Different lactate metabolism subtypes reveal heterogeneity in clinical outcomes and immunotherapy in lung adenocarcinoma patients.

Background: The excessive accumulation of lactate within the tumor microenvironment (TME) has been demonstrated to facilitate tumor advancement and evade the immune system. Nonetheless, the metabolic status of lactate in lung adenocarcinoma (LUAD) remains uncertain. Method: By analyzing the transcriptome profile of patients with LUAD, we created a lactate metabolism score (LMS) to predict survival. We then conducted a comprehensive examination of the biological functions and immune infiltration among different LMS patient groups. Moreover, we assessed the LMS predictive efficacy in chemotherapy and immunotherapy. Finally, we validated the detrimental phenotypic effects of SLC16A3 on LUAD cell lines (PC9 and A549) through in vitro experiments. We collected clinical samples to assess the prognostic impact of SLC16A3. Results: We constructed an LMS model with 6 lactate metabolism regulatory factors using LASSO regression. The high LMS model indicates worse clinical outcomes for LUAD patients. High LMS patients are associated with metabolic dysregulation and increased infiltration of M0 and M1 macrophages. Low LMS patients are related to upregulated citric acid metabolism pathways and memory immune cells. High LMS patients are suitable for traditional chemotherapy, while patients with low LMS are more likely to benefit from immunotherapy. Lastly, downregulating SLC16A3 significantly reduces the proliferative and invasive capabilities of LUAD cell lines. Clinical cohort shows that patients with high expression of SLC16A3 have a worse prognosis. Conclusions: The LMS model constructed based on the lactate metabolism pathway displays high effectiveness in predicting the outcome of patients with LUAD. LMS can offer direction regarding chemotherapy as well as immunotherapy in LUAD.

Control of carbon dioxide exchange fluxes by rainfall and biological carbon pump in karst river-lake systems.

As an important component of inland water, the primary factors affecting the carbon cycle in karst river-lake systems require further investigation. In particular, the impacts of climatic factors and the biological carbon pump (BCP) on carbon dioxide (CO2) exchange fluxes in karst rivers and lakes deserve considerable attention. Using quarterly sampling, field monitoring, and meteorological data collection, the spatiotemporal characteristics of CO2 exchange fluxes in Erhai Lake (a typical karst lake in Yunnan, SW China) and its inflow rivers were investigated and the primary influencing factors were analyzed. The average river CO2 exchange flux reached 346.80 mg m-2 h-1, compared to -6.93 mg m-2 h-1 for the lake. The carbon cycle in rivers was strongly influenced by land use within the basin; cultivated and construction land were the main contributors to organic carbon (OC) in the river (r = 0.66, p < 0.01) and the mineralization of OC was a major factor in CO2 oversaturation in most rivers (r = 0.76, p < 0.01). In addition, the BCP effect of aquatic plants and the high pH in karst river-lake systems enhance the ability of water body to absorb CO2, resulting in undersaturated CO2 levels in the lake. Notably, under rainfall regulation, riverine OC and dissolved inorganic carbon (DIC) flux inputs controlled the level of CO2 exchange fluxes in the lake (rOC = 0.78, p < 0.05; rDIC = 0.97, p < 0.01). We speculate that under future climate and human activity scenarios, the DIC and OC input from rivers may alleviate the CO2 limitation of BCP effects in karst eutrophication lakes, possibly enabling aquatic plants to convert more CO2 into OC for burial. The results of this research can help advance our understanding of CO2 emissions and absorption mechanisms in karst river-lake systems.

Ameliorative effect of resveratrol on acute ocular hypertension induced retinal injury through the SIRT1/NF-κB pathway.

