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With the escalation of global climate change and human activity, geohazards become increasingly frequent which cause severe casualties and property losses to local communities. To alleviate this situation and provide scientific guidance for risk reduction, it is imperative to address some of the basic questions related to geohazards, including: i) how to detect active geohazards (AGs) rapidly and automatically over a wide area; ii) how to determine the region with a high level of hazard activity; iii) what are the primary conditioning factors (CFs) of AGs; and iv) do factors operate independently or are they interconnected. To tackle these issues, we propose a universally applicable framework for wide area automated detection of AGs. The framework is based on multi-source Earth observations which capture surface deformation ranging from millimeters to meters. Our study has focused on the Hexi Corridor (HXC) in Gansu Province, China, covering an area of 210,000 km2 with a length of 1100 km. First, we construct an AGs database for the HXC with high automatic and rapid update capabilities, including a total of 4492 AGs (3652 active landslides and 840 land subsidence areas). Second, using the Geographic Detectors method, we determine the primary CFs including elevation, land surface temperature, and precipitation. We find that faults exert greater control over very slow-moving landslides, but are less effective over slow-moving landslides. Third, we analyzed the interactive effects of dual CFs on geohazard actives. Any interaction effect of dual CFs contributes to the bivariate enhancement of geohazard activity. This study significantly enhances the capabilities of the wide area automated detection of AGs, and provides a crucial dataset for hazard prediction and mitigation along the HXC.

Emergency response after earthquakes, especially rapid access to building damage information, is of great significance to ensure timely rescue and reduce casualties. However, manual field surveys of building damages are inefficient and dangerous, and optical satellite data are more susceptible to cloud interference after earthquakes. Synthetic aperture radar (SAR) is now widely used in disaster response efforts due to its full-time and all-weather capability. According to the change in coherence between SAR images before and after earthquakes, it is possible to identify damaged buildings that cause coherence loss. However, the accuracy of traditional coherence-based damage detection methods is relatively low due to biases in coherence estimation and inconsistency in spatio-temporal baselines. In this study, we propose a new method to produce a postearthquake building damage proxy map (BDPM) based on multitemporal Sentinel-1 coherence, which incorporates homogeneous SAR pixel coherence estimation and histogram matching techniques. The former is used to reduce estimation biases and the latter to reduce the effect of baseline inconsistencies in adjacent coherence maps. We successfully applied this method to the 2022 Mw 6.2 Afghanistan earthquake, the 2023 strong earthquake sequence in Turkey, and the 2023 Ms 6.2 Jishishan, China earthquake. We also verified its accuracy (over 80%) by comparing the BDPM with results from the United Nations Institute for Training and Research and analyzed various factors affecting the distribution of damaged buildings. These analyses confirm the effectiveness of our method for generating BDPM using free medium-resolution Sentinel-1 data, which will greatly assist in earthquake emergency response.

Abstract Background The temporary pacing lead routinely is placed into right ventricular (RV), which pose a risk of dislocation and cardiac perforation. Objective We aim to evaluate the effectiveness and safety of temporary transvenous cardiac pacing (TTCP) leads placement into the coronary sinus vein (CSV) in patients with sick sinus syndrome (SSS). Methods We investigated patients with SSS who underwent TTCP lead placement into the CSV under the guidance of X‐ray between January 2013 and May 2023. Patients were randomly divided into two groups: RV group (n = 33) and CSV group (n = 22). The ordinary passive bipolar electrodes were applied in both groups. In RV groups, electrodes were placed into RV. In CSV group, electrodes were placed into CSV. We evaluated the operation duration, fluoroscopic exposure, first‐attempt success rate of leads placement, pacing threshold, success rate of leads placement, rate of leads displacement, and complications. Results Compared with that in RV group, the procedure time, fluoroscopic exposure was significantly prolonged, while the first‐attempt success rate of lead placement was obviously increased in CSV group (both p .05). Conclusion TTCP leads placement into the CSV is an effective and safe strategy in patients with SSS. It indicates a high rate of pacing effectiveness with low device replacement and complication rates.

Hypoxia represent a condition in which an adequate amount of oxygen supply is missing in the body, and it could be caused by a variety of diseases, including gastrointestinal disorders. This review is focused on the role of hypoxia in the maintenance of the gut homeostasis and related treatment of gastrointestinal disorders. The effects of hypoxia on the gut microbiome and its role on the intestinal barrier functionality are also covered, together with the potential role of hypoxia in the development of gastrointestinal disorders, including inflammatory bowel disease and irritable bowel syndrome. Finally, we discussed the potential of hypoxia-targeted interventions as a novel therapeutic approach for gastrointestinal disorders. In this review, we highlighted the importance of hypoxia in the maintenance of the gut homeostasis and the potential implications for the treatment of gastrointestinal disorders.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) clinically reduce atherosclerosis and lower blood pressure. However, their impact on endothelial dysfunction in type 2 diabetes (T2D) remains unclear. In this study, we investigated the protective effect and underlying mechanism of the SGLT2 inhibitor dapagliflozin in diabetes. Methods: Vascular reactivity was measured to assess the vasoprotective effect of dapagliflozin in a mouse model of high glucose (HG)-induced T2D. Pulse wave velocity was measured to quantify arterial stiffness. Protein expression was assessed by western blotting and immunofluorescence, oxidative stress was evaluated using dihydroethidium, nitric oxide was evaluated using the Griess reaction, and cellular senescence was assessed based on senescence-associated beta-galactosidase (SA‐β‐gal) activity and the expression of senescence markers. Furthermore, the endothelial nitric oxide synthase (eNOS) acetylation status was determined and eNOS interactions with SIRT1 were evaluated by coimmunoprecipitation assays. Results: Dapagliflozin protected against impaired endothelium-dependent vasorelaxation and improved arterial stiffness in the mouse model of T2D; mouse aortas had significantly reduced levels of senescence activity and senescence-associated inflammatory factors. HG-induced increases in senescence activity, protein marker levels, and oxidative stress in vitro were all ameliorated by dapagliflozin. The decreases in eNOS phosphorylation and nitric oxide (NO) production in senescent endothelial cells were restored by dapagliflozin. SIRT1 expression was reduced in HG-induced senescent endothelial cells, and dapagliflozin restored SIRT1 expression. SIRT1 inhibition diminished the antisenescence effects of dapagliflozin. Coimmunoprecipitation showed that SIRT1 was physically associated with eNOS, suggesting that the effects of dapagliflozin are dependent on SIRT1 activation. Conclusion: These findings indicate that dapagliflozin protects against endothelial cell senescence by regulating SIRT1 signaling in diabetic mice.

