In proteomics, fast, efficient and highly reproducible sample preparation is of utmost importance, particularly in view of fast scanning mass spectrometers enabling analyses of large sample series. To address this need, we have developed the web application MassSpecPreppy that operates on the open science OT-2 liquid handling robot from Opentrons. This platform can prepare up to 96 samples at once, performing tasks like BCA protein concentration determination, sample digestion with normalization, reduction/alkylation and peptide elution into vials or loading specified peptide amounts onto Evotips in an automated and flexible manner. The performance of the developed workflows using MassSpecPreppy was compared with standard manual sample preparation workflows. The BCA assay experiments revealed an average recovery of 101.3% (SD: ±7.82%) for the MassSpecPreppy workflow, while the manual workflow had a recovery of 96.3% (SD: ±9.73%). The species mix used in the evaluation experiments showed that 94.5% of protein groups for OT-2 digestion and 95% for manual digestion passed the significance thresholds with comparable peptide level coefficient of variations. These results demonstrate that MassSpecPreppy is a versatile and scalable platform for automated sample preparation, producing injection-ready samples for proteomics research.
Pathogenic variants in the Surfactant Protein C gene ( SFTPC) result in fibrotic childhood interstitial lung disease (chILD). We previously reported three children with SFTPC pathogenic variants with respiratory failure who were supported by chronic invasive ventilation via tracheostomy as an alternative to lung transplantation or comfort care [(1)](#ref-0001). We present two children with SFTPC pathogenic variants treated with non-invasive ventilation (NIV) (Figure 1).
Rearrangements of the KMT2A gene are characteristic of infantile acute lymphoblastic leukemia (ALL) and are associated with increased lineage plasticity and resistance to therapy. Here, we describe the case of a 9-month-old infant with infantile ALL who experienced multiple immunophenotypic switches in her leukemia throughout therapy and ultimately achieved remission with the combination of CPX-351 and Inotuzumab. This case highlights the unique clinical challenges infantile ALL poses on monitoring therapeutic response with current methods of measuring minimal residual disease as well as the challenges in treating infantile B-ALL.
Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis (HLH), is a group of syndromes in which multiple pathogenic factors lead to the proliferation of activated lymphocytes and histiocytes that secrete large amounts of inflammatory cytokines[](#ref-0001).HLH is a multi-organ hyperinflammatory syndrome caused by the secretion of large amounts of inflammatory cytokines from
SnO2, with its high theoretical capacity, abundant resources, and environmental friendliness, is widely regarded as a potential anode material for lithium-ion batteries (LIBs). Nevertheless, the coarsening of the Sn nanoparticles impedes the reconversion back to SnO2, resulting in low coulombic efficiency and rapid capacity decay. In this study, we fabricated a heterostructure by combining SnO2 nanoparticles with MoS2 nanosheets via plasma-assisted milling. The heterostructure consists of in-situ exfoliated MoS2 nanosheets predominantly in 1T phase, which tightly encase the SnO2 nanoparticles through strong bonding. This configuration effectively mitigates the volume change and particle aggregation upon cycling. Moreover, the strong affinity of Mo, which is the lithiation product of MoS2, toward Sn plays a pivotal role in inhibiting the coarsening of Sn nanograins, thus enhancing the reversibility of Sn to SnO2 upon cycling. Consequently, the SnO2/MoS2 heterostructure exhibits superb performance as an anode material for LIBs, demonstrating high capacity, rapid rate capability, and extended lifespan. Specifically, discharged/charged at a rate of 0.2 A g-1 for 300 cycles, it achieves a remarkable reversible capacity of 1173.4 mAh g-1. Even cycled at high rates of 1.0 and 5.0 A g-1 for 800 cycles, it still retains high reversible capacities of 1005.3 and 768.8 mAh g-1, respectively. Moreover, the heterostructure exhibits outstanding electrochemical performance in both full LIBs and sodium-ion batteries.