Glaucoma is a kind of neurodegenerative disorder characterized by irreversible loss of retinal ganglion cells (RGCs) and permanent visual impairment. It is reported that resveratrol (RES) is a promising drug for neurodegenerative diseases. However, the detailed molecular mechanisms underlying its protective potential have not yet been fully elucidated. The present study sought to investigate whether resveratrol could protect RGCs and retinal function triggered by acute ocular hypertension injury through the SIRT1/NF-κB pathway. An experimental glaucoma model was generated in C57BL/6J mice. Resveratrol was intraperitoneally injected for 5 days. Sirtinol was injected intravitreally on the day of retinal AOH injury. RGC survival was determined using immunostaining. TUNEL staining was conducted to evaluate retinal cell apoptosis. ERG was used to evaluate visual function. The proteins Brn3a, SIRT1, NF-κB, IL-6, Bax, Bcl2, and Cleaved Caspase3 were determined using western blot. The expression and localisation of SIRT1 and NF-κB in the retina were detected by immunofluorescence. Our data indicated that resveratrol treatment significantly increased Brn3a-labelled RGCs and reduced RGC apoptosis caused by AOH injury. Resveratrol administration also remarkably decreased NF-κB, IL-6, Bax, and Cleaved Caspase3 proteins and increased SIRT1 and Bcl2 proteins. Furthermore, resveratrol treatment obviously inhibited the reduction in ERG caused by AOH injury. Importantly, simultaneous administration of resveratrol and sirtinol abrogated the protective effect of resveratrol, decreased NF-κB protein expression, and increased SIRT1 protein levels. These results suggest that resveratrol administration significantly mitigates retinal AOH-induced RGCs loss and retinal dysfunction, and that this neuroprotective effect is partially regulated through the SIRT1/NF-κB pathway.

NeuTox: A weighted ensemble model for screening potential neuronal cytotoxicity of chemicals based on various types of molecular representations.

Chemical-induced neurotoxicity has been widely brought into focus in the risk assessment of chemical safety. However, the traditional in vivo animal models to evaluate neurotoxicity are time-consuming and expensive, which cannot completely represent the pathophysiology of neurotoxicity in humans. Cytotoxicity to human neuroblastoma cell line (SH-SY5Y) is commonly used as an alternative to animal testing for the assessment of neurotoxicity, yet it is still not appropriate for high throughput screening of potential neuronal cytotoxicity of chemicals. In this study, we constructed an ensemble prediction model, termed NeuTox, by combining multiple machine learning algorithms with molecular representations based on the weighted score of Particle Swarm Optimization. For the test set, NeuTox shows excellent performance with an accuracy of 0.9064, which are superior to the top-performing individual models. The subsequent experimental verifications reveal that 5,5'-isopropylidenedi-2-biphenylol and 4,4'-cyclo-hexylidenebisphenol exhibited stronger SH-SY5Y-based cytotoxicity compared to bisphenol A, suggesting that NeuTox has good generalization ability in the first-tier assessment of neuronal cytotoxicity of BPA analogs. For ease of use, NeuTox is presented as an online web server that can be freely accessed via http://www.iehneutox-predictor.cn/NeuToxPredict/Predict.

Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia.

BACKGROUND: To explore whether local transplantation of mesenchymal stem cells (MSCs) in temporal muscle can promote collateral angiogenesis and to analyze its main mechanisms of promoting angiogenesis. METHODS: Bilateral carotid artery stenosis (BCAS) treated mice were administrated with encephalo-myo-synangiosis (EMS), and bone marrow mesenchymal stem cells (BMSCs) were transplanted into the temporal muscle near the cerebral cortex. On the 30th day after EMS, the Morris water maze, immunofluorescence, laser speckle imaging, and light sheet microscopy were performed to evaluate angiogenesis; In addition, rats with bilateral common carotid artery occlusion were also followed by EMS surgery, and BMSCs from GFP reporter rats were transplanted into the temporal muscle to observe the survival time of BMSCs. Then, the concentrated BMSC-derived conditioned medium (BMSC-CM) was used to stimulate HUVECs and BMECs for ki-67 immunocytochemistry, CCK-8, transwell and chick chorioallantoic membrane assays. Finally, the cortical tissue near the temporal muscle was extracted after EMS, and proteome profiler (angiogenesis array) as well as RT-qPCR of mRNA or miRNA was performed. RESULTS: The results of the Morris water maze 30 days after BMSC transplantation in BCAS mice during the EMS operation, showed that the cognitive impairment in the BCAS + EMS + BMSC group was alleviated (P < 0.05). The results of immunofluorescence, laser speckle imaging, and light sheet microscopy showed that the number of blood vessels, blood flow and astrocytes increased in the BCAS + EMS + BMSC group (P < 0.05). The BMSCs of GFP reporter rats were applied to EMS and showed that the transplanted BMSCs could survive for up to 14 days. Then, the results of ki-67 immunocytochemistry, CCK-8 and transwell assays showed that the concentrated BMSC-CM could promote the proliferation and migration of HUVECs and BMECs (P < 0.05). Finally, the results of proteome profiler (angiogenesis array) in the cerebral cortex showed that the several pro-angiogenesis factors (such as MMP-3, MMP-9, IGFBP-2 or IGFBP-3) were notably highly expressed in MSC transplantation group compared to others. CONCLUSIONS: Local MSCs transplantation together with EMS surgery can promote angiogenesis and cognitive behavior in chronic brain ischemia mice. Our study illustrated that MSC local transplantation can be the potential therapeutical option for improving EMS treatment efficiency which might be translated into clinical application.