Recent investigations show that dietary consumption of flavonoids could potentially confer neuroprotective effects through a variety of direct and indirect mechanisms. Numerous flavonoids have been shown to cross the BBB and accumulate within the central nervous system (CNS). Some of these compounds purportedly counteract the accumulation and deleterious effects of reactive oxygen species, fostering neuronal survival and proliferation by inhibiting neuroinflammatory and oxidative stress responses. Moreover, several studies suggest that gut microbiota may participate in regulating brain function and host behavior through the production and modulation of bioactive metabolites. Flavonoids may shape gut microbiota composition by acting as carbon substrates to promote the growth of beneficial bacteria that produce these neuroprotective metabolites, consequently antagonizing or suppressing potential pathogens. By influencing the microbiota-gut-brain axis through this selection process, flavonoids may indirectly improve brain health. This review examines the current state of research into the relationship between bioactive flavonoids, gut microbiota, and the gut-brain axis.

Polysaccharides derived from plants, algae, or fungi serve as the major components of some human diets. Polysaccharides have been shown to exhibit diverse biological activities in improving human health, and have also been proposed to function as potent modulators of gut microbiota composition, thus playing a bi-directional regulatory role in host health. Here, we review a variety of polysaccharide structures potentially linked to biological functions, and cover current research progress in characterizing their pharmaceutical effects in various disease models, including antioxidant, anticoagulant, anti-inflammatory, immunomodulatory, hypoglycemic, and antimicrobial activities. We also highlight the effects of polysaccharides on modulating gut microbiota via enrichment for beneficial taxa and suppression of potential pathogens, leading to increased microbial expression of carbohydrate-active enzymes and enhanced short chain fatty acid production. This review also discusses polysaccharide-mediated improvements in gut function by influencing interleukin and hormone secretion in host intestinal epithelial cells.

Introduction: Most drug-eluting stents (DESs) inhibit intimal hyperplasia but impair re-endothelialization. This study aimed to evaluate in vivo strut coverage and neointimal growth in a new glycyrrhizin acid (GA)-eluting stent.Methods: New Zealand White rabbits (n = 20) with atherosclerotic plaques were randomly divided into three groups based on implanted iliac artery stents: bare-metal stents (BMSs), rapamycin-eluting stents, and GA-eluting stents. After the in vivo intravascular ultrasound (IVUS) assessment at 28 days, the vessels were harvested for scanning electron microscopy (SEM) and histology. After 4 weeks of follow-up, the stent and external elastic lamina (EEL) areas were compared among the groups.Results: The rapamycin- or GA-eluting stents significantly reduced the neointimal area compared with BMSs, though GA-eluting stents had the lowest reduction. There were more uncovered struts for rapamycin-eluting stents than those for GA-eluting stents and bare-metal stents. The endothelial nitric oxide synthase (eNOS) expression in GA-eluting stents was much higher than that in BMSs and rapamycin-eluting stents, even though the endothelial coverage between struts was equivalent between BMSs and GA-eluting stents. Moreover, GA-eluting stents markedly promoted re-endothelialization and improved arterial healing compared to rapamycin-eluting stents in a rabbit atherosclerotic model.Conclusion: In conclusion, the novel GA-coated stent used in this study inhibited intimal hyperplasia and promoted re-endothelialization.

An ideal model containing eight phenothiazine 5,5-dioxide derivatives was established to clearly prove the formation of triplet excimer. Competition between monomer (T1) and excimer (T1*) based on π-π stacking is the origin for their changed RTP properties.

In allogeneic hematopoietic cell transplantation (allo-HSCT), both virus-specific T cells and leukemia-specific T cells need to be reconstituted to protect patients from virus infections and primary disease relapse. Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality after allo-HSCT. Emerging data indicate that CMV reactivation is associated with reduced risk of leukemia relapse in patients with acute myeloid leukemia (AML) undergoing allo-HSCT. In a cohort of 24 WT1+ AML patients during the first year following HSCT, CMV specific CD8+ T cells (CMV-CTL) reconstituted much faster than WT1-specific CD8+ T cell (WT1-CTL) after allo-SCT. Moreover, CMV-CTL expressed lower levels of exhaustion markers and were more functional as identified by production of IFN-γ/TNF-α and expression of Eomes/T-bet. Interestingly, our patients with CMV reactivation presented higher frequency of CMV-CTL, lower levels of Eomes+T-bet- and higher levels of Eomes+T-bet+ expression in response to WT1 and CMV pp65 antigen during the first year after transplantation as compared to patients without CMV reactivation. Kinetics of CMV-CTL and WT1-CTL after transplantation might be associated with measurable residual disease and later leukemia relapse. Our results support that CMV reactivation, aside from the CMV-CTL reconstitution, could influence WT1-CTL reconstitution after allo-HSCT, thus potentially contributing to the remission/relapse of AML.

The present study evaluated risk factors related to persistent atrial fibrillation (AF) at discharge (AF-d) and recurrent atrial fibrillation (rAF) and all-cause death after the maze IV procedure. Two hundred nineteen patients (63 female, aged 52.5±8.8 years) with valve disease and persistent AF undergoing valve surgery and the maze IV procedure in our center between 2015 and 2016 were included. Baseline demographic and clinical data were obtained by review of medical records. The median follow-up period was 27 months (interquartile range 21–34 months) in our patient cohort. The primary end point was all-cause death. The secondary end point was AF-d or rAF. rAF is defined as AF recurrence at 3 months or later after the procedure. Twenty-eight patients (12.8%) died during follow-up. Multiple logistic regression analysis showed that thrombocytopenia, elevated serum total bilirubin level, a larger right atrium, AF-d, and rAF were independent determinants for all-cause death after the maze IV procedure after adjustment for age, sex, and clinical covariates, including New York Heart Association class III/IV disease, hypertension, and aortic regurgitation, while valvular disease duration and left atrial diameter greater than 80.5 mm were independent determinants for AF-d, and thrombocytopenia, elevated serum total bilirubin level, higher mean pulmonary artery pressure, and AF-d were independent predictors for rAF. In conclusion, thrombocytopenia, elevated serum total bilirubin level, an enlarged right atrium, AF-d, and rAF are independent predictors of all-cause death in patients undergoing the maze IV procedure.

Due to the complex diagenesis process, basalt usually contains defects in the form of amygdales formed by diagenetic bubbles, which affect its mechanical properties. In this study, a synthetic rock mass method (SRM) based on the combination of discrete fracture network (DFN) and finite-discrete element method (FDEM) is applied to characterizing the amygdaloidal basalt, and to systematically exploring the effects of the development characteristics of amygdales and sample sizes on the mechanical properties of basalt. The results show that with increasing amygdale content, the elastic modulus (E) increases linearly, while the uniaxial compressive strength (UCS) shows an exponential or logarithmic decay. When the orientation of amygdales is between 0° and 90°, basalt shows a relatively pronounced strength and stiffness anisotropy. Based on the analysis of the geometric and mechanical properties, the representative element volume (REV) size of amygdaloidal basalt blocks is determined to be 200 mm, and the mechanical properties obtained on this scale can be regarded as the properties of the equivalent continuum. The results of this research are of value to the understanding of the mechanical properties of amygdaloidal basalt, so as to guide the formulation of engineering design schemes more accurately.

