inflammatory microglial polarization.

Spinal cord injury (SCI) is a destructive and disabling nerve injury from which complete recovery has not yet been achieved due to complex pathology. Casein kinase II (CK2) is a pleiotropic serine/threonine protein kinase that plays an essential role in the nervous system. This study aimed to investigate the role of CK2 in SCI to understand the pathogenesis of SCI and explore new therapeutic methods. The SCI rat model of C5 unilateral clamp was established by modified clamp method in male adult SD rats. Then, CK2 inhibitor DMAT was used to treat SCI rats, and the behaviour, pathological changes in the spinal cord and microglial polarization were analysed. Additionally, the effects of DMAT on the polarization and autophagy of microglial BV-2 cells were investigated in vitro, and the effects of BV-2 polarization on spinal cord neuronal cells were analysed by Transwell coculture. Results showed that DMAT significantly increased the BBB score, improved histopathological injury, decreased the expression of inflammatory cytokines, and promoted M2 polarization of microglia in SCI rats. In vitro experiments further confirmed that DMAT could promote the polarization of BV-2 to the M2 type, promote autophagy, and reverse the LPS-induced decline in cell viability and increase in apoptosis of neuronal cells. The use of 3-MA confirmed that autophagy plays an important role in DMAT promoting M2 polarization of BV-2 to improve neuronal cell viability. In conclusion, CK2 inhibitor DMAT improved SCI by inducing anti-inflammatory polarization of microglia through autophagy and is a potential therapeutic target for SCI.

Nanostructured N, S, and P-Doped Elaeagnus Angustifolia Gum-Derived Porous Carbon with Electrodeposited Silver for Enhanced Electrochemical Sensing of Acetaminophen.

Acetaminophen (N-acetyl-p-aminophenol, APAP) is regularly used for antipyretic and analgesic purposes. Overdose or long-term exposure to APAP could lead to liver damage and hepatotoxicity. In this study, the approach of enhanced electrochemical detection of APAP by nanostructured biomass carbon/silver was developed. Porous biomass carbon derived from Elaeagnus Angustifolia gum was prepared by pyrolysis with co-doping of electron-rich elements of nitrogen, sulfur, and phosphorus. The electrodeposition of silver onto a glassy carbon electrode modified with porous carbon could enhance the sensing signal towards APAP. Two linear ranges from 61 nM to 500 µM were achieved with a limit of detection of 33 nM. The developed GCE sensor has good anti-interference, stability, reproducibility, and human urine sample analysis performance. The silver-enhanced biomass carbon GCE sensor extends the application of biomass carbon, and its facile preparation approach could be used in constructing disposable sensing chips in the future.

Hybrid reduced graphene oxide nanosheets with negative magnetoresistance for the diagnosis of hypoglycemia.

Few glucometers are available to easily and quickly measure low blood glucose levels (≤4 mmol L-1) from a small amount of blood samples. Here, a hybrid reduced graphene oxide (rGO)-based magnetoresistance (MR) sensor has been developed to monitor blood glucose levels to quickly detect hypoglycemia. Hybrid rGO nanosheets, incorporating Fe50Co50 nanoparticles onto rGO nanosheets, with an unusual large negative MR (-5.7%) at room temperature under a small magnetic field (9.5 kOe) have been successfully fabricated through a one-pot reaction. To quickly detect the low concentration of glucose in a small amount of blood (1 µL), a two-step process has been further developed by using the "sandwich" structural MR sensor. The results show that the higher the negative MR value of the sensor, the lower the concentration of glucose that can be detected. A linear relationship between the MR and the concentration of the spiked plasma glucose taken from streptozotocin-induced diabetic rats can be found when the concentration of glucose is in the range of 0-6 mmol L-1. The limit of detection (LOD) of this MR glucose sensor is 0.867 mmol L-1. The accuracy of the rGO-based MR sensor is improved in measuring low concentration of plasma glucose as compared to that of a commercialized glucometer. Furthermore, the selectivity of the rGO-based MR sensor has been studied. The results demonstrate that the rGO-based MR sensor is a flexible and sensitive detection platform and specifically suitable for monitoring low concentrations of plasma glucose to prevent from hypoglycemia.

Spectrum-effect relationship between UPLC fingerprints and melanogenic effect of Ruta graveolens L.

A total of 29 batches of R. graveolens were used in this study, their fingerprints were obtained by ultra-performance liquid chromatography (UPLC) and their melanogenesis activities were evaluated. The common peaks were identified by quadrupole-orbitrap high-resolution mass spectrometry (Q-Orbitrap-HRMS). Eleven coumarins, six alkaloids, three flavonoids, three phenolic acids, and four other compounds were found. The spectrum-effect relationships between R. graveolens' chemical fingerprints, the melanin synthesis, and tyrosine's activation activities were established through chemometrics methods which in detail principal component analysis (PCA), gray correlation analysis (GRA), bivariate correlation analysis (BCA) and orthogonal partial least squares analysis (OPLS). The results showed that P18 (bergapten), P22 (isoimperatorin), P15 (kokusaginine), P7 (rutin), P12 (psoralen), and P13 (graveolinine) were relevant to intracellular melanin synthesis activity and tyrosinase activity. Among them, P18 (bergapten), P15 (kokusaginine), and P12 (psoralen) were validated with good melanogenesis activities. This study provides a research basis for future quality control and medicinal application of R. graveolens.

