Nitrogen availability and summer drought, but not N:P imbalance, drive carbon use efficiency of a Mediterranean tree-grass ecosystem.

All ecosystems contain both sources and sinks for atmospheric carbon (C). A change in their balance of net and gross ecosystem carbon uptake, ecosystem-scale carbon use efficiency (CUEECO), is a change in their ability to buffer climate change. However, anthropogenic nitrogen (N) deposition is increasing N availability, potentially shifting terrestrial ecosystem stoichiometry towards phosphorus (P) limitation. Depending on how gross primary production (GPP, plants alone) and ecosystem respiration (RECO, plants and heterotrophs) are limited by N, P or associated changes in other biogeochemical cycles, CUEECO may change. Seasonally, CUEECO also varies as the multiple processes that control GPP and respiration and their limitations shift in time. We worked in a Mediterranean tree-grass ecosystem (locally called 'dehesa') characterized by mild, wet winters and summer droughts. We examined CUEECO from eddy covariance fluxes over 6 years under control, +N and + NP fertilized treatments on three timescales: annual, seasonal (determined by vegetation phenological phases) and 14-day aggregations. Finer aggregation allowed consideration of responses to specific patterns in vegetation activity and meteorological conditions. We predicted that CUEECO should be increased by wetter conditions, and successively by N and NP fertilization. Milder and wetter years with proportionally longer growing seasons increased CUEECO, as did N fertilization, regardless of whether P was added. Using a generalized additive model, whole ecosystem phenological status and water deficit indicators, which both varied with treatment, were the main determinants of 14-day differences in CUEECO. The direction of water effects depended on the timescale considered and occurred alongside treatment-dependent water depletion. Overall, future regional trends of longer dry summers may push these systems towards lower CUEECO.

Global Trends and Frontier in Research on Pancreatic Alpha Cells: A Bibliometric Analysis from 2013 to 2023.

PURPOSE: Over the past 20 years, much of the research on diabetes has focused on pancreatic beta cells. In the last 10 years, interest in the important role of pancreatic alpha cells in the pathogenesis of diabetes, which had previously received little attention, has grown. We aimed to summarize and visualize the hotspot and development trends of pancreatic alpha cells through bibliometric analysis and to provide research direction and future ideas for the treatment of diabetes and other islet-related diseases. METHODS: We used two scientometric software packages (CiteSpace 6.1.R6 and VOSviewer1.6.18) to visualize the information and connection of countries, institutions, authors, and keywords in this field. RESULTS: A total of 532 publications, published in 752 institutions in 46 countries and regions, were included in this analysis. The United States showed the highest output, accounting for 39.3% of the total number of published papers. The most active institution was Vanderbilt University, and the authors with highest productivity came from Ulster University. In recent years, research hotspots have concentrated on transdifferentiation, gene expression, and GLP-1 regulatory function. Visualization analysis shows that research hotspots mainly focus on clinical diseases as well as physiological and pathological mechanisms and related biochemical indicators. CONCLUSIONS: This study provides a review and summary of the literature on pancreatic alpha cells through bibliometric and visual methods and shows research hotspot and development trends, which can guide future directions for research.

Cytosolic mtDNA-cGAS-STING axis contributes to sepsis-induced acute kidney injury via activating the NLRP3 inflammasome.