Abstract The Mw 6.3 Yutian earthquake, occurred in northwestern Tibet on 25 June 2020, is one of the major events sequentially occurring in the region following the 2008 Mw 7.2, 2012 Mw 6.2, and 2014 Mw 6.9 earthquakes, and is of great significance for studying the tectonic activity and assessing future seismic hazards in the region. In this study, we used Sentinel‐1 Synthetic Aperture Radar images to retrieve co‐ and post‐seismic deformation and to investigate the coseismic rupture behavior of the fault and the mechanisms of postseismic deformation. Based on the slip models of recent four nearby major earthquakes, we explored the local stress evolution, triggering mechanism of the 2020 event and future regional seismic hazards. Postseismic modeling reveals that afterslip on fault patches surrounding the ruptured co‐seismic patches is the main mechanism responsible for the near‐field deformation, with the poroelastic rebound relaxation only accounts for maximumly 25% of the ground displacement and limited impact on the overall deformation pattern. The Coulomb failure stress changes (ΔCFS) suggest that the 2020 Yutian earthquake was inhibited by the 2008 Mw 7.2 earthquake but facilitated by the 2012 Mw 6.2 and 2014 Mw 6.9 earthquakes, resulting in an overall ΔCFS with a large lateral gradient on the 2020 fault. Stress concentrations on nearby major faults indicate increasing chances of seismic hazards in the eastern section of the Altyn Tagh fault at 82.8°E, the western section of the Guozha Co fault at 81.5°E and the entire section of the Ashikule fault.

BackgroundMahaim-type accessory pathways (MAPs) are rare accessory pathways (APs) with specific properties. They are mostly located in the right side of the heart but rarely exist on the left side.ObjectivesThis study aims to analyze the clinical and electrophysiological (EP) characteristics of both-sided MAPs.MethodsA total of 2,249 patients with AP from our center were enrolled between 1 January 2011 and 27 March 2022. During the EP study (EPS) 17 patients were diagnosed with MAPs (right-sided: n = 13, left-sided: n = 4) according to the properties of Mahaim fibers.ResultsMAPs constitute 0.75% of all APs. Out of 1,553 patients with left-sided APs, four patients (0.26%) were diagnosed with Mahaim fiber-mediated tachycardia. Out of 696 patients with right-sided APs, 13 patients (1.9%) were diagnosed with Mahaim fiber. Most Mahaim fibers were located at the free wall of the tricuspid and mitral annuli. Seven patients of right-sided MAPs were of atriofasicular type, six patients had right-sided MAPs, and all of the patients with left-sided MAPs were of atrioventricular (AV) type. The M potential only was detected in long-length MAPs. Coexistence with other supraventricular tachycardias (SVTs) was also observed both in patients with right-sided and left-sided MAPs. All the patients underwent radiofrequency ablation successfully. Only one patient had tachycardia recurrence during a follow-up.ConclusionAlthough MAPs are commonly located at right sides, left sites are not impossible. The M potential contributes to the improvement of the successful ablation.

A 71-year-old female with a dual-chamber pacemaker presented to our hospital complaining of repeated chest pain. She was diagnosed with unstable angina. On day 7, the patient suddenly suffered cardiopulmonary arrest due to an inferior ST segment elevation myocardial infarction (STEMI). Pacemaker lost capture was suspected and was later confirmed by a pacemaker check with a high pacing threshold and a low sensing parameter. Emergency coronary angiography revealed that a large filling defect remained due to an extensive thrombus in the proximal left circumflex (LCX) with thrombolysis in myocardial infarction (TIMI) grade 2 flow, and then a repeat thrombus aspiration was performed. After reperfusion, the parameters of the right ventricular lead were gradually returned. We conclude that the loss of the right ventricular lead pacing occurred in this case of acute coronary syndrome (ACS) induced by an LCX thrombus due to an LCX supplying the right ventricular septal.

Abstract A 37‐year‐old man was admitted to our hospital with paroxysmal palpitation for half year. A previous electrogram showed a narrow complex tachycardia. Electrophysiologic study (EPS) found a concealed left‐sided free wall pathway accessory. In addition, a transseptal approach was used for radiofrequency ablation. After successful ablation, EPS induced a wide complex tachycardia and a narrow complex tachycardia. The wide complex tachycardia was diagnosed as a right‐sided Mahaim fiber atriofascicular accessory pathway, and the narrow complex tachycardia was diagnosed as atypical atrioventricular nodal reentrant tachycardia (AVNRT). Then, the right‐sided Mahaim fiber atriofascicular accessory pathway and atypical AVNRT were successfully ablated. Herein, we report a rare case of a concealed left‐sided accessory pathway combined with a right atriofascicular Mahaim fiber and atypical AVNRT.

Abstract Background It is difficult to insert cardiac pacing leads in patient with tricuspid valve surgery (TVS). The aim of this study was to evaluate safety and effectiveness of a novel technique applied for bedside temporary pacemaker placement (TPP) in patients with TVS. Methods We investigated patients with TVS who required bedside TPP without X‐ray guidance in cardiac intensive care unit between January 2019 and March 2022. They were divided into Novel pre‐shaped group (N = 21) and Control group (routine pre‐shaped group, N = 26). The ordinary bipolar electrodes were applied in both groups. In Novel pre‐shaped group, electrodes were reshaped by a novel technique with three‐curve with anterior tip method, while electrodes were shaped by traditional strategy in Control group. We evaluated the operation duration, first‐attempt success rate of the lead placement, pacing threshold, success rate of lead placement, the rate of leads displacement, and complications. Results Compared with that in Control group, the procedure time was significantly shortened and the first‐attempt success rate of lead placement was obviously increased in Novel pre‐shaped group (both p

Alkaline rock-type rare-earth (RE) ores have significant utilisation value. However, the exploitation of such resources faces great challenges owing to the complex mineral and element assemblages. Composite collectors exhibit excellent performances, which may provide solutions to the flotation problem of alkaline rock-type RE ores. Therefore, 16 collectors typically used in RE ores flotation were selected. Flotation tests were performed to identify collectors with high selectivity and collection ability for RE minerals, then nine composite collectors were prepared by combining the satisfactory collectors. The flotation performances of single and composite collectors for RE minerals were examined, and the composite collector FA301 with different carbon chain lengths was identified as the best one. When FA301 was applied in optimal conditions of slurry temperature, grinding size, collector and inhibitor dosage, RE concentrate yield of 6.29%, REO grade of 32.013%, and recovery of 59.02% were achieved. According to the results of the zeta potential, FTIR, and XPS test, the functional groups (dominated by carboxyl groups) in FA301 chemically adsorbed onto the main active sites (La, Ce, Y, etc.) on the surface of RE minerals. The findings can provide scientific basis for the development of efficient collectors to facilitate the exploitation of RE resources.

