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Efficient functionalization of peptides and proteins has widespread applications in chemical biology and drug discovery. However, the chemoselective and site-selective modification of proteins remains a daunting task. Herein, a highly efficient chemo-, regio-, and stereoselective hydrosulfuration of ynamide was identified as an efficient method for the precise modification of peptides and proteins by uniquely targeting the thiol group of cysteine (Cys) residues. This novel method could be facilely operated in aqueous buffer and was fully compatible with a wide range of proteins, including small model proteins and large full-length antibodies, without compromising their integrity and functions. Importantly, this reaction provides the Z-isomer of the corresponding conjugates exclusively with superior stability, offering a precise approach to peptide and protein therapeutics. The potential application of this method in peptide and protein chemical biology was further exemplified by Cys-bioconjugation with a variety of ynamide-bearing functional molecules such as small molecule drugs, fluorescent/affinity tags, and PEG polymers. It also proved efficient in redox proteomic analysis through Cys-alkenylation. Overall, this study provides a novel bioorthogonal tool for Cys-specific functionalization, which will find broad applications in the synthesis of peptide/protein conjugates.

Background Several variations of the combined thrombectomy technique for acute ischemic stroke using a stent retriever and aspiration catheter have been described. The aim of our study was to assess how the presence of the microcatheter and stent retriever affect the basic aspiration parameters, namely, flow rate and aspiration force, depending on their position within the aspiration catheter.Methods Two experimental set-ups were designed to assess changes in flow rate and aspiration force according to the position of the stent retriever and microcatheter within the aspiration catheter.Results The transition of the stent retriever and microcatheter from the distal to proximal position resulted in a progressive increase in the flow rate, but with no impact on aspiration force. Additionally, the size of the stent retriever had no significant effect on flow rate changes and the reduction in flow rate was related to the microcatheter diameter. Negative pressure generated inside the aspiration catheter impacted on its distal segment located beyond the radiopaque marker, thus leading to its partial collapse. As a consequence, the measured aspiration force was lower than the theoretical aspiration force level for all tested aspiration catheters.Conclusions In our experimental model, the position of the stent retriever and microcatheter within the aspirator catheter affected the flow rate, but not the aspiration force. Negative pressure generated within the aspiration catheter appeared to determine a partial collapse of the distal segment that resulted in a less effective aspiration force than the theoretical aspiration force level.

Recent evidence suggests an elevated risk of cognitive impairment and dementia in individuals with atrial fibrillation (AF), irrespective of stroke occurrence. AF, known to reduce brain perfusion, particularly through silent cerebral ischemia, underscores the intricate relationship between cardiac and cerebral health. The heart plays a crucial role in supporting normal brain function, and rhythm control, a standard AF treatment, has demonstrated enhancements in brain perfusion. This systematic review aimed to examine published data concerning the influence of rhythm control on brain perfusion in patients with atrial fibrillation. A systematic search for relevant studies was carried out in Scopus, PubMed, Cochrane Reviews, ProQuest, and EBSCOhost, spanning from their inception until April 30, 2023. Studies that specifically examined brain perfusion following any form of rhythm control in atrial fibrillation were included in the review. The review encompassed 10 studies involving 436 participants. Among these, six utilized electrical cardioversion for rhythm control. The majority (8 out of 10) demonstrated that restoring sinus rhythm markedly enhances brain perfusion. In one of the two remaining studies, notable improvement was observed specifically in a region closely linked to cognition. Additionally, both studies reporting data on the Mini‐Mental State Examination (MMSE) showed a consistent and significant increase in scores following rhythm control. Successful rhythm control in AF emerges as a significant contributor to enhanced brain perfusion, suggesting a potential therapeutic avenue for reducing cognitive impairment incidence. However, further validation through larger prospective studies and randomized trials is warranted. This study examines rhythm control's impact on brain perfusion in atrial fibrillation, filling a research gap as there are no systematic reviews on this topic. Analyzing 10 studies with 436 participants, we find a positive association between rhythm control in AF patients and enhanced brain blood flow, improving cognitive function.

