High-resolution single-particle imaging at 100-200 keV with the Gatan Alpine direct electron detector.

Developments in direct electron detector technology have played a pivotal role in enabling high-resolution structural studies by cryo-EM at 200 and 300 keV. Yet, theory and recent experiments indicate advantages to imaging at 100 keV, energies for which the current detectors have not been optimized. In this study, we evaluated the Gatan Alpine detector, designed for operation at 100 and 200 keV. Compared to the Gatan K3, Alpine demonstrated a significant DQE improvement at these energies, specifically a âˆ¼ 4-fold improvement at Nyquist at 100 keV. In single-particle cryo-EM experiments, Alpine datasets yielded better than 2 Å resolution reconstructions of apoferritin at 120 and 200 keV on a ThermoFisher Scientific (TFS) Glacios microscope fitted with a non-standard SP-Twin lens. We also achieved a âˆ¼ 3.2 Å resolution reconstruction of a 115 kDa asymmetric protein complex, proving Alpine's effectiveness with complex biological samples. In-depth analysis revealed that Alpine reconstructions are comparable to K3 reconstructions at 200 keV, and remarkably, reconstruction from Alpine at 120 keV on a TFS Glacios surpassed all but the 300 keV data from a TFS Titan Krios with GIF/K3. Additionally, we show Alpine's capability for high-resolution data acquisition and screening on lower-end systems by obtaining âˆ¼ 3 Å resolution reconstructions of apoferritin and aldolase at 100 keV and detailed 2D averages of a 55 kDa sample using a side-entry cryo holder. Overall, we show that Gatan Alpine performs well with the standard 200 keV imaging systems and may potentially capture the benefits of lower accelerating voltages, bringing smaller sized particles within the scope of cryo-EM.

Fluorescence-activated multi-organelle mapping of subcellular plant hormone distribution.

Auxins and cytokinins are two major families of phytohormones that control most aspects of plant growth, development and plasticity. Their distribution in plants has been described, but the importance of cell- and subcellular-type specific phytohormone homeostasis remains undefined. Herein, we revealed auxin and cytokinin distribution maps showing their different organelle-specific allocations within the Arabidopsis plant cell. To do so, we have developed Fluorescence-Activated multi-Organelle Sorting (FAmOS), an innovative subcellular fractionation technique based on flow cytometric principles. FAmOS allows the simultaneous sorting of four differently labelled organelles based on their individual light scatter and fluorescence parameters while ensuring hormone metabolic stability. Our data showed different subcellular distribution of auxin and cytokinins, revealing the formation of phytohormone gradients that have been suggested by the subcellular localization of auxin and cytokinin transporters, receptors and metabolic enzymes. Both hormones showed enrichment in vacuoles, while cytokinins were also accumulated in the endoplasmic reticulum.

Spatio-temporal plant hormonomics: From tissue to subcellular resolution.

Due to technological advances in mass spectrometry, significant progress has been achieved recently in plant hormone research. Nowadays, plant hormonomics is well established as a fully integrated scientific field focused on the analysis of phytohormones, mainly on their isolation, identification and spatiotemporal quantification in plants. This review represents a comprehensive meta-study of the advances in the phytohormone analysis by mass spectrometry over the past decade. To address current trends and future perspectives, Web of Science data were systematically collected and key features such as mass spectrometry-based analyses were evaluated using multivariate data analysis methods. Our findings showed that plant hormonomics is currently divided into targeted and untargeted approaches. Both aim to miniaturize the sample, allowing high-resolution quantification to be covered in plant organs as well as subcellular compartments. Therefore, we can study plant hormone biosynthesis, metabolism and signalling at a spatio-temporal resolution. Moreover, this trend has recently been accelerated by technological advances such as fluorescence-activated cell sorting or mass spectrometry imaging.

The BJPsych journals: open for business and faster than a speeding bullet in advancing psychiatry internationally.

The Royal College of Psychiatry journals have an outstanding reputation for excellence, integrity and impact in psychiatry. Facilitated by Cambridge University Press, which is equally steeped in tradition, the family of College journals remains committed to enriching our understanding of mental science and exploring the clinical issues that matter.