Lysosomes are membrane-bound organelles with an acidic lumen and are traditionally characterized as a recycling center in cells. Lysosomal ion channels are integral membrane proteins that form pores in lysosomal membranes and allow the influx and efflux of essential ions. Transmembrane protein 175 (TMEM175) is a unique lysosomal potassium channel that shares little sequence similarity with other potassium channels. It is found in bacteria, archaea, and animals. The prokaryotic TMEM175 consists of one six-transmembrane domain that adopts a tetrameric architecture, while the mammalian TMEM175 is comprised of two six-transmembrane domains that function as a dimer in lysosomal membranes. Previous studies have demonstrated that the lysosomal K+ conductance mediated by TMEM175 is critical for setting membrane potential, maintaining pH stability, and regulating lysosome–autophagosome fusion. AKT and B-cell lymphoma 2 regulate TMEM175’s channel activity through direct binding. Two recent studies reported that the human TMEM175 is also a proton-selective channel under normal lysosomal pH (4.5–5.5) as the K+ permeation dramatically decreased at low pH while the H+ current through TMEM175 greatly increased. Genome-wide association studies and functional studies in mouse models have established that TMEM175 is implicated in the pathogenesis of Parkinson’s disease, which sparks more research interests in this lysosomal channel.

MoP is a promising anode material choice for alkali ion storage ascribed to its superior electrochemical performance. However, severe volume expansion and poor stability limited its output performance. Here, well-dispersed MoP nanoparticles are confined in carbon nanofiber skeleton by facile electrospinning method, further introduction of titania enhances the interfacial reaction and structure stability. As a result, the carbon nanofiber encapsulated MoP/TiO2 composite exhibited 150 mAh g−1 at 1 A g−1 for 4000 cycles, without obvious capacity decay. The homogenous dispersion and heterostructure construction contribute to its superior performance. This design provides a simple way for the phosphide preparation.

Due to the large differences in physico-mechanical properties of composite strata, jamming, head sinking and other serious consequences occur frequently during tunnel boring machine (TBM) excavation. To analyse the stability of surrounding rocks in composite strata under the disturbance of TBM excavation, a geomechanical model test was carried out based on the Lanzhou water supply project. The evolution patterns and distribution characteristics of the strain, stress, and tunnel deformation and fracturing were analysed. The results showed that during TBM excavation in the horizontal composite formations (with upper soft and lower hard layers and with upper hard and lower soft layers), a significant difference in response to the surrounding rocks can be observed. As the strength ratio of the surrounding rocks decreases, the ratio of the maximum strain of the hard rock mass to that of the relatively soft rock mass gradually decreases. The radial stress of the relatively soft rock mass is smaller than that of the hard rock mass in both types of composite strata, indicating that the weak rock mass in the composite formation results in the difference in the mechanical behaviours of the surrounding rocks. The displacement field of the surrounding rocks obtained by the digital speckle correlation method (DSCM) and the macro-fracture morphology after tunnel excavation visually reflected the deformation difference of the composite rock mass. Finally, some suggestions and measures were provided for TBM excavation in composite strata, such as advance geological forecasting and effective monitoring of weak rock masses.

The grassland in the Qinghai–Tibetan plateau provide habitat for many indigenous and introduced ruminants which perform important ecological functions that impact the whole Qinghai–Tibetan plateau ecosystem. These indigenous Tibetan ruminants have evolved several adaptive traits to withstand the severe environmental conditions, especially cold, low oxygen partial pressure, high altitude, strong UV radiation, and poor forage availability on the alpine rangelands. Despite the challenges to husbandry associated with the need for enhanced adaptation, several domesticated ruminants have also been successfully introduced to the alpine pasture regions to survive in the harsh environment. For ruminants, these challenging conditions affect not only the host, but also their commensal microbiota, especially the diversity and composition of the rumen microbiota; multiple studies have described tripartite interactions among host-environment-rumen microbiota. Thus, there are significant benefits to understanding the role of rumen microbiota in the indigenous and introduced ruminants of the Qinghai–Tibetan plateau, which has co-evolved with the host to ensure the availability of specific metabolic functions required for host survival, health, growth, and development. In this report, we systemically reviewed the dynamics of rumen microbiota in both indigenous and introduced ruminants (including gut microbiota of wild ruminants) as well as their structure, functions, and interactions with changing environmental conditions, especially low food availability, that enable survival at high altitudes. We summarized that three predominant driving factors including increased VFA production, enhanced fiber degradation, and lower methane production as indicators of higher efficiency energy harvest and nutrient utilization by microbiota that can sustain the host during nutrient deficit. These cumulative studies suggested alteration of rumen microbiota structure and functional taxa with genes that encode cellulolytic enzymes to potentially enhance nutrient and energy harvesting in response to low quality and quantity forage and cold environment. Future progress toward understanding ruminant adaptation to high altitudes will require the integration of phenotypic data with multi-omics analyses to identify host-microbiota co-evolutionary adaptations enabling survival on the Qinghai–Tibetan plateau.

Abstract A 54‐year‐old man had a dual‐chamber pacemaker implantation 9 years ago because of sick sinus syndrome at a different facility. The patient did not undergo any evaluation of his pacemaker for a long time with cardiologist. The patient was admitted to another hospital manifesting dyspnea and palpitation with atrial fibrillation for 1 month, and he was diagnosed with ventricular lead perforation. For further treatment, he was referred to our hospital, and an elective replacement indicator (ERI) of the battery state and a malpositioned ventricular lead into the middle cardiac vein were found. Finally, the pacing lead was left in the primary place and the pacemaker was replaced.

Congenital talipes equinovarus (CTEV) is one of the most common congenital limb defects in children, which is a multifactorial and complex disease that associates with many unknown genetic, social-demographic, and environmental risk factors. Emerging evidence proved that gene expression or mutation might play an important role in the occurrence and development of CTEV. However, the underlying reasons and involved mechanisms are still not clear. Herein, to probe the potential genes and related signaling pathways involved in CTEV, we first identified the differentially expressed genes (DEGs) by mRNA sequencing in pediatric patients with CTEV compared with normal children. The gene of COL1A2 was upregulated, and AKT3 was downregulated at the transcriptional level. Western blot and quantitative polymerase chain reaction (qRT-PCR) results also showed that the expression of COL1A2 in CTEV was enhanced, and the AKT3 was decreased. Furthermore, the COL1A2 Knock-in (+COL1A2) and AKT3 Knock-out (-AKT3) transgenic mice were used to verify the effects of these two genes in the CTEV, and the results of which showed that both COL1A2 and AKT3 were closely related to the CTEV. We also investigated the effect of the PI3K-AKT3 signaling pathway in CTEV by measuring the relative expression of several key genes using Western blot and qRT-PCR. In line with the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis data, the PI3K-AKT3 signaling pathway might play a potentially important role in the regulation of pathological changes of CTEV. This study will provide new ideas for the mechanism investigation and prenatal diagnosis of CTEV.