Graphical abstract: Left: Correlation of CEC and elemental analysis obtained from willow biochars produced at different pyrolysis temperatures. Right: Scanning electron micrographs at the same magnification (1 kX) of willow derived biochar at different pyrolysis temperatures (panel 1: 400 °C, panel 2: 550 °C and panel 3: 650 °C).

Anaerobic digestion (AD) is a well-known biological conversion process to obtain a gaseous biofuel from organic matter: in fact, upgrading biogas to biomethane is a mean to substitute conventional natural gas. It is also known that biochar can improve the biogas production in AD processes. In this work, different biochars have been produced from various feedstocks at different process conditions. Biochars obtained from the carbonization of wheat straw (WS) and poplar (P) were produced in a Thermo Gravimetric Analyser at lab scale, at a temperature of 400 °C and 2 h of retention time at the maximum temperature, with a heating rate of 20 °C min−1. Another biochar from poplar (Pc) was also produced in a pilot plant (CarbOn, RE-CORD) working in oxidative pyrolysis conditions, at a temperature range between 500 and 600 °C. Biochars were oxidized with Oxone® using two different methods (ball-milling and simple aqueous solution mixing) to increase the amount of functional groups on their surface. Oxidized biochars (Ws_Ox and P_Ox) were characterized by FTIR, BET, and CEC, and their impact on biogas production was investigated through a lab scale biochemical methane potential (BMP) test using maize silage as substrate. 0.33 g of biochar was used for each treatment. BMP test shows that all batches containing biochar as additive produced more biogas than control (C). WS_Ox and P_Ox produced respectively a + 7.7% and + 11.3% of biogas than C, obtaining the higher productivities with respect to not oxidized biochars. The addition of P and Pc biochars were similar performances in AD, thus highlighting that no significant differences are due to different biochar production scales and process parameters from the same feedstock. This study highlights how in addition to the various examined parameters (nature of the feedstock, pyrolysis parameters, size of biochar and its concentration in AD), also the presence of specific functional groups on the biochar surface influences the AD performance.

Single-walled carbon nanotube (SWCNT)@metal–organic framework (MOF) field-effect transistor (FET) sensors generate a signal through analytes restricting ion diffusion around the SWCNT surface. Four composites made up of SWCNTs and UiO-66, UiO-66-NH2, UiO-67, and UiO-67-CH3were synthesized to explore the detection of norfentanyl (NF) using SWCNT@MOF FET sensors with different pore sizes. Liquid-gated FET devices of SWCNT@UiO-67 showed the highest sensing response toward NF, whereas SWCNT@UiO-66 and SWCNT@UiO-66-NH2devices showed no sensitivity improvement compared to bare SWCNT. Comparing SWCNT@UiO-67 and SWCNT@UiO-67-CH3indicated that the sensing response is modulated by not only the size-matching between NF and MOF channel but also NF diffusion within the MOF channel. Additionally, other drug metabolites, including norhydrocodone (NH), benzoylecgonine (BZ), and normorphine (NM) were tested with the SWCNT@UiO-67 sensor. The sensor was not responding toward NH and or BZ but a similar sensing result toward NM because NM has a similar size to NF. The SWCNT@MOF FET sensor can avoid interference from bigger molecules but sensor arrays with different pore sizes and chemistries are needed to improve the specificity.

