Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.

Combining Thermochronology and Geochronology to Constrains Orogenic Processes in the Alps and Tibet

Deciphering the kinematics of deformation is key to understand the crustal evolution.In the last decades several techniques have been developed to help constraining the timing of deformation.On one side geochronology techniques allow the dating of a wider range of minerals with higher spatial resolution.On the other side thermochronology,with the help of numerical simulations(PeCube,QTQt…),help to constrain the rock exhumation history that is often linked to the vertical component of deformation.In both cases the deformation timing can accurately be discussed only together with a serious structural analysis.

Geochemistry, mineral paragenesis and geothermal conditions of oreforming fluids from the Ain El Bey Cu–Fe deposit: potential occurrence of native gold and precious metal traces (North African orogenic belt, Northern Tunisia)

The Ain El Bey abandoned mine, in North-West Tunisia, fits into the geodynamic context of the European and African plate boundary. Ore deposit corresponds to veins and breccia of multiphase Cu–Fe-rich mineralization related to various hydrothermal fluid circulations. Petromineralogical studies indicate a rich mineral paragenesis with a minimum of seven mineralization phases and, at least, six pyrite generations. As is also the case for galena and native silver, native gold is observed for the first time as inclusion in quartz which opens up, thus, new perspectives for prospecting and evaluating the potential for noble metals associated with the mineralization. Scanning Electron Microscope--Energy Dispersive Spectroscopy and Transmission electron microscopy analyses show, in addition, a large incorporation of trace elements, including Ag and Au, in mineral structures such as fahlores(tetrahedrite-tennantite) and chalcopyrite ones. The mineral/mineral associations, used as geothermometers, gave estimated temperatures for the mineralizing fluids varying from 254 to 330 ℃ for phase Ⅲ, from 254 to 350 ℃ for phase Ⅳ, and from 200 to 300 ℃ for phases Ⅴ and Ⅵ. The seventh and last identified mineralization phase, marked by a deposit of native gold, reflects a drop in the mineralizing fluid’s temperature(< 200 ℃) compatible with boiling conditions. Such results open up perspectives for the development of precious metal research and the revaluation of the Cu–Fe ore deposit at the Ain El Bey abandoned mine, as well as at the surrounding areas fitting in the geodynamic framework of the Africa-Europe plate boundary.

Bound and Resonating Multiquark Configurations

We review the predictions of quark models for multiquark configurations that are bound or resonant states,and compare different methods for estimating the properties of resonances.

Study of Cassava Contraction during Its Convective Drying

During this study, a focus is placed on the physical transformations that cassava undergoes during convective drying. The product continually changes its size, shape, and even its texture and consistency. The more moisture a product loses, the smaller its size. Firstly, the results show that water parameters such as mass or moisture content are reduced according to the drying principle. The dimensions length L, width l and thickness e decrease following a linear trend. The mathematical equations describing them were determined using the Excel office tool. This trend impacts surface and volume parameters, which in turn decrease almost linearly with the water content of the product. Note that the R2 coefficient is not always acceptable, confirming the complexity of the behavior of organic products.

Physical Transformations on Organic Product during Its Convective Drying: Case of Sweet Potato

This study highlighted the physical transformation that agri-food products undergo during their drying. This transformation enormously affects the customer’s choice and the profit margin of the dried product promoter. The example of the experimental study of the potato reveals that the product continually changes its dimensions during its drying. The more the product loses its water, the more the dimensions decrease. The results initially showed that the water parameters such as mass or water content decrease according to the drying principle. The dimensions length L., width l and thickness e. decrease following a linear trend whose mathematical equations which describe them are determined using the office tool, excel. This trend has repercussions on the surface and volume parameters which in turn decreases almost linearly with the product’s water content. Note that the coefficient R2 is not always acceptable, confirming the complex nature of the behavior of organic products.