ObjectiveTo quantitatively evaluate the effectiveness of the Ponseti method for the correction of clubfoot, we decided to use magnetic resonance imaging (MRI) to evaluate changes in the tarsal bone relationship.MethodsThis is a retrospective study of fifteen children with clubfeet who were treated with the Ponseti method. MRI studies were obtained using a 3.0T Machine (GE Healthcare, United States). T1-weighted and T2-weighted images were acquired in the standard anatomic sagittal, transverse, and coronal planes. For the measurement, the best slice that clearly demonstrated the anatomy was chosen. Sagittal talocalcaneal angle, sagittal tibiocalcaneal angle, coronal tibiocalcaneal angle, transverse talar neck angle, transverse talonavicular angle, and transverse talocalcaneal angle were measured. The eighteen corrected clubfeet were compared with the twelve unilateral normal feet at clinical and radiological levels using a Pirani scoring system and MRI, respectively.ResultsIn total, 15 cases (twelve boys and three girls) with clubfeet were examined by using MRI. Twelve cases had unilateral and three had bilateral involvement (eleven left clubfeet and seven right clubfeet), giving a total of eighteen clubfeet when compared with twelve normal feet. The mean age of patients at examination was 47.7 months (8–96 months). The recovery of the corrected clubfoot in these patients met the goals of Ponseti treatment (functional, normal looking, pain-free, and plantigrade foot). Before Ponseti treatment, the mean Pirani score of clubfoot was 5.5 (5–6). During this follow-up, the Pirani score was 0.07 (0–0.05). The results of the MRI indicated that only the transverse talonavicular angle showed a significant difference between the treated clubfeet and the normal feet (p < 0.001). One case had dorsal talonavicular subluxation in the sagittal plane and had the lateral subluxation of the navicular in the transverse plane, which has never been reported in previous studies.ConclusionAlthough the appearance and function of clubfoot were recovered well after the Ponseti method, the results of MRI indicated that the Ponseti method successfully corrected the varus, cavus, and equinus deformities and incompletely corrected the adduction deformity regarding transverse talonavicular angle. At the same time, the Ponseti method may cause dorsal talonavicular subluxation in the sagittal plane and lateral subluxation of the navicular in the transverse plane on MRI.

Probiotic supplementation is a key therapeutic strategy for promoting gut health and maintaining gut homeostasis by modulating functional microbiota. In this study, we isolated two lactic acid bacteria (LAB) strains, Pediococcus pentosaceus TCM-3 and Lacticaseibacillus paracasei TDM-2, from Qinghai-Tibetan plateau, and evaluated their probiotic properties and antioxidant bioactivity. In which, TDM-2 had higher T-AOC activity than either TCM-3 or LGG (4.10 μmol/mL vs. 3.68 and 3.53 μmol/mL, respectively, p < 0.05). These strains have shown high antioxidant activity compared to the LAB strains and were found to be acid and bile salt tolerant, confronting the safety issues of antibiotic resistance and the capability of surviving in simulated gastric and intestinal juices. In vitro fermentation experiments with human gut microbiota revealed significant differences in microbial community composition between samples supplemented with TCM-3 and TDM-2 and those without. The addition of these two strains resulted in an enrichment of beneficial taxa, such as the Pediococcus, Lactobacillus, and Clostridium_sensu_strictos at the genus level, and Firmicutes and Proteobacteria at the phylum level. Notably, the TCM-3 group exhibited higher short-chain fatty acid production than the TDM-2 group and untreated controls (acetic acid at 12 h: 4.54 mmol L−1 vs. 4.06 mmol L−1 and 4.00 mmol L−1; acetic acid at 24 h: 4.99 mmol L−1 vs. 4.90 mmol L−1 and 4.82 mmol L−1, p < 0.05). These findings demonstrate that LAB supplementation with high antioxidant capacity and probiotic properties can promote gut health by modulating functional microbiota and is enriching for beneficial taxa. Our study provides guidance for therapeutic strategies that use novel LAB strains to maintain gut homeostasis and functional microbiota modulation.

There is no gold standard to tell frustrating outcomes after the catheter ablation of paroxysmal atrial fibrillation (PAF). The study aims to construct a prognostic tool. We retrospectively analyzed 315 patients with PAF who underwent first-time ablation at the Second Xiangya Hospital of Central South University. The endpoint was identified as any documented relapse of atrial tachyarrhythmia lasting longer than 30 s after the three-month blanking period. Univariate Cox regression analyzed eleven preablation parameters, followed by two supervised machine learning algorithms and stepwise regression to construct a nomogram internally validated. Five factors related to ablation failure were as follows: female sex, left atrial appendage emptying flow velocity ≤31 cm/s, estimated glomerular filtration rate 2), P wave duration in lead aVF ≥ 120 ms, and that in lead V1 ≥ 100 ms, which constructed a nomogram. It was correlated with the CHA2DS2-VASc score but outperformed the latter evidently in discrimination and clinical utility, not to mention its robust performances in goodness-of-fit and calibration. In addition, the nomogram-based risk stratification could effectively separate ablation outcomes. Patients at risk of relapse after PAF ablation can be recognized at baseline using the proposed five-factor nomogram.

During oxidative stress, an important factor in the development of many diseases, cellular oxidative and antioxidant activities are imbalanced due to various internal and external factors such as inflammation or diet. The administration of probiotic Lactobacillus strains has been shown to confer a range of antibacterial, anti-inflammatory, antioxidant, and immunomodulatory effects in the host. This review focuses on the potential role of oxidative stress in inflammatory bowel diseases (IBD), cancer, and liver-related diseases in the context of preventive and therapeutic effects associated with Lactobacillus. This article reviews studies in cell lines and animal models as well as some clinical population reports that suggest that Lactobacillus could alleviate basic symptoms and related abnormal indicators of IBD, cancers, and liver damage, and covers evidence supporting a role for the Nrf2, NF-κB, and MAPK signaling pathways in the effects of Lactobacillus in alleviating inflammation, oxidative stress, aberrant cell proliferation, and apoptosis. This review also discusses the unmet needs and future directions in probiotic Lactobacillus research including more extensive mechanistic analyses and more clinical trials for Lactobacillus-based treatments.

Objective The epidemiological characteristics and patterns of foodborne disease events in Nanping City were analyzed to provide a basis for formulating prevention and control strategies of foodborne disease. Methods Foodborne disease incidents reported from all over Nanping City during 1998 and 2017 were collected, and a retrospective descriptive analysis was conducted. Results A total of 184 foodborne disease incidents were reported in Nanping, with 2 871 cases and 40 deaths, with an annual average incidence of 5.12/100 000 and a case fatality rate of 1.39%. The peak season for foodborne illness was the third quarter, with the highest number of incidents and deaths in August. The number of incidents and patients with the largest number were pathogenic microbial events, accounting for 43.48% (80/184) and 64.86% (1 862/2 871) respectively. Toxic plant accounted for 35.87% (66/184) and 10.80% (310/2 871). The most common pathogenic factor was the accidental eating of poisonous mushrooms, accounting for 29.89% (55/184). Vibrio parahaemolyticus was the second factor, accounting for 12.50% (23/184). The most fatal cases were from mushroom, accounting for 87.50% (35/40). Family were the most occurred site, accounted for 39.13% (72/184), and 66.67% (48/72) were caused by toxic plants. Hotels and restaurants accounted for 22.28% (41/184) and 80.49% (33/41) were pathogenic microorganisms. Conclusion The control strategy of foodborne disease events in Nanping should focus on reducing wild mushroom poisoning and changing bad eating habits, carrying out a wide range of food safety education in vulnerable seasons, months and regions, establishing an effective early warning, monitoring and government supervision mechanism, and reducing the occurrence of foodborne disease.

