Environmental factors shaping the gut microbiome in a Dutch population.

The gut microbiome is associated with diverse diseases1-3, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.

Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

Observation of room-temperature polar skyrmions.

Complex topological configurations are fertile ground for exploring emergent phenomena and exotic phases in condensed-matter physics. For example, the recent discovery of polarization vortices and their associated complex-phase coexistence and response under applied electric fields in superlattices of (PbTiO3)n/(SrTiO3)n suggests the presence of a complex, multi-dimensional system capable of interesting physical responses, such as chirality, negative capacitance and large piezo-electric responses1-3. Here, by varying epitaxial constraints, we discover room-temperature polar-skyrmion bubbles in a lead titanate layer confined by strontium titanate layers, which are imaged by atomic-resolution scanning transmission electron microscopy. Phase-field modelling and second-principles calculations reveal that the polar-skyrmion bubbles have a skyrmion number of +1, and resonant soft-X-ray diffraction experiments show circular dichroism, confirming chirality. Such nanometre-scale polar-skyrmion bubbles are the electric analogues of magnetic skyrmions, and could contribute to the advancement of ferroelectrics towards functionalities incorporating emergent chirality and electrically controllable negative capacitance.

Photothermal-Controllable Microneedles with Antitumor, Antioxidant, Angiogenic, and Chondrogenic Activities to Sequential Eliminate Tracheal Neoplasm and Reconstruct Tracheal Cartilage.

The optimal treatment for tracheal tumors necessitates sequential tumor elimination and tracheal cartilage reconstruction. This study introduces an innovative inorganic nanosheet, MnO2 /PDA@Cu, comprising manganese dioxide (MnO2 ) loaded with copper ions (Cu) through in situ polymerization using polydopamine (PDA) as an intermediary. Additionally, a specialized methacrylic anhydride modified decellularized cartilage matrix (MDC) hydrogel with chondrogenic effects is developed by modifying a decellularized cartilage matrix with methacrylic anhydride. The MnO2 /PDA@Cu nanosheet is encapsulated within MDC-derived microneedles, creating a photothermal-controllable MnO2 /PDA@Cu-MDC microneedle. Effectiveness evaluation involved deep insertion of the MnO2 /PDA@Cu-MDC microneedle into tracheal orthotopic tumor in a murine model. Under 808 nm near-infrared irradiation, facilitated by PDA, the microneedle exhibited rapid overheating, efficiently eliminating tumors. PDA's photothermal effects triggered controlled MnO2 and Cu release. The MnO2 nanosheet acted as a potent inorganic nanoenzyme, scavenging reactive oxygen species for an antioxidant effect, while Cu facilitated angiogenesis. This intervention enhanced blood supply at the tumor excision site, promoting stem cell enrichment and nutrient provision. The MDC hydrogel played a pivotal role in creating a chondrogenic niche, fostering stem cells to secrete cartilaginous matrix. In conclusion, the MnO2 /PDA@Cu-MDC microneedle is a versatile platform with photothermal control, sequentially combining antitumor, antioxidant, pro-angiogenic, and chondrogenic activities to orchestrate precise tracheal tumor eradication and cartilage regeneration.

Coherent feedback enhanced quantum-dense metrology in a lossy environment.

Quantum dense metrology (QDM) performs high-precision measurements by a two-mode entangled state created by an optical parametric amplifier (PA), where one mode is a meter beam and the other is a reference beam. In practical applications, the photon losses of meter beam are unavoidable, resulting in a degradation of the sensitivity. Here, we employ coherent feedback that feeds the reference beam back into the PA by a beam splitter to enhance the sensitivity in a lossy environment. The results show that the sensitivity is enhanced significantly by adjusting the splitting ratio of the beam splitter. This method may find its potential applications in QDM. Furthermore, such a strategy that two non-commuting observables are simultaneous measurements could provide a new way to individually control the noise-induced random drift in phase or amplitude of the light field, which would be significant for stabilizing the system and long-term precision measurement.