The development of self-charging supercapacitor power cells (SCSPCs) has profound implications for smart electronic devices used in different fields. Here, we epitaxially electrodeposited Mo- and Fe-codoped MnO2 films on piezoelectric ZnO nanoarrays (NAs) grown on the flexible carbon cloth (denoted ZnO@Mo-Fe-MnO2 NAs). An SCSPC device was assembled with the ZnO@Mo-Fe-MnO2 NA electrode and poly(vinylidenefluoride-co-trifluoroethylene) (PVDF-Trfe) piezoelectric film doped with BaTiO3 (BTO) and carbon nanotubes (CNTs) (denoted PVDF-Trfe/CNTs/BTO). The SCSPC device exhibited an energy density of 30 μWh cm-2 with a high-power density of 40 mW cm-2, and delivered an excellent self-charging performance of 363 mV (10 N) driven by both the piezoelectric ZnO NAs and the PVDF-Trfe/CNTs/BTO films. More intriguingly, the device also could also be self-charged by 184 mV due to residual stress alone, and showed excellent energy conversion efficiency and low self-discharge rate. This work illustrates for the first time the self-charging mechanism involving electrolyte ion migration driven by both electrodes and films. A comprehensive analysis strongly confirmed the important contribution of the piezoelectric ZnO NAs in the self-charging process of the SCSPC device. This work provides novel directions and insights for the development of SCSPCs.
The emergence of polymerized small molecule acceptors (PSMAs) has significantly improved the performance of all-polymer solar cells (all-PSCs). However, the pace of device engineering lacks behind that of materials development, so that a majority of the PSMAs have not fulfilled their potentials. Furthermore, most high-performance all-PSCs rely on the use of chloroform as the processing solvent. For instance, the recent high-performance PSMA named PJ1-γ, with high LUMO and HOMO levels, could only achieve a PCE of 16.1% with a high-energy-level donor (JD40) using chloroform. Herein, we present a methodology combining sequential processing (SqP) with the addition of 0.5%wt PC71BM as a solid additive (SA) to achieve an impressive efficiency of 18.0% for all-PSCs processed from toluene, an aromatic hydrocarbon solvent. Compared to the conventional blend-casting (BC) method whose best efficiency (16.7%) could only be achieved using chloroform, the SqP method significantly boosted the device efficiency using toluene as the processing solvent. In addition, the donor we employ is the classic PM6 that has deeper energy levels than JD40, which provides low energy loss for the device. We compare the results with another PSMA (PYF-T-o) with the same method. Finally, an improved photostability of the SqP devices with the incorporation of SA is demonstrated.
Climate suitability analyses based on ecological niche modeling provide a powerful tool for biological control practitioners to assess the likelihood of establishment of different candidate agents prior to their introduction in the field. These same analyses could also be performed to understand why some agents establish more easily than others. The release of three strains of Aphalara itadori (Shinji) (Hemiptera: Pysllidae), each from a different source locality in Japan, for the biological control of invasive knotweed species, Reynoutria spp. Houtt. (Caryophyllales: Polygonaceae), provides an important opportunity to compare the utility of climate suitability analyses for identifying potential climate-based limitations for successful biological control introductions. Here we predict climate suitability envelopes for three target species of knotweed in Europe and two target species of knotweed in North America and compare these suitability estimates for each of these species to the source localities of each A. itadori strain. We find that source locality of one strain, the Kyushu strain, has little-to-no suitability compared to other locations in Japan based on knotweed records from Europe, supporting an earlier study based on North American Japanese knotweed records. The source locality of a second strain, the Murakami strain, was predicted to have medium-to-high suitability based on records of knotweeds from North America. In contrast, European records of R. bohemica Chrtek & Chrtková and R. sachalinensis (F. Schmidt) Nakai predicted no suitability for this locality compared to other locations in Japan, while European records for R. japonica Houtt. predicted low suitability. The source locality of the final strain, the Hokkaido strain, was predicted as having medium-to-high suitability based on knotweed records of all examined species from both North America and Europe.
