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Trend in the reduction on use of synthetic pesticides is continuously growing. Their substitution with natural substances is well studied because of the environmental vantages. Consumers require safe foods. Their risk perception concerns the presence of synthetic pesticides and marketing is oriented toward food with lower and lower residue levels. Essential oils (EOs) could be a reliable alternative. Their components are in a variable range of concentrations determining, in some cases, for the chemotypes. Lots of rosemary, oregano, and clove oil were purchased on the market and their main components were analyzed. Four EOs formulations were prepared to test their effectiveness against zucchini powdery mildew. Moreover, rosemary leaves were collected from the CREA-DC garden (Rome) and rosemary essential oil, distilled in-house, in combination with oregano essential oil were also tested. Metrafenone and penconazole were synthetic fungicides used for reference treatments. Two trials were carried out in a greenhouse.

Approximately 740 million symptomatic patients are affected by otitis media every year. Being an inflammatory disease affecting the middle ear, it is one of the primary causes of tympanic membrane (TM) perforations, often resulting in impaired hearing abilities. Antibiotic therapy using broad-spectrum fluoroquinolones, such as ciprofloxacin (CIP), is frequently employed and considered the optimal route to treat otitis media. However, patients often get exposed to high dosages to compensate for the low drug concentration reaching the affected site. Therefore, this study aims to integrate tissue engineering with drug delivery strategies to create biomimetic scaffolds promoting TM regeneration while facilitating a localized release of CIP. Distinct electrospinning (ES) modalities were designed in this regard either by blending CIP into the polymer ES solution or by incorporating nanoparticles-based co-ES/electrospraying. The combination of these modalities was investigated as well. A broad range of release kinetic profiles was achieved from the fabricated scaffolds, thereby offering a wide spectrum of antibiotic concentrations that could serve patients with diverse therapeutic needs. Furthermore, the incorporation of CIP into the TM patches demonstrated a favorable influence on their resultant mechanical properties. Biological studies performed with human mesenchymal stromal cells confirmed the absence of any cytotoxic or anti-proliferative effects from the released antibiotic. Finally, antibacterial assays validated the efficacy of CIP-loaded scaffolds in suppressing bacterial infections, highlighting their promising relevance for TM applications.

In light of recent conflicting reports regarding the hydroformylation catalytic activity derived from cationic Co(II) precatalysts of the form [Co(acac)(bis(phosphine))]BF4, the synthetic procedures and characterization of [Co(acac)(dppBz)]BF4, 1, are evaluated. Leveraging calibrated ESI-TOF MS methodologies, substantial quantities of Co(acac)2(dppBz), 2, were observed within samples of 1. The source of the impurity, 2, is determined to derive from incomplete protonolysis of the Co(acac)2precursor and ligand scrambling occurring during the synthesis of 1. Revised synthetic procedures using lower temperature conditions and longer reaction times afford analytically pure samples of 1based on ESI-TOF MS and NMR spectroscopic analysis. Complex 1is demonstrated to act as a hydroformylation precatalyst for the conversion of 1-hexene to 1-heptanal under relatively mild conditions at 51.7 bar and 140 °C. The presence of impurity 2is shown to dramatically decrease the catalytic performance derived from 1.

Introduction: This retrospective study investigates the efficacy of cemiplimab, a monoclonal antibody targeting the PD-1 receptor, in treating squamous cell carcinoma (SCC) of the skin. Methods: The study analyzes data from 50 patients with SCC, focusing on various clinical parameters, including patient demographics, tumor characteristics, treatment history, disease status at the beginning of therapy, and survival outcomes. Results: Of the patients who received at least one cycle of cemiplimab, 42% showed a clinical response. Adverse reactions were generally low, with the safety profile deemed excellent. During a median follow-up of 9.6 months, 17 patients experienced progression or death. Among these, 15 patients had died at the time of the analysis. The median progression-free survival (PFS) for the entire cohort was approximately 20.8 months, while median overall survival (OS) was not reached. Univariate Cox regression analysis for PFS showed that tumors in the arms and legs were associated with higher progression risk, while age above 65 years was not statistically significant. Distant metastasis exhibited a trend towards improved PFS. In terms of OS, distant metastasis was a significant predictor of reduced survival, while age above 65 years was not statistically significant. In a multivariate model, only the absence of distant metastasis remained significant, with an adjusted odds ratio (OR) of 12.3 (95% confidence interval 1.3–112.1). Conclusion: These findings provide valuable insights into the real-world effectiveness of cemiplimab in SCC management.