Predictive value of admission red cell distribution width-to-platelet ratio for 30-day death in patients with spontaneous intracerebral hemorrhage: an analysis of the MIMIC database.

Aim: Prognostic assessment plays an important role in the effective management of patients with spontaneous intracerebral hemorrhage (ICH). The study aimed to investigate whether elevated red cell distribution width-to-platelet ratio (RPR) at admission was related to 30-day death in patients with spontaneous intracerebral hemorrhage (ICH). Methods: This retrospective cohort study included 2,823 adult patients with ICH from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) III and IV databases between 2001 and 2019. The Cox proportional hazard model was utilized to evaluate the relationship between RPR levels and 30-day death risk. The area under receiver-operating characteristic curve (AUC) was used to assess the predictive ability of RPR for 30-day death in patients with ICH. Results: At the end of the 30-day follow-up, 799 (28.30%) patients died, and the median RPR level was 0.066 (0.053, 0.087). After adjusting for confounders, the tertile 3 of RPR levels [hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.15-1.64] were associated with a higher risk of 30-day death in patients with ICH compared with tertile 1. In the stratified analyses, elevated RPR levels were found to be associated with an increased risk of 30-day death in patients aged <65 years (HR = 1.77, 95%CI: 1.29-2.43), aged ≥65 years (HR = 1.30, 95%CI: 1.05-1.61), with Glasgow Coma Score (GCS) <14 (HR = 1.65, 95%CI: 1.27-2.14), with Charlson comorbidity index (CCI) ≥4 (HR = 1.45, 95%CI: 1.17-1.80), with (HR = 1.66, 95%CI: 1.13-2.43) or without sepsis (HR = 1.32, 95%CI: 1.08-1.61), and female patients (HR = 1.75, 95%CI: 1.35-2.26) but not in male patients (P = 0.139) and patients with GCS ≥14 (P = 0.058) or CCI <4 (P = 0.188). The AUC for RPR to predict 30-day death in patients with ICH was 0.795 (95%CI: 0.763-0.828) in the testing set, indicating a good predictive ability. Conclusion: Elevated RPR levels were correlated with an increased risk of 30-day death in patients with ICH, and RPP levels showed good predictive ability for 30-day death.

Uncover DNA damage and repair-related gene signature and risk score model for glioma.

BACKGROUND: Glioma is a common primary central nervous system tumor with complex pathogenesis. DNA damage and repair (DDR) is widely involved in regulating cell proliferation and tumorigenesis by correcting and repairing DNA damage mechanisms. Recent studies have reported the following properties in cancer cells in glioma, increased DNA damage and reduced DNA repair capacity. However, the relationship between glioma and DDR-related genes was unclear. METHODS: DDR-related risk score model was built. The validity of this model was validated in detail through the Kaplan-Meier survival analysis, tumor mutational burden (TMB) analysis, immune cell infiltration, sensitivity to treatment regimens. Moreover, the model's adaptability was validated in different glioma data cohorts and different glioma subgroups. To further investigate the molecular mechanism of one of DDR-related gene (NUDT1) in glioma, U251 cell was used for the knockdown experiment, followed by MTT, wound healing and transwell analysis. RESULTS: Ten prognostic-related DDR-related signature genes were obtained, including EID3, MGMT, YWHAG, PMS1, SHPRH, HUS1, NUDT1, GADD45G, APEX1 and FAM175A. The RT-qPCR results suggested that the latter five genes were highly expressed in glioma patients. Interestingly, high TMB score had longer survival. In high-risk score groups, reduced immune cell infiltration in the tumor microenvironment lead to poorer patient outcomes. Sensitivity to treatment regimens analysis indicated that low-risk score groups were more sensitive to chemotherapeutics. Moreover, the risk score model had a good prediction effect on different glioma datasets and different glioma subgroups. In vitro mechanism study showed that knockdown of NUDT1 reduced tumorigenesis. Furthermore, knockdown of NUDT1 remarkably reduced the expression level of HIF-1α. CONCLUSION: DDR-related risk score model built-in this work has good predictive performance for glioma.Key messagesTen prognostic-related DDR-related signature genes were obtained, including EID3, MGMT, YWHAG, PMS1, SHPRH, HUS1, NUDT1, GADD45G, APEX1 and FAM175A.In high-risk score groups, reduced immune cell infiltration in the tumor microenvironment leads to poorer patient outcomes.The risk score model had a good prediction effect on different glioma datasets and different glioma subgroups.Knockdown of NUDT1 reduced tumorigenesis of glioma and remarkably reduced the expression level of HIF-1α.