ChatGPT Generated Literature Review: Quod Erat Demonstrandum or Ends Justifying the Means?Dear Editor,We would like to draw your attention to the increasing popularity of the generative artificial intelligence (AI) chatbot, ChatGPT (OpenAI, 2023), and its relationship with scientific literature. We have attempted to replicate two literature reviews recently published in Clinical Otolaryngology using ChatGPT, comparing results, conclusions and references.Lee et al. (2022): Posterior nasal neurectomy for intractable rhinitis: A systematic review, was assessed. ChatGPT’s conclusions generated with the same research questions were comparable. However, ChatGPT’s references were confabulated raising questions of provenance and quality.Cereceda-Monteoliva et al. (2021), reviewed sarcoidosis of the ear, nose, and throat. Again, identical research questions generated near-identical results, including numerical values for incidence, features, and management. One generated reference appeared to be ‘similar’ in terms of the author’s name, but the title and journal were entirely incorrect. Of the remaining four references provided by ChatGPT, only one was a recognisable article. Further investigation shows ChatGPT lacks access to research databases, raising doubts about the reliability of the conclusions it presents.It is interesting that ChatGPT should generate correct conclusions but with incorrect working. We are reminded of school mathematics,quad erat demonstrandum (Q.E.D.), and where incorrect working affords you no marks regardless of a correct answer.ChatGPT is a Large Language Model (LLM) AI. Fundamentally, it mimics human intelligence but does not replicate it. ChatGPT does this by analysing vast quantities of data to predict the next most likely word in an answer – erroneously exemplified by the generated references. A scientific literature review follows a superficially similar process, analysing data and outputting a most likely conclusion. Crucially, the latter involves higher-order evaluation and critical thought based on myriad factors that seem currently out of reach for ChatGPT in this specific use case. Readers familiar with Bloom’s Taxonomy of Cognition will identify its relevance here.Often literature review produces an already anticipated conclusion but provides some of the highest quality evidence to base medical practice. Therefore, with ChatGPT, the ends do not justify the means for practiced medicine, even if the most likely worded conclusion is accurate.However, the exponential growth of LLM AIs is extraordinary. Near-future iterations of ChatGPT climbing to the top of Bloom’s Taxonomy are easily imagined. Improved critical reasoning with access to accurate databases of peer-reviewed material would substantiate an output, even if the conclusions are unchanged. An accurate ‘show of working’ could provide a meaningful AI-generated literature review to responsibly guide medical practice.Q.E.D. - Quod Erat DemonstrandumReferencesBloom, B.S.,Engelhart, M. D., Furst, E. J., Hill, W. H., & Krathwohl, D. R. (1956). Taxonomy of educational objectives: The classification of educational goals. Handbook I: Cognitive domain. New York: David McKay Company.Cereceda-Monteoliva, N., Rouhani, M. J., Maughan, E. F., Rotman, A., Orban, N. T., Yaghchi, C. A., & Sandhu, G. S. (2021b). Sarcoidosis of the ear, nose and throat: A review of the literature. Clinical Otolaryngology , 46 (5), 935–940.https://doi.org/10.1111/coa.13814Lee, M. L., Chakravarty, P., & Ellul, D. (2022). Posterior nasal neurectomy for intractable rhinitis: A systematic review of the literature. Clinical Otolaryngology , 48 (2), 95–107.https://doi.org/10.1111/coa.13991OpenAI. (2023). OpenAI. Retrieved from https://openai.com/
Background: Aberrant migration of parathyroid glands from their embryologic origin may result in undescended parathyroid glands. We present a case of an ectopic parathyroid adenoma at the level of the pyriform sinus. Methods: A 41-year-old female was evaluated for primary hyperparathyroidism. Following non-localizing ultrasound and planar sestamibi imaging, the patient underwent
Carbon monoxide (CO) has become one of the most relevant and versatile renewable C1 building blocks for chemical synthesis, especially in the fine chemicals industry, due to the development of efficient and selective catalysts for its activation. In this review, we present a comprehensive critical analysis of the last 10 years literature on the use of CO as a renewable feedstock for fine chemicals production. The review is organized by type of catalytic reaction, namely alkene and alkyne carbonylation, hydroformylation, carbonylation of aryl halides, carbonylative cross-coupling and C–H carbonylation. Notable examples of the synthesis of relevant building blocks and/or known pharmaceuticals are highlighted. Emphasis is placed on examples of utilizing CO as the C1 building block in one or more catalytic steps. The catalyst used and the reaction conditions are consistently presented throughout all of the examples.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 glycoproteins differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink ( Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 glycoproteins. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 glycoprotein is bound to the receptor-binding domain (RBD) of the S glycoprotein in a “down” position, approximately 34° lower than previously reported “up” RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry.