Bioactive principles administered in the form of finely dispersed particles are a major innovation in plant protection. At present, the most promising formulations are those in which natural functional compounds are transported by vectors obtained from agrifood by-products, in that these systems are able to maximize both efficacy and biocompatibility. Here we present new nanovectors obtained by combining olive pomace (OP) and egg yolk phosphatidylcholine (EPC) to deliver hydroxytyrosol (HT) as a pest control agent. In this way, a valuable antioxidant found in agricultural waste can be reused to develop biopesticides according to the concept of circular economy. Specifically, nanocarriers obtained by natural lipid mixtures were loaded with HT and dispersed in water. The stable and reproducible character of these formulations was assessed by in-depth physicochemical characterization. For this purpose, empty and HT-loaded nanosystems were investigated by dynamic light scattering, zeta potential, and small-angle X-ray scattering. Combining these tools allowed reaching a comprehensive picture of the obtained particles in terms of size and structure at the submicron scale. The concentration of HT used was 2.5–5 mg mL−1, a range of values which are not attainable in the absence of encapsulating objects. The newly prepared biopesticides were subsequently tested against the Mediterranean fruit fly Ceratitis capitata(Wiedemann, 1824), belonging to Diptera, Tephritidae, and Sitophilus oryzae(Linnaeus, 1763), belonging to Coleoptera, Curculionidae. Multifactorial analysis was used to examine the relationships among different groups of variables, such as number of insect eggs and number of egg clusters. This in-depth data treatment showed increased repellency and limited oviposition in samples protected by formulations, thus opening new perspectives for applications in sustainable agriculture.

Objective: To assess financial toxicity experienced by caregivers of children with long-term tracheostomies.Methods: Cross-sectional survey study with comparison group conducted at a tertiary pediatric hospital and outpatient clinic. Pediatric (<18 years) patients with tracheostomies for ≥12 months were recruited for the study. Patients who underwent tympanostomy tube placement or adenotonsillectomy were recruited as controls. Eligible patients’ caregivers were contacted to fill out a questionnaire including the validated Comprehensive Score for Financial Toxicity survey.Results: Surveys were completed for 72 patients, including 31 in the study group (mean age, 6.58 years, 95% confidence interval [CI], 4.85-8.30 years) and 41 controls (mean age, 6.42 years, 95% CI, 5.15-10.52 years) (P= .864). The mean duration of tracheostomy was 3.98 years (95% CI, 2.91-5.05 years). The mean household income and education level were lower in the study group than in the control group. Caregivers of the study group were more likely to have public health insurance or be uninsured. Caregivers of study patients reported greater financial toxicity, with a lower mean Comprehensive Score for Financial Toxicity (18.23 [95% CI, 15.20-21.25]) than caregivers of controls (34.27 [95% CI, 32.05-36.49]; P< .001). Linear regression analysis showed that survey scores were lower for caregivers who employed home nursing care (P< .001).Conclusion: Caregivers of pediatric patients requiring long-term tracheostomies experience greater financial toxicity than caregivers of pediatric patients who have typical otolaryngologic surgery.

Color-tunable metal–organic frameworks (MOFs) are emerging materials for light harvesting, molecular sensing, biological imaging, and lighting applications, and their continued development necessitates straightforward and predictive approaches for adjusting the MOF optical absorption across the visible spectrum. We report a strategy for facile diversification of MOF color that combines (i) postsynthetic modification (PSM) of the chromophoric linkers of an amino-functionalized UiO-68 MOF and (ii) computationally guided selection of specific linker modifiers to rationally tune chromophore band gap. This approach is used to identify and generate a family of seven new modified MOFs having incrementally red-shifted absorption spectra spanning ∼400–650 nm. This combination of experiment and computation provides a relatively simple pathway for the rational and facile tuning of MOF color and the creation of new families of light-responsive materials.

The objective of this chapter is to describe lingual tonsillectomy (LT) as a treatment strategy for children with persistent obstructive sleep apnea after adenotonsillectomy. Drug-induced sleep endoscopy is a useful tool that enables physicians to identify sites of obstruction resulting from dynamic airway collapse and direct surgical interventions accordingly. Lingual tonsil hypertrophy is graded according to the degree of effacement of the vallecula and the posterior displacement of the epiglottis. The surgical technique for microscopic- and endoscopic-assisted coblation LT is described along with postoperative care and complications. LT is an important and efficacious technique for the treatment of pediatric obstructive sleep apnea in patients with base of tongue obstruction. [ABSTRACT FROM AUTHOR]