Single crystals of a family of rare-earth-metal–organic frameworks (RE-MOFs), RE-UiO-66 where RE = Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III), Er(III), Tm(III), Yb(III), and Lu(III), are successfully synthesized and their structures resolved through single-crystal X-ray diffraction. Different structural parameters, including unit cell dimensions and bond distances, are explored to discover trends between those structural parameters, ionic radii of the RE ions in the MOF structures, and their thermal stability. Results suggest that subtle differences in metal-linker bond length can have a notable effect on thermal stability (± 60 °C).

We advance a novel computational model of multi-agent, cooperative joint actions that is grounded in the cognitive framework of active inference. The model assumes that to solve a joint task, such as pressing together a red or blue button, two (or more) agents engage in a process of interactive inference. Each agent maintains probabilistic beliefs about the joint goal (e.g., Should we press the red or blue button?) and updates them by observing the other agent’s movements, while in turn selecting movements that make his own intentions legible and easy to infer by the other agent (i.e., sensorimotor communication). Over time, the interactive inference aligns both the beliefs and the behavioral strategies of the agents, hence ensuring the success of the joint action. We exemplify the functioning of the model in two simulations. The first simulation illustrates a “leaderless” joint action. It shows that when two agents lack a strong preference about their joint task goal, they jointly infer it by observing each other’s movements. In turn, this helps the interactive alignment of their beliefs and behavioral strategies. The second simulation illustrates a “leader–follower” joint action. It shows that when one agent (“leader”) knows the true joint goal, it uses sensorimotor communication to help the other agent (“follower”) infer it, even if doing this requires selecting a more costly individual plan. These simulations illustrate that interactive inference supports successful multi-agent joint actions and reproduces key cognitive and behavioral dynamics of “leaderless” and “leader–follower” joint actions observed in human–human experiments. In sum, interactive inference provides a cognitively inspired, formal framework to realize cooperative joint actions and consensus in multi-agent systems.

ABSTRACTBackgroundUstekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting.Research design and methodsThis is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24.ResultsWe included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy.ConclusionThis real-world study shows that UST effectively and safely treats patients with UC.

The article presents a multiphysics modelling approach to design an integrated electric propulsion system for ship dynamic positioning purposes. The simulation platform integrates the model of the shipboard power plant, the hydrodynamic and environmental forces and the dynamic positioning controller. The shipboard power system has been modelled considering the electro-mechanical behaviour, i.e. the power-frequency dynamic, so that the platform can run in real time and be linked with the control hardware. The simulation platform has been tested through a detailed simulation campaign by using as a study case a Platform Supply Vessel where its behaviour in harsh conditions has been validated. Moreover, a control hardware-in-the-loop configuration has been realized, where the controller logic has been implemented in a real PCL. Finally, a comparison between the two simulation approaches is shown and the results are discussed.

Presented work focuses on the development of biodegradable polymer nanoparticles loaded with antibiotics as drug delivery systems deposited on electrospun scaffolds for tissue engineering. The innovative ciprofloxacin-loaded poly(dl-lactide-co-glycolide) NPs ensure a continuous slow release and high local concentration at the site of action for an optimal therapy. The local delivery of antibiotics as an integrated part of electrospun scaffolds offers an effective, safe, and smart enhancement supporting tissue regeneration. Presented data provides solid scientific evidence for fulfilling the requirements of local nano antibiotic delivery systems with biodegradability and biocompatibility for a wide range of tissue engineering applications, including middle ear tissues (e.g., tympanic membranes) which are subject to bacterial infections. Further characterization of such systems, including in vivo studies, is required to ensure successful transfer from lab to clinical applications.

