Versatile Deep Learning Pipeline for Transferable Chemical Data Extraction.

Chemical information disseminated in scientific documents offers an untapped potential for deep learning-assisted insights and breakthroughs. Automated extraction efforts have shifted from resource-intensive manual extraction toward applying machine learning methods to streamline chemical data extraction. While current extraction models and pipelines have ushered in notable efficiency improvements, they often exhibit modest performance, compromising the accuracy of predictive models trained on extracted data. Further, current chemical pipelines lack both transferability─where a model trained on one task can be adapted to another relevant task with limited examples─and extensibility, which enables seamless adaptability for new extraction tasks. Addressing these gaps, we present ChemREL, a versatile chemical data extraction pipeline emphasizing performance, transferability, and extensibility. ChemREL utilizes a custom, diverse data set of chemical documents, labeled through an active learning strategy to extract two properties: normal melting point and lethal dose 50 (LD50). The normal melting point is selected for its prevalence in diverse contexts and wider literature, serving as the foundation for pipeline training. In contrast, LD50 evaluates the pipeline's transferability to an unrelated property, underscoring variance in its biological nature, toxicological context, and units, among other differences. With pretraining and fine-tuning, our pipeline outperforms existing methods and GPT-4, achieving F1-scores of 96.1% for entity identification and 97.0% for relation mapping, culminating in an overall F1-score of 95.4%. More importantly, ChemREL displays high transferability, effectively transitioning from melting point extraction to LD50 extraction with 10 randomly selected training documents. Released as an open-source package, ChemREL aims to broaden access to chemical data extraction, enabling the construction of expansive relational data sets that propel discovery.

An examination of the associations between nutritional peaking strategies in physique sport and competitor characteristics.

BACKGROUND: Physique athletes are subjectively judged on their on-stage esthetic per their competition division criteria. To succeed, competitors look to acutely enhance their appearance by manipulating nutritional variables in the days leading up to competition, commonly referred to as peak week (PW). Despite their documented wide adoption, PW strategies lack experimental evidence. Further, the relationship between the specific strategies and the characteristics of the competitors who implement them are unknown. The aim of this research was to examine the effect of competitor characteristics on the specific nutritional peaking strategies implemented, the length of these strategies, and the range of daily carbohydrate (CHO) intakes during these strategies. METHODS: A 58-item survey was developed to gather information on peak week nutrition and training practices of physique athletes. A total of 160 respondents above the age of 18 who had competed in the last 5 years completed the nutrition section. The topics analyzed for this paper included competitor demographics, peaking strategies utilized, and PW CHO intakes. Competitor demographics are presented with the use of descriptive statistics. Associations between competitor demographics and peaking strategies implemented, peaking strategy length, and daily CHO intake ranges were assessed using multiple logistic regression, multiple ordinal logistic regression, and linear mixed models, respectively. RESULTS: From the sampled population, ages 24-39 years (71.2%), male (68.8%), natural (65%), and amateur (90%) were the most common characteristics from their respective categories, while mean competition preparation length was 20.35 ± 8.03 weeks (Males: 19.77 ± 7.56 weeks, Females: 21.62 ± 8.93 weeks), competition preparation body mass loss was 11.5 ± 5.56 kg (M: 12.7 ± 5.76 kg, F: 7.16 ± 3.99 kg), and competition body mass was 72.09 ± 15.74 kg (M: 80.15 ± 11.33 kg, F: 54.34 ± 7.16 kg). For males, the highest and lowest daily CHO intake during PW were 489.63 ± 224.03 g (6.22 ± 2.93 g/kg body mass) and 148.64 ± 152.01 g (1.94 ± 2.17 g/kg), respectively, while for females these values were 266.73 ± 131.23 g (5.06 ± 2.67 g/kg) and 94.42 ± 80.72 g (1.81 ± 1.57 g/kg), respectively. CHO back loading (45%) and water loading (40.6%) were the most popular peaking strategies, while the most prevalent peaking strategy length was 7 days (27.2%). None of the competitor characteristics predicted the use of CHO-based peaking strategies nor peaking strategy length. For non-CHO-based strategies, drug-enhanced competitors were more likely to restrict water than non-drug enhanced, while males and professional competitors had greater odds of loading sodium than females and amateurs, respectively. Finally, when comparing the disparity in highest and lowest CHO intakes during peak week, sex was the only significant factor. CONCLUSIONS: The results of this survey provide further information on the nutritional peaking strategies implemented by competitors. Certain characteristics were identified as predictors of sodium loading and water restriction, and the range of daily PW CHO intake. Contrastingly, no associations were found for CHO-based peaking strategies or peaking strategy length. While our analyses may be underpowered, and thus results should be interpreted with caution, it appears the nutritional peaking strategies implemented by physique competitors are seemingly complex and highly individual.