This review describes the current state of the evaluation and diagnosis of pediatric sleep apnea. Sleep apnea in children differs in important ways from sleep apnea in adults and commonly presents with more subtle symptoms. While there can be snoring, noisy breathing, and sleepiness, not all children with sleep apnea snore. Early symptoms can be speech delay, nap refusal, nocturnal enuresis, headaches, and hyperactivity. Children with sleep apnea may have tonsil and/or adenoid hypertrophy, adenoid facies, mouth-breathing, hyponasality, or low-hanging soft palate on exam. While many screening tools exist, definitive diagnosis of sleep apnea in children requires polysomnography. Nocturnal oximetry and home studies are not conclusive but can serve as a screening tool where pediatric polysomnography is not available. In conclusion, pediatric obstructive sleep apnea presents differently than adults and can only be definitively diagnosed with an in-lab polysomnography. [ABSTRACT FROM AUTHOR]

Periprosthetic femoral bone fractures are frequent complications of Total Hip Arthroplasty (THA) and may occur during the insertion of uncemented Femoral Stems (FS), due to the nature of the press-fit fixation. Such fracture may lead to the surgical failure of the THA and require a revision surgery, which may have dramatic consequences. Therefore, an early detection of intra-operative fractures is important to avoid worsening the fracture and/or to enable a peroperative treatment. The aim of this in vitrostudy is to determine the sensitivity of a method based on resonance frequency analysis of the bone-stem-ancillary system for periprosthetic fractures detection. A periprosthetic fracture was artificially created close to the lesser-trochanter of 10 femoral bone mimicking phantoms. The bone-stem-ancillary resonance frequencies in the range (2–12) kHz were measured on an ancillary instrumented with piezoelectric sensors, which was fixed to the femoral stem. The measurements were repeated for different fracture lengths from 4 to 55 mm. The results show a decrease of the resonance frequencies due to the fracture occurrence and propagation. The frequency shift reached up to 170 Hz. The minimum fracture length that can be detected varies from 3.1±1.7mm to 5.9±1.9mm according to the mode and to the specimen. A significantly higher sensitivity (p= 0.011) was obtained for a resonance frequency around 10.6 kHz, corresponding to a mode vibrating in a plane perpendicular to the fracture. This study opens new paths toward the development of non-invasive vibration-based methods for intra-operative periprosthetic fractures detection.

Assembling nanoparticles (NPs) into well-defined superstructures can lead to emergent collective properties that depend on their 3-D structural arrangement. Peptide conjugate molecules designed to both bind to NP surfaces and direct NP assembly have proven useful for constructing NP superstructures, and atomic- and molecular-level alterations to these conjugates have been shown to manifest in observable changes to nanoscale structure and properties. The divalent peptide conjugate, C16-(PEPAu)2(PEPAu= AYSSGAPPMPPF), directs the formation of one-dimensional helical Au NP superstructures. This study examines how variation of the ninth amino acid residue (M), which is known to be a key Au anchoring residue, affects the structure of the helical assemblies. A series of conjugates of differential Au binding affinities based on variation of the ninth residue were designed, and Replica Exchange with Solute Tempering (REST) Molecular Dynamics simulations of the peptides on an Au(111) surface were performed to determine the approximate surface contact and to assign a binding score for each new peptide. A helical structure transition from double helices to single helices is observed as the peptide binding affinity to the Au(111) surface decreases. Accompanying this distinct structural transition is the emergence of a plasmonic chiroptical signal. REST-MD simulations were also used to predict new peptide conjugate molecules that would preferentially direct the formation of single-helical AuNP superstructures. Significantly, these findings demonstrate how small modifications to peptide precursors can be leveraged to precisely direct inorganic NP structure and assembly at the nano- and microscale, further expanding and enriching the peptide-based molecular toolkit for controlling NP superstructure assembly and properties.