BACKGROUND: NLRP3 inflammasome activation is significantly associated with sepsis-induced acute kidney injury (S-AKI). Cytosolic DNA derived from damaged mitochondria has been reported to activate NLRP3 inflammasome via upregulating the cyclic GMP-AMP synthase (cGAS)-the stimulator of interferon genes (STING) axis in nucleus pulposus cell and cardiomyocytes. However, the regulatory effect of mitochondria DNA (mtDNA)-cGAS-STING axis on the NLRP3 inflammasome in S-AKI remains unclear. METHODS: In the current study, we established an in vivo model of S-AKI by intraperitoneally injecting male C57BL/6 J mice with lipopolysaccharide (LPS). Next, selective cGAS inhibitor RU.521, and STING agonist DMXAA were intraperitoneally injected in the mice; then, blood urea nitrogen (BUN), serum creatinine (CRE), urinary kidney injury molecular-1 (KIM-1), pathological changes, and infiltrated neutrophils were detected to assess kidney injury. We also performed western blot and immunofluorescence assays to evaluate STING, cGAS, TBK-1, p-TBK-1, IRF3, p-IRF3, NF-kB, p-NF-kB, NLRP3, cleaved caspase-1, caspase-1, GSDMD-N, and GSDMD expression levels in kidney tissues. IL-18 and IL-1ß in renal tissue were identified by ELISA. In vitro, we treated HK-2 cells with LPS to establish a cell model of S-AKI. Furthermore, ethidium bromide (EtBr) was administered to deplete mitochondria DNA (mtDNA). LPS-induced cytotoxicity was evaluated by LDH release assay. Protein expression of cGAS, STING, and NLRP3 in was quantified by western blot. Cytosolic mtDNA was detected by immunofluorescence and q-PCR. Released IL-1ß and IL-18 in HK-2 supernatants were detected by ELISA. RESULTS: LPS injection induced S-AKI in mice, as evidenced by neutrophil infiltration, tubular vacuolation, and increased levels of serum creatinine (CRE), blood urea nitrogen (BUN), and urinary KIM-1. In addition, LPS activated the cGAS-STING axis and NLRP3 inflammasome in vivo, illustrated by increased phosphorylation levels of TBK-1, IRF3, and NF-kB protein, increased ratio of cleaved caspase-1 to caspase-1 and GSDMD-N to GSDMD, and increased IL-1ß and IL-18 levels. Moreover, the cGAS inhibitor RU.521 effectively attenuated NLRP3 inflammasome and S-AKI; however, these effects were abolished by treatment with the STING agonist DMXAA. Furthermore, cytosolic release of mtDNA and activation of the cGAS-STING-NLRP3 axis were observed in LPS-treated HK-2 cells. Inhibiting mtDNA replication by Ethidium Bromide (EtBr) treatment reduced cytosolic mtDNA accumulation and downregulated the cGAS-STING-NLRP3 axis, ameliorating the cytotoxicity induced by LPS. CONCLUSION: This study demonstrated that the cGAS-STING axis was triggered by cytosolic mtDNA and participated in the development of S-AKI by activating NLRP3 inflammasome. Reducing cytosolic mtDNA accumulation or inhibiting the cGAS-STING axis may be potential therapeutic targets for S-AKI.

Clinical Characteristics and Pathogen Spectrum of Male Genital Fungal Infections in Nanchang Area, South China.

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.

Evaluating the effectiveness of immediate vs. elective thoracic endovascular aortic repair for blunt thoracic aortic injury.

PURPOSE: To evaluate the relationship between the timing of thoracic endovascular aortic repair (TEVAR) for blunt thoracic aortic injury (BTAI) and prognosis. METHODS: This is a single-center retrospective cohort study. Patients who received TEVAR for BTAI at our institution from October 2016 to September 2023 were divided into 2 categories depending on the injury severity score (ISS) (≤ 25 vs. > 25) and when the TEVAR was performed for BTAI (within 24 h vs. after 24 h), respectively. The analysis included all patients who received TEVAR treatment after being diagnosed with BTAI through whole-body CT angiography. Patients treated with open repair and non-operative management were excluded. After propensity-score matching for various factors, outcomes during hospitalization and follow-up were compared. These factors included demographics, comorbidities, concomitant injuries, cause and location of aortic injury, Glasgow coma scale score, society for vascular surgery grading, hemoglobin concentration, creatinine concentration, shock, systolic blood pressure, and heart rate at admission. The comparison was conducted using SPSS 26 software. Continuous variables were presented as either the mean ± standard deviation or median (Q1, Q3), and were compared using either the t-test or the Mann-Whitney U test. Categorical variables were expressed as n (%), and comparisons were made between the 2 groups using the χ2 test or Fisher's exact test. Statistical significance was defined as a 2-sided p < 0.05. RESULTS: In total, 110 patients were involved in the study, with 65 (59.1%) patients having ISS scores > 25 and 32 (29.1%) receiving immediate TEVAR. The perioperative overall mortality rate in the group with ISS > 25 was significantly higher than that in the group with ISS ≤ 25 (11 (16.9%) vs. 2 (4.4%), p < 0.001). Upon admission, the elective group exhibited a notably higher Glasgow coma scale score (median (Q1, Q3)) compared to the immediate group (15 (12, 15) vs. 13.5 (9, 15), p = 0.039), while the creatinine concentration (median (Q1, Q3)) at admission was significantly higher in the immediate group (90.5 (63.8, 144.0) vs. 71.5 (58.3, 80.8), p = 0.012). The final sample included 52 matched patients. Complications occurred significantly less frequently in the elective group compared to the immediate group (16 (50.0%) vs. 3 (10.0%), p < 0.001). Single-factor analysis of variance showed that complications in hospitalized patients were significantly associated with immediate TEVAR as the sole independent risk factor (odds ratio: 9.000, 95% confidence interval: 2.266 - 35.752, p = 0.002). CONCLUSION: In this propensity-score matched analysis of patients undergoing TEVAR for BTAI, elective TEVAR was significantly associated with a lower risk of complication rates. In this study using propensity-score matching, patients who underwent elective TEVAR for BTAI had lower complication rates than immediate TEVAR.