Viral modulation of type II interferon increases T cell adhesion and virus spread.

During primary varicella zoster virus (VZV) infection, infected lymphocytes drive primary viremia, causing systemic dissemination throughout the host, including the skin. This results in cytokine expression, including interferons (IFNs), which partly limit infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. It is not clear how VZV achieves this while evading the cytokine response. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity, increasing the expression of a subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of keratinocytes facilitates lymphocyte function-associated antigen 1-dependent T cell adhesion and expression of gC during infection increases VZV spread to peripheral blood mononuclear cells. This constitutes the discovery of a strategy to modulate IFN-γ activity, upregulating a subset of ISGs, promoting enhanced lymphocyte adhesion and virus spread.

Promoting Photocatalytic Direct C-H Difluoromethylation of Heterocycles using Synergistic Dual-Active-Centered Covalent Organic Frameworks.

Difluoromethylation reactions are increasingly important for the creation of fluorine-containing heterocycles, which are core groups in a diverse range of biologically and pharmacologically active ingredients. Ideally, this typically challenging reaction could be performed photocatalytically under mild conditions. To achieve this separation of redox processes would be required for the efficient generation of difluoromethyl radicals and the reduction of oxygen. A covalent organic framework photocatalytic material was, therefore, designed with dual reactive centers. Here, anthracene was used as a reduction site and benzothiadiazole was used as an oxidation site, distributed in a tristyryl triazine framework. Efficient charge separation was ensured by the superior electron-donating and -accepting abilities of the dual centers, creating long-lived photogenerated electron-hole pairs. Photocatalytic difluoromethylation of 16 compounds with high yields and remarkable functional group tolerance was demonstrated; compounds included bioactive molecules such as xanthine and uracil. The structure-function relationship of the dual-active-center photocatalyst was investigated through electron spin resonance, femtosecond transient absorption spectroscopy, and density functional theory calculations.

Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes neurological disease in the peripheral and central nervous system (PNS and CNS, respectively) of some patients. It is not clear whether SARS-CoV-2 infection or the subsequent immune response are the key factors that cause neurological disease. Here, we addressed this question by infecting human induced pluripotent stem cell-derived CNS and PNS neurons with SARS-CoV-2. SARS-CoV-2 infected a low number of CNS neurons and did not elicit a robust innate immune response. On the contrary, SARS-CoV-2 infected a higher number of PNS neurons. This resulted in expression of interferon (IFN) λ1, several IFN-stimulated genes and proinflammatory cytokines. The PNS neurons also displayed alterations characteristic of neuronal damage, as increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein, and lower levels of cytoskeletal proteins. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neuronal damage, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. Our results provide a basis to study coronavirus disease 2019 (COVID-19) related neuronal pathology and to test future preventive or therapeutic strategies.

Triazine Frameworks for the Photocatalytic Selective Oxidation of Toluene.

