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Abstract The resonant excitation of electronic transitions with coherent laser sources creates quantum coherent superpositions of the involved electronic states. Most time-resolved studies have focused on gases or isolated subsystems embedded in insulating solids, aiming for applications in quantum information. Here, we focus on the coherent control of orbital wavefunctions in the correlated quantum material Tb2Ti2O7, which forms an interacting spin liquid ground state. We show that resonant excitation with a strong THz pulse creates a coherent superposition of the lowest energy Tb 4f states. The coherence manifests itself as a macroscopic oscillating magnetic dipole, which is detected by ultrafast resonant x-ray diffraction. We envision the coherent control of orbital wavefunctions demonstrated here to become a new tool for the ultrafast manipulation and investigation of quantum materials.

The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads. NAF-derived EXs (NAF-EXs) were used for loading ormeloxifene (ORM), a potent anti-cancer and desmoplasia inhibitor as a model drug. We found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype, which may be due to regulation of Ca2+ influx in fibroblast cells. NAF-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition (EMT) and repressed tumor growth in xenograft mouse model. In conclusion, our data suggests preferential tropism of NAF-EXs for PDAC tumors, thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer drugs. Additionally, it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.

Abstract Background Cellobiose dehydrogenase (CDH) is an extracellular fungal oxidoreductase with multiple functions in plant biomass degradation. Its primary function as an auxiliary enzyme of lytic polysaccharide monooxygenase (LPMO) facilitates the efficient depolymerization of cellulose, hemicelluloses and other carbohydrate-based polymers. The synergistic action of CDH and LPMO that supports biomass-degrading hydrolases holds significant promise to harness renewable resources for the production of biofuels, chemicals, and modified materials in an environmentally sustainable manner. While previous phylogenetic analyses have identified four distinct classes of CDHs, only class I and II have been biochemically characterized so far. Results Following a comprehensive database search aimed at identifying CDH sequences belonging to the so far uncharacterized class III for subsequent expression and biochemical characterization, we have curated an extensive compilation of putative CDH amino acid sequences. A sequence similarity network analysis was used to cluster them into the four distinct CDH classes. A total of 1237 sequences encoding putative class III CDHs were extracted from the network and used for phylogenetic analyses. The obtained phylogenetic tree was used to guide the selection of 11 cdhIII genes for recombinant expression in Komagataella phaffii. A small-scale expression screening procedure identified a promising cdhIII gene originating from the plant pathogen Fusarium solani (FsCDH), which was selected for expression optimization by signal peptide shuffling and subsequent production in a 5-L bioreactor. The purified FsCDH exhibits a UV-Vis spectrum and enzymatic activity similar to other characterized CDH classes. Conclusion The successful production and functional characterization of FsCDH proved that class III CDHs are catalytical active enzymes resembling the key properties of class I and class II CDHs. A detailed biochemical characterization based on the established expression and purification strategy can provide new insights into the evolutionary process shaping CDHs and leading to their differentiation into the four distinct classes. The findings have the potential to broaden our understanding of the biocatalytic application of CDH and LPMO for the oxidative depolymerization of polysaccharides.

Jung and Pauli found a link between the psyche and quantum mechanics by formulating the idea of Synchronicity. Synchronicity provides a conceptual acausal framework for both meaningful coincidences of life and random physical events of the quantum world. These two geniuses also tried to generalize Synchronicity to become the organizing principle of matter and psyche. Their work could not be completed because of growing disagreement between them. In this work, we briefly retrace the genesis of synchronicity and discuss the concepts that precede it. Upon considering the quantum-classical nature of the physical world and the wave function’s collapse of quantum mechanics, we conjecture that a further extension of the meaning of Synchronicity is given as an acausal organizing principle of quantum-classical phenomena. Additional analysis is required to validate this conjecture.