Epigenetic alterations and advancement of lymphoma treatment.

Lymphomas, complex and heterogeneous malignant tumors, originate from the lymphopoietic system. These tumors are notorious for their high recurrence rates and resistance to treatment, which leads to poor prognoses. As ongoing research has shown, epigenetic modifications like DNA methylation, histone modifications, non-coding RNA regulation, and RNA modifications play crucial roles in lymphoma pathogenesis. Epigenetic modification-targeting drugs have exhibited therapeutic efficacy and tolerability in both monotherapy and combination lymphoma therapy. This review discusses pathogenic mechanisms and potential epigenetic therapeutic targets in common lymphomas, offering new avenues for lymphoma diagnosis and treatment. We also discuss the shortcomings of current lymphoma treatments, while suggesting potential areas for future research, in order to improve the prediction and prognosis of lymphoma.

Advances and future perspectives of water defluoridation by adsorption technology: A review.

Fluoride contamination in water sources poses a significant challenge to human health and the environment. In recent years, adsorption technology has emerged as a promising approach for water defluoridation due to its efficiency and cost-effectiveness. This review article comprehensively explores the advances in water defluoridation through adsorption processes. Various adsorbents, including natural and synthetic materials, have been investigated for their efficacy in removing fluoride ions from water. The mechanisms underlying adsorption interactions are elucidated, shedding light on the factors influencing defluoridation efficiency. Moreover, the review outlines the current state of technology, highlighting successful case studies and field applications. Future perspectives in the field of water defluoridation by adsorption are discussed, emphasizing the need for sustainable and scalable solutions. The integration of novel materials, process optimization, and the development of hybrid technologies are proposed as pathways to address existing challenges and enhance the overall efficacy of water defluoridation. This comprehensive assessment of the advances and future directions in adsorption-based water defluoridation provides valuable insights for researchers, policymakers, and practitioners working towards ensuring safe and accessible drinking water for all.

Interrogating the microenvironmental landscape of tumors with computational image analysis approaches.

The tumor microenvironment is an interacting heterogeneous collection of cancer cells, resident as well as infiltrating host cells, secreted factors, and extracellular matrix proteins. With the growing importance of immunotherapies, it has become crucial to be able to characterize the composition and the functional orientation of the microenvironment. The development of novel computational image analysis methodologies may enable the robust quantification and localization of immune and related biomarker-expressing cells within the microenvironment. The aim of the review is to concisely highlight a selection of current and significant contributions pertinent to methodological advances coupled with biomedical or translational applications. A further aim is to concisely present computational advances that, to our knowledge, have currently very limited use for the assessment of the microenvironment but have the potential to enhance image analysis pipelines; on this basis, an example is shown for the detection and segmentation of cells of the microenvironment using a published pipeline and a public dataset. Finally, a general proposal is presented on the conceptual design of automation-optimized computational image analysis workflows in the biomedical and clinical domain.

Poxvirus Vaccines: Past, Present, and Future.

Smallpox was a significant cause of mortality for over three thousand years, amounting to 10% of deaths yearly. Edward Jenner discovered smallpox vaccination in 1796, which rapidly became a smallpox infection preventive practice throughout the world and eradicated smallpox infection by 1980. After smallpox eradication, monkeypox vaccines have been used primarily in research and in outbreaks in Africa, where the disease is endemic. In the present, the vaccines are being used for people who work with animals or in high-risk areas, as well as for healthcare workers treating patients with monkeypox. Among all orthopoxviruses (OPXV), monkeypox viral (MPXV) infection occurs mainly in cynomolgus monkeys, natural reservoirs, and occasionally causes severe multi-organ infection in humans, who were the incidental hosts. The first case of the present epidemic of MXPV was identified on May 7, 2022, and rapidly increased the number of cases. In this regard, the WHO declared the outbreak, an international public health emergency on July 23, 2022. The first monkeypox vaccine was developed in the 1960s by the US Army and was based on the vaccinia virus, which is also used in smallpox vaccines. In recent years, newer monkeypox vaccines have been developed based on other viruses such as Modified Vaccinia Ankara (MVA). These newer vaccines are safer and can provide longer-lasting immunity with fewer side effects. For the future, there is ongoing research to improve the current vaccines and to develop new ones. One notable advance has been the development of a recombinant vaccine that uses a genetically modified vaccinia virus to express monkeypox antigens. This vaccine has shown promising results in pre-clinical trials and is currently undergoing further testing in clinical trials. Another recent development has been the use of a DNA vaccine, which delivers genetic material encoding monkeypox antigens directly into cells. This type of vaccine has shown effectiveness in animal studies and is also undergoing clinical testing in humans. Overall, these recent advances in monkeypox vaccine development hold promise for protecting individuals against this potentially serious disease.

