Recent Advances in Photoinduced Modification of Amino Acids, Peptides, and Proteins.

The chemical modification of biopolymers like peptides and proteins is a key technology to access vaccines and pharmaceuticals. Similarly, the tunable derivatization of individual amino acids is important as they are key building blocks of biomolecules, bioactive natural products, synthetic polymers, and innovative materials. The high diversity of functional groups present in amino acid-based molecules represents a significant challenge for their selective derivatization Recently, visible light-mediated transformations have emerged as a powerful strategy for achieving chemoselective biomolecule modification. This technique offers numerous advantages over other methods, including a higher selectivity, mild reaction conditions and high functional-group tolerance. This review provides an overview of the most recent methods covering the photoinduced modification for single amino acids and site-selective functionalization in peptides and proteins under mild and even biocompatible conditions. Future challenges and perspectives are discussed beyond the diverse types of photocatalytic transformations that are currently available.

Disentangling the Role of the SnO Layer on the Pyro-Phototronic Effect in ZnO-Based Self-Powered Photodetectors.

Self-powered photodetectors (PDs) have been recognized as one of the developing trends of next-generation optoelectronic devices. Herein, it is shown that by introducing a thin layer of SnO film between the Si substrate and the ZnO film, the self-powered photodetector Al/Si/SnO/ZnO/ITO exhibits a stable and uniform violet sensing ability with high photoresponsivity and fast response. The SnO layer introduces a built-in electrostatic field to highly enhance the photocurrent by over 1000%. By analyzing energy diagrams of the p-n junction, the underlying physical mechanism of the self-powered violet PDs is carefully illustrated. A high photo-responsivity (R) of 93 mA W-1 accompanied by a detectivity (D*) of 3.1 × 1010 Jones are observed under self-driven conditions, when the device is exposed to 405 nm excitation laser wavelength, with a laser power density of 36 mW cm-2 and at a chopper frequency of 400 Hz. The Si/SnO/ZnO/ITO device shows an enhancement of 3067% in responsivity when compared to the Al/Si/ZnO/ITO. The photodetector holds an ultra-fast response of ≈ 2 µs, which is among the best self-powered photodetectors reported in the literature based on ZnO.

Divergent Functionalization of Styrenes via Radical/Polar Crossover with CO2 and Sodium Sulfinates.

Sulfones and carboxylic acids are prominent motifs widely present in the chemical structure of agrochemicals, pharmaceuticals and many other highly valuable compounds. Herein, we describe a conjunctive strategy for the precise installation of these functionalities onto styrenes using sodium sulfinates and CO2 as coupling partners. The protocol allowed the preparation of carboxy-sulfonylated compounds in good yields and broad functional group tolerance. Additionally, taking advantage of the leaving group ability of the sulfone moiety, a one-pot photocatalytic carboxy-sulfonylation-elimination strategy was developed for the synthesis of α-aryl-acrylates.

Physics-informed machine learning and its structural integrity applications: state of the art.

The development of machine learning (ML) provides a promising solution to guarantee the structural integrity of critical components during service period. However, considering the lack of respect for the underlying physical laws, the data hungry nature and poor extrapolation performance, the further application of pure data-driven methods in structural integrity is challenged. An emerging ML paradigm, physics-informed machine learning (PIML), attempts to overcome these limitations by embedding physical information into ML models. This paper discusses different ways of embedding physical information into ML and reviews the developments of PIML in structural integrity including failure mechanism modelling and prognostic and health management (PHM). The exploration of the application of PIML to structural integrity demonstrates the potential of PIML for improving consistency with prior knowledge, extrapolation performance, prediction accuracy, interpretability and computational efficiency and reducing dependence on training data. The analysis and findings of this work outline the limitations at this stage and provide some potential research direction of PIML to develop advanced PIML for ensuring structural integrity of engineering systems/facilities. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

Photodynamic Therapy for Colorectal Cancer: An Update and a Look to the Future.

