Melatonin Improves Vasogenic Edema via Inhibition to Water Channel Aquaporin-4 (AQP4) and Metalloproteinase-9 (MMP-9) Following Permanent Focal Cerebral Ischemia.

Background: The efficacy of melatonin in reducing vasogenic and cytotoxic edema was investigated using a model of permanent middle cerebral artery occlusion (pMCAO). Methods: Rats underwent pMCAO, followed by intravenous administration of either melatonin (5 mg/kg) or a vehicle 10 min post-insult. Brain infarction and edema were assessed, and Western blot analyses were conducted to examine the expression levels of aquaporin-4 (AQP4), metalloproteinase-9 (MMP-9), and the neurovascular tight-junction protein ZO-1 upon sacrifice. The permeability of the blood-brain barrier (BBB) was measured using spectrophotometric quantification of Evans blue dye leakage. Results: Compared to controls, melatonin-treated rats exhibited a significant reduction in infarct volume by 26.9% and showed improved neurobehavioral outcomes (p < 0.05 for both). Melatonin treatment also led to decreased Evans blue dye extravasation and brain edema (p < 0.05 for both), along with lower expression levels of AQP4 and MMP-9 proteins and better preservation of ZO-1 protein (p < 0.05 for all). Conclusions: Therefore, melatonin offers neuroprotection against brain swelling induced by ischemia, possibly through its modulation of AQP4 and MMP-9 activities in glial cells and the extracellular matrix (ECM) during the early phase of ischemic injury.

Viscolin-mediated antiapoptotic and neuroprotective effects in cortical neurons exposed to oxygen-glucose deprivation and rats subjected to transient focal cerebral ischemia.

OBJECTIVE: Previously, we have successfully purified and synthesized viscolin, an agent derived from Viscum coloratum extract, which has shown significant potential in the treatment of stroke. Our study aimed to evaluate the neuroprotective effects of viscolin. METHODS: We first assessed the cytotoxicity of viscolin on primary neuronal cultures and determined its antioxidant and radical scavenging properties. Subsequently, we identified the optimal dose-response of viscolin in protecting against glutamate-induced neurotoxicity. RESULTS: Our results demonstrated that viscolin at a concentration of 10 µM effectively reduced neuronal cell death up to 6 hours after glutamate-induced neurotoxicity. Additionally, we investigated the therapeutic window of opportunity and the potential of viscolin in preventing necrotic and apoptotic damage in cultured neurons exposed to oxygen glucose deprivation-induced neurotoxicity. Our findings showed that viscolin treatment significantly reduced DNA breakage, prevented the release of cytochrome c from mitochondria to cytosol, increased the expression of anti-apoptotic protein Bcl-2, decreased the expression of pro-apoptotic protein Bax, and reduced the number of TUNEL-positive cells. Additionally, our in vivo investigation demonstrated a reduction in brain infarction following middle cerebral artery occlusion. CONCLUSION: Viscolin has potential utility as a therapeutic agent in the treatment of stroke.

Erector Spinae Plane Block Versus Thoracolumbar Interfascial Plane Block in Lumbar Spine Surgery: A Meta-Analysis of Randomized Controlled Trials.

STUDY DESIGN: Meta-analysis. OBJECTIVE: To compare the effectiveness of postoperative pain control between erector spinae plane block (ESPB) and thoracolumbar interfascial plane (TLIP) block in lumbar spine surgery. METHODS: PubMed, Embase, and MEDLINE electronic databases were searched for articles containing randomized controlled trials (RCTs) published between January 1900 and January 2024. We extracted the postoperative mean pain score, the first 24-h postoperative morphine consumption, and their standard deviation from the included studies. Meta-analysis was performed using the functions available in the metafor package in R software. We pooled continuous variables using an inverse variance method with a random-effects model and summarized them as standardized mean differences. RESULTS: Five RCTs that directly compared the ESPB and TLIP block in lumbar spine surgery were included, enrolling 432 participants randomly into the two groups with 216 participants in each group. The pooled analyses showed that there was no significant difference between the ESPB and TLIP groups in terms of lower pain scores during the early (1 h) (standardized mean difference [SMD] -1.49, 95% confidence interval [CI], -3.10; 0.11), middle (12 h) (SMD -3.12, 95% CI, -6.86; 0.61), and late (24 h) (SMD -1.38, 95% CI, -3.01; 0.24) postoperative periods. There was also no significant difference in the first 24-h postoperative morphine equivalent consumption between the ESPB and TLIP groups (SMD -0.46 mg, 95% CI -1.23; 0.31). CONCLUSION: No significant difference was observed between the ESPB and TLIP block in terms of postoperative pain control and 24-h morphine equivalent consumption for lumbar spine surgery.