Cryptocrystalline basalt is one of the two major types of rocks exposed in the super large-scale underground powerhouse in Baihetan hydropower station in China. The rock of this type shows various site-specific mechanical responses (e.g. fragmentation, fracturing, and relaxation) during excavation. Using conventional triaxial testing facility MTS 815.03, we obtained the stress–strain curves, macroscopic failure characteristics, and strength characteristics of cryptocrystalline basalt. On this basis, evolution of crack initiation and propagation was explored using the finite-discrete element method (FDEM) to understand the failure mechanism of cryptocrystalline basalt. The test results showed that: (1) under different confining stresses, almost all the pre-peak stress–strain curves of cryptocrystalline basalt were linear and the post-peak stresses decreased rapidly; (2) the cryptocrystalline basalt showed a failure mode in a form of fragmentation under low and medium confining stresses while fragmentation-shear coupling failure dominated at high confining stresses; and (3) the initial strength ratio (σci/σf, where σci and σf are the crack initiation strength and peak strength, respectively) ranged from 0.45 to 0.55 and the damage strength ratio (σcd/σf, where σcd is the crack damage strength) exceeded 0.9. The stress–strain curve characteristics and failure modes of cryptocrystalline basalt could be reflected numerically. For this, FDEM simulation was employed to reveal the characteristics of cryptocrystalline basalt, including high σcd/σf values and rapid failure after σcd, with respect to the microscopic characteristics of mineral structures. The results showed that the fragmentation characteristics of cryptocrystalline basalt were closely related to the development of tensile cracks in rock samples prior to failure. Moreover, the decrease in degree of fragmentation with increasing confining stress was also correlated with the dominant effect of confining stress on the tensile cracks. Keywords: Baihetan hydropower station, Cryptocrystalline basalt, Deformation and failure characteristics, Characteristic strengths, Crack propagation evolution

On 22 July 2020, an Mw 6.3 earthquake occurred in Nima County, central Qinghai-Tibet Plateau, China. We used the synthetic aperture radar interferometry (InSAR) technique with Sentinel-1 images to retrieve the line of sight (LOS) coseismic deformation fields which indicate that the maximum surface displacement reached ~30 cm. We then processed a series of interferograms spanning one year after the Nima earthquake with the Small Baseline Subset Interferometric SAR (SBAS-InSAR) technique. The maximum cumulative postseismic LOS surface displacement reached ~8 cm and approximately followed a logarithmic function over time. The inversion of the fault geometry and co- and afterslip distribution shows that the epicenter location was (33.18°N, 86.88°E) at a depth of 7.4 km, and the causative fault had an N29.1°E strike and 50.2° dip. The most coseismic slip was concentrated at depths between 3 to 12 km with a peak value of 2.0 m at 7.4 km, whilst most afterslips were concentrated at depths between 0 to 12 km with a peak value of 0.2 m at 5 km. The postseismic moment energy was about 5.04 × 1017 N∙m 308 days after the event, which was approximately 13.8% of the coseismic moment energy. By analyzing the contribution of afterslip and poroelastic rebound to postseismic deformation, it was concluded that afterslip was the main early postseismic deformation mechanism. Future attention should be paid to the northern segment of the West Yibug Caka fault and East Yibug Caka fault.

Landslides pose a greater potential risk to the Sichuan-Tibet Transportation Project, and extensive landslide inventory and mapping are essential to prevent and control geological hazards along the Sichuan-Tibet Transportation Corridor (STTC). Recently proposed landslide detection methods mainly focused on new landslides with high vegetation. In addition, there are still challenges in automatic detection of old landslides using optical images. In this paper, two methods, namely mask region-based convolutional neural networks (Mask R-CNN) and transfer learning Mask R-CNN (TL-Mask R-CNN), are presented for detecting and segmenting new and old landslides, respectively. An optical remote sensing dataset for landslide recognition along the Sichuan-Tibet Transportation Corridor (LRSTTC) is constructed as an evaluation benchmark. Our experimental results show that the recall rate and F1-score of the proposed method for new landslide detection can reach 78.47% and 79.80%, respectively. Transfer learning is adopted to detect old landslides, and our experimental results show that evaluation indices can be further improved by about 10%. Furthermore, TL-Mask R-CNN has been applied to identify ice avalanches based on the characteristics of landslides. It appears that our proposed methods can detect and segment landslides effectively along the STTC with the constructed LRSTTC dataset, which is essential for studying and preventing landslide hazards in mountainous areas.

Abstract Background Patients with brain tumor or pancreatic cancer exhibit the poorest prognosis, while immune fitness and cellular immune exhaustion impacts their survival immensely. This work identifies differences in the immune reactivity to the common human pathogens cytomegalovirus (CMV) and Epstein–Barr virus (EBV) between patients with brain tumor in comparison to those with pancreatic cancer and healthy individuals. Methods We characterized the humoral and cellular immune responses of patients with brain tumor or pancreatic cancer to cytomegalovirus structural protein pp65 (CMV-pp65) as well as Epstein–Barr nuclear antigen-1 (EBNA-1) by whole-blood assay and ELISA. Results Anti-CMV-pp65 plasma immunoglobulin gamma (IgG) titers were significantly lower in patients with brain tumor compared to healthy donors and patients with pancreatic cancer. Among the responding patients with GBM, those with a weak anti-CMV IgG response also had a decreased median overall survival (p = 0.017, 667 vs 419 days) while patients with brain tumor showed a generally suppressed anti-CMV immune-reactivity. Patients with brain tumor exhibited a significantly lower interferon gamma (IFNγ) response to EBNA-1 and CMV-pp65 compared to patients with pancreatic cancer or healthy donors. This antigen-specific response was further amplified in patients with brain tumor upon conditioning of whole blood with IL-2/IL-15/IL-21. Exclusively in this setting, among the responding patients with GBM, those exhibiting a EBV-specific cellular immune response above the median also displayed an increased median overall survival pattern compared to weak responders (753 vs 370 days, p

Herein, a simple and cost-effective chemiluminescence immunoassay combined with the magnetic particles (MPCLIA) is presented for the rapid detection and analysis of Aflatoxin B1, which is a potent carcinogen found in the environment. Several physicochemical factors that potentially influence the assay performance of the proposed method were investigated in detail, including concentrations of FITC-labelled antibody, AFB1-alkaline phosphatase and magnetic particles concentration. Under the optimized experiment condition, the method showed: (i) a low limit detection of 0.05 ng/mL; (ii) satisfactory recoveries in real grain and oil samples ranging from 78% to 109%, which was well within the requirement of residue analysis, and (iii) excellent sensitivity, wide dynamic range and easy to separate in the washing process, which was superior to enzyme-linked immunosorbent assay (ELISA) method. In addition, the device used is of low cost. Moreover, the MPCLIA results for the real samples were in good agreement with that obtained by the high-performance liquid chromatography. These results suggest that the proposed MPCLIA method has potential application for screening other toxic mycotoxins occur in the food industry or other applied fields.