This review provides an update on the current state of photodynamic therapy (PDT) for colorectal cancer (CRC) and explores potential future directions in this field. PDT has emerged as a promising minimally invasive treatment modality that utilizes photosensitizers and specific light wavelengths to induce cell death in targeted tumor tissues. In recent years, significant progress has been made in understanding the underlying mechanisms, optimizing treatment protocols, and improving the efficacy of PDT for CRC. This article highlights key advancements in PDT techniques, including novel photosensitizers, light sources, and delivery methods. Furthermore, it discusses ongoing research efforts and potential future directions, such as combination therapies and nanotechnology-based approaches. By elucidating the current landscape and providing insights into future directions, this review aims to guide researchers and clinicians in harnessing the full potential of PDT for the effective management of CRC.

Zero-mode waveguides visualize the first steps during gelsolin-mediated actin filament formation.

Actin filament dynamics underlie key cellular processes. Although the elongation of actin filaments has been extensively studied, the mechanism of nucleation remains unclear. The micromolar concentrations needed for filament formation have prevented direct observation of nucleation dynamics on the single molecule level. To overcome this limitation, we have used the attoliter excitation volume of zero-mode waveguides to directly monitor the early steps of filament assembly. Immobilizing single gelsolin molecules as a nucleator at the bottom of the zero-mode waveguide, we could visualize the actin filament nucleation process. The process is surprisingly dynamic, and two distinct populations during gelsolin-mediated nucleation are observed. The two populations are defined by the stability of the actin dimers and determine whether elongation occurs. Furthermore, by using an inhibitor to block flattening, a conformational change in actin associated with filament formation, elongation was prevented. These observations indicate that a conformational transition and pathway competition determine the nucleation of gelsolin-mediated actin filament formation.

Flexible Neural Probe Fabrication Enhanced with a Low-Temperature Cured Polyimide and Platinum Electrodeposition.

Polyimide is an emerging and very interesting material for substrate and passivation of neural probes. However, the standard curing temperature of polyimide (350 °C) is critical for the microelectrodes and contact pads of the neural probe, due to the thermal oxidation of the metals during the passivation process of the neural probe. Here, the fabrication process of a flexible neural probe, enhanced with a photosensitive and low-temperature cured polyimide, is presented. Annealing tests were performed with metallic films deposited on polyimide, which led to the reduction of the curing temperature to 250 °C, with no significant irregularities in the metallic sample annealed at that temperature and an effective polyimide curing. The use of a lower curing temperature reduces the thermal oxidation of the metals during the polyimide curing process to passivate the neural probe. Additionally, in this fabrication process, the microelectrodes of the neural probe were coated with electrodeposited platinum (Pt), only after the passivation process, and its electrochemical performance was accessed. At 1 kHz, the impedance of the microelectrodes before Pt electrodeposition was approximately 1.2 MΩ, and after Pt electrodeposition, it was approximately 350 kΩ. Pt electrodeposition changed the equivalent circuit of the microelectrodes and reduced their impedance, which will be crucial for future in-vivo tests to acquire the electrical activity of the neurons with the fabricated neural probe.

Association between Duddingtonia flagrans, dimethylsulfoxide and ivermectin for the control of Rhabditis spp. in cattle.

Cattle parasitic otitis caused by the nematode Rhabditis spp. is a serious health problem in Brazil, a situation which is confounded by lack of effective control measures. In vitro studies associating biological and chemical control as an alternative method showed promising results. The objective was to evaluate the combined use of Duddingtonia flagrans (AC001), 10% dimethylsulfoxide (DMSO), and 1.9% ivermectin for the in vivo control of Rhabditis spp., in naturally infected Gyr cattle. For this purpose, 48 animals, whose infection in both ears was diagnosed, were randomly assigned to 6 groups: group 1 (ivermectin 1.9%); group 2 (10% DMSO); group 3 (AC001); group 4 (ivermectin 1.9% + 10% DMSO w/v); group 5 (1.9% ivermectin + AC001 w/v); group 6 (10% DMSO + AC001 v/v). The treatments were performed in a single dose, in the right ears, with the left ears remaining untreated, as a control group. There was a significant reduction (p < 0.01) in the number of nematodes in the treated groups in relation to the control, with the following best efficacies: groups 1 and 2, 47% and 52.9%, respectively, 7 days after treatment; groups 3, 4, and 5, 47.8%, 48.6% and 36.7%, respectively, 14 days post-treatment; group 6, 38.4%, 21 days post-treatment. It was concluded that the combination of chemical compounds and D. flagrans in a single application was effective for the in vivo control of Rhabditis spp. in naturally infected cattle.