Anti-oxidative and anti-inflammatory effects of Ginkgo biloba extract (EGb761) on hindlimb skeletal muscle ischemia-reperfusion injury in rats.

In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 µg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.

Outcomes of surgery and subsequent therapy for central nervous system oligoprogression in EGFR-mutated NSCLC patients.

BACKGROUND: Oligoprogression is an emerging issue in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the surgical treatment for central nervous system (CNS) oligoprogression is not widely discussed. We investigated the outcomes of craniotomy with adjuvant whole-brain radiotherapy (WBRT) and subsequent therapies for CNS oligoprogression in patients with EGFR-mutated NSCLC. METHODS: NSCLC patients with CNS oligoprogression were identified from a tertiary medical center. The outcomes of surgery with adjuvant WBRT or WBRT alone were analyzed, along with other variables. Overall survival and progression-free survival were analyzed using the log-rank test as the primary and secondary endpoints. A COX regression model was used to identify the possible prognostic factors. RESULTS: Thirty-seven patients with CNS oligoprogression who underwent surgery or WBRT were included in the study after reviewing 728 patients. Twenty-one patients underwent surgery with adjuvant WBRT, and 16 received WBRT alone. The median overall survival for surgery and WBRT alone groups was 43 (95% CI 17-69) and 22 (95% CI 15-29) months, respectively. Female sex was a positive prognostic factor for overall survival (OR 0.19, 95% CI 0.06-0.57). Patients who continued previous tyrosine kinase inhibitors (OR 3.48, 95% CI 1.06-11.4) and induced oligoprogression (OR 3.35, 95% CI 1.18-9.52) were associated with worse overall survival. Smoking history (OR 4.27, 95% CI 1.54-11.8) and induced oligoprogression (OR 5.53, 95% CI 2.1-14.7) were associated with worse progression-free survival. CONCLUSIONS: Surgery combined with adjuvant WBRT is a feasible treatment modality for CNS oligoprogression in patients with EGFR-mutated NSCLC. Changing the systemic-targeted therapy after local treatments may be associated with improved overall survival.

RNA-binding protein-regulated fibronectin is essential for EGFR-activated metastasis of head and neck squamous cell carcinoma.

There is a higher expression level of epidermal growth factor receptor (EGFR) in up to 90% of advanced head and neck squamous cell carcinoma (HNSCC) tissue than in normal surrounding tissues. However, the role of RNA-binding proteins (RBPs) in EGFR-associated metastasis of HNSCC remains unclear. In this study, we reveal that RBPs, specifically nucleolin (NCL) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), correlated with the mesenchymal phenotype of HNSCC. The depletion of RBPs significantly attenuated EGF-induced HNSCC metastasis. Intriguingly, the EGF-induced EMT markers, such as fibronectin, were regulated by RBPs through the ERK and NF-κB pathway, followed by the enhancement of mRNA stability of fibronectin through the 5' untranslated region (5'-UTR) of the gene. The upregulation of fibronectin triggered the integrin signaling activation to enhance tumor cells' attachment to endothelial cells and increase endothelial permeability. In addition, the concurrence of EGFR and RBPs or EGFR and fibronectin was associated with overall survival and disease-free survival of HNSCC. The in vivo study showed that depletion of NCL, hnRNPA2B1, and fibronectin significantly inhibited EGF-promoted extravasation of tumor cells into lung tissues. The depletion of fibronectin or treatment with integrin inhibitors dramatically attenuated EGF-induced HNSCC metastatic nodules in the lung. Our data suggest that the RBPs/fibronectin axis is essential for EGF-induced tumor-endothelial cell interactions to enhance HNSCC cell metastasis.

Quantification of vessel separation using the carotid-jugular angle to predict the nerve origin of neck peripheral nerve sheath tumours: a pooled analysis of cases from the literature and a single-center cohort.