Pharmacokinetic and Pharmacodynamic Interactions Between Henagliflozin, a Novel Selective SGLT-2 Inhibitor, and Warfarin in Healthy Chinese Subjects.

PURPOSE: While controlling blood glucose, patients with diabetes and abnormal coagulation should be treated with positive anticoagulation because the hypercoagulable state of their blood is the primary cause of macroangiopathy. The goal of this study was to evaluate the pharmacokinetic and pharmacodynamic (PK/PD) interactions between henagliflozin, a novel selective sodium-glucose cotransporter 2 inhibitor, and warfarin in healthy subjects. METHODS: This single-center, open-label, single-arm clinical study was conducted in 16 healthy male Chinese subjects. According to the study protocol, the PK properties of henagliflozin 10 mg/d and warfarin 5 mg/d were collected and tabulated in accordance with sampling time. All study drugs were given with once-daily administration. Subjects were monitored for adverse reactions and their severity, outcomes, and relationship to study drug. This influences of warfarin on the PK properties of henagliflozin (Cmax,ss and AUCτ,ss), the effects of henagliflozin on the PK properties of warfarin (Cmax, AUC0-t, and AUC0-∞), and the influences of henagliflozin on the PD properties of warfarin (PTmax, PTAUC, INRmax, and INRAUC) were evaluated. FINDINGS: The geometric mean ratios (GMRs; 90% CIs) of henagliflozin Cmax,ss and AUCτ,ss were 101.75% (96.11%-107.72%) and 102.21% (100.04%-104.42%), respectively. The GMRs (90% CIs) of S- and R-warfarin Cmax, AUC0-t, and AUC0-∞ were as follows: Cmax, 114.31% (106.30%-122.91%) and 115.09% (109.46%-121.01%), respectively; AUC0-t, 120.15% (116.71%-123.69%) and 119.01% (116.32%-121.76%); and AUC0-∞, 120.81% (117.17%-124.58%) and 121.94% (118.90%-125.05%). The GMRs (90% CIs) of warfarin PTmax and PTAUC were 92.73% (91.25%-94.22%) and 97.42% (96.61%-98.24%). The GMRs (90% CIs) of warfarin INRmax and INRAUC were 92.66% (91.17%-94.17%) and 97.36% (96.52%-98.21%). A total of 32 cases of mild adverse events were reported, and were recovered/resolved. There were no serious adverse events reported. IMPLICATIONS: No significant clinically relevant effects on the PK/PD properties of henagliflozin or warfarin were found with coadministration of the two drugs in these healthy male Chinese subjects. Based on these findings, it is expected that henagliflozin and warfarin can be used in combination without dose adjustment. Chinadrugtrials.org.cn identifier: CTR20190240.

Galectin-1-dependent ceRNA network in HRMECs revealed its association with retinal neovascularization.

BACKGROUND: Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein. RESULTS: A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells (HRMECs). We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. Additionally, the expression of six lncRNAs and eleven differentially expressed angiogenic genes were validated by qPCR in HRMECs with or without siLGALS1. Several hub genes, such as NRIR, ZFPM2-AS1, LINC0121, apelin, claudin-5, and C-X-C motif chemokine ligand 10, were found to potentially interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response. CONCLUSIONS: The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV.