Context: Axillary vein puncture is an alternative method for pacemaker leads implantation. However, the safety and effectiveness of axillary vein puncture become an issue for debate now. Aims: The aim of this study was to investigate the safety, feasibility, and efficacy of a modified axillary vein technique for pacemaker implantation. Settings and Design: This modified axillary vein technique refers to a novel axillary vein puncture method combined with caudal 35° fluoroscopy and surface anatomic landmarks including deltopectoral groove, coracoid process, and the first rib. Subjects and Methods: This technique was applied to 139 consecutive patients referred for pacemaker implantation between March 1, 2016, and December 31, 2016, at our department. Statistical Analysis Used: None. Results: Success rate of pacemaker implantation was 96.4% (134/139). Five patients (3.60%) were switched to an alternate approach for leads implantation. There were no procedure-related complications such as pneumothorax, hemopneumothorax, major bleeding, and significant pocket hematoma. Conclusion: This modified axillary vein puncture strategy combining caudal 35° fluoroscopy and surface anatomic landmarks is safe and feasible for pacemaker implantation.

Sirtuin type 1 (Sirt1) and protein kinase B (Akt2) are associated with development of obesity and inflammation, but the molecular mechanisms of Sirt1 and Akt2 interaction on adipose inflammation remain unclear. To explore these mechanisms, a mouse model was used. Mice were fed with a high-fat diet (HFD) for 8 weeks, with interventions of resveratrol (RES) or nicotinamide (NAM) during the last 15 days. The HFD reduced Sirt1 mRNA in adipose tissue and elevated interleukin-6 (IL-6) expression. RES reduced the adipose tissue weight, increased the Sirt1 mRNA level, and reduced both mRNA and protein levels of IL-6, MCP-1, inducible nitric oxide synthase, and TNF-α by inhibiting phosphorylation of Akt2 in adipose tissue. Additionally, macrophage type I marker genes were reduced while macrophage type II marker genes were elevated by RES addition. Moreover, activation of Akt2 signal by using insulin significantly blunted the inhibitory effect of RES on adipose inflammation. Immunoprecipitation assay demonstrated that RES enhances the protein-protein interaction between Sirt1 and Akt2, but NAM inhibits this interaction. Furthermore, Sirt1 significantly reduced the levels of raptor and inactivated mammalian target of rapamycin (mTOR)C1 signal by interacting with Akt2, and confirmed that RES attenuated adipose inflammation by inhibiting the mTOR/S6K1 pathway via rapamycin.

Zearalenone (ZEN) is a prevalent mycotoxin that needs intensive monitoring. A semi-quantitative and quantitative immunochromatographic assay (ICA) was assembled for investigating ZEN contamination in 187 samples of cereal and their products from China in 2019. The semi-quantitative detection model had a limit of detection (LOD) of 0.50 ng/mL with visual judgment and could be completely inhibited within 5 min at 3.0 ng/mL ZEN. The quantitative detection model had a lower LOD of 0.25 ng/mL, and ZEN could be accurately and digitally detected from 0.25–4.0 ng/mL. The ICA method had a high sensitivity, specificity, and accuracy for on-site ZEN detection. For investigation of the authentic samples, the ZEN-positive rate was 62.6%, and the ZEN-positive levels ranged from 2.7 to 867.0 ng/g, with an average ZEN-positive level being 85.0 ng/g. Of the ZEN-positive samples, 6.0% exceeded the values of the limit levels. The ZEN-positive samples were confirmed to be highly correlated using LC-MS/MS (R2 = 0.9794). This study could provide an efficiency and accuracy approach for ZEN in order to achieve visual and digitized on-site investigation. This significant information about the ZEN contamination levels might contribute to monitoring mycotoxin occurrence and for ensuring food safety.

Forkhead box C2 (Foxc2) protein is a transcription factor in regulation of development, metabolism, and immunology. However, the regulatory mechanisms of Foxc2 on proliferation and apoptosis of preadipocytes are unclear. In this study, we found that high-fat-diet-induced obesity elevated the expression of Foxc2 and cyclin E after 6 weeks. Additionally, Foxc2 suppressed preadipocyte differentiation, increased cell counts and augmented G1-S transition of preadipocytes, along with the elevation of cyclin E expression and the reduction levels of p27 and p53. Furthermore, Foxc2 knockdown reduced early apoptotic cells with accompanying reduction of mitochondrial membrane potential and increased fragmentation of genomic DNA. We show that Foxc2 reduces the expression of Bax, caspase-9, and caspase-3 in both serum-starved and palmitic acid-induced cell apoptotic models, which confirms the anti-apoptotic role of Foxc2. Moreover, the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)C1 signaling pathway and the ERK/mTORC1 signaling pathway were activated along with preadipocyte proliferation in response to Foxc2 overexpression, whereas apoptosis marker genes were downregulated during this process. Those effects were blocked by the interference of Foxc2 or signal pathways specific inhibitors. These data collectively reveal that Foxc2 enhances proliferation of preadipocytes and inhibits apoptosis of preadipocytes by activating the Akt/mTORC1 and ERK/mTORC1 signaling pathways.

Leptin is an adipocyte-derived hormone and maintains adipose function under challenged conditions. Autophagy is also essential to maintain cellular homeostasis and regulate characteristics of adipose tissue. However, the effects of leptin on autophagy of adipocyte remain elusive. Here, we demonstrated endoplasmic reticulum (ER) stress and leptin were correlated with autophagy and inflammation by transcriptome sequencing of adipose tissue. Leptin-mediated inhibition of autophagy was involved in upstream reduction of ER stress proteins such as Chop, GRP78, and Atf4, since blockage of autophagy using pharmacological approach had no effect on tunicamycin-induced ER stress. Moreover, we determined KLF4, the potential transcriptional factor of Atf4, was required for the leptin-mediated autophagy in the regulation of adipocyte inflammation. Importantly, ATF4 physically interacted with ATG5 and subsequently formed a complex to promote adipocyte autophagy. Further analysis revealed that Atg5, a core component of autophagosome, was the target for leptin-mediate autophagy. In addition, leptin alleviated ER stress-induced inflammation by reducing autophagy-mediated degradation of IκB in adipocytes. Exogenous leptin treatment also ameliorated autophagy and inflammation of white adipose tissue in ob/ob mice. Taken together, our results indicated that leptin inhibited ER stress-mediated autophagy and inflammation through the negatively regulation of Atf4/Atg5 complex in adipocytes. These findings identify a new potential means for intervention of autophagy to prevent or treat obese caused metabolic syndrome of mammals.