BACKGROUND: Postoperative nerve palsy is a major complication following resection of neck peripheral nerve sheath tumours (PNSTs). Accurate preoperative identification of the nerve origin (NO) can improve surgical outcomes and patient counselling. MATERIAL AND METHODS: This study was a retrospective cohort and quantitative analysis of the literature. The authors introduced a parameter, the carotid-jugular angle (CJA), to differentiate the NO. A literature review of neck PNST cases from 2010 to 2022 was conducted. The CJA was measured from eligible imaging data, and quantitative analysis was performed to evaluate the ability of the CJA to predict the NO. External validation was performed using a single-centre cohort from 2008 to 2021. RESULTS: In total, 17 patients from our single-centre cohort and 88 patients from the literature were analyzed. Among them, 53, 45, and 7 patients had sympathetic, vagus, and cervical nerve PNSTs, respectively. Vagus nerve tumours had the largest CJA, followed by sympathetic tumours, whereas cervical nerve tumours had the smallest CJA ( P <0.001). Multivariate logistic regression identified a larger CJA as a predictor of vagus NO ( P <0.001), and receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.907 (0.831-0.951) for the CJA to predict vagus NO ( P <0.001). External validation showed an AUC of 0.928 (0.727-0.988) ( P <0.001). Compared with the AUC of the previously proposed qualitative method (AUC=0.764, 0.673-0.839), that of the CJA was greater ( P =0.011). The cut-off value identified to predict vagus NO was greater than or equal to 100°. Receiver operating characteristic analysis showed an AUC of 0.909 (0.837-0.956) for the CJA to predict cervical NO ( P <0.001), with a cut-off value less than 38.5°. CONCLUSIONS: A CJA greater than or equal to 100° predicted a vagus NO and a CJA less than 100° predicted a non-vagus NO. Moreover, a CJA less than 38.5 was associated with an increased likelihood of cervical NO.

Evaluation of the safety, radiographic and resident training results of thoracic pedicle screws placement using resection of the transverse process.

OBJECTIVE: This study aimed at the evaluation and assessment of a simple method, the transverse process resection (TPR) technique, for freehand thoracic pedicle screw placement and the learning curve for trainee surgeons. METHODS: In the TPR technique, the tip of the thoracic transverse process (TP) is removed to create an entry point in the cancellous bone of the TP, and the thoracic pedicle is cannulated from the TP. We retrospectively evaluated the safety and radiographic results of the TPR technique and compared with that of conventional pedicle screws. The training performance of seven neurosurgical residents with TPR techniques were evaluated. RESULTS: Among 46 patients, a total of 322 thoracic screws were analyzed, including 178 screws placed using the TPR technique and 144 screws using the conventional straight-forward (SF) technique. TPR screws had greater medial angulations in all levels from T2 to T12 compared to SF screws (p < 0.001). The incidence of pedicle breach was lower in the TPR screws compared to SF screws (6.2% vs. 21.5%, p < 0.001), especially for screws placed by residents (6.7% vs. 29.6%, p < 0.001). Residents had improved performance following a cadaveric training course on the TPR technique (p = 0.001). CONCLUSION: This study demonstrated the safety of the TPR technique for thoracic pedicle screw placement and its short learning curve for trainee surgeons.

Risk Factors for 30-day Unplanned Readmission following Surgery for Lumbar Degenerative Diseases: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: Surgical procedures for lumbar degenerative diseases (LDD), which have emerged in the 21-century, are commonly practiced worldwide. Regarding financial burdens and health costs, readmissions within 30days following surgery are inconvenient. We performed a systematic review to integrate real-world evidence and report the current risk factors associated with 30-day readmission following surgery for LDD. METHODS: The Cochrane Library, Embase, and Medline electronic databases were searched from inception to April 2022 to identify relevant studies reporting risk factors for 30-day readmission following surgery for LDD. RESULTS: Thirty-six studies were included in the review. Potential risk factors were identified in the included studies that reported multivariate analysis results, including age, race, obesity, higher American Society of Anesthesiologists score, anemia, bleeding disorder, chronic pulmonary disease, heart failure, dependent status, depression, diabetes, frailty, malnutrition, chronic steroid use, surgeries with anterior approach, multilevel spinal surgeries, perioperative transfusion, presence of postoperative complications, prolonged operative time, and prolonged length of stay. CONCLUSIONS: There are several potential perioperative risk factors associated with unplanned readmission following surgery for LDD. Preoperatively identifying patients that are at increased risk of readmission is critical for achieving the best possible outcomes.

Analysis of Long Noncoding RNA ZNF667-AS1 as a Potential Biomarker for Diagnosis and Prognosis of Glioma Patients.