BackgroundGrowing evidence reveals the important role of clinical psychological factors in chronic-immune diseases. The aim of this study was to investigate Health-Related Quality of Life (HR-QoL), depression, anxiety, and alexithymia in patients with severe hypersensitivity reactions such as Severe Allergic Asthma (SAA) and Hymenoptera Venom Anaphylaxis (HVA).MethodsThe Short-Form Health Survey-36 (SF-36), the Beck Depression Inventory Questionnaire (BDI-II), the Hamilton Anxiety Rating Scale (HAM-A) and the Toronto Alexithymia Scale (TAS-20) were used to assess HR-QoL and clinical psychological features of patients with SAA and HVA.ResultsOverall, 78 patients were recruited. Patients with SAA (n = 35) reported lower scores for physical functioning [65 (58–75) vs. 90 (85–95); p =

Neurotrophins (NTs) are four small proteins produced by both neuronal and non-neuronal cells; they include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). NTs can exert their action through both genomic and non-genomic mechanisms by interacting with specific receptors. Initial studies on NTs have identified them only as functional molecules of the nervous system. However, recent research have shown that some tissues and organs (such as the lungs, skin, and skeletal and smooth muscle) as well as some structural cells can secrete and respond to NTs. In addition, NTs perform several roles in normal and pathological conditions at different anatomical sites, in both fetal and postnatal life. During pregnancy, NTs are produced by the mother, placenta, and fetus. They play a pivotal role in the pre-implantation process and in placental and embryonic development; they are also involved in the development of the brain and respiratory system. In the postnatal period, it appears that NTs are associated with some diseases, such as sudden infant death syndrome (SIDS), asthma, congenital central hypoventilation syndrome (CCHS), and bronchopulmonary dysplasia (BPD).

The nucleophilic substitution of chlorine into the 5-chloromethylfurfural (CMF) by methanol is a high potential route for the production of 5-methoxymethylfurfural (MMF), allowing the production of 2,5-furandicarboxylic acid, an important intermediate for polyester synthesis with larger yield and selectivity than 5-hydroxymethylfurfural. However, HCl, produced during the nucleophilic substitution, leads to the formation of by-products like humins or methyl levulinate, and it is faced by adding bases to the reaction with the side effect of producing large amounts of waste as salts. On the contrary, optimizing the MMF yields in the absence of any base could allow the recycling of the produced HCl into the CMF production process, with benefits for the whole route. To optimize the reaction, CMF was reacted with methanol at low concentration, using a multi-reactor in batch mode, to maximize the MMF yield at 10, 20, 40, and 50 °C. Finally, a lumped kinetic model was employed to analyse the reaction further. The yield of MMF and its corresponding acetal increase with a reaction time and temperature of up to 60 % in 1.5 h.

Background/Aim: has shown that sketching while narrating facilitates the elicitation of information and verbal veracity cues in single interviews. We examined if these effects are retained when suspects are shown their sketch after one week in a repeated interview. Method: Participants (N = 173) completed a mock mission and then told the truth or lied about it in an immediate interview (interview 1). Participants either verbally reported the mission (Free recall condition) or sketched it while describing what they were sketching (sketch condition). After one week, all participants were asked for a free recall without sketching (interview 2). Half of the participants in the Sketch condition had access to their sketch while they verbally reported the event whereas the remaining half did not access the sketch. Results: Truth tellers provided more information than lie tellers in both interviews, and sketching elicited more information than a free recall but only in Interview 1. Participants who had access to their sketch in interview 2 repeated more information than those who did not have access, but accessing the sketch did not have an effect on veracity cues. Conclusions: Thus, sketching enhanced the elicitation of information in Interview 1 and access to the sketch in interview 2 seemed helpful for recalling previously reported information.