Glioblastoma multiforme (GBM) is the most common and most severe form of malignant gliomas. The prognosis is poor with current combinations of pharmaceutical, radiotherapy, and surgical therapy. A continuous search for new treatments has therefore been ongoing for many years. Therapy with tumor-infiltrating lymphocytes (TILs) is a clinically promising strategy to treat various cancers, including GBM. An endovascular intraarterial injection of TILs as a method of delivery may, instead of intravenous infusion, result in better retention of effector cells within the tumor. Prior to clinical trials of intra-arterial injections with any cells, preclinical safety data with special emphasis on embolic–ischemic events are necessary to obtain. We used native rabbits as a model for intra-arterial injections with routine clinical catheter material and a clinical angiography suite. We selectively infused a total dose of 20 million activated T cells at a cell concentration of 4,000 cells/ml over 8 min of injection time. The rabbits were evaluated for ischemic lesions by 9.4 T magnetic resonance imaging (MRI) ( n = 6), and for tracking of injected cells, single-photon emission computed tomography/computed tomography (SPECT/CT) was used ( n = 2). In this study, we show that we can selectively infuse activated T cells to a CNS volume of 3.5 cm 3 (estimated from the volumetric MRI) without catastrophic embolic– ischemic adverse events. We had one adverse event with a limited basal ganglia infarction, probably due to catheter-induced mechanical occlusion of one of the lateral lenticulostriatal arteries. The cells pass through the native brain without leaving SPECT signals. The cells then, over the first hours, end up in the liver to a large extent and to a lesser degree by the spleen, pancreas, and kidneys. Virtually no uptake could be detected in the lungs. This indicates a difference in biodistribution as opposed to other cell types when infused intravenously.

Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i.e., NY-ESO-1, Survivin or EGFRvIII). TILs were analyzed by flow cytometry, including T-cell receptor (TCR) Vβ family composition, exhaustion/activation and T-cell differentiation markers (CD45RA/CCR7). IL-2/IL-15/IL-21 expanded TILs exhibited a mixture of CD4+, CD8+, as well as CD3+ CD4−CD8− T cells with a predominant central memory CD45RA−CCR7+ phenotype. TIL showed low frequencies of T cells testing positive for PD-1, TIM-3 and CTLA-4. LAG3 tested positive in up to 30% of CD8+ TIL, with low (1.25%) frequencies in CD4+ T cells. TIL cultures exhibited preferential usage of Vβ families and recognition of autologous tumor cells defined by cytokine production and cytotoxicity. IL-2/IL-15/IL-21 expanded TILs represent a viable source for the cellular therapy of patients with gliomas.

The large Shuangwang gold deposit (>80 t gold) is located in the Western Qinling Orogen (WQO) of central China. It is an orogenic-type gold deposit hosted in an NW-extending breccia belt in the Devonian Xinghongpu Formation. Gold mineralization of the Shuangwang deposit is featured by hydrothermal breccia ores with strata fragments cemented by hydrothermal minerals dominated by ankerite, quartz, and pyrite with minor amounts of calcite and albite. Pyrite is the major gold-hosting sulfide and the most abundant ore mineral. Crystal habits, thermoelectricity, and trace-element composition of pyrites from the main ore-forming stage of the Shuangwang gold deposit were studied by microbinocular, BHTE-06 thermoelectric coefficient measuring instrument, and high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Spatial distribution of the above data for pyrites was delineated by contour maps of morphology index, P-type frequency, and primary halo elements (e.g., supraore halo elements Ba and Sb; near-ore halo elements Pb, Zn, and Cu; and subore halo elements Co, Mo, and Bi). Based on the above results, four target areas (areas between prospecting lines 0 and 1, between lines 14 and 18 below orebody KT9; areas between prospecting lines 30 and 34, between lines 44 and 46 below orebody KT8) were put forward for deep gold exploration in the future. These targets are consistent with the depth extrapolation of proven gold orebodies, indicating the practicality of typomorphic characterization of pyrites as vector to deep/concealed gold orebodies. The effectiveness of the pyrite typomorphic parameter for deep gold prediction seems to be chemical composition, crystal habits, and then thermoelectricity.

The Haoyaoerhudong gabbro is a mafic intrusion located in the Haoyaoerhudong gold deposit, which is a giant gold deposit (148 t Au) hosted in Proterozoic strata on the northern margin of the North China Craton. In this paper, we present integrated SHRIMP U⁻Pb, geochemical and Sr⁻Nd isotopic data from gabbro of the Haoyaoerhudong gold deposit to reveal the magmatic processes behind its origin. SHRIMP zircon U⁻Pb dating constrains the timing of crystallization of the Haoyaoerhudong gabbro to 278.8 ± 0.81 Ma. Whole-rock geochemical results indicate that the Haoyaoerhudong gabbro has calc-alkaline features with enrichments of large-ion lithophile elements (LILE) and light rare-earth elements (REE) as well as depletions of high-field strength elements (HFSE). The relatively high (87Sr/86Sr)i (0.7053 to 0.7078) and low εNd(t) (−4.6 to −15.1) values of the gabbro indicate the involvement of crustal materials. Low Ce/Pb ratios (1.35 to 7.38), together with nearly constant La/Sm and Th/Yb ratios and variable Ba/Th and Sr/Nd ratios, suggest that the ancient mantle was modified by slab dehydration fluids. Based on new geochemical data and regional geological investigations, we propose that both the Haoyaoerhudong gold deposit and the Haoyaoerhudong gabbro formed in a post-orogenic extensional setting.

Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection.

BackgroundIn the European Union (EU), the use of diniconazole-M is no longer authorized. However, residues of diniconazole-M occur in various plant commodities.Methodology/principal findingsA selective and simple analytical method for the trace level determination of diniconazole in soil, fruit, vegetables and water samples was developed based on immunoaffinity extraction followed by Enzyme-linked immunosorbent assay (ELISA) and the high-performance liquid chromatography (HPLC) analysis. The ELISA was based on monoclonal antibodies highly specific to diniconazole and was a fast, cost-effective, and selective screening method for the detection of diniconazole. The results of the ELISA correlated well with gas chromatography (GC) results, with the correlation coefficient of 0.9879 (n = 19). A simple gel permeation chromato- graphy clean-up method was developed to purify extracts from matrices containing high amounts of fat and natural pigments, without the need for a large dilution of the sample. The immunoaffinity column (IAC) capacity was 0.180 mg g(-1). The columns could be re-used approximately 20 times with no significant alteration in capacity. The recoveries from complex samples were in the range of 89.2% to 96.1% with a relative standard deviation (RSD) of 0.770%-6.11% by ELISA. The results were in good agreement with those obtained by HPLC method.Conclusion/significanceThe IAC extraction procedure coupled with HPLC and ELISA analysis could be also used as alternative effective analytical methods for the determination of diniconazole concentrations in complex samples.