Photocatalyzed Intramolecular [2+2] Cycloaddition of N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides.

N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides are converted into natural product inspired scaffolds via iridium photocatalyzed intramolecular [2+2] photocycloaddition. The protocol has a broad substrate scope, whilst operating under mild reaction conditions. Tethering four components forming a trisubstituted cyclobutane core builds rapidly high molecular complexity. Our approach allows the design and synthesis of a variety of tetrahydrocyclobuta[c]quinolin-3(1H)-ones, in yields ranging between 20-99 %, and with excellent regio- and diastereoselectivity. Moreover, it was demonstrated that the intramolecular [2+2]-cycloaddition of 1,7-enynes-after fragmentation of the cyclobutane ring-leads to enyne-metathesis-like products.

Recent Advances on Photoinduced Cascade Strategies for the Synthesis of N-Heterocycles.

Over the last decade, visible-light photocatalysis has proved to be a powerful tool for the construction of N-heterocyclic frameworks, important constituents of natural products, insecticides, pharmacologically relevant therapeutic agents and catalysts. This account highlights recent developments and established methods towards the photocatalytic cascades for preparation of different classes of N-heterocycles, giving emphasis on our contribution to the field.

Oromandibular Limb Hypogenesis Syndrome: Overlap of Moebius and Ankyloglossia Superior With Severe Limb Defects.

The oromandibular limb hypogenesis syndromes (OLHS) represent a group of rare conditions characterized by congenital malformations involving the tongue, mandible, and limbs. In this report, we describe a newborn girl with paralysis of abducens and facial nerves, transverse agenesis of the distal segments of the limbs, micrognathia, cleft lip and palate, and ankyloglossia superior. This observation confirms an overlap between Moebius syndrome and ankyloglossia superior syndrome with severe limb defects. The etiology of the OLHS is not clearly understood. The intriguing link between facial and limb anomalies can result from their simultaneous development from the fourth to eighth week of gestation, making both areas susceptible to the same teratogenic stimuli. There is an overlap between OLHS conditions, supporting a clustering, rather than a divided nosology and requiring an appropriate classification of these conditions. Patients with OLHS can be successfully managed using a multidisciplinary approach.

Design, synthesis and cytotoxicity of the antitumor agent 1-azabicycles for chemoresistant glioblastoma cells.

Twelve multi-functional pyrrolizidinones, indolizidinones and pyrroliazepinones were prepared from formal aza-[3 + 2] and aza-[3 + 3] cycloadditions of five- to seven-membered heterocyclic enaminones as diverse ambident electrophiles. The antitumor activity of these alkaloid-like compounds was investigated through an initial screening performed on human glioblastoma multiform (GBM) cell lines (GL-15, U251), on murine glioma cells line (C6) and on normal glial cells. Of the compounds tested, the new pyrrolo[1,2a]azepinone, [ethyl (3-oxo-1,2-diphenyl-6,7,8,9-tetrahydro-3H-pyrrolo[1,2a]azepin-9a(5H)-yl)acetate] or (Compound-13) exhibited selective cytotoxic effects on GBM-temozolomide resistant cells. Compound-13 exerted dose-dependent cytotoxic activity by promoting arrest of cells in the G0/G1 phase of the cell cycle in the first 24 h. The apoptotic effect observed was in a time-dependent manner. Anti-migratory effect promoted by the treatment with compound-13 was also observed. Moreover, healthy mixed glial cell cultures from rat brain exhibited no cytotoxicity effect upon exposure to compound-13. Thus, the present study paves the way for the use of compound-13 as novel antitumor scaffold candidate for glioma cell therapy.

Metal-Free Photoinduced Hydroalkylation Cascade Enabled by an Electron-Donor-Acceptor Complex.