Quantifying effects of cold acclimation and delayed springtime photosynthesis resumption in northern ecosystems.

Land carbon dynamics in temperate and boreal ecosystems are sensitive to environmental change. Accurately simulating gross primary productivity (GPP) and its seasonality is key for reliable carbon cycle projections. However, significant biases have been found in early spring GPP simulations of northern forests, where observations often suggest a later resumption of photosynthetic activity than predicted by models. Here, we used eddy covariance-based GPP estimates from 39 forest sites that differ by their climate and dominant plant functional types. We used a mechanistic and an empirical light use efficiency (LUE) model to investigate the magnitude and environmental controls of delayed springtime photosynthesis resumption (DSPR) across sites. We found DSPR reduced ecosystem LUE by 30-70% at many, but not all site-years during spring. A significant depression of LUE was found not only in coniferous but also at deciduous forests and was related to combined high radiation and low minimum temperatures. By embedding cold-acclimation effects on LUE that considers the delayed effects of minimum temperatures, initial model bias in simulated springtime GPP was effectively resolved. This provides an approach to improve GPP estimates by considering physiological acclimation and enables more reliable simulations of photosynthesis in northern forests and projections in a warming climate.

Neglected Adult Tinea Capitis in South China: A Retrospective Study in Nanchang, Jiangxi Province, from 2007 to 2021.

Tinea capitis (TC) in adults is much less frequently diagnosed in comparison to TC in children. In this study, we explored retrospectively adult TC in a specialized dermatology hospital, located in South China, during the years 2007-2021. Among 1037 TC cases, 168 (16.2%) patients were older than 18 years. The majority of adults with TC, 77.38% (130/168), were older than 40, with a peak in the age of 51-60 years (40/168, 23.81%). Before presenting at our hospital, many of patients did not got proper treatment due to misdiagnosis or simply did not consulted an appropriate clinic. 60.71% (102/168) of the patients reported symptoms lasting for more than 1 year and 29.76% (50/168) reported chronic scalp problems of at least 10 years. And 27.38% (46/168) of the patients had an immunocompromised status, including long-term use of corticosteroids shampoo, type 2 diabetes mellitus (DM), psoriasis vulgaris, rheumatoid arthritis, systemic lupus erythematosus or bullous pemphigoid. As for clinical presentation, 87.5% (147/168) of the cases presented as black dot type of TC and anthropophilic dermatophytes were the predominant etiology, with Trichophyton violaceum (126), T. tonsurans (15), T. rubrum (8) and T. shoenleinii (6). Grey patch type of TC (3.57%, 6/168) was seldom in Jiangxi Province and zoophilic/geophilic dermatophytes were rare. Our study indicates that anthropophilic Trichophyton species can cause long-lasting TC in adults. Not in all cases, the manifestation had symptom clearly indicating a dermatophyte-related TC. Thus, patients with long-lasting scalp inflammation, also older ones, should be examined for the presence of dermatophyte-related TC.

Monitoring nature's calendar from space: Emerging topics in land surface phenology and associated opportunities for science applications.

