Improved medical waste plasma gasification modelling based on implicit knowledge-guided interpretable machine learning.

Ensuring the interpretability of machine learning models in chemical engineering remains challenging due to inherent limitations and data quality issues, hindering their reliable application. In this study, a qualitatively implicit knowledge-guided machine learning framework is proposed to improve plasma gasification modelling. Starting with a pre-trained machine learning model, parameters are further optimized by integrating the heuristic algorithm to minimize the data fitting errors and resolving implicit monotonic inconsistencies. The latter is comprehensively quantified through Monte Carlo simulations. This framework is adaptive to different machine learning techniques, exemplified by artificial neural network (ANN) and support vector machine (SVM) in this study. Validated by a case study on plasma gasification, the results reveal that the improved models achieve better generalizability and scientific interpretability in predicting syngas quality. Specifically, for ANN, the root mean square error (RMSE) and knowledge-based error (KE) reduce by 36.44% and 83.22%, respectively, while SVM displays a decrease of 2.58% in RMSE and a remarkable 100% in KE. Importantly, the improved models successfully capture all desired implicit monotonicity relationships between syngas quality and feedstock characteristics/operating parameters, addressing a limitation that traditional machine learning struggles with.

Mechanism and application of gas phase trapping by spontaneous imbibition.

For fractured gas reservoirs with strong water drive, gas phase trapping affects the gas recovery significantly. The recovery may be less than 50% for some reservoirs while it is only 12% for Beaver River gas field. The gas phase trapping mechanism has been revealed by the results of depletion experimental test. The residual pressure of the trapped gas is as high as 11.75 MPa with a 12.8 cm imbibition layer resulting in gas recovery deceased 49.5% compared with that without imbibition layer. A mathematical model is built to calculate the imbibition thickness based on capillary pressure and relative permeability of the matrix. The gas phase trapping are analyzed by two representative wells in Weiyuan gas field, the intermittent production reinforces the imbibition thickness and result in gas trapped in the matrix block with high residual pressure for the low performace gas wells, the extremely low gas recovery can be explained more rationally. That lays a foundation of improving the gas recovery for fractured reservoirs.

IL-23 Priming Enhances the Neuroprotective Effects of MSC-Derived Exosomes in Treating Retinal Degeneration.

Purpose: Neuroinflammation is a characteristic feature of neurodegenerative diseases. Mesenchymal stem cell-derived exosomes (MSC-exo) have shown neuroprotective effects through immunoregulation, but the therapeutic efficacy remains unsatisfactory. This study aims to enhance the neuroprotective capacity of MSC-exo through IL-23 priming for treating retinal degeneration in mice. Methods: MSC were primed with IL-23 stimulation in vitro, and subsequently, exosomes (MSC-exo and IL-23-MSC-exo) were isolated and characterized. Two retinal degenerative disease models (NaIO3-induced mice and rd10 mice) received intravitreal injections of these exosomes. The efficacy of exosomes was assessed by examining retinal structural and functional recovery. Furthermore, exosomal microRNA (miRNA) sequencing was conducted, and the effects of exosomes on the M1 and M2 microglial phenotype shift were evaluated. Results: IL-23-primed MSC-derived exosomes (IL-23-MSC-exo) exhibited enhanced capability in protecting photoreceptor cells and retinal pigment epithelium (RPE) cells against degenerative damage and fostering the restoration of retinal neural function in both NaIO3-induced retinal degeneration mice and rd10 mice when compared with MSC-exo. The exosomal miRNA suppression via Drosha knockdown in IL-23-primed MSC would abolish the neuroprotective role of IL-23-MSC-exo, highlighting the miRNA-dependent mechanism. Bioinformatic analysis, along with further in vivo biological studies, revealed that IL-23 priming induced a set of anti-inflammatory miRNAs in MSC-exo, prompting the transition of M1 to M2 microglial polarization. Conclusions: IL-23 priming presents as a potential avenue for amplifying the immunomodulatory and neuroprotective effects of MSC-exo in treating retinal degeneration.

The efficacy and safety of anti-vascular endothelial growth factor combined with Ahmed glaucoma valve implantation in the treatment of neovascular glaucoma: a systematic review and meta-analysis.