Polarization self-compensation in a laser-driven interferometric fiber optic gyroscope with high long-term stability.

We present a laser-driven interferometric fiber optic gyroscope (IFOG) with polarization self-compensation to achieve high scale-factor stability, sensitivity, and long-term stability. Coherent light with 200kHz linewidth is employed to keep the scale factor stable. The optical scheme ensures polarization reciprocity as well as the optimal working point for good sensitivity. Furthermore, a hybrid machine learning loop (MLL) method, combining the advantages of PID fast response and artificial neural network (ANN) dynamic search, can control a liquid crystal rotator (LCR) to dynamically compensate for slow drift induced by polarization coupling. In open environment, when the sensitivity is 0.005 ∘/h, the bias instability (BI) is significantly optimized from 0.6723°/h at 60s (PID) to 0.3869°/h at 200s (MLL), which is close to the Sagnac interferometric limit (SIL). Such IFOG can meet the real-time and robust requirements for inertial navigation systems in long-term measurement.

Energy-Conversion Device Using a Quantum Engine with the Work Medium of Two-Atom Entanglement.

Although entanglement is considered as an essential resource for quantum information processing, whether entanglement helps for energy conversion or output in the quantum regime is still lack of experimental witness. Here, we report on an energy-conversion device operating as a quantum engine with the working medium acted by two entangled ions confined in a harmonic potential. The two ions are entangled by virtually coupling to one of the vibrational modes shared by the two ions, and the quantum engine couples to a quantum load, which is another shared vibrational mode. We explore the energy conversion efficiency of the quantum engine and investigate the useful energy (i.e., the maximum extractable work) stored in the quantum load by tuning the two ions in different degrees of entanglement as well as detecting the change of the phonons in the load. Our observation provides, for the first time, quantitative evidence that entanglement fuels the useful energy produced by the quantum engine, but not helpful for the energy conversion efficiency. We consider that our results may be useful to the study of quantum batteries for which one of the most indexes is the maximum extractable energy.

Single-Atom Verification of the Optimal Trade-Off between Speed and Cost in Shortcuts to Adiabaticity.

The approach of shortcuts to adiabaticity enables the effective execution of adiabatic dynamics in quantum information processing with enhanced speed. Owing to the inherent trade-off between dynamical speed and the cost associated with the transitionless driving field, executing arbitrarily fast operations becomes impractical. To understand the accurate interplay between speed and energetic cost in this process, we propose theoretically and verify experimentally a new trade-off, which is characterized by a tightly optimized bound within s-parametrized phase spaces. Our experiment is carried out in a single ultracold ^{40}Ca^{+} ion trapped in a harmonic potential. By exactly operating the quantum states of the ion, we execute the Landau-Zener model as an example, where the quantum speed limit as well as the cost are governed by the spectral gap. We witness that our proposed trade-off is indeed tight in scenarios involving both initially eigenstates and initially thermal equilibrium states. Our work helps understanding the fundamental constraints in shortcuts to adiabaticity and illuminates the potential of underutilized phase spaces that have been traditionally overlooked.

New radiofrequency ablation procedure for selective reduction in complicated monochorionic twin or triplet pregnancy using multistep, incremental expansion technique.