Vegetation phenology has been viewed as the nature's calendar and an integrative indicator of plant-climate interactions. The correct representation of vegetation phenology is important for models to accurately simulate the exchange of carbon, water, and energy between the vegetated land surface and the atmosphere. Remote sensing has advanced the monitoring of vegetation phenology by providing spatially and temporally continuous data that together with conventional ground observations offers a unique contribution to our knowledge about the environmental impact on ecosystems as well as the ecological adaptations and feedback to global climate change. Land surface phenology (LSP) is defined as the use of satellites to monitor seasonal dynamics in vegetated land surfaces and to estimate phenological transition dates. LSP, as an interdisciplinary subject among remote sensing, ecology, and biometeorology, has undergone rapid development over the past few decades. Recent advances in sensor technologies, as well as data fusion techniques, have enabled novel phenology retrieval algorithms that refine phenology details at even higher spatiotemporal resolutions, providing new insights into ecosystem dynamics. As such, here we summarize the recent advances in LSP and the associated opportunities for science applications. We focus on the remaining challenges, promising techniques, and emerging topics that together we believe will truly form the very frontier of the global LSP research field.

Nutrients and water availability constrain the seasonality of vegetation activity in a Mediterranean ecosystem.

Anthropogenic nitrogen (N) deposition and resulting differences in ecosystem N and phosphorus (P) ratios are expected to impact photosynthetic capacity, that is, maximum gross primary productivity (GPPmax ). However, the interplay between N and P availability with other critical resources on seasonal dynamics of ecosystem productivity remains largely unknown. In a Mediterranean tree-grass ecosystem, we established three landscape-level (24 ha) nutrient addition treatments: N addition (NT), N and P addition (NPT), and a control site (CT). We analyzed the response of ecosystem to altered nutrient stoichiometry using eddy covariance fluxes measurements, satellite observations, and digital repeat photography. A set of metrics, including phenological transition dates (PTDs; timing of green-up and dry-down), slopes during green-up and dry-down period, and seasonal amplitude, were extracted from time series of GPPmax and used to represent the seasonality of vegetation activity. The seasonal amplitude of GPPmax was higher for NT and NPT than CT, which was attributed to changes in structure and physiology induced by fertilization. PTDs were mainly driven by rainfall and exhibited no significant differences among treatments during the green-up period. Yet, both fertilized sites senesced earlier during the dry-down period (17-19 days), which was more pronounced in the NT due to larger evapotranspiration and water usage. Fertilization also resulted in a faster increase in GPPmax during the green-up period and a sharper decline in GPPmax during the dry-down period, with less prominent decline response in NPT. Overall, we demonstrated seasonality of vegetation activity was altered after fertilization and the importance of nutrient-water interaction in such water-limited ecosystems. With the projected warming-drying trend, the positive effects of N fertilization induced by N deposition on GPPmax may be counteracted by an earlier and faster dry-down in particular in areas where the N:P ratio increases, with potential impact on the carbon cycle of water-limited ecosystems.

Prevalence and antifungal susceptibility of Sporothrix species in Jiangxi, central China.

Sporotrichosis is a subcutaneous mycosis caused by traumatic inoculation of pathogenic Sporothrix species. Until recently, Sporothrix globosa was considered as the unique Chinese species causing this disorder. In the present study, 33 clinical Sporothrix strains isolated from Jiangxi, China, were classified and antifungal susceptibility for each strain was determined. Thirteen S. globosa strains and 20 S. schenckii strains were identified by morphology and by multilocus analysis using rDNA ITS, CAL, and EF1α (i.e., internal transcribed spacer, calmodulin and elongation factor-1α). In vitro antifungal susceptibility testing of yeast phases indicated that itraconazole, terbinafine, and posaconazole were most effective against both species, followed by amphotericin B and voriconazole, while fluconazole, 5-fluorocytosine had low efficacy with high MICs. Co-occurrence of S. schenckii and S. globosa in central China may indicate different routes of transmission in this area.

Secure Transmission for Simultaneous Wireless Information and Power Transfer in AF Untrusted Relay Networks.

This paper investigates secure communications of energy harvesting untrusted relay networks, where the destination assists jamming signal to prevent the untrusted relay from eavesdropping and to improve the forwarding ability of the energy constrained relay. Firstly, the source and the destination transmit the signals to the relay with maximal ratio transmission (MRT) technique or transmit antenna selection (TAS) technique. Then, the destination utilizes maximal ratio combining (MRC) technique or receive antenna selection (RAS) technique to receive the forwarded information. Therefore, four transmission and reception schemes are considered. For each scheme, the closed-form expressions of the secrecy outage probability (SOP) and the connection outage probability (COP) are derived. Besides, the effective secrecy throughput (EST) metric is analyzed to achieve a good tradeoff between security and reliability. In addition, the asymptotic performance of EST is also considered at the high signal-to-noise ratio (SNR). Finally, simulation results illustrate that: (1) the EST of the system with MRT and MRC scheme are superior to other schemes, however, in the high SNR regime, the EST of the system with MRT scheme is inferior to TAS; and (2) for the source node, there exists an optimal number of antennas to maximize the EST of the proposed schemes.