Alleviating eutrophication by reducing the abundance of Cyanophyta due to dissolved inorganic carbon fertilization: Insights from Erhai Lake, China.

The eutrophication of lakes is a global environmental problem. Regulating nitrogen (N) and phosphorus (P) on phytoplankton is considered to be the most important basis of lake eutrophication management. Therefore, the effects of dissolved inorganic carbon (DIC) on phytoplankton and its role in mitigating lake eutrophication have often been overlooked. In this study, the relationships between phytoplankton and DIC concentrations, carbon isotopic composition, nutrients (N and P), and hydrochemistry in the Erhai Lake (a karst lake) were investigated. The results showed that when the dissolved carbon dioxide (CO2(aq)) concentrations in the water were higher than 15 µmol/L, the productivity of phytoplankton was controlled by the concentrations of TP and TN, especially by that of TP. When the N and P were sufficient and the CO2(aq) concentrations were lower than 15 µmol/L, the phytoplankton productivity was controlled by the concentrations of TP and DIC, especially by that of DIC. Additionally, DIC significantly affected the composition of the phytoplankton community in the lake (p<0.05). When the CO2(aq) concentrations were higher than 15 µmol/L, the relative abundance of Bacillariophyta and Chlorophyta was much higher than those of harmful Cyanophyta. Thus, high concentrations of CO2(aq) can inhibit harmful Cyanophyta blooms. During lake eutrophication, when controlling N and P, an appropriate increase in CO2(aq) concentrations by land-use changes or pumping of industrial CO2 into water may reduce the proportion of harmful Cyanophyta and promote the growth of Chlorophyta and Bacillariophyta, which may provide effectively assist in mitigating water quality deterioration in surface waters.

Astrocyte-derived exosomal lncRNA 4933431K23Rik modulates microglial phenotype and improves post-traumatic recovery via SMAD7 regulation.

Astrocyte-microglial interaction plays a crucial role in brain injury-associated neuroinflammation. Our previous data illustrated that astrocytes secrete microRNA, leading to anti-inflammatory effects on microglia. Long non-coding RNAs participate in neuroinflammation regulation after traumatic brain injury. However, the effect of astrocytes on microglial phenotype via long non-coding RNAs and the underlying molecular mechanisms remain elusive. We used long non-coding RNA sequencing on murine astrocytes and found that exosomal long non-coding RNA 4933431K23Rik attenuated traumatic brain injury-induced microglial activation in vitro and in vivo and ameliorated cognitive function deficiency. Furthermore, microRNA and messenger RNA sequencing together with binding prediction illustrated that exosomal long non-coding RNA 4933431K23Rik up-regulates E2F7 and TFAP2C expression by sponging miR-10a-5p. Additionally, E2F7 and TFAP2C, as transcription factors, regulated microglial Smad7 expression. Using Cx3cr1-Smad7 overexpression of adeno-associated virus, microglia specifically overexpressed Smad7 in the attenuation of neuroinflammation, resulting in less cognitive deficiency after traumatic brain injury. Mechanically, overexpressed Smad7 physically binds to IκBα and inhibits its ubiquitination, preventing NF-κB signaling activation. The Smad7 activator asiaticoside alleviates neuroinflammation and protects neuronal function in traumatic brain injury mice. This study revealed that an exosomal long non-coding RNA from astrocytes attenuates microglial activation after traumatic brain injury by up-regulating Smad7, providing a potential therapeutic target.

Efficacy Evaluation of Tissue Plasminogen Activator with Anti-Vascular Endothelial Growth Factor Drugs for Submacular Hemorrhage Treatment: A Meta-Analysis.

Submacular hemorrhage (SMH) is the accumulation of blood in the macular area that can severely damage the macular structure and visual function. Recently, the intraocular administration of tissue plasminogen activator (TPA) with anti-vascular endothelial growth factor (anti-VEGF) drugs was reported to have a positive effect on SMH. This meta-analysis aimed to explore the efficacy and safety of the drug combination. We systematically searched the Web of Science, MEDLINE, EMBASE, and Cochrane Library databases and screened relevant full-length literature reports. The quality of the reports was assessed by two independent reviewers. The best-corrected visual acuity (BCVA) and foveal thickness (FT) were considered the main indicators of efficacy. RevMan 5.4 software was used for this meta-analysis. Twelve studies were analyzed, and the results showed that BCVA at 1 month (p < 0.001), 3 months (p < 0.001), 6 months (p < 0.001), and the last follow-up (p < 0.001) was improved relative to the preoperative value. The postoperative FT was lower than the preoperative FT (p < 0.001). No significant difference in efficacy was observed between subretinal and intravitreal TPA injections (p = 0.37). TPA with anti-VEGF drugs is safe for SMH treatment and can significantly improve BCVA and reduce FT.