A novel follow-the-leader approach for azimuth-driven vessels is devised and experimentally tested in a model-scale outdoor scenario. The vessels are equipped with global navigation satellite and inertial navigation systems. A line-of-sight algorithm ensures the yaw-check ability of the follower vessel along the leader's path, while a speed-regulation allows to track its velocity. Track generation, guidance, navigation, and control modules are designed and assembled to be executed on-board in real time. The results of an outdoor experimental campaign are illustrated to show the effectiveness of the proposed approach.

The centre of the Milky Way Galaxy hosts a black hole with a solar mass of about 4 million (Sagittarius A*(Sgr A)) that is very quiescent at present with a luminosity many orders of magnitude below those of active galactic nuclei1. Reflection of X-rays from Sgr A*by dense gas in the Galactic Centre region offers a means to study its past flaring activity on timescales of hundreds and thousands of years2. The shape of the X-ray continuum and the strong fluorescent iron line observed from giant molecular clouds in the vicinity of Sgr A*are consistent with the reflection scenario3–5. If this interpretation is correct, the reflected continuum emission should be polarized6. Here we report observations of polarized X-ray emission in the direction of the molecular clouds in the Galactic Centre using the Imaging X-ray Polarimetry Explorer. We measure a polarization degree of 31% ± 11%, and a polarization angle of −48° ± 11°. The polarization angle is consistent with Sgr A*being the primary source of the emission, and the polarization degree implies that some 200 years ago, the X-ray luminosity of Sgr A*was briefly comparable to that of a Seyfert galaxy.

ABSTRACTBackgroundVedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn’s disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ.Research design and methods Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints.Results729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6thmonth of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6thmonth of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016).ConclusionWe found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug’s longterm efficacy.

Background: The prevalence of certain multidrug-resistant organisms (MDROs), especially Gram-negative bacteria, is dramatically increasing in patient care settings, including pediatric and neonatal units. However, most of the new drugs available for the treatment of MDROs have not yet been studied in children and newborns. Case report: We report the clinical case of a preterm neonate, born at 31 weeks gestation + 1 day of age by emergency Cesarean Section (CS), with a bloodstream infection (BSI) due to a Verona integron-borne metallo-β-lactamase (VIM)-producing Klebsiella pneumoniae. We successfully treated the infection with cefiderocol in an off-labelregimen at the following dose: loading dose 60 mg/kg and then 40 mg/kg every 8 h in extended infusion for 9 days. The baby showed a quick clinical and biochemical improvement and tolerated well the treatment. Follow-up blood cultures at 48 h after the start of cefiderocol were negative. Conclusions: Antimicrobial-resistant pathogens are of increasing concern in neonatal settings. More studies in this unique population are necessary to better describe the pharmacokinetic and pharmacodynamic profile of the new drugs against MDROs, such as cefiderocol, and to define a proper effective dose.

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization—the only range available until now—probe extended regions of the jet containing particles that left the acceleration site days to years earlier1–3, and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree ΠXof around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock.

ABSTRACTBackgroundTo compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy.Research Design and MethodsThree hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint.Results197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn’s Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6–36) months were compared: 230 (60.5%) were naïve to anti-TNFα, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004).ConclusionThis first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