Investigations into the selective oxidation of inert sp3 C-H bonds using polymer photocatalysts under mild conditions have been limited. Additionally, the structure-activity relationship of photocatalysts often remains insufficiently explored. Here, a series of thiophene-based covalent triazine frameworks (CTFs) are used for the efficient and selective oxidation of hydrocarbons to aldehydes or ketones under ambient aerobic conditions. Spectroscopic methods conducted in situ and density functional theory (DFT) calculations revealed that the sulfur atoms within the thiophene units play a pivotal role as oxidation sites due to the generation of photogenerated holes. The effect of photogenerated holes on photocatalytic toluene oxidation was investigated by varying the length of the spacer in a CTF donor-acceptor based photocatalyst. Furthermore, the manipulation of reactive oxygen species was employed to enhance selectivity by weakening the peroxidative capacity. As an illustrative example, this study successfully demonstrated the synthesis of a precursor of the neurological drug AMG-579 using a photocatalytic protocol.

Peak Week Carbohydrate Manipulation Practices in Physique Athletes: A Narrative Review.

BACKGROUND: Physique athletes are ranked by a panel of judges against the judging criteria of the corresponding division. To enhance on-stage presentation and performance, competitors in certain categories (i.e. bodybuilding and classic physique) achieve extreme muscle size and definition aided by implementing acute "peaking protocols" in the days before competition. Such practices can involve manipulating nutrition and training variables to increase intramuscular glycogen and water while minimising the thickness of the subcutaneous layer. Carbohydrate manipulation is a prevalent strategy utilised to plausibly induce muscle glycogen supercompensation and subsequently increase muscle size. The relationship between carbohydrate intake and muscle glycogen saturation was first examined in endurance event performance and similar strategies have been adopted by physique athletes despite the distinct physiological dissimilarities and aims between the sports. OBJECTIVES: The aim of this narrative review is to (1) critically examine and appraise the existing scientific literature relating to carbohydrate manipulation practices in physique athletes prior to competition; (2) identify research gaps and provide direction for future studies; and (3) provide broad practical applications based on the findings and physiological reasoning for coaches and competitors. FINDINGS: The findings of this review indicate that carbohydrate manipulation practices are prevalent amongst physique athletes despite a paucity of experimental evidence demonstrating the efficacy of such strategies on physique performance. Competitors have also been observed to manipulate water and electrolytes in conjunction with carbohydrate predicated on speculative physiological mechanisms which may be detrimental for performance. CONCLUSIONS: Further experimental evidence which closely replicates the nutritional and training practices of physique athletes during peak week is required to make conclusions on the efficacy of carbohydrate manipulation strategies. Quasi-experimental designs may be a feasible alternative to randomised controlled trials to examine such strategies due to the difficulty in recruiting the population of interest. Finally, we recommend that coaches and competitors manipulate as few variables as possible, and experiment with different magnitudes of carbohydrate loads in advance of competition if implementing a peaking strategy.

Emerging conjugated polymers for heterogeneous photocatalytic chemical transformation.

In recent decades, the efficient utilization of solar energy through heterogeneous photocatalytic chemical transformation has attracted much attention. As emerging metal-free, pure organic and heterogeneous photocatalysts, π-conjugated polymers (CPs) have been used in visible-light-driven chemical transformations due to their stability, high specific surface area, metal-free nature, and high structural designability. In this review, we summarize the synthesis protocols and design strategies for efficient CP-based photocatalysts based on the photocatalytic mechanisms. Then we highlight the key progress in light-driven chemical transformation using CPs developed by our group. Finally, we present the outlook and possible challenges for future progress of the field.

Colonization of peripheral ganglia by herpes simplex virus type 1 and 2.

Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) infect and establish latency in neurons of the peripheral nervous system to persist lifelong in the host and to cause recurrent disease. During primary infection, HSV replicates in epithelial cells in the mucosa and skin and then infects neurites, highly dynamic structures that grow or retract in the presence of attracting or repelling cues, respectively. Following retrograde transport in neurites, HSV establishes latency in the neuronal nucleus. Viral and cellular proteins participate in the chromatinization of the HSV genome that regulates gene expression, persistence, and reactivation. HSV-2 modulates neurite outgrowth during primary infection and upon reactivation, probably to facilitate infection and survival of neurons. Whether HSV-1 modulates neurite outgrowth and the underlying mechanism is currently under investigation. This review deals with HSV-1 and HSV-2 colonization of peripheral neurons, with a focus on the modulation of neurite outgrowth by these viruses.