Comparison of different approaches of percutaneous vertebroplasty in the treatment of osteoporotic spinal compression fractures and analysis of influencing factors of re-fracture.

Objective: To compare the functional and radiological outcome of different approaches of percutaneous vertebroplasty (PVP) in the treatment of osteoporotic vertebral compression fractures (OVCF), and to analyze the factors affecting postoperative re-fracture in patients with OVCF. Methods: Medical data of 76 patients with OVCF who underwent PVP in our hospital from January 2021 to December 2021 were analyzed retrospectively. Based on the different intraoperative approaches, patients were divided into Unilateral-group (n=36) and Bilateral-group (n=40). The perioperative indexes, clinical efficacy, and spinal nerve function of the two groups were compared. Logistic regression analysis was used to determine the risk factors of postoperative re-fracture in patients with OVCF. The functional outcome was assessed with Oswestry disability index (ODI), American Spinal Injury Association (ASIA) nerve function classification and pain with Visual analogue scale (VAS). The radiological outcome was assessed by noting change of anterior vertebral height and change of kyphosis Cobb angle. Results: The amount of intraoperative bleeding, the number of X-ray irradiation and the volume of injected bone cement in the Unilateral-group were lower, and the operation time was shorter than Bilateral-group (all P<0.05). One week after the operation, the anterior height of the vertebral body was higher, the Cobb angle of kyphosis was lower, the VAS score was higher, and the ASIA grade was lower in the Unilateral-group compared to the Bilateral-group (P<0.05). Logistic regression analysis showed that the age, bone mineral density, volume of bone cement injection and PD were risk factors of postoperative re-fracture in patients with OVCF. Conclusion: Unilateral PVP treatment of OVCF has the advantages of less intraoperative bleeding, less X-ray irradiation and shorter operation time. At the same time, bilateral PVP is associated with improved bone cement dispersion, and the effect of improving patients' pain is better than that in the Unilateral PVP. Postoperative risk of re-fracture in OVCF patients correlated with age, bone mineral density, amount of bone cement injection and pedicle diameter.

Long Non-Coding RNAs in Retinal Ganglion Cell Apoptosis.

Traumatic optic neuropathy or other neurodegenerative diseases, including optic nerve transection, glaucoma, and diabetic retinopathy, can lead to progressive and irreversible visual damage. Long non-coding RNAs (lncRNAs), which belong to the family of non-protein-coding transcripts, have been linked to the pathogenesis, progression, and prognosis of these lesions. Retinal ganglion cells (RGCs) are critical for the transmission of visual information to the brain, damage to which results in visual loss. Apoptosis has been identified as one of the most essential modes of RGC death. Emerging evidence suggests that lncRNAs can regulate RGC degeneration by directly or indirectly modulating apoptosis-associated signaling pathways. This review presents a comprehensive overview of the role of lncRNAs in RGC apoptosis at transcriptional, post-transcriptional, translational, and post-translational levels, emphasizing on the potential mechanisms of action. The current limitations and future perspectives of exploring the connection between lncRNAs and RGC apoptosis have been summarized. Understanding the intricate molecular interaction network of lncRNAs and RGC apoptosis will open new avenues for the identification of novel diagnostic biomarkers, therapeutic targets, and molecules for prognostic evaluation of diseases related to RGC injury.

Long non-coding RNAs in retinal neovascularization: current research and future directions.