Location-Aware Incentive Mechanism for Traffic Offloading in Heterogeneous Networks: A Stackelberg Game Approach.

This article investigates the traffic offloading problem in the heterogeneous network. The location of small cells is considered as an important factor in two aspects: the amount of resources they share for offloaded macrocell users and the performance enhancement they bring after offloading. A location-aware incentive mechanism is therefore designed to incentivize small cells to serve macrocell users. Instead of taking the amount of resources shared as the basis of the reward division, the performance promotion brought to the macro network is taken. Meanwhile, in order to ensure the superiority of small cell users, the significance of them weighs heavier than macrocell users instead of being treated equally. The offloading problem is formulated as a Stackelberg game where the macro cell base station is the leader and small cells are followers. The Stackelberg equilibrium of the game is proved to be existing and unique. It is also proved to be the optimum of the proposed problem. Simulation and numerical results verify the effectiveness of the proposed method.

Evolution of tinea capitis in the Nanchang area, Southern China: a 50-year survey (1965-2014).

Tinea capitis remains a common public health problem worldwide especially in developing areas. Aetiologic agents and clinical pattern vary with geography and history of socioeconomic conditions. Three community surveys and a prospective study were carried out over the past 50 years (1965-2014) in the Qingyunpu District of Nanchang, Southern China. Clinical presentation and spectrum of aetiological agents were monitored to understand the evolution of tinea capitis. In 1965 favus was highly epidemic and Trichophyton schoenleinii presented as the overwhelming aetiological agents of scalp infection in the study area, with a prevalence of 3.41% of the population. During a governmental campaign to eliminate tinea capitis initiated in mid of 1960s, favus was successfully controlled and the prevalence decreased to less than 0.01% in 1977. After that period, clinical presentation and spectrum of fungi changed with social development. Trichophyton schoenleinii was replaced by Trichophyton violaceum and Trichophyton mentagrophytes. Nowadays, the species corresponds with a dominant black dot type of tinea capitis in the Nanchang area. The prevalence of causative agents of tinea capitis is not only related to geography but also to socioeconomic factors. Multiple factors have to be considered for the management for control of this disease.

TXNIP knockdown protects rats against bupivacaine-induced spinal neurotoxicity via the inhibition of oxidative stress and apoptosis.

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity.

Construction and validation of a clinical prediction model for asymptomatic obstructive coronary stenosis in patients with carotid stenosis.

Background: Coronary artery stenosis occurs frequently in patients with carotid artery stenosis. We developed a clinical predictive model to investigate the clinical risk of asymptomatic obstructive coronary artery stenosis in patients with carotid artery stenosis ≥ 50%. Methods: From January 2018 to January 2022, carotid stenosis patients hospitalized at the First Affiliated Hospital of Zhengzhou University's Department of Endovascular Surgery were subjected to a retrospective analysis of their clinical information and imaging results. Excluded criteria were patients with lacking data, symptomatic coronary stenosis, prior coronary artery bypass grafting, and coronary stent implantation. Patients were separated into case and control groups according to whether or not they had obstructive coronary stenosis. Independent predictors were screened using univariate and multivariate logistic regression, and their accuracy was confirmed using least absolute shrinkage and selection operator (LASSO) regression. A Nomogram prediction model was developed using the aforementioned filtered factors. The model's discrimination and specificity were evaluated using the receiver operating characteristic curve (ROC) and Hosmer-Lemeshow goodness-of-fit test. Internal validation employed the Bootstrap procedure. The clinical decision curve analysis (DCA) of the prediction model was developed to assess the clinical applicability of the model. Results: The investigation included a total of 227 patients, of whom 132 (58.1%) had coronary artery stenosis. Hypertension, Grade I plaque, HbA1c ≥ 7.0%, MPV ≥ 9.2fl, and Fib ≥ 3.0 g/L were independent predictors, with OR values of (2.506, 0.219, 0.457, 1.876, 2.005), according to multivariate logistic regression. Risk factor screening and validation using lasso regression. The predictors chosen based on the optimal λ value are consistent with the predictors identified by multiple regression. The area under the ROC curve (AUC) of the model based on the above predictors was 0.701 (0.633-0.770), indicating that the model discriminated well. The calibration curve of the model closely matched the actual curve, and P > 0.05 in the Hosmer-Lemeshow goodness-of-fit test indicated the model's accuracy. The results of the DCA curve demonstrate the clinical applicability of the prediction model. Conclusion: Hypertension, grade I plaque, HbA1c ≥ 7.0%, MPV ≥ 9.2 fl, and Fib ≥ 3.0 g/L are predictors of asymptomatic coronary stenosis in patients with carotid stenosis ≥50%. The diagnostic model is clinically applicable and useful for identifying patients at high risk.