Biosorption of cadmium(II) and lead(II) ions from aqueous solutions onto dried activated sludge

The removal of heavy-metal ions from aqueous solutions by using dried activated sludge has been investigated in batch systems. Effect of solution pH, initial metal ion concentration, and temperature were determined. The results of the kinetic studies showed that the uptake processes of the two metal ions（Cd（Ⅱ） and Pb（Ⅱ）） followed the pseudo-second-order rate expression. The equilibrium data fitted very well to both the Langmuir and Freundlich adsorption models. The FT-IR analysis showed that the main mechanism of Cd（Ⅱ） and Pb（Ⅱ） biosorption onto dried activated sludge was their binding with amide I group.

Evaluation of renal function in patients with cirrhosis:Where are we now?

In the clinical context of the patients with liver cirrhosis, accurate evaluation of the renal function is potentially crucial. Indeed, it can lead to early diagnosis of both acute kidney injury and chronic kidney disease and to reliable characterization of the renal status of the patient before performing a liver transplantation. Despite some limitations, the assay of serum creatinine (SCr) is universally used to estimate glomerular filtration rate (GFR) because of its wide availability, its simplicity and because it is inexpensive. Nevertheless, several reports show that the value of this assay to estimate GFR is strongly challenged in cirrhotic patients, especially in patients with liver failure and/or severely impaired renal function. This has led to seek new alternatives to estimate more reliably the GFR in these patients. Although the reference methods, based on the utilization of exogenous markers, allow measuring GFR and thereby constitute the &#x0201c;gold standard&#x0201d; to evaluate renal function, they are not feasible in routine clinical practice. Several studies have shown that a cystatin C (CysC) based formula perform better than the SCr-based estimates in cirrhotic patients and the estimation of GFR by these formulas could therefore lead to optimize the management of the patients. A new estimate based on CysC has been recently developed using a large number of patients and the first results regarding the evaluation of its performance are promising, making this new formula the best candidate for a reference estimate of the renal function in cirrhotic patients.

Immune therapies in pancreatic ductal adenocarcinoma: Where are we now?

Pancreatic ductal adenocarcinoma(PDAC)is one of the deadliest cancers,mostly due to its resistance to treatment.Of these,checkpoint inhibitors(CPI)are inefficient when used as monotherapy,except in the case of a rare subset of tumors harboring microsatellite instability(<2%).This inefficacy mainly resides in the low immunogenicity and non-inflamed phenotype of PDAC.The abundant stroma generates a hypoxic microenvironment and drives the recruitment of immunosuppressive cells through cancerassociated-fibroblast activation and transforming growth factorβsecretion.Several strategies have recently been developed to overcome this immunosuppressive microenvironment.Combination therapies involving CPI aim at increasing tumor immunogenicity and promoting the recruitment and activation of effector T cells.Ongoing studies are therefore exploring the association of CPI with vaccines,oncolytic viruses,MEK inhibitors,cytokine inhibitors,and hypoxia-and stroma-targeting agents.Adoptive T-cell transfer is also under investigation.Moreover,translational studies on tumor tissue and blood,prior to and during treatment may lead to the identification of biomarkers with predictive value for both clinical outcome and response to immunotherapy.

Current strategies for the restoration of adequate lordosis during lumbar fusion

Not restoring the adequate lumbar lordosis during lumbar fusion surgery may result in mechanical low back pain, sagittal unbalance and adjacent segment degeneration. The objective of this work is to describe the current strategies and concepts for restoration of adequate lordosis during fusion surgery. Theoretical lordosis can be evaluated from the measurement of the pelvic incidence and from the analysis of spatial organization of the lumbar spine with 2/3 of the lordosis given by the L4-S1 segment and 85% by the L3-S1 segment. Technical aspects involve patient positioningon the operating table, release maneuvers, type of instrumentation used(rod, screw-rod connection, interbody cages), surgical sequence and the overall surgical strategy. Spinal osteotomies may be required in case of fixed kyphotic spine. AP combined surgery is particularly efficient in restoring lordosis at L5-S1 level and should be recommended. Finally, not one but several strategies may be used to achieve the need for restoration of adequate lordosis during fusion surgery.