In type 2 diabetes (T2D), several differences have been described between men and women, concerning risk factors, clinical manifestations and chronic complications. The impact of gender on the efficacy and safety of hypoglycaemic drugs is still to be clarified. Some data suggest that GLP1-RAs may have greater efficacy on body weight in women, but comparable efficacy on glycaemic control and cardiovascular risk (CVD) in both sexes. The aim of our study was to evaluate in real-life clinical practice the possible influence of gender on the effectiveness and safety of GLP1-RAs long-acting therapy in T2D outpatients. In this single-centre observational study, we evaluated laboratory parameters, chronic complications, hypoglycaemic episodes, and any adverse events of subjects with T2D who started treatment with GLP1-RAs long-acting between 1 June 2018 and 31 May 2019, in add on to metformin or other hypoglycaemic drugs, and who practiced this therapy for at least two years. In the present analysis, 391 subjects with T2D were included (men 59.3%, women 40.7%), with a mean age of 64.1 years and mean duration of diabetes of 18.4 years. At baseline, patients were on average obese (BMI 32.8 kg/m2) with an inadequate glycaemic control (HbA1c 7.8%). Women had higher BMI values than men; glycaemic control was similar in both genders. After two years of follow-up, therapy with GLP1-RAs long-acting determined a significant reduction of BMI and blood pressure values, HbA1c, fasting glucose and GPT levels and an improvement in lipid profile. The reduction observed in BMI values was significantly greater in T2D women than in men. At stepwise regression analysis, female gender was among the independent predictors of the effectiveness of GLP1-RAs in terms of BMI reduction, together with fasting blood glucose, but not in terms of reduction of HbA1c levels, which was significantly associated with baseline blood glucose levels and metformin use, irrespective of gender. Overall, the treatment with GLP1-RAs was well tolerated, and only mild gastro-intestinal adverse events were observed (n=22; 5.6%, 14 men and 12 women P0.05), in both genders. In conclusion, in real-life clinical practice, the therapy with GLP1-RAs long-acting is safe and effective in both men and women, and it seems to be associated with a more beneficial effect on body weight in women than in men.

Asymmetric organocatalyzed multicomponent reactions represent an important toolbox in the field of organic synthesis to build complex scaffolds starting from simple starting materials. The Enders three-component cascade reaction was a cornerstone in the field and a plethora of organocatalyzed cascade reactions followed. However, acetaldehyde was not shown as a successful reaction partner, probably because of its high reactivity. Herein, we report the Enders-type cascade reaction using acetaldehyde dimethyl acetal, as a masked form of acetaldehyde. This strategy directly converts acetaldehyde, nitroalkenes and enals into stereochemically dense cyclohexenals in good yield and excellent enantioselectivity.

In the past few years, non-native blue crab has been expanding its range in the Adriatic and Mediterranean Seas. However, when non-indigenous species establish a lasting presence in a novel ecosystem and actively expand into other regions, posing potential risks to local biodiversity and economic harm, they are classified as invasive species. For this study, two different batches of blue crabs were collected: one from the Mediterranean Sea and the other from the Adriatic coast area. Considering the negative ecological impact that blue crab has had and continues to have on the Italian coasts, this work was aimed to evaluate the characteristics of the Adriatic Sea “variant”; another goal was to propose the potential use of blue crab as a commercially profitable source due to its organoleptic characteristics. Data obtained revealed a high protein content, a good lipid profile, a low number of plastic particles, and the absence of toxic metals and pathogenic microorganisms. A deep statistical analysis was conducted to compare different portions of blue crab from the Adriatic and Mediterranean Seas. The results suggest that Callinectes sapidus is beneficial for human consumption and represents a valuable seafood, and its carapace could be used as compliant feed for aquaculture due to its metal composition and microbiological content.

The incidence of respiratory and cutaneous allergic disorders may be variable if we consider work activity. These disorders are reported in the current literature to have a relevant psychosomatic involvement. The aim of the study was to submit a survey on the self-reported occurrence of allergic respiratory and cutaneous diseases in outdoor and indoor workers to verify the onset or exacerbations of such pathologies, encourage surveillance, and suggest the need for further studies. Two groups of workers were compared when exposed and not exposed to air pollutants. An outdoor population of motorway toll collectors (153 workers; M: 58.03 years old, SD: 6.1; and female prevalence of 66.01%) and an indoor group of office employees (59 workers; mean age 54.44 years, SD: 8.50; and male prevalence of 61.02%) entered the study. The results of three multivariate analyses of the obtained data, investigating contributions of external factors, including age, sex, smoking habits, working type, and seniority, on allergic conditions were significant in both workers’ groups. The findings highlighted that age and smoking habits were significant contributors to allergic conditions, both independently and in combination with other factors, such as sex and working type. The data suggest the presence of phenomena related to different etiological domains, as already reported in the literature. Through the collection of these data, it was possible to highlight the need to analyze clinical signs from different perspectives.