Viral modulation of type II interferon increases T cell adhesion and virus spread.

During primary infection, varicella zoster virus (VZV) infects epithelial cells in the respiratory lymphoid organs and mucosa. Subsequent infection of lymphocytes, T cells in particular, causes primary viremia allowing systemic spread throughout the host, including the skin. This results in the expression of cytokines, including interferons (IFNs) which partly limit primary infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. How VZV infects lymphocytes from epithelial cells while evading the cytokine response has not been fully established. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity. Transcriptomic analysis revealed that gC in combination with IFN-γ increased the expression of a small subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), as well as several chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of epithelial cells resulted in lymphocyte function-associated antigen 1 (LFA-1)-dependent T cell adhesion. This gC activity required a stable interaction with IFN-γ and signalling through the IFN-γ receptor. Finally, the presence of gC during infection increased VZV spread from epithelial cells to peripheral blood mononuclear cells. This constitutes the discovery of a novel strategy to modulate the activity of IFN-γ, inducing the expression of a subset of ISGs, leading to enhanced T cell adhesion and virus spread.

Emerging covalent triazine framework-based nanomaterials for electrochemical energy storage and conversion.

Recently, the increasing concerns regarding environmental and energy-related issues due to the use of fossil fuels have triggered extensive research on sustainable electrochemical energy storage and conversion (EESC). In this case, covalent triazine frameworks (CTFs) possess a large surface area, tailorable conjugated structures, electron donating-accepting/conducting moieties, and excellent chemical and thermal stabilities. These merits make them leading candidates for EESC. However, their poor electrical conductivity impedes electron and ion conduction, leading to unsatisfactory electrochemical performances, which limit their commercial applications. Thus, to overcome these challenges, CTF-based nanocomposites and their derivatives such as heteroatom-doped porous carbons, which inherit most of the merits of pristine CTFs, lead to excellent performances in the field of EESC. In this review, initially, we briefly highlight the existing strategies for the synthesis of CTFs with application-targeted properties. Next, we review the contemporary progress of CTFs and their derivatives related to electrochemical energy storage (supercapacitors, alkali-ion batteries, lithium-sulfur batteries, etc.) and conversion (oxygen reduction/evolution reaction, hydrogen evolution reaction, carbon dioxide reduction reaction, etc.). Finally, we discuss perspectives on current challenges and recommendations for the further development of CTF-based nanomaterials in burgeoning EESC research.

Direct Synthesis of 1-Butanol with High Faradaic Efficiency from CO2 Utilizing Cascade Catalysis at a Ni-Enhanced (Cr2O3)3Ga2O3 Electrocatalyst.

Electrochemical transformation of CO2 into energy-dense liquid fuels provides a viable solution to challenges regarding climate change and nonrenewable resource dependence. Here, we report on the modification of a Cr-Ga oxide electrocatalyst through the introduction of nickel to generate a catalyst that generates 1-butanol at unprecedented faradaic efficiencies (ξ = 42%). This faradaic efficiency occurs at -1.48 V vs Ag/AgCl, with 1-butanol production commencing at an overpotential of 320 mV. At this potential, minor products include formate, methanol, acetic acid, acetone, and 3-hydroxybutanal. At -1.0 and -1.4 V, 3-hydroxybutanal becomes the primary product. This is in contrast to the nickel-free (Cr2O3)3(Ga2O3) system, where neither 3-hydroxybutanal nor 1-butanol was detected. Mechanistic studies show that formate is the initial CO2 reduction product and identify acetaldehyde as the key intermediate. Nickel is found responsible for the coupling and reduction of acetaldehyde to generate the higher molecular weight carbon products observed. To the best of our knowledge, this is the first electrocatalyst to generate 1-butanol with high faradaic efficiency.