PURPOSE: Retinal neovascularization (RNV) is an intractable pathological hallmark of numerous ocular blinding diseases, including diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. However, current therapeutic methods have potential side effects and limited efficacy. Thus, further studies on the pathogenesis of RNV-related disorders and novel therapeutic targets are critically required. Long non-coding RNAs (lncRNAs) have various functions and participate in almost all biological processes in living cells, such as translation, transcription, signal transduction, and cell cycle control. In addition, recent research has demonstrated critical modulatory roles of various lncRNAs in RNV. In this review, we summarize current knowledge about the expression and regulatory functions of lncRNAs related to the progression of pathological RNV. METHODS: We searched databases such as PubMed and Web of Science to gather and review information from the published literature. CONCLUSIONS: In general, lncRNA MEG3 attenuates RNV, thus protecting the retina from excessive and dysregulated angiogenesis under high glucose stress. In contrast, lncRNAs MALAT1, MIAT, ANRIL, HOTAIR, HOTTIP, and SNHG16, have been identified as causative molecules in the pathological progression of RNV. Comprehensive and in-depth studies of the roles of lncRNAs in RNV indicate that targeting lncRNAs may be an alternative therapeutic approach in the near future, enabling new options for attenuating RNV progression and treating RNV-related retinal diseases.

Endothelial Cell-Derived Let-7c-Induced TLR7 Activation on Smooth Muscle Cell Mediate Vascular Wall Remodeling in Moyamoya Disease.

Moyamoya disease (MMD) is characterized by frequent migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) in the intima layer of blood vessels. However, the underlying mechanism is unclear. Toll-like receptor (TLR) 7 is abundantly expressed in smooth muscle cells (SMCs) in multiple vascular diseases, which might be linked to the disease-associated vascular remodeling. In the present study, the expression of TLR7 in MMD vessels was examined using the superficial temporal artery (STA) and middle cerebral artery (MCA) from MMD patients. Furthermore, the effect of TLR7 activation on the VSMC phenotype switch in vitro and vascular remodeling in vivo was assessed using a 9.4Tesla MRI. Our results demonstrated that the TLR7 and microRNA Let-7c expression are upregulated in VSMCs and the plasma of MMD patients, respectively. Additionally, TLR7 stimulation by Let-7c or Imiquimod induces a synthetic phenotype switch in VSMCs. Mechanistic studies revealed that Akt/mTOR signaling is responsible for this TLR-induced VSMC phenotypic switch. The Let-7c or Imiquimod treatment also resulted in reduced blood flow of internal carotid arteries (ICAs) in an in vivo model, while TLR7 inhibition attenuated the ICA stenosis. Besides, Let-7c was also found to be elevated in the hypoxic endothelial cells. Taken together, our study demonstrates that Let-7c released by endothelial cells under hypoxic conditions may activate TLR7 on VSMCs, ultimately leading to the phenotype switch and vascular wall remodeling. These findings thus elucidate the putative mechanisms underlying progressive stenosis of blood vessels in MMD and provide prospective therapeutic targets for further exploration.

CircZXDC Promotes Vascular Smooth Muscle Cell Transdifferentiation via Regulating miRNA-125a-3p/ABCC6 in Moyamoya Disease.

Moyamoya disease (MMD) is an occlusive, chronic cerebrovascular disease affected by genetic mutation and the immune response. Furthermore, vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) participate in the neointima of MMD, but the etiology and pathophysiological changes in MMD vessels remain largely unknown. Therefore, we established the circZXDC (ZXD family zinc finger C)-miR-125a-3p-ABCC6 (ATP-binding cassette subfamily C member 6) axis from public datasets and online tools based on "sponge-like" interaction mechanisms to investigate its possible role in VSMCs. The results from a series of in vitro experiments, such as dual luciferase reporter assays, cell transfection, CCK-8 assays, Transwell assays, and Western blotting, indicate a higher level of circZXDC in the MMD plasma, especially in those MMD patients with the RNF213 mutation. Moreover, circZXDC overexpression results in a VSMC phenotype switching toward a synthetic status, with increased proliferation and migration activity. CircZXDC sponges miR-125a-3p to increase ABCC6 expression, which induces ERS (endoplasmic reticulum stress), and subsequently regulates VSMC transdifferentiation from the contractive phenotype to the synthetic phenotype, contributing to the intima thickness of MMD vessels. Our findings provide insight into the pathophysiological mechanisms of MMD and indicate that the circZXDC-miR-125a-3p-ABCC6 axis plays a pivotal role in the progression of MMD. Furthermore, circZXDC might be a diagnostic biomarker and an ABCC6-specific inhibitor and has the potential to become a promising therapeutic option for MMD.