Philadelphia chromosome-positive leukemia stem cells in acute lymphoblastic leukemia and tyrosine kinase inhibitor therapy

Leukemia stem cells(LSCs),which constitute a minority of the tumor bulk,are functionally defined on the basis of their ability to transfer leukemia into an immunodeficient recipient animal.The presence of LSCs has been demonstrated in acute lymphoblastic leukemia(ALL),of which ALL with Philadelphia chromosome-positive(Ph+).The use of imatinib,a tyrosine kinase inhibitor(TKI),as part of front-line treatment and in combination with cytotoxic agents,has greatly improved the proportions of complete response and molecular remission and the overall outcome in adults with newly diagnosed Ph+ ALL.New challenges have emerged with respect to induction of resistance to imatinib via Abelson tyrosine kinase mutations.An important recent addition to the arsenal against Ph+ leukemias in general was the development of novel TKIs,such as nilotinib and dasatinib.However,in vitro experiments have suggested that TKIs have an antiproliferative but not an antiapoptotic or cytotoxic effect on the most primitive ALL stem cells.None of the TKIs in clinical use target the LSC.Second generation TKI dasatinib has been shown to have a more profound effect on the stem cell compartment but the drug was still unable to kill the most primitive LSCs.Allogeneic stem cell transplantation(SCT) remains the only curative treatment available for these patients.Several mechanisms were proposed to explain the resistance of LSCs to TKIs in addition to mutations.Hence,TKIs may be used as a bridge to SCT rather than monotherapy or combination with standard chemotherapy.Better understanding the biology of Ph+ ALL will open new avenues for effective management.In this review,we highlight recent findings relating to the question of LSCs in Ph+ ALL.

Femtosecond Laser-Induced Breakdown Spectroscopy for Detection of Trace Elements in Sophora Leaves

Sophora leaves from several areas in Beijing are analysed by femtosecond laser-induced breakdown spectroscopy （femto-LIBS）. Although the used spectral detection system is not time-resolved, the spectral lines of trace mineral elements are detected and analysed. It is proven that the femto-LIBS can be an efficient method to detect mineral trace elements contained in tree leaves which is a biomonitor for atmospheric pollution assessment or botanic studies. An interesting case of correlation between trace elements detected in tree leaves and the pollution of the concerned area is presented, for the first time to our knowledge.

Selection of patients and staging of peritoneal surface malignancies

Peritoneal carcinomatosis (PC) is a common evolution of cancer of the gastrointestinal tract, and has been traditionally regarded as a terminal disease with short median survival. During the last 20 years, thanks to its favourable oncologic results, a new loco-regional therapeutic approach, combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), has an important development. Due to its significant, but acceptable, morbidity and mortality, and high cost, this comprehensive management plan requires knowledgeable patient selection. Quantitative prognostic indicators are required to assess a patient’s eligibility. Large multicenter studies have identified several prognostic factors, which can be used for a better selection of patients who would benefit from the combination of cytoreductive surgery with HIPEC. Indications for treatment of PC with cytoreduction and HIPEC are now validated for several diseases: peritoneal mesothelioma, pseudomyxoma peritonei, PC from the appendix, and colorectal cancer. Indications are still under discussion for gastric and ovarian carcinomatosis. Computed tomography is the best radiological for staging the disease. The extent of peritoneal carcinomatosis is, however, difficult to evaluate preoperatively, and precise evaluation is most often performed during surgical exploration. Cytoreductive surgery associated with HIPEC for the treatment of peritoneal carcinomatosis should be performed for young patients with limited and resectable carcino-matosis, in specialized institutions involved in the management of peritoneal surface malignancies.

