Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal crohn's disease

AIM To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor(GMCSF) auto-antibodies(Ab) level and time to surgical recurrence after initial surgery for Crohn's disease(CD). METHODS We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA Ig G and Ig A, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16 L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence.RESULTS Ninety six percent of patients underwent initial ileocecal resection(ICR) or ileal resection(IR) and subsequently 40% of patients required a second ICR/IR for CD. GMCSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio(HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine(HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators(HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking(HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16 L1(HR = 0.65, 95%CI: 0.49-0.88, P = 0.006).CONCLUSION GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior.

Forward modeling and inversion of the relation model between the gas content of plume and its seismic attribute

The methane bubble plume attracts interest because it offers direct evidence of seafloor gas leakage and plays an indirect role in the exploration and identification of natural gas hydrate.In this study,based on established plume models and their migration sections,three amplitude-class attributes were extracted from three formations for the migration sections of five plumes,and the correlation between the gas content and seismic attribute was obtained.As the gas content increases,the amplitude attribute correspondingly increases,and the linear correlation is relatively good.Moreover,correlation coefficients between gas content and amplitude attributes are close to 1.0.By using linear fitting,the relation model between the gas content of the plume and the seismic attribute was obtained.The relation model was subsequently used to invert the gas content from a real databearing plume.Comparison of the gas content section of the plume with the attribute section and real seismic section reveals common distribution characteristics,namely,the color of the section in the lower right corner is dark.If the amplitude value is large in the seismic section of the real plume,the amplitude attribute value is also large in the corresponding attribute section,and the inverted value of the gas content is also large(because gas content and amplitude are linearly correlated),which indicates that the plume bubbles of the section in the lower right corner is intensively distributed.Finally,the obtained gas content section of the plume can reflect the distribution of the plume bubble content more simply and intuitively,from which the distribution law of seafloor bubbles can be deduced,and this lays a foundation for the further estimation of the gas content of the plume and hydrate reserves.

Thienothiophene-centered ladder-type π-systems that feature distinct quinoidal π-extension

Quinoidalπ-conjugated structures,a kind of fundamental subunits for organicπ-systems,may produce some intriguing optical,electronic and magnetic properties of polycyclic hydrocarbons(PHs).Herein,we report two thienothiophene-centered ladder-type polycyclic molecules(1 and 2),which possess one quinoidal thienothiophene moiety and two para-quinodimethane(p-QDM)subunits,respectively.As theoretically and experimentally studied,while 1 is a fully closed-shell molecule,2 owns an open-shell structure along with partial contribution of tetraradical state that is induced by the resonance of p-QDM.Moreover,although 2 has a largerπ-conjugated skeleton and open-shell electronic state,it exhibits larger bandgap and blue-shifted absorption.On the other hand,the reversible oxidation activity of 1 enables the preparation of its dication 1^(2+),and the studies on its single-crystal and aromatic structures demonstrate that its two positive charges are delocalized onto the oxygen atoms,thus achieving fullyπ-extended structure and near-infrared absorption.This study not only gains insight into quinoidalπ-subunits,but also provides an important basis for the development of antiaromatic and open-shellπ-electron materials.

Tumor biomarkers for diagnosis,prognosis and targeted therapy

Tumor biomarkers,the substances which are produced by tumors or the body’s responses to tumors during tumorigenesis and progression,have been demonstrated to possess critical and encouraging value in screening and early diagnosis,prognosis prediction,recurrence detection,and therapeutic efficacy monitoring of cancers.Over the past decades,continuous progress has been made in exploring and discovering novel,sensitive,specific,and accurate tumor biomarkers,which has significantly promoted personalized medicine and improved the outcomes of cancer patients,especially advances in molecular biology technologies developed for the detection of tumor biomarkers.Herein,we summarize the discovery and development of tumor biomarkers,including the history of tumor biomarkers,the conventional and innovative technologies used for biomarker discovery and detection,the classification of tumor biomarkers based on tissue origins,and the application of tumor biomarkers in clinical cancer management.In particular,we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies.We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field.Collectively,the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine,broaden horizons in future research directions,and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.

B-cell immune checkpoint TIM-1: a potential target for tumour immunotherapy

Recently,Lloyd Bod et al.published a study in Nature that identified the B-cell immune checkpoint T cell immunoglobulin and mucin domain 1(TIM-1)and mechanistically elucidated that targeting TIM-1 enhances the responses to type I interferon(IFN-I),promotes B cells antigen presentation and activation,subsequently enhances anti-tumour responses of CD4^(+) and CD8^(+)T cells and inhibits tumour growth.This study provides important implications for anti-tumour therapy.