Comparative Analysis on the Effect of Surface Reflectance for Laser 3D Scanner Calibrator.

The calibrator is one of the most important factors in the calibration of various laser 3D scanning instruments. The requirements for the diffuse reflection surface are emphasized in many national standards. In this study, spherical calibrator and plane calibrator comparative measurement experiments were carried out. The black ceramic standard sphere, white ceramic standard sphere, metal standard sphere, metal standard plane, and white ceramic standard plane were used to test the laser 3D scanner. In the spherical calibrator comparative measurement experiments, the results indicate that the RMS of the white ceramic spherical calibrator with a reflectance of approximately 60% is 10 times that of the metal spherical calibrator with the reflectance of approximately 15%, and the RMS of the black ceramic spherical calibrator with reflectance of approximately 11% is of the same order as the metal spherical calibrator. In the plane calibrators comparative measurement experiments, the RMS of the flatness measurement is 0.077 mm for the metal plane calibrator with a reflectance of 15%, and 2.915 mm for ceramic plane calibrator with a reflectance of 60%. The results show that when the optimal measurement distance and incident angle are selected, the reflectance of the calibrator has a great effect on the measurement results, regardless of the outlines or profiles. Based on the experiments, it is recommended to use the spherical calibrator or the standard plane with a reflectance of around 18% as the standard, which can obtain reasonable results. In addition, it is necessary to clearly provide the material category and surface reflectance information of the standard when calibrating the scanner according to the measurement standard.

Risk Factors of Transient Neurological Deficits and Perioperative Stroke after Revascularization in Patients with Moyamoya Disease.

OBJECTIVE: To analyze the risk factors of transient neurological deficits (TND) and perioperative stroke in patients with MMD after extracranial-intracranial revascularization. METHODS: A retrospective analysis of the clinical data of 183 patients with MMD undergoing 203 EC-IC bypass operation procedures from January 2018 to August 2020. According to whether TND and stroke occurred within 14 days after operation, univariate analysis and multivariate logistic regression were used. RESULTS: TND occurred in 26 cases (12.8%) of revascularization. The results of the univariate analysis showed that history of diabetes, multiple episodes of preoperative symptoms, lesions involving the posterior circulation, and high postoperative blood pressure are the risk factors of TND. Further multivariate logistic regression analysis showed that multiple episodes of preoperative symptoms (p = 0.016) and lesions involving the posterior circulation (p = 0.014) are the independent risk factors for TND. Perioperative stroke occurred in 12 cases (5.9%). The results of the univariate analysis showed that older age, history of hypertension, preoperative cerebral infarction as the main symptom, lesions involving the posterior circulation, and high perioperative blood pressure are the risk factors of perioperative stroke. The results of multivariate logistic regression analysis showed that preoperative cerebral infarction as the main symptom (p = 0.015) is an independent risk factor for perioperative stroke. The occurrence of perioperative complications was not related to the improvement of follow-up mRS (Modified Rankin Scale) score and long-term cerebral rehemorrhage. CONCLUSIONS: Clinically, patients with MMD have multiple episodes of preoperative symptoms, lesions involving the posterior circulation, and preoperative cerebral infarction and should be attached when undergoing revascularization.

High stability of autochthonous dissolved organic matter in karst aquatic ecosystems: Evidence from fluorescence.