OBJECTIVE: Radiofrequency ablation (RFA) is the preferred approach for selective reduction in complex monochorionic (MC) multiple pregnancies owing to the ease of operation and minimal invasiveness. To optimize the RFA technique and reduce the risk of adverse pregnancy outcome resulting from the heat-sink effect of RFA therapy, we used an innovative RFA method, in which an electrode needle was expanded incrementally and stepwise. This study aimed to assess the efficacy and safety profile of this novel multistep incremental expansion RFA method for selective fetal reduction in MC twin and triplet pregnancies. METHODS: This was a single-center retrospective cohort study of all MC multiple pregnancies undergoing RFA between March 2016 and October 2022 at our center. The multistep RFA technique involved the use of an expandable needle, which was gradually expanded during the RFA procedure until cessation of umbilical cord blood flow was achieved. The needle used for the single-step RFA method was fully extended from the start of treatment. RESULTS: In total, 132 MC multiple pregnancies underwent selective reduction using RFA, including 50 cases undergoing multistep RFA and 82 cases undergoing single-step RFA. The overall survival rates were not significantly different between the multistep and single-step RFA groups (81.1% vs 72.3%; P = 0.234). Similarly, the rates of preterm prelabor rupture of the membranes within 2 weeks after RFA, procedure-related complications, spontaneous preterm delivery and pathological findings on cranial ultrasound, as well as gestational age at delivery and birth weight, did not differ between the two groups. However, there was a trend towards a prolonged procedure-to-delivery interval following multistep RFA compared with single-step RFA (median, 109 vs 99 days; P = 0.377). Moreover, the fetal loss rate within 2 weeks after RFA in the multistep RFA group was significantly lower than that in the single-step RFA group (10.0% vs 24.4%; P = 0.041). The median ablation time was shorter (5.3 vs 7.8 min; P < 0.001) and the median ablation energy was lower (10.2 vs 18.0 kJ; P < 0.001) in multistep compared with single-step RFA. There were no significant differences in neonatal outcomes following multistep vs single-step RFA. CONCLUSIONS: Overall survival rates were similar between the two RFA methods. However, the multistep RFA technique was associated with a lower risk of fetal loss within 2 weeks after RFA. The multistep RFA technique required significantly less ablation energy and a shorter ablation time compared with single-step RFA in selective fetal reduction of MC twin and triplet pregnancies. Additionally, there was a trend towards a prolonged procedure-to-delivery interval with the multistep RFA technique. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Effect of a second-generation motion correction algorithm on image quality and measurement reproducibility of coronary CT angiography in patients with a myocardial bridge and mural coronary artery.

AIM: To determine the effect of second-generation motion correction (MC2) on image quality and measurement reproducibility of cardiac CT images in patients with a myocardial bridge and mural coronary artery (MB-MCA) compared to standard (STD) images without motion correction and with first-generation motion correction (MC1). MATERIALS AND METHODS: A total of 66 patients with MB-MCA in the left anterior descending branch who underwent 256-detector CT with single-heartbeat acquisition were included. Images were reconstructed at 45% and 75% R-R intervals using STD, MC1, and MC2 algorithms. Image quality for MB-MCA was assessed by two observers on a four-point scale (1 = poor and 4 = excellent) and compared among STD, MC1, and MC2. Depth and length of MB, lumen area, and minimal diameter of MCA were measured and compared. RESULTS: At 45% R-R interval, image quality scores were 1.59 ± 0.78, 2.21 ± 0.97, and 3.21 ± 0.62 for MCA, and 2.48 ± 0.79, 2.76 ± 0.75, and 3.58 ± 0.58 for MB with STD, MC1 and MC2, respectively. At 75% R-R interval, these values were 2.26 ± 0.60, 3.03 ± 0.89, and 3.59 ± 0.55 for MCA and 3.00 ± 0.93, 3.17 ± 0.83, and 3.80 ± 0.44 for MB. Although MC1 was superior to STD in displaying MCA, there was no statistical difference between the two algorithms for MB (p>0.05). Compared with STD and MC1, MC2 statistically improved image quality and interpretability for both MCA and MB and had narrower limits in interobserver agreement for measurements at both 45% and 75% R-R intervals. CONCLUSION: MC2 improves CT image quality and measurement reproducibility in patients with MB-MCA compared to STD and MC1.

Optimizing the indication of initial radioiodine oncolytic treatment for metastatic differentiated thyroid cancer by diagnostic 131I scan.