Deploying an airbag when a vehicle occupant is too close to it can cause injury. An adaptive Airbag Control Unit (ACU) would improve the effectiveness of the safety system, provided it is aware of the actual position of the occupants once the crash is going to occur. Occupants can be monitored with vision-based and radar-based sensing in the vehicle, but the research question is whether other reliable devices exist. In this research, a real seat is equipped with four sensors in the supports from the floor, as well as an Inertial Measurement Unit (IMU) and a microcontroller. The device is capable of identifying correct position or different Out of Position (OP) conditions and inform an adaptive ACU. The paper presents the seat layout in detail and its testing in extensive driving experiments with multiple participants. Depending on the position of the driver, the identification is correct 45–100% of the time. Monitoring the occupant position by a sensorized seat is feasible and can improve the reliability of the onboard safety system when integrated with other occupant monitoring devices.

The introduction of continuous glucose monitoring (CGM) systems in clinical practice has allowed a more detailed picture of the intra- and interdaily glycemic fluctuations of individuals with type 1 diabetes (T1D). However, CGM-measured glucose control indicators may be occasionally inaccurate. This study aims to assess the discrepancy between the glucose management indicator (GMI) and glycated hemoglobin (HbA1c) (ΔGMI-HbA1c) within a cohort of children and adolescents with T1D, exploring its correlation with other CGM metrics and blood count parameters. In this single-center, cross-sectional study, we gathered demographic and clinical data, including blood count parameters, HbA1c values, and CGM metrics, from 128 pediatric subjects with T1D (43% female; mean age, 13.4 ± 3.6 years). Our findings revealed higher levels of the coefficient of variation (CV) (p < 0.001) and time above range > 250 mg/dL (p = 0.033) among subjects with ΔGMI-HbA1c > 0.3%. No association was observed between blood count parameters and ΔGMI-HbA1c. In conclusion, despite the advancements and the widespread adoption of CGM systems, HbA1c remains an essential parameter for the assessment of glycemic control, especially in individuals with suboptimal metabolic control and extreme glycemic variability.

IntroductionThe mechanism underlying radiation-induced gut microbiota dysbiosis is undefined. This study examined the effect of radiation on the intestinal Paneth cell α-defensin expression and its impact on microbiota composition and mucosal tissue injury and evaluated the radio-mitigative effect of human α-defensin 5 (HD5).MethodsAdult mice were subjected to total body irradiation, and Paneth cell α-defensin expression was evaluated by measuring α-defensin mRNA by RT-PCR and α-defensin peptide levels by mass spectrometry. Vascular-to-luminal flux of FITC-inulin was measured to evaluate intestinal mucosal permeability and endotoxemia by measuring plasma lipopolysaccharide. HD5 was administered in a liquid diet 24 hours before or after irradiation. Gut microbiota was analyzed by 16S rRNA sequencing. Intestinal epithelial junctions were analyzed by immunofluorescence confocal microscopy and mucosal inflammatory response by cytokine expression. Systemic inflammation was evaluated by measuring plasma cytokine levels.ResultsIonizing radiation reduced the Paneth cell α-defensin expression and depleted α-defensin peptides in the intestinal lumen. α-Defensin down-regulation was associated with the time-dependent alteration of gut microbiota composition, increased gut permeability, and endotoxemia. Administration of human α-defensin 5 (HD5) in the diet 24 hours before irradiation (prophylactic) significantly blocked radiation-induced gut microbiota dysbiosis, disruption of intestinal epithelial tight junction and adherens junction, mucosal barrier dysfunction, and mucosal inflammatory response. HD5, administered 24 hours after irradiation (treatment), reversed radiation-induced microbiota dysbiosis, tight junction and adherens junction disruption, and barrier dysfunction. Furthermore, HD5 treatment also prevents and reverses radiation-induced endotoxemia and systemic inflammation.ConclusionThese data demonstrate that radiation induces Paneth cell dysfunction in the intestine, and HD5 feeding prevents and mitigates radiation-induced intestinal mucosal injury, endotoxemia, and systemic inflammation.

The development of micellar catalysis offers a sustainable alternative to organic solvents, and represents an environmental milestone in organic synthesis. Here, the first Michael addition of masked acetaldehyde under neutral, cationic and anionic micellar catalysis is reported, affording the products in high yields and enantiomeric excess, despite the use of water as solvent.