Background: The intraocular injections of anti-vascular endothelial growth factor (anti-VEGF) demonstrates significant efficacy in inhibiting the formation of ocular neovascularization in neovascular glaucoma (NVG). Ahmed glaucoma valve implantation (AGVI) is extensively employed for the management of diverse glaucoma types. Objective: To further evaluate the efficacy and safety of anti-VEGF combined with AGVI in the treatment of neovascular glaucoma. Methods: A thorough search for randomized controlled trials (RCTs) was conducted across eight databases: PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP. The search period was set from the inception of each database until March 2, 2024, to identify RCTs investigating the effectiveness and safety of combining AGVI with anti-VEGF therapy for NVG. We used the Cochrane Risk of Bias Assessment Tool to evaluate the quality of the literature and performed statistical analysis using Stata 15.0 software. Results: Fourteen RCTs were included in this study. Compared with AGVI alone, the combination of anti-VEGF drugs and AGVI can reduce postoperative intraocular pressure (IOP) at 1 week [WMD = -4.03, 95% CI (-5.73, -2.34), p < 0.001], 1 month [WMD = -5.39, 95% CI (-7.05, -3.74), p < 0.001], 3 months [WMD = -6.59, 95% CI (-7.85, -5.32), p < 0.001], 6 months [WMD = -4.99, 95% CI (-9.56, -0.43), p = 0.032], and more than 12 months [WMD = -3.86, 95% CI (-6.82, -0.90), p = 0.011], with a higher Effective rate [RR = 1.27, 95% CI (1.18, 1.37), p < 0.001], decreased incidence of postoperative hyphema [RR = 0.24, 95% CI (0.15, 0.39), p < 0.001], reduced use of postoperative antiglaucoma medications [WMD = -0.48, 95% CI (-0.61, -0.35), p < 0.001], and decreased aqueous humor VEGF levels [SMD = -2.84, 95% CI (-4.37, -1.31), p < 0.001]. Conclusion: In comparison to AGVI alone, the combination of AGVI with anti-VEGF therapy has better effects in reducing IOP at various time intervals, diminishing postoperative antiglaucoma medication requirements and reducing aqueous humor VEGF levels. Furthermore, it effectively minimizes the incidence of postoperative hyphema. Nevertheless, due to the variability in the quality of the trials included, further high-quality experiments will be required in the future to substantiate this conclusion. Systematic review registration: PROSPERO, identifier CRD42024519862, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024519862.

Assessing daily patterns in stimulant use during the COVID-19 pandemic in Melbourne, Australia using wastewater analysis.

During the COVID-19 pandemic, one of Australia's biggest cities, Melbourne, experienced three major isolation ("lockdown") periods in 2020 (160 days) and in 2021 (111 days) which makes it one of the most locked down cities world-wide. This study assessed how the pandemic affected temporal trends in methamphetamine, MDMA and cocaine consumption using wastewater-based epidemiology. Daily samples were collected for most of 2020 and 2021 (n = 660 days). Concentrations were measured using direct-injection LC-MS/MS and back-calculated to consumption estimates. Results indicate that methamphetamine use was increasing before the first lockdown and decreased after the end of the first lockdown in 2020. Methamphetamine trends appeared to have remained steady throughout the second lockdown period before increasing steeply after it ended. For most of 2020, cocaine use remained steady, with an increase after the second lockdown. MDMA use decreased after the start of the first lockdown and remained steady throughout most of 2020 and 2021. In comparison to 2020, trends in 2021 were less variable and stimulant use did not appear to be as associated with COVID-19 restrictions. Overall, this study was able to show the impact of lockdown periods and the related social restrictions on illicit stimulant use. ENVIRONMENTAL IMPLICATION: Illicit drugs are hazardous chemicals, of concern both to humans and the environment. While studies have been undertaken to understand their temporal trends, this work utilizes wastewater-based epidemiology and daily sampling to provide a comprehensive understanding of the impact of the COVID-19 pandemic on the use of methamphetamine, MDMA and cocaine on one of the most locked-down cities in the world. Understanding the consequences of this significant intervention on illicit drug use could provide valuable insights into its potential environmental impact.