Resveratrol­mediated activation of SIRT1 inhibits the PERK­eIF2α­ATF4 pathway and mitigates bupivacaine­induced neurotoxicity in PC12 cells.

Endoplasmic reticulum (ER) stress and apoptosis play significant roles in the development of neurotoxicity caused by bupivacaine (BUP). By activating sirtuin 1 (SIRT1), resveratrol (RSV) can regulate various cellular processes associated with anti-oxidative stress, anti-apoptosis and anti-inflammatory responses, thereby exerting neuroprotective effects. However, it remains unknown whether the activation of SIRT1 by RSV is able to attenuate BUP-induced ER stress and apoptosis. Therefore, the present study aimed to explore the effect of RSV on BUP-induced cytotoxicity in PC12 cells and the underlying mechanism. Cell Counting Kit-8 assays, flow cytometry and inverted phase-contrast microscopy were used to assess the viability, apoptosis rate and morphological changes of the cells, respectively. Western blotting and immunofluorescence staining were used to analyze the levels of SIRT1, the apoptosis-related proteins Bax, Bcl-2 and cleaved caspase-3, the ER stress-related proteins glucose-regulated protein 78, caspase-12 and CHOP, and the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2 α (eIF2α)-activating transcription factor 4 (ATF4) pathway-associated proteins phosphorylated (p)-PERK, PERK, p-eIF2α, eIF2α and ATF4. The results revealed that BUP induced cell apoptosis and decreased cell viability, accompanied by the downregulation of SIRT1. However, RSV restored SIRT1 protein expression, downregulated the expression of the pro-apoptotic protein Bax, upregulated the expression of the anti-apoptotic protein Bcl-2, decreased the apoptosis rate of the cells and increased cell viability. Furthermore, the anti-apoptotic effects exhibited by RSV were associated with inhibition of the PERK-eIF2α-ATF4 pathway of ER stress. However, the protective effect of RSV was significantly mitigated by the SIRT1 inhibitor EX527. These results indicate that the activation of SIRT1 by RSV alleviates BUP-induced PC12 cell ER stress and apoptosis via regulation of the PERK-eIF2α-ATF4 pathway. These findings offer insights into the molecular mechanism underlying BUP-induced apoptosis and suggest the potential of RSV as a therapeutic agent against the neurotoxicity caused by BUP.

A dynamic study of the postoperative management of thyroid cancer from 2003 to 2022: a bibliometric analysis.

Background: Over the past 20 years, the global incidence of thyroid cancer has continued to increase. The volume of literature on the postoperative management of thyroid cancer comprises 1,040 articles, from 64 countries, with 1,400 journals publishing the relevant literature, and several guidelines on the treatment of thyroid cancer. This study used bibliometric methods to identify research hotspots and explore future directions in this field. Methods: We comprehensively searched the Science Citation Index Expanded (SCI-E) database of the Web of Science Core Collection (WOSCC) for articles published from 2003 to 2022 on the postoperative management of thyroid cancer. Using CiteSpace 6.1.R6 and Microsoft Office Excel 2010, we evaluated and visualized the search results. Using R Studio, we generated a network of spatial geographic distribution maps and cooperative network. Results: A total of 1,040 publications were included in the study. The results revealed an overall upward trend in the number of publications and citations over the past 20 years. The United States of America (USA) had the largest number of publications and the highest centrality (n=282, centrality =0.28). Johns Hopkins University had highest centrality (centrality =0.15) and was the academic center of the field. Thyroid was the journal with the highest number of citations (n=826), and the American Journal of Surgical Pathology was the journal with the highest centrality (centrality =0.08). The top 10 citations in the literature were mainly guidelines and consensus statements on the management of thyroid cancer. A keyword-based clustering analysis revealed the prominence of clusters of keywords, such as follow-up, recurrent laryngeal nerve, and medullary thyroid carcinoma (MTC). A keyword burst detection analysis showed that the term papillary had the highest burst intensity (strength =8.02), while management guidelines, association guidelines, active surveillance (AS), microcarcinoma, and differentiated thyroid cancer were the current burst words. Conclusions: Over the past two decades, the number of relevant publications in the postoperative management of thyroid cancer field has continued to grow. Among the many research directions, follow-up, recurrent laryngeal nerve, and MTC are research hotspots. Future research is likely to revolve around guidelines and consensus statements on the management of thyroid cancer, AS, and microcarcinoma in differentiated thyroid cancer.