NH_3 Plasma Surface Treatments of Engineering Fluoropolymers: A Way to Enhance Adhesion of Ni or Cu Thin Films Deposited by Electroless Plating

This paper describes the electroless Ni or Cu plating of some fiuoropolymer substrates through a tin-free activation process. Materials subjected to surface metallization are commercial Teflon() FEP, Nafion(), ACLAR() and LaRCTM-CP1 thin films which have recently gained a large scientific and technological interest due to their excellent thermal, chemical, mechanical and dielectric properties. The original approach implemented in the present work involves: (i)the grafting of nitrogen-containing functionalities on the polymer surfaces through plasma treatments in ammonia, (ii) the direct catalysis of the so-modified surfaces via their immersion in a simple acidic PdCl2 solution (i.e. without using a prior surface sensitization in an acidic SnCl2 solution), and finally (iii) the electroless metallization itself. However, prior to the immersion in the industrial plating baths, the chemical reduction of the Pd+2 species (species covalently tethered on the nitrogen-containing groups) to metallic palladium (PdO) is shown to be a key factor in catalyzing the electroless deposition initiation. This is made by immersion in an hypophosphite (H2PO2-) solution. Wettability measurements and X-ray photoelectron spectroscopy (XPS) experiments are used to characterize every surface modification step of the developed process. A cross-hatch tape test was used to asses the adhesion strength of the electroless films that is shown qualitatively good. In addition, a fragmentation test was developed in combination with electrical measurements. Its use allows to distinguish different adhesion levels at the metal/polymer interface and to evidence the influence of some processing parameters.

Energy Filtering and Coaxial Detection of the Backscattered Electrons in Scanning Electron Microscope

A new detection system in scanning electron microscope,which filters in energy and detects the backscattered electrons close to the microscope axis,is described.This technique ameliorates the dependence of the back.scat tering coefficient on atomic number,and suppresses effectively the relief contrast at the same time.Therefore this new method is very suitable to the composition analysis.

Lorentz force electrical impedance tomography using pulse compression technique

Lorentz force electrical impedance tomography （LFEIT） combines ultrasound stimulation and electromagnetic field detection with the goal of creating a high contrast and high resolution hybrid imaging modality. In this study, pulse compression working together with a linearly frequency modulated ultrasound pulse was investigated in LFEIT. Experiments were done on agar phantoms having the same level of electrical conductivity as soft biological tissues. The results showed that：（i） LFEIT using pulse compression could detect the location of the electrical conductivity variations precisely; （ii） LFEIT using pulse compression could get the same performance of detecting electrical conductivity variations as the traditional LFEIT using high voltage narrow pulse but reduce the peak stimulating power to the transducer by 25.5 dB; （iii） axial resolution of 1 mm could be obtained using modulation frequency bandwidth 2 MHz.

Long-term stability of gentamicin sulfate-ethylenediaminetetraacetic acid disodium salt (EDTA-Na_2) solution for catheter locks

A lock solution composed of gentamicin sulfate(5 mg/mL) and ethylenediaminetetraacetic acid disodium salt(EDTA-Na2, 30 mg/mL) could fully eradicate in vivo bacterial biofilms in totally implantable venous access ports(TIVAP). In this study, fabrication, conditioning and sterilization processes of antimicrobial lock solution(ALS) were detailed and completed by a stability study. Stability of ALS was conducted for12 months in vial(25 °C 7 2 °C, 60% 7 5% relative humidity(RH), and at 40 °C 7 2 °C, RH 75% 7 5%)and for 24 h and 72 h in TIVAP(40 °C 7 2 °C, RH 75% 7 5%). A stability indicating HPLC assay with UV detection for simultaneous quantification of gentamicin sulfate and EDTA-Na2 was developed. ALS was assayed by ion-pairing high performance liquid chromatography(HPLC) needing gentamicin derivatization, EDTA-Na2 metallocomplexation of samples and gradient mobile phase. HPLC methods to separate four gentamicin components and EDTA-Na2 were validated. Efficiency of sterility procedure and conditioning of ALS was confirmed by bacterial endotoxins and sterility tests. Physicochemical stability of ALS was determined by visual inspection, osmolality, pH, and sub-visible particle counting. Results confirmed that the stability of ALS in vials was maintained for 12 months and 24 h and 72 h in TIVAP.