Effects of genetically proxied statins on diabetic nephropathy and retinopathy: a Mendelian randomization study.

There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p < 0.0125 was considered significant after Bonferroni Correction. To triangulate the findings, genetic variants of whole blood-derived targets gene expression (cis-eQTL) and plasma-derived protein (cis-pQTL) levels were used to perform secondary MR analyses and data from the National Health and Nutrition Examination Survey were used for cross-sectional analysis. Genetically proxied inhibition of HMGCR was associated with higher risks of DN and DR (DN: OR = 1.79, p = 0.01; DR: OR = 1.41, p = 0.004), while no such association was found for PCSK9. Secondary MR analyses confirmed these associations. Cross-sectional analysis revealed a positive link between statin use and DR incidence (OR = 1.26, p = 0.03) and a significant negative association with glomerular filtration rate (Beta = - 1.9, p = 0.03). This study provides genetic evidence that genetically proxied inhibition of HMGCR is associated with increased risks of DN/DR, and this effect may not be attributed to their LDL-C-lowering properties. For patients with diabetic dyslipidemia, PCSK9 inhibitors may be a preferable alternative.

The Prognostic Hub Gene POLE2 Promotes BLCA Cell Growth via the PI3K/AKT Signaling Pathway.

BACKGROUND: BLCA is a common urothelial malignancy characterized by a high recurrence rate. Despite its prevalence, the molecular mechanisms underlying its development remain unclear. AIMS: This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA). OBJECTIVE: The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease. METHODS: We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays. RESULTS: In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels. CONCLUSION: In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.

Characterizing and identifying of miRNAs involved in berberine modulating glucose metabolism of Megalobrama amblycephala.

The present study, as one part of a larger project that aimed to investigate the effects of dietary berberine (BBR) on fish growth and glucose regulation, mainly focused on whether miRNAs involve in BBR's modulation of glucose metabolism in fish. Blunt snout bream Megalobrama amblycephala (average weight of 20.36 ± 1.44 g) were exposed to the control diet (NCD, 30% carbohydrate), the high-carbohydrate diet (HCD, 43% carbohydrate) and the berberine diet (HCB, HCD supplemented with 50 mg/kg BBR). After 10 weeks' feeding trial, intraperitoneal injection of glucose was conducted, and then, the plasma and liver were sampled at 0 h, 1 h, 2 h, 6 h, and 12 h. The results showed the plasma glucose levels in all groups rose sharply and peaked at 1 h after glucose injection. Unlike the NCD and HCB groups, the plasma glucose in the HCD group did not decrease after 1 h, while remained high level until at 2 h. The NCD group significantly increased liver glycogen content at times 0-2 h compared to the other two groups and then liver glycogen decreased sharply until at times 6-12 h. To investigate the role of BBR that may cause the changes in plasma glucose and liver glycogen, miRNA high-throughput sequencing was performed on three groups of liver tissues at 2 h time point. Eventually, 20 and 12 differentially expressed miRNAs (DEMs) were obtained in HCD vs NCD and HCB vs HCD, respectively. Through function analyzing, we found that HCD may affect liver metabolism under glucose loading through the NF-κB pathway; and miRNAs regulated by BBR mainly play roles in adipocyte lipolysis, niacin and nicotinamide metabolism, and amino acid transmembrane transport. In the functional exploration of newly discovered novel:Chr12_18892, we found its target gene, adenylate cyclase 3 (adcy3), was widely involved in lipid decomposition, amino acid metabolism, and other pathways. Furthermore, a targeting relationship of novel:Chr12_18892 and adcy3 was confirmed by double luciferase assay. Thus, BBR may promote novel:Chr12_18892 to regulate the expression of adcy3 and participate in glucose metabolism.

Geomagnetic Disturbances and Pulse Amplitude Anomalies Preceding M > 6 Earthquakes from 2021 to 2022 in Sichuan-Yunnan, China.