A metal- and photocatalyst-free photoinduced radical cascade hydroalkylation of 1,7-enynes has been disclosed. The process is triggered by a single electron transfer (SET) event involving a photoexcited electron-donor-acceptor complex between an NHPI ester and a Hantzsch ester, which decomposes to afford a tertiary radical that is readily trapped by the enyne. The method provides an operationally simple, robust, and step-economical approach toward the construction of diversely functionalized dihydroquinolinones bearing quaternary centers. A sequential one-pot hydroalkylation-isomerization approach is also offered, giving access to a family of quinolinones. A wide substrate scope and high functional group tolerance were observed in both approaches.

Brønsted-acid-catalyzed selective Friedel-Crafts monoalkylation of isatins with indolizines in water.

The controlled mono-addition of indolizines to isatins under very mild conditions is described. The reaction occurs in water using diphenylphosphate as the catalyst, which is dramatically accelerated by surfactant addition. 3-Hydroxy-3-indolizinyl-2-oxindole scaffolds were synthesized in up to >99% yield. Notably, in organic solvents only bis-addition products were observed.

BioChaperone Lispro versus faster aspart and insulin aspart in patients with type 1 diabetes using continuous subcutaneous insulin infusion: A randomized euglycemic clamp study.

We investigated the pharmacodynamics (PD) and pharmacokinetics (PK) of BioChaperone insulin Lispro (BCLIS), faster insulin aspart (FIA) and insulin aspart (ASP) in patients with type 1 diabetes using an insulin pump. In this randomized, double-blind, three-way crossover glucose clamp study, 43 patients received a bolus dose of each insulin (0.15 U/kg) in addition to a basal rate (0.01 U/kg/h), delivered via an insulin pump. With BCLIS, the AUC-GIR,0-60 minutes (primary endpoint) was improved compared to ASP (least square means ratio, 1.63; 95% CI, 1.44-1.88; P < 0.0001) and was similar compared to FIA (least square means ratio, 1.06; 95% CI, 0.94-1.18; P = 0.4609). BCLIS showed faster-on PD (tearly0.5GIRmax ) than ASP and faster-off PD (tlate0.5GIRmax ) than both FIA and ASP. BCLIS also demonstrated significantly higher early exposure (AUCins, 0-60 minutes) and lower late exposure (AUCins,120-600 minutes) than both other insulins. In patients with type 1 diabetes using an insulin pump, BCLIS better mimics prandial insulin secretion and action than ASP and shows a faster off-PD than FIA.

Transient elastography: should XL probe be used in all overweight patients?

Background: Obesity is one of the main factors of transient elastography (TE) failure, considering body mass index (BMI) ≥28 kg/m2 as a limiting factor. The XL probe was designed to overcome this limitation. Aim: To compare the feasibility of the M and XL probes in patients with BMI ≥ 28 kg/m2, to evaluate differences in mean values of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) between the two probes and find predictive factors of TE failure. Material and methods: Prospective study, including all patients with BMI ≥ 28 kg/m2 consecutively admitted for TE. Results: Included 161 patients. Measurements with M probe were reliable in 69.6% of the patients, with 68.2% of valid measurements in obese population and 58.9% in patients with skin-capsule distance (SCD) >25 mm. In 40 patients (81.6%) with an invalid M probe measurement, a reliable result was obtained with XL probe. We found that SCD >25 mm was the only predictor of M probe failure (OR: 4.9, CI: 1.64-14.63, p = .004). In those patients in which TE was possible with both probes (n = 112), mean CAP was 304 ± 49 dB/m2 with M probe and 301 ± 50 dB/m2 with XL probe (p = .59). Regarding liver stiffness, a mean value of 7.58 ± 3.47 kpas was obtained with the M probe and 6.21 ± 3.44 kpas with the XL probe (p < .001). Conclusion: There is a reliable applicability of the M probe in a high number (68.2%) of patients with a BMI ≥30 kg/m2. A SCD >25 mm was the only predictive factor of M probe failure. Mean values of LSM with XL probe were lower than those obtained with M probe.

PDMS Microlenses for Focusing Light in Narrow Band Imaging Diagnostics.