Advances in pediatric anesthesia services over the past 10 years in French-speaking sub-Saharan Africa.

INTRODUCTION: To improve and maintain quality and safety in anesthesia, standards have been proposed regarding human resources, facilities and equipment, medications and intravenous fluids, monitoring, and the conduct of anesthesia. Compliance with these standards remains a challenge in French-speaking sub-Saharan Africa (SSA) and results in high morbidity and mortality particularly in children. This aim of this study was to assess the progress made in improving the pediatric anesthesia infrastructures, human resources, education, medications, and equipment in French-speaking SSA over the past 10 years (2013-2022). METHODS: This is a descriptive, multicenter, cross-sectional study with retrospective data collection, conducted from September 1 to November 5, 2023. Comparative data from 2012 to 2022 were collected through an online survey. Descriptive statistics were used to summarize data. RESULTS: Data were obtained from 12 countries out of 14. The number of hospitals providing pediatric surgery and anesthesia rose from 94 in 2012 to 142 in 2022 (+51%). The total number of physician anesthesiologists rose from 293 (0.1 physician anesthesiologists/100 000 inhabitants) in 2012 to 597 (0.2 physician anesthesiologists/100 000 inhabitants) in 2022 (+103.7%). Five (0.006 physician anesthesiologists/100 000 children) had completed a fellowship in pediatric anesthesia and intensive care in 2012, and 15 (0.01 physician anesthesiologists/100 000 children) in 2022 (+200%). Five physician anesthesiologists had an exclusive pediatric anesthesia practice in 2012, whereas they were 32 in 2022 (+540%). There is no specialized training in pediatric anesthesia and intensive care in any of these countries. Halothane was always available in 81.5% of the hospitals in 2012, and in 50.4% of the hospitals in 2022. Sevoflurane was always available in 5% of the hospitals in 2012, and in 36.2% in 2022. Morphine was always available in 32.2% in 2012, whereas it was available in 52.9% of them in 2022. Pediatric pulse oximeter sensors were available in 36% of the hospitals in 2012, and in 63.4% in 2022. Capnography was available in 5.3% of the hospitals in 2012, and in 48% in 2022. CONCLUSION: Progress have been made over the last 10 years in French-speaking SSA to improve infrastructures, human resources, education, medications, and equipment for pediatric anesthesia in French-speaking SSA. However, major efforts must be continued. Standards adapted to the local context should be formulated.

Chagas Disease: A Silent Threat for Dogs and Humans.

Chagas disease (CD) is a vector-borne Neglected Zoonotic Disease (NZD) caused by a flagellate protozoan, Trypanosoma cruzi, that affects various mammalian species across America, including humans and domestic animals. However, due to an increase in population movements and new routes of transmission, T. cruzi infection is presently considered a worldwide health concern, no longer restricted to endemic countries. Dogs play a major role in the domestic cycle by acting very efficiently as reservoirs and allowing the perpetuation of parasite transmission in endemic areas. Despite the significant progress made in recent years, still there is no vaccine against human and animal disease, there are few drugs available for the treatment of human CD, and there is no standard protocol for the treatment of canine CD. In this review, we highlight human and canine Chagas Disease in its different dimensions and interconnections. Dogs, which are considered to be the most important peridomestic reservoir and sentinel for the transmission of T. cruzi infection in a community, develop CD that is clinically similar to human CD. Therefore, an integrative approach, based on the One Health concept, bringing together the advances in genomics, immunology, and epidemiology can lead to the effective development of vaccines, new treatments, and innovative control strategies to tackle CD.