Compelling evidence has shown that geomagnetic disturbances in vertical intensity polarization before great earthquakes are promising precursors across diverse rupture conditions. However, the geomagnetic vertical intensity polarization method uses the spectrum of smooth signals, and the anomalous waveforms of seismic electromagnetic radiation, which are basically nonstationary, have not been adequately considered. By combining pulse amplitude analysis and an experimental study of the cumulative frequency of anomalies, we found that the pulse amplitudes before the 2022 Luding M6.8 earthquake show characteristics of multiple synchronous anomalies, with the highest (or higher) values occurring during the analyzed period. Similar synchronous anomalies were observed before the 2021 Yangbi M6.4 earthquake, the 2022 Lushan M6.1 earthquake and the 2022 Malcolm M6.0 earthquake, and these anomalies indicate migration from the periphery toward the epicenters over time. The synchronous changes are in line with the recognition of previous geomagnetic anomalies with characteristics of high values before an earthquake and gradual recovery after the earthquake. Our study suggests that the pulse amplitude is effective for extracting anomalies in geomagnetic vertical intensity polarization, especially in the presence of nonstationary signals when utilizing observations from multiple station arrays. Our findings highlight the importance of incorporating pulse amplitude analysis into earthquake prediction research on geomagnetic disturbances.

Three-pressure prediction method of jointing well-seismic data in JT1 well area of Sichuan Basin in China.

With the high yield of many wells represented by Well JT1 in the Maokou Formation, has catalyzed a surge in exploration activities along the platform margin facies of the Maokou Formation in central Sichuan and further showed the significant exploration potential of the Maokou Formation in the northern slope. However, the fracture cave body of the Maokou Formation exhibits a high degree of development, strong longitudinal and horizontal heterogeneity, large formation pressure differences, and drilling events such as gas kicks and lost circulation occur frequently, which seriously affects the efficient implementation of drilling. Understanding the spatial distribution of the three-pressure in the formation can help better deal with and solve the above problems. Therefore, in order to help the safe, high-quality and rapid drilling of the Maokou Formation in the study area, and enhance the efficiency of oil and gas development, this paper explores the research on the prediction method of the three-pressure of jointing well-seismic data based on the geomechanical experimental data and the actual drilling data. In the process of prediction of pore pressure, this study found that the pore pressure and formation velocity in the study area have an exponential relationship. In order to enhance the applicability of the Filippone's method in the study area and improve the prediction accuracy of pore pressure, the linear relationship between pore pressure and formation velocity in the Filippone's method is modified to an exponential relationship, and a pore pressure prediction model suitable for the work area was established. Based on the Mohr-Coulomb criterion and Huang's model, the prediction models of collapse pressure and fracture pressure applicable to the study area were established, respectively. Then, the elastic parameters were obtained through pre-stack inversion, and the three-pressure bodies were calculated based on the elastic parameter bodies. The results indicate that: (1) The three-pressure prediction method of the jointing well-seismic data in this paper can predict the formation's longitudinal and transverse pressure anomaly zones in advance. (2) The Maokou Formation in the study area is characterized by abnormally high pressure, to balance the pressure of the high-ground formation, high-density drilling fluid is necessary. (3) The prediction results of three-pressure in this paper are highly consistent with the actual drilling engineering events, which verifies the reliability of the three-pressure prediction results presented in this study. The results of the study can provide a basis for decision-making in drilling geological design, such as the determination of drilling fluid density, the evaluation of borehole stability and other engineering problems that require support from three-pressure data.

Establishment of Primary Cell Cultures from Canine Oral Melanomas via Fine-Needle Aspiration: A Novel Tool for Tumorigenesis and Cancer Progression Studies.

Oral melanomas are the most common oral malignancies in dogs and are characterized by an aggressive nature, invasiveness, and poor prognosis. With biological and genetic similarities to human oral melanomas, they serve as a valuable spontaneous comparative model. Primary cell cultures are widely used in human medicine and, more recently, in veterinary medicine to study tumorigenesis, cancer progression, and innovative therapeutic approaches. This study aims to establish two- and three-dimensional primary cell lines from oral canine melanomas using fine-needle aspiration as a minimally invasive sampling method. For this study, samples were collected from six dogs, represented by four primary oral melanomas and five lymph nodal metastases. The cells were digested to obtain single-cell suspensions, seeded in flasks, or processed with Matrigel® to form organoids. The cell cultures were characterized through flow cytometry using antibodies against Melan-A, PNL2, and Sox-10. This technique offers a minimally invasive means to obtain cell samples, particularly beneficial for patients that are ineligible for surgical procedures, and enables the establishment of in vitro models crucial for comparative studies in mucosal melanoma oncology. To the best of our knowledge, this is the first work establishing neoplastic primary cell cultures via fine-needle aspiration in dogs.