Who is at risk in the French mountains? Profiles of the accident victims in outdoor sports and mountain recreation

The risk of both severe and frequent injury associated with active pursuits in mountain areas is acknowledged. This phenomenon is all the most relevant to investigate in France that there is a growing enthusiasm for outdoor sports and recreation. This paper focuses on the social-demographic and sporting profiles of accident victims. Our intent is to better understand who is specifically at risk, while practicing mountain recreation, in the French mountains. Such identification doubtlessly constitutes an important asset in order to enhance prevention. Three critical activities are notably tackled, among some others: hiking, a widespread activity that exposes many practitioners to hazardous settings; mountaineering and ski touring, supposedly entailing the most severe injuries.In order to align the information collected, then provide estimations based on the reasoned crossing of these secondary data, we consulted and summarised all the databases that we knew of on the French territory: rescue team intervention reports, aggregated statistics from the sports ministry, sporting federation accident declarations, avalanche experts statistics, mountain guides union accident/incident reports, healthcare facilities admissions, etc. Only the sources consideredto be the most reliable and representative were used, owing to the number of cases processed, the exhaustive nature of data collection, or the level of information detail available. Our method also included consultation of all the parties playing an active role in prevention, training and mountain rescue, thus ensuring a participative, co-constructive approach to the study with the people that have the best knowledge of victim profiles. Around fifty such parties were interviewed on the methods implemented, the benefits and limits of current data, and the main expectations in terms of accidentology progress, thus further enhancing the credibility of the study proposed in this paper. Our results show that the parent population profiles(in terms of age, gender, place of residence, etc.), weighted by the level of exposure(frequency of participation, level of engagement, etc.) appears to have an impact on the accident victim profiles. There is certainly a very marked gender bias and a serious age impact to be taken into account, as well as the influence of the level of experience, which counter certain preconceived ideas and which, at the very least, go against instinct. However, aside from a probable over-exposure of experienced or expert participants, much remains to be explained concerning the accident mechanisms and circumstances involved. At this stage, we regret the analytic deficiencies induced by a lack ofknowledge concerning the parent populations in many cases, which makes interpretation difficult.

Preparation and Characterization of Sol-Gel Derived Au Nanoparticle Dispersed Y_2O_3∶Eu Films

Gold nanoparticles dispersed Y2O3 films were prepared through a sol-gel method by using yttrium acetate and Au nanoparticles colloid as precursors. The films were characterized by X-ray diffraction （XRD）, transmission electron microscopy （TEM） and UV-VIS absorption spectra. XRD patterns and TEM images of Y2O3 ＋ Au films give the same resuits on structure and particle size as that of pure Y2O3 films. The surface plasma resonance （SPR） of Au nanoparticles in Y2O3 ＋ Au film was observed around 550 nm in the absorption spectrum and its position shifts to red with increasing annealing temperature is caused by the increase of dielectric constant of Y2O3 matrix and the size of Au nanoparticles. The second and third order nonlinear optical effects of Y2O3 ＋ Au films were also observed. The photoluminescent properties of Y2O3 ： Eu ＋ Au films were investigated and results indicate that there exist an energy transfer from Eu^3 ＋ to Au nanoparticles and this energy transfer decreases the emission of Eu^3 ＋ in Y2O3 ： Eu ＋ Au film.

Natural history, treatment and prevention of hepatitis C recurrence after liver transplantation: Past, present and future

Hepatitis C virus(HCV)-related liver disease, including cirrhosis and hepatocellular carcinoma is the main indication for liver transplantation(LT) worldwide. Posttransplant HCV re-infection is almost universal and results in accelerated progression from acute hepatitis to chronic hepatitis, and liver cirrhosis. Comprehension and treatment of recurrent HCV infection after LT have been major issues for all transplant hepatologists and transplant surgeons for the last decades. The aim of this paper is to review the evolution of our knowledge on the natural history of HCV recurrence after LT, including risk factors for disease progression, and antiviral therapy. We will focus our attention on possible ways(present and future) to improve the final longterm results of LT for HCV-related liver disease.