Dual Molecular Oxygen Activation Sites on Conjugated Microporous Polymers for Enhanced Photocatalytic Formation of Benzothiazoles.

Oxidative formation of high value compounds involving active oxygen species using heterogeneous polymeric photocatalysts has become a useful tool in catalysis. Controlling the interaction between the active sites on polymer photocatalysts and oxygen molecules is still challenging due to the rather large polymer backbone structure. Here, we design a triazine-containing donor acceptor-type conjugated microporous polymer (CMP) containing dual major active sites at F and N atoms for molecular oxygen activation. Introducing fluorine atoms on the CMP backbone led to a combined effect of enhanced adsorption and electron transfer of oxygen. Time-resolved photoluminescence, electronic paramagnetic resonance spectra, and DFT calculation revealed favorable absorption energy and electron transfer kinetics between the CMP and oxygen molecules, thus efficiently generating superoxide radicals (O2•-) and singlet oxygen (1O2) as main active oxygen species. The photocatalytic activity, selectivity, and reusability of the CMP was demonstrated by the photocatalytic formation of a variety of benzothiazoles.

Visible-Light-Promoted Switchable Selective Oxidations of Styrene Over Covalent Triazine Frameworks in Water.

Using photocatalytic oxidation to convert basic chemicals into high value compounds in environmentally benign reaction media is a current focus in catalytic research. The challenge lies in gaining controllability over product formation selectivity. We design covalent triazine frameworks as heterogeneous, metal-free, and recyclable photocatalysts for visible-light-driven switchable selective oxidation of styrene in pure water. Selectivity in product formation was achieved by activation or deactivation of the specific photogenerated oxygen species. Using the same photocatalyst, by deactivation of photogenerated H2 O2 , benzaldehyde was obtained with over 99 % conversion and over 99 % selectivity as a single product. The highly challenging and sensitive epoxidation of styrene was carried out by creating peroxymonocarbonate as an initial epoxidation agent in the presence of bicarbonate, which led to formation of styrene oxide with a selectivity up to 76 % with near quantitative conversion. This study demonstrates a preliminary yet interesting example for simple control over switchable product formation selectivity for challenging oxidation reactions of organic compounds in pure water.

Innate immune response to SARS-1 CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection causes neurological disease in some patients suggesting that infection can affect both the peripheral and central nervous system (PNS and CNS, respectively). It is not clear whether the outcome of SARS-CoV-2 infection of PNS and CNS neurons is similar, and which are the key factors that cause neurological disease: SARS-CoV-2 infection or the subsequent immune response. Here, we addressed these questions by infecting human induced-pluripotent stem cell-derived CNS and PNS neurons with the {beta} strain of SARS-CoV-2. Our results show that SARS-CoV-2 infects PNS neurons more efficiently than CNS neurons, despite lower expression levels of angiotensin converting enzyme 2. Infected PNS neurons produced interferon {lambda}1, several interferon stimulated genes and proinflammatory cytokines. They also displayed neurodegenerative-like alterations, as indicated by increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and -synuclein and lower levels of nicotinamide mononucleotide adenylyltransferase 2 and {beta}-III-tubulin. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neurodegeneration, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS.

Convolution Neural Networks and Targeted Fluorescent Nanoparticles to Detect and ICDAS Score Caries.

Previous work has shown targeted fluorescent starch nanoparticles (TFSNs) can label the subsurface of carious lesions and assist dental professionals in the diagnostic process. In this study, we aimed to evaluate the potential of using artificial intelligence (AI) to detect and score carious lesions using ICDAS in combination with fluorescent imaging following application of TFSNs on teeth with a range of lesion severities, using ICDAS-labeled images as the reference standard. A total of 130 extracted human teeth with ICDAS scores from 0 to 6 were selected by a calibrated cariologist. Then, the same surface was imaged with a stereomicroscope under white light illumination, without visible fluorescence, and blue light illumination with an orange filter following application of the TFSNs. Both sets of images were labeled by another blinded ICDAS-calibrated cariologist to demarcate lesion position and severity. Convolutional neural networks, state-of-the-art models in imaging AI, were trained to determine the presence, location, ICDAS score (severity), and lesion surface porosity (as an indicator of activity) of carious lesions, and tested by 30 k-fold validation for white light, blue light, and the combined image sets. The best models showed high performance for the detection of carious lesions (sensitivity 80.26%, PPV 76.36%), potential for determining the severity via ICDAS scoring (accuracy 72%, SD 5.67%), and the detection of surface porosity as an indicator of the activity of the lesions (accuracy 90%, SD 7.00%). More broadly, the combination of targeted biopolymer nanoparticles with imaging AI is a promising combination of novel technologies that could be applied to many other applications.