AIM: As a classic theranostic radiopharmaceutical, radioiodine (131I) has been utilized in the management of differentiated thyroid cancer (DTC) for more than 8 decades, and the refinement of its clinical practice has been raised recently. This study was conducted to evaluate the efficiency of a diagnostic (Dx) 131I scan in optimizing the indication of initial radioiodine oncolytic treatment (ROT) for metastatic DTC by predicting therapeutic outcomes. RESULTS: A total of 100 patients (Dx positive, n=29; Dx negative, n=71) were eligible for patient-based analysis. The matching rate was 83.0% between the Dx and the post-therapeutic scans (kappa = 0.648, P<0.001). The biochemical remission rate and structural shrinkage rate induced by the initial ROT in the Dx-positive group were, respectively, greater than those in the Dx-negative group (83.3% vs. 17.4%, P<0.001; 37.9% vs. 4.2%, P<0.001). Notably, the predictive values of positive Dx scans for ROT responsiveness and negative Dx scans for ROT nonresponsiveness reached up to 89.7% and 84.5%, respectively. CONCLUSION: This Dx scan approach seems viable in characterizing the 131I-avidity of metastatic DTC and plays a pivotal role in optimizing the indication of initial ROT for metastatic DTC.

Bioactivity and genome analysis of Bacillus amyloliquefaciens GL18 isolated from the rhizosphere of Kobresia myosuroides in an alpine meadow.

The unique eco-environment of the Qinghai-Tibet Plateau breeds abundant microbial resources. In this research, Bacillus amyloliquefaciens GL18, isolated from the rhizosphere of Kobresia myosuroides from an alpine meadow, and the antagonistic activity, bacteriostatic hydrolase activity, and low temperature, salt, and drought resistance of it were determined and analysed. The seedlings of Avena sativa were root-irrigated using bacteria suspensions (cell concentration 1 × 107 cfu/mL) of GL18, and the growth-promoting effect of GL18 on it was determined under cold, salt and drought stress, respectively. The whole genome of GL18 was sequenced, and its functional genes were analysed. GL18 presented significant antagonistic activity to Fusarium graminearum, Fusarium acuminatum, Fusarium oxysporum and Aspergillus niger (inhibition zone diameter > 17 mm). Transparent zones formed on four hydrolase detection media, indicating that GL18 secreted cellulase, protease, pectinase and ß-1,3-glucanase. GL18 tolerated conditions of 10 °C, 11% NaCl and 15% PEG-6000, presenting cold, salt and drought resistance. GL18 improved the cold, salt and drought tolerance of A. sativa and it showed significant growth effects under different stress. The total length of the GL18 genome was 3,915,550 bp, and the number of coding DNA sequence was 3726. Compared with the clusters of orthologous groups of proteins, gene ontology and kyoto encyclopedia of genes and genomes databases, 3088, 2869 and 2357 functional genes were annotated, respectively. GL18 contained gene clusters related to antibacterial substances, functional genes related to the synthesis of plant growth-promoting substances, and encoding genes related to stress resistance. This study identified an excellent Bacillus strain and provided a theoretical basis for improving stress resistance and promoting the growth of herbages under abiotic stress.

Clinical characteristics, outcomes and risk factors for mortality in hospitalized diabetes and chronic kidney disease patients after COVID-19 infection following widespread vaccination.

BACKGROUND: COVID-19 poses a significant threat to patients with comorbidities, such as diabetes and chronic kidney disease (CKD). China experienced a nationwide COVID-19 endemic from December 2022 to January 2023, which is the first occurrence of such an outbreak following China's widespread administration of COVID-19 vaccinations. METHODS: A total of 338 patients with diabetes and CKD combined with COVID-19 infection between December 7, 2022 and January 31, 2023 were included in this study. The end follow-up date was February 10, 2023. Univariate analysis and multivariate Cox analysis were used to analyze risk factors for death. RESULTS: During the 50-day median follow-up period, 90 patients in the study cohort died, for a mortality rate of 26.63%. The median age of the study cohort was 74 years, with a male predominance of 74%. During hospitalization, 21% of patients had incident AKI, 17% of patients experienced stroke, and 40% of patients experienced respiratory failure. Cox proportional hazard regression showed that older age, a diagnosis of severe or critically severe COVID-19 infection, incident AKI and respiratory failure, higher level of average values of fasting glucose during hospitalization, UA, and total bilirubin were independent risk factors for death in our multivariate model. CONCLUSIONS: These findings highlight the critical importance of identifying and managing comorbid risk factors for COVID-19, especially among the elderly, in order to optimize clinical outcomes, even after COVID-19 vaccination.