OBJECTIVE: Long noncoding RNAs (lncRNAs) have been strongly associated with various types of cancer. The present study aimed at exploring the diagnostic and prognostic value of lncRNA Zinc finger protein 667-antisense RNA 1 (ZNF667-AS1) in glioma patients. Patients and Methods. The expressions of ZNF667-AS1 were detected in 155 glioma tissues and matched normal brain tissue samples by qRT-PCR. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of ZNF667-AS1. The association between the ZNF667-AS1 expression and clinicopathological characteristics was analyzed by the chi-square test. The Kaplan-Meier method was performed to determine the influence of the ZNF667-AS1 expression on the overall survival and disease-free survival of glioma patients. The Cox regression analysis was used to evaluate the effect of independent prognostic factors on survival outcome. Cell proliferation was measured by the respective cell counting Kit-8 (CCK-8) assays. RESULTS: We observed that ZNF667-AS1 was significantly upregulated in glioma tissues compared to normal tissue samples (p < 0.01). Higher levels of ZNF667-AS1 were positively associated with the WHO grade (p = 0.018) and KPS score (p = 0.008). ROC assays revealed that the high ZNF667-AS1 expression had an AUC value of 0.8541 (95% CI: 0.8148 to 0.8934) for glioma. Survival data revealed that glioma patients in the high ZNF667-AS1 expression group had significantly shorter 5-year overall survival (p = 0.0026) and disease-free survival (p = 0.0005) time than those in the low ZNF667-AS1 expression group. Moreover, multivariate analyses confirmed that the ZNF667-AS1 expression was an independent predictor of the overall survival and disease-free survival for glioma patients. Functionally, we found that knockdown of ZNF667-AS1 suppressed the proliferation of glioma cells. CONCLUSIONS: Our results suggest that ZNF667-AS1 could be used as a potential diagnostic and prognostic biomarker in glioma.

Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice.

Islet transplantation has been clinically proven to be effective at treating type 1 diabetes. However, the current intrahepatic transplantation strategy may incur acute whole blood reactions and result in poor islet engraftment. Here, we report a robust protocol for the transplantation of islets at the extrahepatic transplantation site-the epididymal fat pad (EFP)-in a diabetic mouse model. A protocol to isolate and purify islets at high yields from C57BL/6J mice is described, as well as a transplantation method performed by seeding islets onto a decellularized scaffold (DCS) and implanting them at the EFP site in syngeneic C57BL/6J mice rendered diabetic by streptozotocin. The DCS graft containing 500 islets reversed the hyperglycemic condition within 10 days, while the free islets without DCS required at least 30 days. The normoglycemia was maintained for up to 3 months until the graft was explanted. In conclusion, DCS enhanced the engraftment of islets into the extrahepatic site of the EFP, which could easily be retrieved and might provide a reproducible and useful platform for investigating the scaffold materials, as well as other transplantation parameters required for a successful islet engraftment.

Polarization dependent solar cell conversion efficiency at oblique incident angles and the corresponding improvement using surface nanoparticle coating.

Despite tremendous efforts on improving the solar cell conversion efficiency at normal incidence, improvement at oblique angles has not been widely addressed, not to mention the corresponding light absorption behaviors at different polarizations. Here we report the characterization of the solar cell conversion efficiency and the spectra of photoresponsivity at various tilted angles. The results show that TM (transverse magnetic) polarized light possesses higher photoresponsivity than TE (transverse electric) polarized light and the difference becomes larger with the incidence angle. To address the issue, a monolayer of silica nanoparticles on the solar cell surface was employed to improve the light absorption. Even though both TE and TM waves show a decrease in the surface reflectivity with the presence of nanoparticles, the interaction between the silica particles and the TE wave is more significant. The improvement of the conversion efficiency for obliquely incident light is explained from the refractive index difference of the nanoparticles for the TE and TM polarizations.

Investigation of the strain induced optical transition energy shift of the GaN nanorod light emitting diode arrays.

Strain in the semiconductor light emitting layers has profound effect on the energy band structure and the optical properties of the light emitting diodes (LEDs). Here, we report the fabrication and characterization of GaN nanorod LED arrays. We found that the choice of nanorod passivation materials results in the variation of strain in the InGaN/GaN quantum wells, and thus the corresponding change of light emission properties. The results were further investigated by performing Raman measurement to understand the strain of nanorods with different passivation materials and by calculating the optical transition energy of the devices under the influence of strain-induced deformation potential and the piezoelectric polarization field.

Investigation of low-temperature electroluminescence of InGaN/GaN based nanorod light emitting arrays.

For InGaN/GaN based nanorod devices using a top-down etching process, the optical output power is affected by non-radiative recombination due to sidewall defects (which decrease light output efficiency) and the mitigated quantum confined Stark effect (QCSE) due to strain relaxation (which increases internal quantum efficiency). Therefore, the exploration of low-temperature optical behaviors of nanorod light emitting diodes (LEDs) will help identify the correlation between these two factors. In this work, low-temperature electroluminescent (EL) spectra of InGaN/GaN nanorod arrays were explored and compared with those of planar LEDs. The nanorod LED exhibits a much higher optical output percentage increase when the temperature decreases. The increase is mainly attributed to the increased carriers in the quantum wells for radiative recombination. Also, due to a better spatial overlap of electrons and holes in the quantum wells, the increased number of carriers can be more efficiently recombined in the nanorod device. Next, while the nanorod array shows nearly constant peak energy in the EL spectra at various injection currents at the temperature of 300 K, a blue shift has been observed at 190 K. The results suggest that with less non-radiative recombination and thus more carriers in the quantum wells, carrier screening and band filling still prevail in the partially strain relaxed nanorods. Moreover, when the temperature drops to 77 K, the blue shift of both nanorod and planar devices disappears and the optical output power decreases since there are fewer carriers in the quantum wells for radiative recombination.