Introduction: The risk of relapse in retinoblastoma is currently determined by the presence of high-risk histopathologic factors in the enucleated eye. However, the probability of developing metastatic disease is heterogeneous among these patients. Evaluating a biological marker to identify high-risk patients could be useful in clinical setting. This study aims to evaluate whether the expression of TFF1, a surrogate for subtype 2 retinoblastoma, is a prognostic marker for relapse and death. Methods: This multicenter cohort study included 273 patients, 48 of whom had extraocular disease. Immunohistochemical staining were performed for CRX, ARR3, TFF1 and Ki67. Tumors were classified as histological subtype 1 (HS1) if they had low or no expression of TFF1 (quick score (QS) ≤ 50) and as histological subtype 2 (HS2) if they expressed TFF1 diffusely (QS > 50). We studied the association between HS classification and outcome. Results: Of 273 patients, 35.9% were classified as HS1, 59.3% as HS2 and 4.8% were not evaluable. In multivariate analysis, patients with HS2 tumors had a higher probability of relapse and death than those with HS1 ( P < 0.0001 and P = 0.00020, respectively). We identified a higher-risk subgroup among HS2 tumors, presenting non-mutually exclusive expression of ARR3 and TFF1 and had an increased risk of relapse and death compared to tumors that displayed mutually exclusive expression ( P = 0.012 and P = 0.027, respectively). Conclusions: Expression of TFF1, especially when it is not-mutually exclusive with ARR3, is an independent prognostic marker of poor outcome in retinoblastoma.
Long-wavelength fluorescence of carbon dots (CDs) show the great importance in multiple fields, especially for the biochemical sensing. Here we proposed one type of CDs doped with nitrogen and sulfur through the hydrothermal method, which exhibited the obvious yel-low-fluorescence in aqueous. Importantly, their fluorescence intensity of CDs decreased with pH decreasing in the acidic range, thus a linear relationship between pH and fluorescence intensity was established, and exhibiting the potential of pH sensing. Additionally, in-troducing tigecycline into CDs resulted in their decreased fluorescence, thus we further established a strategy of detecting tigecycline with the concentration range of 200 μM to 7 nM. Meanwhile, we elucidated the static quenching as the major mechanism for CDs responding tigecycline, which was induced by the formed new complex between CDs and tigecycline. Furthermore, the practicality of the method was verified by examining the recovery of tigecycline in the actual lake-water samples.
The efficacy of nanoparticle (NP)-based drug delivery technology is hampered by aberrant tumor stromal microenvironments (TSMs) that hinder NP transportation. Therefore, the promotion of NP permeation into deep tumor sites via the regulation of tumor microenvironments is of critical importance. Herein, we propose a potential solution using a dihydrazidine (HDZ)-loaded nanoparticle drug delivery system containing a pH-responsive, cyclic RGD peptide-modified prodrug based on doxorubicin (cRGD-Dex-DOX). With a combined experimental and theoretical approach, we find that the designed NP system can recognize the acid tumor environments and precisely release the encapsulated HDZ into tumor tissues. HDZ can notably downregulate the expression levels of hypoxia-inducible factor 1α (HIF1α), α-smooth muscle actin, and fibronectin through the dilation of tumor blood vessels. These changes in the TSMs enhance the enrichment and penetration of NPs and also unexpectedly promote the infiltration of activated T cells into tumors, suggesting that such a system may offer an effective “multifunctional therapy” through both improving the chemotherapeutic effect and enhancing the immune response to tumors. In vivo experiments on 4T1 breast cancer bearing mice indeed validate that this therapy has the most outstanding antitumor effects over all the other tested control regimens, with the lowest side effects as well.
：Explore the digital rendering mode with texturing brush and ink effect, analyze and simulate the brush and ink characteristics of traditional Chinese ink painting, especially the art of landscape painting, and try to integrate the texture of wrinkle method synthesis map and modeling technology based on particle deposition and stacking (overlapping) to render, thus realizing the computer simulation of small freehand brushwork and large freehand brushwork (splash ink) ink effects in traditional landscape painting. This research inherits and develops the aesthetic theory and thought of traditional ink painting art, and makes some beneficial exploration in the field of digital freehand ink painting, which has positive reference value and promotion significance for the development of Chinese ink painting.