Pb(II) Adsorption Properties of a Three-Dimensional Porous Bacterial Cellulose/Graphene Oxide Composite Hydrogel Subjected to Ultrasonic Treatment.

A three-dimensional porous bacterial cellulose/graphene oxide (BC/GO) composite hydrogel (BC/GO) was synthesized with multi-layer graphene oxide (GO) as the modifier and bacterial cellulose as the skeleton via an ultrasonic shaking process to absorb lead ions effectively. The characteristics of BC/GO were investigated through TEM, SEM, FT-IR, NMR and Zeta potential experiments. Compared to bacterial cellulose, the ultrasonic method and the carboxyl groups stemming from GO helped to enhance the availability of O(3)H of BC, in addition to the looser three-dimensional structure and enriched oxygen-containing groups, leading to a significantly higher adsorption capacity for Pb(II). In this paper, the adsorption behavior of BC/GO is influenced by the GO concentration, adsorption time, and initial concentration. The highest adsorption capacity for Pb(II) on BC/GO found in this study was 224.5 mg/g. The findings implied that the pseudo-second-order model explained the BC/GO adsorption dynamics and that the data of its adsorption isotherm fit the Freundlich model. Because of the looser three-dimensional structure, the complexation of carboxyl groups, and the enhanced availability of O(3)H, bacterial cellulose exhibited a much better adsorption capacity.

Functional Properties, Rheological Characteristics, Simulated Digestion, and Fermentation by Human Fecal Microbiota of Polysaccharide from Morchella importuna.

Morchella importuna polysaccharide (MIP) has been proven to have obvious hypoglycemic effects on mice with type 2 diabetes (T2DM). This study looked at the functional and rheological characteristics of MIP, and investigated the effects of MIP on the human fecal microbiota through in vitro fermentation experiments. The outcomes demonstrate the excellent oil-holding capacity, emulsifying, foaming, and rheological characteristics of MIP. After salivary gastrointestinal digestion, the Mw of MIP decreased from 398.2 kDa and 21.5 kDa to 21.9 kDa and 11.7 kDa. By 16S rRNA sequencing of bacteria fermented in vitro, it was found that MIP did not improve the richness and diversity of intestinal microorganisms, but it may exert an anti-T2DM function by significantly increasing the relative abundance of Firmicutes and promoting Ruminococcaceae_UCG_014, Bacteroides, and Blautia proliferation. Escherichia-Shigella could also be inhibited to improve the intestinal microenvironment. In addition, the fermentation of MIP increased the total short-chain fatty acid (SCFA) concentration from 3.23 mmol/L to 39.12 mmol/L, and the propionic acid content increased significantly. In summary, MIP has excellent processing performance and is expected to exert potential anti-T2DM activity through the human intestinal microbiota, which has broad market prospects.

Chronic pericarditis and recurrent pericardial effusion of unknown origin in a kitten: a case report.

A 3-month-old kitten was presented after successful cardiopulmonary resuscitation, including a presumed intracardial injection by its primary care veterinarian. Throughout the subsequent hospitalization in the intensive care unit, the cat exhibited recurrent hemorrhagic pericardial effusions, along with concurrent pleural and abdominal effusions, resulting in multiple clinical deteriorations, necessitating pericardiocentesis and thoracocentesis. Despite more than 3 days of intensive care, the cat experienced another cardiopulmonary arrest with unsuccessful attempts to achieve the return of spontaneous circulation. Necropsy and histopathological findings revealed diffuse chronic-active pericarditis and hemorrhagic pericardial effusion, a condition that has not been documented in the context of cardiopulmonary resuscitation or pericardiocentesis.

A New Evaluation Method of Recoverable Reserves and Its Application in Carbonate Gas Reservoirs.