The uneven worldwide vaccination coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emergence of variants escaping immunity call for broadly effective and easily deployable therapeutic agents. We have previously described the human single-chain scFv76 antibody, which recognizes SARS-CoV-2 Alpha, Beta, Gamma and Delta variants. We now show that scFv76 also neutralizes the infectivity and fusogenic activity of the Omicron BA.1 and BA.2 variants. Cryoelectron microscopy (cryo-EM) analysis reveals that scFv76 binds to a well-conserved SARS-CoV-2 spike epitope, providing the structural basis for its broad-spectrum activity. We demonstrate that nebulized scFv76 has therapeutic efficacy in a severe hACE2 transgenic mouse model of coronavirus disease 2019 (COVID-19) pneumonia, as shown by body weight and pulmonary viral load data. Counteraction of infection correlates with inhibition of lung inflammation, as observed by histopathology and expression of inflammatory cytokines and chemokines. Biomarkers of pulmonary endothelial damage were also significantly reduced in scFv76-treated mice. The results support use of nebulized scFv76 for COVID-19 induced by any SARS-CoV-2 variants that have emerged so far.

AbstractInterrogating the relationship between politeness and violence in Warrane/Sydney, 1788–ca. 1816, this article investigates the impact of Enlightenment thought in the transoceanic British colonial world. The author argues that polite sociability was crucial to the imposition and self-justification of the British occupation of Eora country. Principally examining the published and personal journals and diaries of First Fleet officers, the author reveals how politeness was a display of European notions of civility understood within a stadial model of progress: Enlightenment ideology enabled the ruling naval elite to consider their invasion friendly, despite the lethal violence of colonial occupation. Foregrounding the construction and performance of a status-specific whiteness in colonial space, the author shows how politeness in the colonial context justified rather than mitigated violence. In so doing, they hope to destabilize our understanding of the Scottish Enlightenment, politeness, and violence. In what is primarily a study of Enlightenment and settler colonialism, Indigenous perspectives provide a crucial framework to comprehend the British naval elites’ commitment to the imposition of civility by force in Warrane/Sydney.

Sewage released from lakeside development can reshape ecological communities. Nearshore periphyton can rapidly assimilate sewage‐associated nutrients, leading to increases of filamentous algal abundance, thus altering both food abundance and quality for grazers. In Lake Baikal, a large, ultra‐oligotrophic, remote lake in Siberia, filamentous algal abundance has increased near lakeside developments, and localized sewage input is the suspected cause. These shifts are of particular interest in Lake Baikal, where endemic littoral biodiversity is high, lakeside settlements are mostly small, tourism is relatively high (~1.2 million visitors annually), and settlements are separated by large tracts of undisturbed shoreline, enabling investigation of heterogeneity and gradients of disturbance. We surveyed sites along 40 km of Baikal's southwestern shore for sewage indicators—pharmaceuticals and personal care products (PPCPs) and microplastics—as well as periphyton and macroinvertebrate abundance and indicators of food web structure (stable isotopes and fatty acids). Summed PPCP concentrations were spatially related to lakeside development. As predicted, lakeside development was associated with more filamentous algae and lower abundance of sewage‐sensitive mollusks. Periphyton and macroinvertebrate stable isotopes and essential fatty acids suggested that food web structure otherwise remained similar across sites; yet, the invariance of amphipod fatty acid composition, relative to periphyton, suggested that grazers adjust behavior or metabolism to compensate for different periphyton assemblages. Our results demonstrate that even low levels of human disturbance can result in spatial heterogeneity of nearshore ecological responses, with potential for changing trophic interactions that propagate through the food web.

ABSTRACTIntroductionPustular psoriasis (PP) is a rare subtype of psoriasis. Overall, the growing evidence – in particular for acute generalized PP (GPP) – supports that it is a separate entity with a specific pathogenetic pathway. Interleukin (IL)-17/T-helper 17 (Th17) axis involvement may play an important role in the pathophysiology of PP. Biologicals, often required to achieve clinical remission, have changed the treatment of PP.Areas coveredWe provide the reader with an overview of all the available evidence on the use of the antibody-based therapy targeting IL-17A in patients with PP.Expert opinionAlthough papers reported in this review do not provide definitive evidence (due to methodological limitations) to support the use of IL-17 inhibitors as potential first-line for the treatment of PP, based on our own experience and according to most of the reported literature, targeting IL-17A, may represent the best therapeutical approach in this peculiar clinical spectrum of psoriasis.