Correlation study between bone metabolic markers, bone mineral density, and sarcopenia.

OBJECTIVE: To investigate the correlation between bone metabolism markers, bone mineral density (BMD), and sarcopenia. METHODS: A total of 331 consecutive patients aged ≥ 60 years who were hospitalized between November 2020 and December 2021 were enrolled. Participants were divided into sarcopenia and non-sarcopenia groups according to the Asian Working Group on Sarcopenia criteria (AWGS, 2019). The clinical data, bone metabolism markers (ß-CTX, N-MID, and TP1NP), and BMD were compared between the two groups. RESULTS: Age, ß-CTX, and N-MID of the sarcopenia group were higher than those of the non-sarcopenia group (P < 0.05), but the BMD T values were lower than those of the non-sarcopenia group (P < 0.05). Binary logistic regression analysis showed that increased femoral neck BMD (FNBMD) was a protective factor for sarcopenia, while increased ß-CTX was a risk factor. Pearson/Spearman correlation analysis showed that the diagnostic indices of sarcopenia were positively correlated with FNBMD and negatively correlated with ß-CTX and N-MID. Multiple linear regression analysis revealed that BMI and FNBMD significantly positively affected muscle strength and appendicular skeletal muscle mass (ASM). The FNBMD significantly positively affected physical performance, while ß-CTX significantly negatively affected muscle strength, ASM, and physical performance. CONCLUSION: Increased FNBMD may be a protective factor against sarcopenia, and increased ß-CTX may be a risk factor. The FNBMD significantly positively affected the diagnostic indices of sarcopenia, while ß-CTX significantly negatively affected them. BMD and bone metabolism marker levels may be considered in early screening for sarcopenia.

Effects of heat stress on feed intake, milk yield, milk composition, and feed efficiency in dairy cows: A meta-analysis.

Heat stress compromises dairy production by decreasing feed intake and milk yield, and it may also alter milk composition and feed efficiency. However, little information is available for evaluating such effects across different levels of heat stress and cows enrolled in heat stress studies. The objectives of this study were to evaluate the effects of heat stress on dry matter intake (DMI), energy-corrected milk (ECM), milk composition, and feed efficiency (kg ECM/kg DMI) and to investigate the relationship between such effects and heat stress intervention and animal characteristics by using meta-analytical approaches. Data from 31 studies (34 trials) fulfilled the inclusion criteria and were used for analysis. Results showed that heat stress decreased DMI, ECM, and milk protein concentration, but did not alter milk fat concentration or feed efficiency. Meta-regression confirmed that such reductions in DMI and ECM were significantly associated with increasing temperature-humidity index (THI). Over the period of heat stress, for each unit increase in THI, DMI and ECM decreased by 4.13% and 3.25%, respectively, in mid-lactation cows. Regression models further revealed the existence of a strong interaction between THI and lactation stage, which partially explained the large heterogeneity in effect sizes of DMI and ECM. The results indicated a need for more research on the relationship between the effect of heat stress and animal characteristics. This study calls for the implementation of mitigation strategies in heat-stressed herds due to the substantial decrease in productivity.

Rev-erbα attenuates refractory periapical periodontitis via M1 polarization: An in vitro and in vivo study.