Recent Advances on Single-Atom Catalysts for Photocatalytic CO2 Reduction.

The present energy crisis and environmental challenges may be efficiently resolved by converting carbon dioxide (CO2 ) into various useful carbon products. The development of more effective catalysts has been the main focus of current research on photocatalytic CO2 reduction. Due to their high atomic efficiency and superior catalytic activity, single-atom catalysts (SACs) have attracted considerable interest in catalytic CO2 conversion. This review discusses the current research developments, obstacles, and potential of SACs for photocatalytic CO2 reduction. And further, discusses the principle of photocatalytic carbon dioxide reduction. This work has compared and analyzed the effects of support materials and active site types in SACs on photocatalytic CO2 reduction performance. This work believes that by sharing these developments, some inspiration for the rational design and development of stable and effective photocatalytic CO2 reduction catalysts based on SACs can be provided.

Nanomaterials for fluorescent detection of vitamin B2: A review.

Vitamin B2 plays vital roles in maintaining human health. It is of tremendous significance to construct sensitive sensors of VB2. In this review, we first briefly presented the sensing mechanisms of fluorescent nanomaterials for sensing VB2. Subsequently, the advances of nanomaterials for fluorescent determination of VB2 were highlighted. And sensing performance of traditional approaches and fluorescent nanosensors was further compared. In last section, the challenges and perspectives concerning the topic were discussed.

Revolutionizing viral disease vaccination: the promising clinical advancements of non-replicating mRNA vaccines.

The mRNA vaccine technology was developed rapidly during the global pandemic of COVID-19. The crucial role of the COVID-19 mRNA vaccine in preventing viral infection also have been beneficial to the exploration and application of other viral mRNA vaccines, especially for non-replication structure mRNA vaccines of viral disease with outstanding research results. Therefore, this review pays attention to the existing mRNA vaccines, which are of great value for candidates for clinical applications in viral diseases. We provide an overview of the optimization of the mRNA vaccine development process as well as the good immune efficacy and safety shown in clinical studies. In addition, we also provide a brief description of the important role of mRNA immunomodulators in the treatment of viral diseases. After that, it will provide a good reference or strategy for research on mRNA vaccines used in clinical medicine with more stable structures, higher translation efficiency, better immune efficacy and safety, shorter production time, and lower production costs than conditional vaccines to be used as preventive or therapeutic strategy for the control of viral diseases in the future.

Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations.

Until the advent of immune checkpoint inhibitors (ICIs), definitive radiotherapy (RT) concurrently with chemotherapy was recommended for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC). The trimodality paradigm with consolidation ICIs following definitive concurrent chemoradiotherapy has been the standard of care since the PACIFIC trial. Preclinical evidence has demonstrated the role of RT in the cancer-immune cycle and the synergistic effect of RT combined with ICIs (iRT). However, RT exerts a double-edged effect on immunity and the combination strategy still could be optimized in many areas. In the context of LA-NSCLC, optimized RT modality, choice, timing, and duration of ICIs, care for oncogenic addicted tumors, patient selection, and novel combination strategies require further investigation. Targeting these blind spots, novel approaches are being investigated to cross the borders of PACIFIC. We discussed the development history of iRT and summarized the updated rationale for the synergistic effect. We then summarized the available research data on the efficacy and toxicity of iRT in LA-NSCLC for cross-trial comparisons to eliminate barriers. Progression during and after ICIs consolidation therapy has been regarded as a distinct resistance scenario from primary or secondary resistance to ICIs, the subsequent management of which has also been discussed. Finally, based on unmet needs, we probed into the challenges, strategies, and auspicious orientations to optimize iRT in LA-NSCLC. In this review, we focus on the underlying mechanisms and recent advances of iRT with an emphasis on future challenges and directions that warrant further investigation. Taken together, iRT is a proven and potential strategy in LA-NSCLC, with multiple promising approaches to further improve the efficacy. Video Abstract.

Biomarkers for the diagnosis, treatment follow-up, and prediction of cardiac complications in Chagas disease in chronic phase: Recent advances.