Biological carbon pump (BCP) in karst areas has received intensive attention for years due to their significant contribution to the global missing carbon sink. The stability of autochthonous dissolved organic matter (Auto-DOM) produced by BCP in karst aquatic ecosystems may play a critical role in the missing carbon sink. However, the source of dissolved organic matter (DOM) in inland waters and its consumption by planktonic bacteria have not been thoroughly examined. Recalcitrant dissolved organic matter (RDOM) may exist in karst aquatic ecosystem as in the ocean. Through the study of the chromophoric dissolved organic matter (CDOM) and the interaction between CDOM and the planktonic bacterial community under different land uses at the Shawan Karst Water-carbon Cycle Test Site, SW China, we found that C2, as the fluorescence component of Auto-DOM mineralised by planktonic bacteria, may have some of the characteristics of RDOM and is an important DOM source in karst aquatic ecosystems. The stability ratio (Fmax(C2/(C1+C2))) of Auto-DOM reached 89.6 ± 6.71% in winter and 64.1 ± 7.19% in spring. Moreover, correlation-based network analysis determined that the planktonic bacterial communities were controlled by different fluorescence types of CDOM, of which C1 (fresh Auto-DOM), C3 (conventional allochthonous DOM (Allo-DOM)) and C4 (the Allo-DOM mineralised by bacteria) were clustered in one module together with prevalent organic-degrading planktonic bacteria; C2 was clustered in another tightly combined module, suggesting specific microbial utilization strategies for the C2 component. In addition, some important planktonic bacterium and functional genes (including chemotrophic heterotrophs and photosynthetic bacteria) were found to be affected by high Ca2+ and dissolved inorganic carbon (DIC) concentrations in karst aquatic ecosystems. Our research showed that Auto-DOM may be as an important carbon sink as the Allo-DOM in karst ecosystems, the former generally being neglected based on a posit that it is easily and first mineralized by planktonic bacteria.

Application Progress of High-Throughput Sequencing in Ocular Diseases.

Ocular diseases affect multiple eye parts and can be caused by pathogenic infections, complications of systemic diseases, genetics, environment, and old age. Understanding the etiology and pathogenesis of eye diseases and improving their diagnosis and treatment are critical for preventing any adverse consequences of these diseases. Recently, the advancement of high-throughput sequencing (HTS) technology has paved wide prospects for identifying the pathogenesis, signaling pathways, and biomarkers involved in eye diseases. Due to the advantages of HTS in nucleic acid sequence recognition, HTS has not only identified several normal ocular surface microorganisms but has also discovered many pathogenic bacteria, fungi, parasites, and viruses associated with eye diseases, including rare pathogens that were previously difficult to identify. At present, HTS can directly sequence RNA, which will promote research on the occurrence, development, and underlying mechanism of eye diseases. Although HTS has certain limitations, including low effectiveness, contamination, and high cost, it is still superior to traditional diagnostic methods for its efficient and comprehensive diagnosis of ocular diseases. This review summarizes the progress of the application of HTS in ocular diseases, intending to explore the pathogenesis of eye diseases and improve their diagnosis.

Inhibition of p66Shc attenuates retinal ischemia-reperfusion injury-induced damage by activating the akt pathway.

Retinal ganglion cell (RGC) death is the direct cause of several optic neuropathies. Several studies have reported that the loss of p66Shc ameliorates neuronal injury and vascular abnormalities in ischemia-reperfusion (I/R) injury. However, whether p66Shc is involved in the loss of RGC remains unclear. Therefore, this study aimed to investigate the function of p66Shc due to retinal ischemia in mice. The retinal I/R model was constructed after an intravitreal injection of recombinant adeno-associated viruses (rAAV-EGFP or rAAV-p66Shc-EGFP) for 4 weeks. The expression of p66Shc was detected by western blotting, quantitative real-time polymerase chain reaction, and immunofluorescence staining. The survival of RGCs was determined using immunofluorescence staining. Retinal function was analyzed based on electroretinogram (ERG) findings. Retinal cell apoptosis was detected by TdT-mediated dUTP nick-end labeling staining. The protein expressions of Akt, phospho-Akt, Bax, and PARP were analyzed by western blotting. After rAAVs were successfully transfected, enhanced green fluorescent protein was expressed in all retinal cell layers, and the level of p66Shc after I/R injury was successfully reduced. We found that inhibition of p66Shc expression remarkably decreased the death of RGCs and prevented the loss of ERG a- and b-wave amplitudes caused by retinal ischemia. Mechanistically, downregulation of p66Shc resulted in reduced Bax, whereas increased phospho-Akt and PARP. Taken together, our study revealed that p66Shc acts through the Akt pathway to protect RGCs from retinal I/R injury-induced apoptosis and retinal dysfunction, making p66Shc a possible therapeutic target for glaucoma treatment.