Resveratrol Suppresses Bupivacaine-Induced Spinal Neurotoxicity in Rats by Inhibiting Endoplasmic Reticulum Stress via SIRT1 Modulation.

Bupivacaine (BUP) may cause neurotoxic effects after spinal anesthesia. Resveratrol (RSV), a natural agonist of Silent information regulator 1 (SIRT1), protects various tissues and organs from damage by regulating endoplasmic reticulum (ER) stress. The aim of this study is to explore whether RSV could alleviate the neurotoxicity induced by bupivacaine via regulating ER stress. We established a model of bupivacaine-induced spinal neurotoxicity in rats using intrathecal injection of 5% bupivacaine. The protective effect of RSV was evaluated by injecting intrathecally with 30 µg/µL RSV in total of 10 µL per day for 4 consecutive days. On day 3 after bupivacaine administration, tail-flick latency (TFL) tests and the Basso, Beattie, and Bresnahan (BBB) locomotor scores were assessed to neurological function, and the lumbar enlargement of the spinal cord was obtained. H&E and Nissl staining were used to evaluate the histomorphological changes and the number of survival neurons. TUNEL staining was conducted to determine apoptotic cells. The expression of proteins was detected by IHC, immunofluorescence, and western blot. The mRNA level of SIRT1 was determined by RT-PCR. Bupivacaine caused spinal cord neurotoxicity by inducing cell apoptosis and triggering ER stress. RSV treatment promoted the recovery of neurological dysfunction after bupivacaine administration by suppressing neuronal apoptosis and ER stress. Furthermore, RSV upregulated SIRT1 expression and inhibited PERK signaling pathway activation. In summary, resveratrol suppresses bupivacaine-induced spinal neurotoxicity in rats by inhibiting endoplasmic reticulum stress via SIRT1 modulation.

Ferrostatin-1 ameliorates Bupivacaine-Induced spinal neurotoxicity in rats by inhibiting ferroptosis.

Bupivacaine (BUP) has previously been shown to trigger neurotoxicity after spinal anesthesia. Further, ferroptosis has been implicated in the pathological processes associated with various central nervous system diseases. Although the impact of ferroptosis on BUP-induced neurotoxicity in the spinal cord has not been fully understood, this research aims to investigate this relationship in rats. Additionally, this study aims to determine whether ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, can provide protection against BUP-induced spinal neurotoxicity. The experimental model for BUP-induced spinal neurotoxicity involved the administration of 5% bupivacaine through intrathecal injection. Then, the rats were randomized into the Control, BUP, BUP + Fer-1, and Fer-1 groups. BBB scores, %MPE of TFL, and H&E and Nissl stainings showed that intrathecal Fer-1 administration improved functional recovery, histological outcomes, and neural survival in BUP-treated rats. Moreover, Fer-1 has been found to alleviate the BUP-induced alterations related to ferroptosis, such as mitochondrial shrinkage and disruption of cristae, while also reducing the levels of malondialdehyde (MDA), iron, and 4-hydroxynonenal (4HNE). Fer-1 also inhibits the accumulation of reactive oxygen species (ROS) and restores the normal levels of glutathione peroxidase 4 (GPX4), cystine/glutamate transporter (xCT), and glutathione (GSH). Furthermore, double-immunofluorescence staining revealed that GPX4 is primarily localized in the neurons instead of microglia or astroglia in the spinal cord. In summary, we demonstrated that ferroptosis play a pivotal role in mediating BUP-induced spinal neurotoxicity, and Fer-1 ameliorated BUP-induced spinal neurotoxicity by reversing the underlying ferroptosis-related changes in rats.