Distributed bearing-based formation control of unmanned aerial vehicle swarm via global orientation estimation

Most existing formation control approaches for Unmanned Aerial Vehicle(UAV)swarm assume that global position and global coordinate frame are directly available for each agent.To extend the application domain,this paper proposes a distributed bearing-based formation control scheme,without any reliance on global position or global coordinate frame.The interactions among UAVs are described by a directed topology with two-leader structure.To address the issue of unavailable global coordinate frame,we first present a distributed orientation estimation law for each UAV to determine its orientation under the coordinate frame of the first leader.Based on the orientation estimation,we then design a bearing-based formation control law to globally asymptotically track target moving formations.Finally,simulation results are provided to validate the proposed method,which show that the translation,scale and orientation of the formation can be flexibly controlled via two leaders.

Extracellular vesicles based electrochemical biosensors for detection of cancer cells:A review

Extracellular vesicles(EVs)derived from cancer cells are considered as ideal biomarker for liquid biopsy in cancer diagnosis,and are stable and abundant.Electrochemical methods for the detection of EVs are prefe rred over co nventional methods such as Western blotting and enzyme-linked immunosorbent assay for their high sensitivity and real-time detection.This article summaries studies proposing the electrochemical methods utilizing immunological and molecular methodologies for detecting EVs derived biomacromolecules such as miRNAs and transme mbrane protein for cancer diagnosis.Moreover,the electrochemical detection methods are compared and future prospects for the development of electrochemical methods for EVs detection are concluded.

A green MXene-based organohydrogel with tunable mechanics and freezing tolerance for wearable strain sensors

Conductive hydrogels have attracted considerable attention owing to their potential for use as electronic skin and sensors.However,the loss of the inherent elasticity or conductivity in cold environments severely limits their working conditions.Generally,organic solvents or inorganic salts can be incorporated into hydrogels as cryoprotectants.However,their toxicity and/or corrosive nature as well as the significant water loss during the solvent exchange present serious difficulties.Herein,a liquid-like yet non-toxic polymer-polyethylene glycol(PEG) was attempted as one of the components of solvent for hydrogels.In the premixed PEG-water hybrid solvent,polyacrylamide(PAAm) was in situ polymerized,overcoming the inevitable water loss induced by the high osmotic pressure of the PEG solution and achieving tailored water capacity.Interestingly,the mechanical strength( "soft-to-rigid" transition) and anti-freezing properties of organohydrogels can be simultaneously tuned over a very wide range through adjusting PEG content.This was due to that with increasing PEG in solvent,the PAAm chains transformed from stretching to curling conformation,while PEG bonded with water molecules via hydrogen bonds,weakening the crystallization of water at subzero temperature.Additionally,a highly conductive Ti_(3)C_(2)T_(x)-MXene was further introduced into the organohydrogels,achieving a uniform distribution triggered by the attractive interaction between the rich functional groups of the nanofillers and the polymer chains.The nanocomposite hydrogels demonstrate high electrical conductivity and strain sensitivity,along with a wide working temperature window.Such a material can be used for monitoring human joint movement even at low temperature and has potential applications in wearable strain sensors.

Enhancing stability of diradical polycyclic hydrocarbons via P=O-attaching

Diradical polycyclic hydrocarbons(PHs)have unique open-shell structures and interesting physical prop-erties.However,owing to high reactivity of unpaired electrons,such open-shell organic diradicaloids are usually less stable than closed-shell systems,limiting their practical applications.In this study,we report P=O-attaching of diradical PHs as a new strategy to enhance their stability while maintaining diradi-cal properties.Three P=O-attached PHs containing the indeno[1,2-b]fluorene,fluoreno[3,2-b]fluorene and indeno[2,1-b]fluoreneπ-skeletons,respectively,were designed and synthesized.As theoretically and ex-perimentally proved,two of them have the relatively large diradical characters and open-shell singlet diradical nature.In comparison to their all-carbon analogues,the attached electron-withdrawing P=O groups endow them with much lower LUMO/HOMO energy levels but preserved magnetic activities and physical properties,such as thermally accessible triplet species and multi-redox ability.Moreover,the P=O groups effectively decrease their oxidation activities and thereby lead to their remarkably excellent ambient stabilities.Thus,this P=O-attaching strategy will be applicable to other diradical PH systems and may promote the generation of stable organic diradicaloids for radical chemistry and materials.