The propagation pattern of pressure drawdown effectively reflects the recoverable reserves range around the gas well and serves as a crucial basis for development strategies. However, it is not easy to detect the pressure propagation boundary near the producing well, especially in low-permeability reservoirs where the drainage radius is small. Physical simulation experiments can serve as a crucial method as the whole pressure profile and gas rate can be obtained in real time. Using long core plugs with permeabilities of 2.300 mD, 0.486 mD, and 0.046 mD, physical simulation experiments were carried out under varying initial water saturation (Swi) conditions of 0%, 20%, 40%, and 55% to observe the dynamic variations in pressure profiles of the core plugs during pressure depletion. Based on the material balance equation and pressure profile characteristics of the core plugs, a method for evaluating recoverable reserves within a well-spacing radius through laboratory experiments was proposed and performed. Mechanism analysis was conducted based on mercury injection tests, and suggestions for enhancing gas recovery were presented. Research findings indicate that lower permeability, higher initial water saturation, and higher abandonment gas rates result in reduced reserve utilization range and degree. Under abandoned gas rate conditions, for type I and II rocks, the pore radius is primarily distributed between 0.1 and 1 µm, the pressure drawdown can reach the well-spacing radius of 600 m, and the ultimate recovery efficiencies are more than 70.6%. For type III rocks, the pore radius mainly falls below 0.1 µm, the drainage radius is smaller than 10 m with Swi greater than 40%, and the ultimate recovery is below 10%. This paper provides an experimental method for recoverable reserves evaluation while formulating gas reservoir development strategies before well testing.

Therapeutic intervention in neuroinflammation for neovascular ocular diseases through targeting the cGAS-STING-necroptosis pathway.

The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.

[Therapeutic effect of calcaneal beak-like fracture secondary to calcaneal osteomyelitis caused by diabetic foot].

OBJECTIVE: To explore clinical effect of vancomycin calcium sulfate combined with internal fixation on calcaneal beak-like fracture secondary to calcaneal osteomyelitis caused by diabetic foot. METHODS: From April 2018 to October 2021, a retrospective analysis was performed on 5 patients with calcaneal bone osteomyelitis secondary to diabetic foot, including 2 males and 3 females, aged from 48 to 60 years old;diabetes course ranged from 5 to 13 years;the courses of diabetic foot disease ranged from 18 to 52 days;5 patients were grade Ⅲ according to Wagner classification. All patients were treated with debridement, vancomycin bone cement implantation, negative pressure aspiration at stageⅠ, vancomycin calcium sulfate and internal fixation at stageⅡfor calcaneal beak-like fracture. Surgical incision and fracture healing time were recorded, and the recurrence of osteomyelitis was observed. American Orthopedic Foot Andankle Society (AOFAS) score and exudation at 12 months after operation were evaluated. RESULTS: Five patients were successfully completed operation without lower extremity vascular occlusion, and were followed up for 16 to 36 months. The wound healing time after internal fixation ranged from 16 to 26 days, and healing time of fractures ranged from 16 to 27 weeks. AOFAS score ranged from 65 to 91 at 12 months after operation, and 2 patients got excellent result, 2 good and 1 fair. Among them, 1 patient with skin ulcer on the back of foot caused by scalding at 5 months after operation (non-complication), was recovered after treatment;the wound leakage complication occurred in 2 patients, and were recovered after dressing change. No osteomyelitis or fracture occurred in all patients. CONCLUSION: Vancomycin calcium sulfate with internal fixation in treating calcaneal osteomyelitis secondary to calcaneal osteomyelitis caused by diabetic foot could not only control infection, but also promote fracture healing, and obtain good clinical results.

Increasing Adoption of Left Atrial Appendage Occlusion in Isolated Coronary Artery Bypass Grafting.