AIM: Rev-erbα has been reported to regulate the healing of inflammatory lesions through its effect on the immune system in a variety of inflammatory disease. Moreover, the balance of macrophages polarization plays a crucial role in immune response and inflammatory progression. However, in refractory periapical periodontitis (RAP), the role of Rev-erbα in inflammatory response and bone resorption by regulating macrophage polarization remains unclarified. The aims of the present study were to investigate the expression of Rev-erbα in experimental RAP and to explore the relationship between Rev-erbα and macrophage polarization through the application of its pharmacological agonist SR9009 into the in vivo and in vitro experiments. METHODOLOGY: Enterococcus faecalis-induced RAP models were established in SD rats. Histological staining and micro-computed tomography scanning were used to evaluate osteoclastogenesis and alveolar bone resorption. The expression of Rev-erbα and macrophage polarization were detected in the periapical tissues from rats by immunofluorescence, flow cytometry, and western blots. Furthermore, immunohistochemical staining and enzyme-linked immunosorbent assay were performed to explore the relationship between Rev-erbα and inflammatory cytokines related to macrophage polarization. RESULT: Compared to healthy periapical tissue, the expression of Rev-erbα was significantly down-regulated in macrophages from inflammatory periapical area, especially in Enterococcus faecalis-induced periapical lesions, with obvious type-1 macrophage (M1)-like dominance and the production of pro-inflammatory cytokines. In addition, Rev-erbα activation by SR9009 could induce type-2 macrophage (M2)-like polarization in periapical tissue and THP1 cell line, followed by increased secretion of anti-inflammatory cytokines IL-10 and TGF-ß. Furthermore, intracanal application of SR9009 reduced the lesion size and promoted the repair of RAP by decreasing the number of osteoclasts and enhancing the formation of mineralized tissue in periapical inflammatory lesions. CONCLUSIONS: Rev-erbα played an essential role in the pathogenesis of RAP through its effect on macrophage polarization. Targeting Rev-erbα might be a promising and prospective therapy method for the prevention and management of RAP.

Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries.

OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use. STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries. METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set. RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior. CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

Influence of intracranial hemorrhage on clinical outcome in acute vertebrobasilar artery occlusion undergoing endovascular treatment.

BACKGROUND AND PURPOSE: The effect of intracranial hemorrhage (ICH) on the outcome of patients with large-vessel occlusion undergoing endovascular treatment (EVT) has mainly focused on the anterior circulation. Knowledge of the relationship between ICH and outcomes in patients with acute vertebrobasilar artery occlusion (VBAO) receiving EVT is limited. We aimed to assess whether ICH is a prognostic marker for acute VBAO following EVT. METHODS: Patients who underwent EVT for acute VBAO in the acute posterior circulation ischemic stroke (PERSIST) registry were included. All patients were classified as having no or any-ICH. Any-ICH was subdivided into asymptomatic and symptomatic ICH. A multivariate regression analysis was performed to evaluate the association between ICH and functional outcomes in patients with acute VBAO after receiving EVT. RESULTS: Five hundred and forty-seven patients, including 107 patients with ICH (19.6%): 38 (7.0%) and 69 (12.6%) with symptomatic and asymptomatic ICH, respectively. After adjustment for potential confounders, any-ICH was independently associated with reduced chance of favorable outcome (OR 0.39, 95% CI 0.21-0.72, P=0.003), functional independence (OR 0.24, 95% CI 0.16-0.52, P<0.001), and excellent outcome (OR 0.34, 95% CI 0.15-0.75, P=0.008), and increased mortality risk (OR 2.14, 95% CI 1.30-3.51, P=0.003). Symptomatic ICH had a similar association. Moreover, asymptomatic ICH was a negative predictor of functional independence (OR 0.39, 95% CI 0.17-0.88, P=0.024). CONCLUSION: Any- and symptomatic ICH were strongly associated with worse clinical outcomes and increased mortality in patients with acute VBAO who underwent EVT. Asymptomatic ICH was an inverse predictor of functional independence.

[The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms].

Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated (r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 (r=-0.167, P=0.044), the level of serum CEA (r=-0.061, P=0.032), and the level of serum ALT(r=-0.147,P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 (r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT (r=0.164, P=0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.