Fast and Noninvasive Hair Test for Preliminary Diagnosis of Mood Disorders.

The main objective of this study was to develop a test for the fast and noninvasive prediagnosis of mood disorders based on the noninvasive analysis of hair samples. The database included 75 control subjects (who were not diagnosed with depression) and 40 patients diagnosed with mood disorders such as depression or bipolar disorder. Both women and men, aged 18-65 years, participated in the research. After taking the hair samples, they were washed (methanol-water-methanol by shaking in a centrifuge for two min) and air-dried in a fume hood. Each hair collection was analyzed using Fourier transform infrared spectroscopy attenuated total reflection (ATR-FTIR) spectroscopy. Subsequently, the results obtained were analyzed based on chemometric methods: hierarchical cluster analysis (HCA) and principal component analysis (PCA). As a results of the research conducted, potential differences were noticed. There was a visible change in the spectra intensity at around 2800-3100 cm-1 and smaller differences around 1460 cm-1; the bands can be assigned to protein vibrations. However, these are preliminary studies that provide a good basis for the development of a test for the initial diagnosis of mood disorders.

Design and testing of drift free force probe experiments with absolute distance control.

After almost 35 years of truly successful and transformative advancements, Atomic Force Microscopy (AFM) and, in general, scanning probe microscopy still have a fundamental limitation. This is constant drift and uncontrolled motion of probe and tested surface structures with respect to each other. This is inherently linked to the currently accepted design principle-only forces are measured, and distances are inferred from force measurements and piezo motions. Here, we demonstrate and test a new setup, which combines advantages of AFM and the surface forces apparatus, where absolute distances are measured by Multiple Beam White Light Interferometry (MBI). The novel and unique aspect of this apparatus consists of a synergistic combination of white light interferometric measurement of the absolute distance by direct reflection from an AFM cantilever and a fast distance clamping and drift correction using an IR-laser Fabry-Pérot interferometry-based approach (FPI). We demonstrate the capabilities of the system by force/distance measurements, benchmarking of distance control by direct comparison of MBI and FPI, and discuss potential applications of the system. This novel setup has the potential to form, monitor, and stress a single molecule or ligand/receptor bond on the molecular hook with sub-nanometer control of molecular distances over in principle infinite times.

Catalytic cycling of human mitochondrial Lon protease.

The mitochondrial Lon protease (LonP1) regulates mitochondrial health by removing redundant proteins from the mitochondrial matrix. We determined LonP1 in eight nucleotide-dependent conformational states by cryoelectron microscopy (cryo-EM). The flexible assembly of N-terminal domains had 3-fold symmetry, and its orientation depended on the conformational state. We show that a conserved structural motif around T803 with a high similarity to the trypsin catalytic triad is essential for proteolysis. We show that LonP1 is not regulated by redox potential, despite the presence of two conserved cysteines at disulfide-bonding distance in its unfoldase core. Our data indicate how sequential ATP hydrolysis controls substrate protein translocation in a 6-fold binding change mechanism. Substrate protein translocation, rather than ATP hydrolysis, is a rate-limiting step, suggesting that LonP1 is a Brownian ratchet with ATP hydrolysis preventing translocation reversal. 3-fold rocking motions of the flexible N-domain assembly may assist thermal unfolding of the substrate protein.