Minimally invasive medical devices can greatly benefit from Narrow Band Imaging (NBI) diagnostic capabilities, as different wavelengths allow penetration of distinct layers of the gastrointestinal tract mucosa, improving diagnostic accuracy and targeting different pathologies. An important performance parameter is the light intensity at a given power consumption of the medical device. A method to increase the illumination intensity in the NBI diagnostic technique was developed and applied to minimally invasive medical devices (e.g., endoscopic capsules), without increasing the size and power consumption of such instruments. Endoscopic capsules are generally equipped with light-emitting diodes (LEDs) operating in the RGB (red, green, and blue) visible light spectrum. A polydimethylsiloxane (PDMS) µ-lens was designed for a maximum light intensity at the target area of interest when placed on top of the LEDs. The PDMS µ-lens was fabricated using a low-cost hanging droplet method. Experiments reveal an increased illumination intensity by a factor of 1.21 for both the blue and green LEDs and 1.18 for the red LED. These promising results can increase the resolution of NBI in endoscopic capsules, which can contribute to early gastric lesions diagnosis.

Environmental and economic advantages of adopting reverse logistics for recycling construction and demolition waste: A case study of Brazilian construction and recycling companies.

The aim of this study was to assess the economic and environmental advantages of implementing reverse logistics to recycle solid waste from construction companies. The adopted research method was based on a systematic literature review and two case studies. For the economic assessment, the return on investment, the internal rate of return, and the discounted payback factors were considered, while the material intensity factor was used for the environmental impact assessment. This study shows that there are economic and environmental advantages associated with the use of reverse logistics for solid waste treatment and recycling. In 2016, the purchase of recycled blocks resulted in a profit of over US$45,000 for one company, and another company earned almost US$250,000 in the same year by recycling solid waste from manufacturing blocks and selling iron, wood, paper, and plastics. Furthermore, the environmental impact was reduced. This paper contributes to the dissemination of knowledge regarding the advantages of adopting reverse logistics for recycling construction and demolition waste, and creates new opportunities for companies.

Catalytic Asymmetric Conjugate Addition of Indolizines to α,ß-Unsaturated Ketones.

A catalytic enantioselective conjugate addition of indolizines to enones is described. The chiral phosphoric acid (S)-TRIP activates α,ß-unsaturated ketones, thereby promoting an enantioface-differentiating attack by indolizines. Using this reaction, several alkylated indolizines were synthesized in good yields and with enantiomeric ratios of up to 98:2.

Efficacy of medical grade honey in the management of canine otitis externa - a pilot study.

BACKGROUND: The high prevalence of antimicrobial resistance within otic pathogens has created a need for alternative therapies of otitis externa (OE). Evidence suggests that medical grade honey (MGH) may be effective against drug-resistant pathogens. HYPOTHESIS/OBJECTIVES: The efficacy of a commercial MGH compound was assessed in an open clinical trial. We hypothesized that it would be an effective alternative to conventional treatments. ANIMALS: Client-owned dogs (n = 15) with a confirmed diagnosis of infectious OE were enrolled in this pilot study. METHODS: Dogs were prescribed MGH (1 mL daily per ear) until cure was achieved or for a maximum of 21 d. Evaluation was based on weekly clinical scores, cytological progression and owner assessments of pruritus. Swab samples were submitted for culture and susceptibility testing. MGH was tested for biocidal activity against the bacterial isolates. RESULTS: Medical grade honey promoted rapid clinical progress, with 70% of dogs achieving clinical cure between days 7 and 14 and over 90% having resolved by Day 21. There was a decrease in clinical scores throughout the duration of the trial (P < 0.001) and owner-assessed pruritus also decreased significantly (P < 0.05). In vitro assays of the biocidal activity of MGH showed activity against all bacterial isolates, including meticillin-resistant strains of Staphylococcus pseudintermedius (MRSP) and other species of drug-resistant bacteria. CONCLUSION AND CLINICAL IMPORTANCE: Medical grade honey was successful in both clinical and laboratory settings, thus demonstrating its potential of becoming an alternative treatment for canine OE.