BACKGROUND: Recent randomized trial data showed fewer strokes with left atrial appendage occlusion (LAAO) following cardiac surgery in patients with atrial fibrillation. We developed a quality initiative to increase LAAO adoption. METHODS: Among 11,099 patients undergoing isolated CABG between January 2019-March 2021 at 33 hospitals in Michigan, those with atrial fibrillation undergoing first-time, on-pump CABG were eligible (n=1,241). A goal LAAO rate of 75% was selected as a quality improvement target through a statewide collaborative. An interrupted time series analysis evaluated the change in LAAO rate before (January-December 2019) versus after (January 2020-March 2021) implementation. RESULTS: Implementation of the quality metric improved LAAO rate from 61% (357/581) before to 79% (520/660) after implementation (p<0.001). Compared to patients not undergoing concomitant LAAO, LAAO patients (71%, 877/1,241) were older, more frequently male, and had a lower STS-PROM (2.9±3.5% vs. 3.7±5.7%, p=0.003), while other baseline characteristics including CHA2DS2-VASc scores were similar. Mean bypass and cross-clamp times were 7 and 6 minutes longer, respectively, in the LAAO group among those who did not undergo concomitant ablation. Operative mortality, major morbidity, blood product administration, and thromboembolic events were similar between groups. Interrupted time series analysis showed a significant increase in LAAO rate after implementation (p=0.009). CONCLUSIONS: LAAO in patients with atrial fibrillation undergoing isolated CABG did not add operative risk versus isolated CABG without LAAO. A statewide quality improvement initiative was successful in increasing the rate of concomitant LAAO and could be further evaluated as a potential quality metric in cardiac surgery.

When surface-enhanced Raman spectroscopy meets complex biofluids: A new representation strategy for reliable and comprehensive characterization.

BACKGROUND: Surface-enhanced Raman spectroscopy (SERS) has gained increasing importance in molecular detection due to its high specificity and sensitivity. Complex biofluids (e.g., cell lysates and serums) typically contain large numbers of different bio-molecules with various concentrations, making it extremely challenging to be reliably and comprehensively characterized via conventional single SERS spectra due to uncontrollable electromagnetic hot spots and irregular molecular motions. The traditional approach of directly reading out the single SERS spectra or calculating the average of multiple spectra is less likely to take advantage of the full information of complex biofluid systems. RESULTS: Herein, we propose to construct a spectral set with unordered multiple SERS spectra as a novel representation strategy to characterize full molecular information of complex biofluids. This new SERS representation not only contains details from each single spectra but captures the temporal/spatial distribution characteristics. To address the ordering-independent property of traditional chemometric methods (e.g., the Euclidean distance and the Pearson correlation coefficient), we introduce Wasserstein distance (WD) to quantitatively and comprehensively assess the quality of spectral sets on biofluids. WD performs its superiority for the quantitative assessment of the spectral sets. Additionally, WD benefits from its independence of the ordering of spectra in a spectral set, which is undesirable for traditional chemometric methods. With experiments on cell lysates and human serums, we successfully achieve the verification for the reproducibility between parallel samples, the uniformity at different positions in the same sample, the repeatability from multiple tests at one location of the same sample, and the cardinality effect of the spectral set. SERS spectral sets also manage to distinguish different classes of human serums and achieve higher accuracy than the traditional prostate-specific antigen in prostate cancer classification. SIGNIFICANCE: The proposed SERS spectral set is a robust representation approach in accessing full information of biological samples compared to relying on a single or averaged spectra in terms of reproducibility, uniformity, repeatability, and cardinality effect. The application of WD further demonstrates the effectiveness and robustness of spectral sets in characterizing complex biofluid samples, which extends and consolidates the role of SERS.

SERSomes for metabolic phenotyping and prostate cancer diagnosis.

Molecular phenotypic variations in metabolites offer the promise of rapid profiling of physiological and pathological states for diagnosis, monitoring, and prognosis. Since present methods are expensive, time-consuming, and still not sensitive enough, there is an urgent need for approaches that can interrogate complex biological fluids at a system-wide level. Here, we introduce hyperspectral surface-enhanced Raman spectroscopy (SERS) to profile microliters of biofluidic metabolite extraction in 15 min with a spectral set, SERSome, that can be used to describe the structures and functions of various molecules produced in the biofluid at a specific time via SERS characteristics. The metabolite differences of various biofluids, including cell culture medium and human serum, are successfully profiled, showing a diagnosis accuracy of 80.8% on the internal test set and 73% on the external validation set for prostate cancer, discovering potential biomarkers, and predicting the tissue-level pathological aggressiveness. SERSomes offer a promising methodology for metabolic phenotyping.