ABSTRACTBackground:Weight homeostasis is complex in Parkinson’s disease (PD) and body weight changes substantially throughout the course of the disease. We designed a case–control study to (i) investigate whether PD is associated with changes in resting energy expenditure (REE), (ii) to assess how accurately REE could be predicted for individuals with PD utilizing the equations constructed for healthy individuals, and (iii) to eventually construct a new equation.Materials & Methods:Measured REE (mREE) was compared between 122 PD patients and 122 gender and body mass index (BMI)-matched controls. The accuracy of estimated REE by 5 common equations (Harris/Benedict-1919, Roza/Shizgal-1984, Mifflin St. Jeor, WHO/FAO and aggregate formula) was investigated in PD using Bland–Altman analysis and reported as the frequency of accurate predictions (±10%). Concordance correlation coefficients (CCC) were also calculated. Then, we regressed a new REE equation – using gender, age, weight, height and Hoehn-Yahr stage – and validated it in an independent sample (N = 100).Results:No significant difference in mREE was recorded between the whole PD sample and healthy controls. However, mREE was increased in patients with BMI ≥ 30 kg/m2and Hoehn-Yahr stage ≥ 3. Limited accuracy was present in the available REE equations (accurate prediction [±10%] frequency, <60% for all). For the new equation, the proportion of accurate prediction was 67.0% (overestimation, 24.0%) and CCC was 0.77.Conclusion:PD patients are not commonly characterized by an increase in REE. This is limited to patients suffering from obesity and more severe disease. Common REE equations appear to be inaccurate. The new predictive equation proposed in this study provided better REE estimates.

Pulsar wind nebulae are formed when outflows of relativistic electrons and positrons hit the surrounding supernova remnant or interstellar medium at a shock front. The Vela pulsar wind nebula is powered by a young pulsar (B0833-45, aged 11,000 years)1and located inside an extended structure called Vela X, which is itself inside the supernova remnant2. Previous X-ray observations revealed two prominent arcs that are bisected by a jet and counter jet3,4. Radio maps have shown high linear polarization of 60% in the outer regions of the nebula5. Here we report an X-ray observation of the inner part of the nebula, where polarization can exceed 60% at the leading edge—approaching the theoretical limit of what can be produced by synchrotron emission. We infer that, in contrast with the case of the supernova remnant, the electrons in the pulsar wind nebula are accelerated with little or no turbulence in a highly uniform magnetic field.

Postsynthetic modification of metal–organic frameworks (MOFs) is an important strategy for accessing MOF analogues that cannot be easily synthesized de novo. In this work, the rare-earth (RE) cluster-based MOF Y-CU-10 with shptopology was modified through transmetalation using a series of RE ions, including La(III), Nd(III), Eu(III), Tb(III), Er(III), Tm(III), and Yb(III). In all cases, metal exchange higher than 70% was observed, with reproducible results. All transmetalated materials were fully characterized and compared to the parent MOF Y-CU-10 with regard to crystallinity, surface area, and morphology. Additionally, single-crystal X-ray diffraction measurements were performed to provide further evidence of transmetalation occurring in the nonanuclear cluster nodes of the MOF.

For many years, plant protection products have been used to manage plant diseases in agriculture, contributing to increase agricultural production. However, plant protection products could cause undesirable adverse effects on human health and the environment. This research aims to highlight the efficacy of plant protection strategies based on natural products. In order to find an alternative to the use of synthetic fungicides, different formulates based on essential oils, single and in combination, have been tested against zucchini powdery mildew. Their effectiveness against fungal pathogens has been studied extensively, showing that their antifungal activity is closely associated with monoterpenic phenols, i.e. thymol, carvacrol, eugenol. The tested essential oils included Rosmarinus officinalis(L.), Syzygium aromaticum(L.) Merr. & L.M. Perry and Origanum vulgare(L.). The performed experiments pointed out that when using the combination of essential oils, the formulate showed better disease protection compared to the ones based on single oils, confirming the results obtained in previous trials. The good level of disease reduction, also observed in these trials, allows us to carry on the work for the development of formulations based on essential oils at low dosages, taking advantage of the essential oils mixtures’ synergistic effect.