Characterizations of low-temperature electroluminescence from ZnO nanowire light-emitting arrays on the p-GaN layer.

Low-temperature electroluminescence from ZnO nanowire light-emitting arrays is reported. By inserting a thin MgO current blocking layer in between ZnO nanowire and p-GaN, high-purity UV light emission at wavelength 398 nm was obtained. As the temperature is decreased, contrary to the typical GaN-based light emitting diodes, our device shows a decrease of optical output intensity. The results are associated with various carrier tunneling processes and frozen MgO defects.

High performance InGaN/GaN nanorod light emitting diode arrays fabricated by nanosphere lithography and chemical mechanical polishing processes.

We fabricated InGaN/GaN nanorod light emitting diode (LED) arrays using nanosphere lithography for nanorod formation, PECVD (plasma enhanced chemical vapor deposition) grown SiO(2) layer for sidewall passivation, and chemical mechanical polishing for uniform nanorod contact. The nano-device demonstrates a reverse current 4.77nA at -5V, an ideality factor 7.35, and an optical output intensity 6807mW/cm(2) at the injection current density 32A/cm(2) (20mA). Moreover, the investigation of the droop effect for such a nanorod LED array reveals that junction heating is responsible for the sharp decrease at the low current.

Investigation of light absorption properties and acceptance angles of nanopatterned GZO/a-Si/p(+)-Si photodiodes.

In this work, n-GZO/a:amorphous-Si(i:intrinsic)/p( + )-Si photodiodes are fabricated. We employed a nanosphere lithographic technique to obtain nanoscale patterns on either the a-Si(i) or p( + )-Si surface. As compared with the planar n-GZO/p( + )-Si diode, the devices with nanopatterned a-Si(i) and nanopatterned p( + )-Si substrates show a 32% and 36.2% enhancement of photoresponsivity. Furthermore, the acceptance angle measurement reveals that the nanostructured photodiodes have larger acceptance angles than the planar structure. It also shows that the device with the nanocone structure has a higher acceptance angle than that with the nanorod structure.

Nanoparticle-coated n-ZnO/p-Si photodiodes with improved photoresponsivities and acceptance angles for potential solar cell applications.

In this work, n-ZnO/p-Si photodiodes were fabricated and characterized to explore their potential applications in solar cells. With a coating of silica nanoparticles, we observed the enhancement of photoresponsivity and acceptance angle at a wavelength between 400 and 650 nm. The 17.6% increase of the photoresponsivity over the conventional device is due to the improved optical transmission toward the semiconductor through the silica nanoparticles. Furthermore, the acceptance angle of the nanoparticle coated device is dramatically increased, which is attributed to the effect of Bragg diffraction.

UV light emission from GZO/ZnO/GaN heterojunction diodes with carrier confinement layers.

In this work, GZO/ZnO/GaN diodes with the light emitting ZnO layer sandwiched between two SiO(2) thin films was fabricated and characterized. We observed a strong excitonic emission at the wavelength 377nm with the Mg(2+) deep level transition and oxygen vacancy induced recombination significantly suppressed. In comparison, light emission from the GZO/GaN device (without SiO(2) barriers) is mainly dominant by defect radiation. Furthermore, the device with confinement layers demonstrated a much higher UV intensity than the blue-green emission of the GZO/GaN p-n device.

GaN nanorod light emitting diode arrays with a nearly constant electroluminescent peak wavelength.

A practical process to fabricate InGaN/GaN multiple quantum well light emitting diodes (LEDs) with a self-organized nanorod structure is demonstrated. The nanorod array is realized by using nature lithography of surface patterned silica spheres followed by dry etching. A layer of spin-on-glass (SOG), which intervening the rod spacing, serves the purpose of electric isolation to each of the parallel nanorod LED units. The electroluminescence peak wavelengths of the nanorod LEDs nearly remain as constant for an injection current level between 25mA and 100mA, which indicates that the quantum confined stark effect is suppressed in the nanorod devices. Furthermore, from the Raman light scattering analysis we identify a strain relaxation mechanism for lattice mismatch layers in the nanostructure.