Due to the morbidity and lethality of pulmonary diseases, new biomaterials and scaffolds are needed to support the regeneration of lung tissues, while ideally providing protective effects against inflammation and microbial aggression. In this study, we investigated the potential of nanocomposites of poly(vinylidene fluoride-co-trifluoroethylene) [P(VDF-TrFE)] incorporating zinc oxide (ZnO), in the form of electrospun fiber meshes for lung tissue engineering. We focused on their anti-inflammatory, antimicrobial, and mechanoelectrical character according to different fiber mesh textures (i.e., collected at 500 and 4000 rpm) and compositions: (0/100) and (20/80) w/w% ZnO/P(VDF-TrFE), plain and composite, respectively. The scaffolds were characterized in terms of morphological, physicochemical, mechanical, and piezoelectric properties, as well as biological response of A549 alveolar epithelial cells in presence of lung-infecting bacteria. By virtue of ZnO, the composite scaffolds showed a strong anti-inflammatory response in A549 cells, as demonstrated by a significant decrease of interleukin (IL) IL-1α, IL-6, and IL-8 expression in 6 h. In all the scaffold types, but remarkably in the aligned composite ones, transforming growth factor β (TGF-β) and the antimicrobial peptide human β defensin-2 (HBD-2) were significantly increased. The ZnO/P(VDF-TrFE) electrospun fiber meshes hindered the biofilm formation by Staphylococcus aureusand Pseudomonas aeruginosaand the cell/scaffold constructs were able to impede S. aureusadhesion and S. aureusand P. aeruginosainvasiveness, independent of the scaffold type. The data obtained suggested that the composite scaffolds showed potential for tunable mechanical properties, in the range of alveolar walls and fibers. Finally, we also showed good piezoelectricity, which is a feature found in elastic and collagen fibers, the main extracellular matrix molecules in lungs. The combination of all these properties makes ZnO/P(VDF-TrFE) fiber meshes promising for lung repair and regeneration.Impact statementAirway tissue engineering is still a major challenge and an optimally designed scaffold for this application should fulfill a number of key requirements. To help lung repair and regeneration, this study proposes a nondegradable scaffold, with potential for tuning mechanical properties. This scaffold possesses a strong anti-inflammatory character, and is able to hinder microbial infections, sustain epithelial cell growth, and provide physiological signals, like piezoelectricity. The development of such a device could help the treatment of pulmonary deficiency, including the ones induced by inflammatory phenomena, primary and secondary to pathogen infections.

Copper(II)-based electrocatalysts for water oxidation in aqueous solution have been studied previously, but photodriving these systems still remains a challenge. In this work, a bis(diimine)copper(I)-based donor–chromophore–acceptor system is synthesized and applied as the light-harvesting component of a photoanode. This molecular assembly was integrated onto a zinc oxide nanowire surface, and upon photoexcitation, chronoamperometric studies reveal that the integrated triad can inject electrons directly into the conduction band of zinc oxide, generating oxidizing equivalents that are then transferred to a copper(II) water oxidation catalyst in aqueous solution, yielding O2from water with a Faradaic efficiency of 76%.

The wavelength dependence of atomic force microscope apertureless tip-enhanced laser ablation was studied using a series of organic dyes to assess the effect of surface optical absorption. An optical parametric oscillator laser with a tunable wavelength range of 410–2100 nm was used to irradiate a gold-coated atomic force microscope tip which was held 15 nm above the surface of a dye thin film vibrating in tapping mode to generate tip-enhanced laser ablation. Crater formation was investigated for rhodamine B, methylene blue, and IR 797 dye thin films which have absorption maxima near 550, 650, and 700 nm, respectively. Crater formation was not observed for wavelengths greater than 700 nm for any of the dyes. Below 700 nm, the crater size was greatest near 500 nm for all dyes and decreased from 500 to 700 nm, and no ablation was observed at longer wavelengths. The crater size did not correlate with the solution or thin film optical absorption of the dyes. The mechanism for tip-enhanced laser ablation is postulated to be either ballistic ejection of gold atoms or direct heat transfer from the tip to the surface.