Chagas disease is caused by the Trypanosoma cruzi parasite and is transmitted by infected triatomine bugs. This infection affects approximately 8 million people in the Americas, and due to globalisation and displacement, it is becoming increasingly common to find infected patients worldwide. Diagnosis of the disease in its acute form is relatively simple, as the parasite can be detected in peripheral blood smears, and symptoms are visible. However, in its chronic condition, the parasite is almost undetectable, and indirect tests are necessary to determine the presence of antibodies in infected patients. It is important to note that a single test is not enough to confirm the disease in this phase, as a second serological test should confirm the diagnosis. If the results are contradictory, a third test should be performed to confirm or discard the disease. Unfortunately, laboratories may not have access to all necessary tests in many rural areas where the disease is more frequent. Rapid tests to diagnose this disease present problems, such as significant variations in sensitivity and specificity in different countries. Therefore, searching for new biomarkers that allow for optimal correlation is essential. In this work, we have searched scientific literature from the last 10 years for mentions of novel biomarkers for diagnosis, treatment follow-up, and prediction of cardiac complications in Chagas disease in its chronic phase.

Post-stroke Everything.

PURPOSE OF REVIEW: This review aims at providing updates on selected post-stroke complications. We examined recent advances in diagnosing and treating the following post-stroke complications: cognitive impairment, epilepsy, depression, fatigue, tremors, dysphagia, and pain. RECENT FINDINGS: Advances in understanding the mechanisms of post-stroke complications, in general, are needed despite advances made in understanding, treating, and preventing these complications. There are growing progresses in integrating new tools to diagnose post-stroke cognitive impairment. The potential role of acute stroke reperfusion treatment in post-stroke epilepsy and its impact on other stroke complications is getting more transparent. Post-stroke depression remains underestimated and new tools to diagnose depression after stroke are being developed. New promising pharmacological approaches to treating post-stroke pain are emerging. Tremors related to stroke are poorly understood and under-evaluated, while treatment towards post-stroke dysphagia has benefited from new non-pharmacological to pharmacological approaches. CONCLUSIONS: An integrative approach to stroke complications and collaborations between providers across specialties are more likely to improve stroke outcomes.

Uncovering the Depths of the Human Proteome: Antibody-based Technologies for Ultrasensitive Multiplexed Protein Detection and Quantification.

Probing the human proteome in tissues and biofluids such as plasma is attractive for biomarker and drug target discovery. Recent breakthroughs in multiplex, antibody-based, proteomics technologies now enable the simultaneous quantification of thousands of proteins at as low as sub fg/ml concentrations with remarkable dynamic ranges of up to 10-log. We herein provide a comprehensive guide to the methodologies, performance, technical comparisons, advantages, and disadvantages of established and emerging technologies for the multiplexed ultrasensitive measurement of proteins. Gaining holistic knowledge on these innovations is crucial for choosing the right multiplexed proteomics tool for applications at hand to critically complement traditional proteomics methods. This can bring researchers closer than ever before to elucidating the intricate inner workings and cross talk that spans multitude of proteins in disease mechanisms.

Advances in the Synthesis and Analysis of Biologically Active Phosphometabolites.

Phosphorus-containing metabolites cover a large molecular diversity and represent an important domain of small molecules which are highly relevant for life and represent essential interfaces between biology and chemistry, between the biological and abiotic world. The large but not unlimited amount of phosphate minerals on our planet is a key resource for living organisms on our planet, while the accumulation of phosphorus-containing waste is associated with negative effects on ecosystems. Therefore, resource-efficient and circular processes receive increasing attention from different perspectives, from local and regional levels to national and global levels. The molecular and sustainability aspects of a global phosphorus cycle have become of much interest for addressing the phosphorus biochemical flow as a high-risk planetary boundary. Knowledge of balancing the natural phosphorus cycle and the further elucidation of metabolic pathways involving phosphorus is crucial. This requires not only the development of effective new methods for practical discovery, identification, and high-information content analysis, but also for practical synthesis of phosphorus-containing metabolites, for example as standards, as substrates or products of enzymatic reactions, or for discovering novel biological functions. The purpose of this article is to review the advances which have been achieved in the synthesis and analysis of phosphorus-containing metabolites which are biologically active.

Vermicomposting technology - A perspective on vermicompost production technologies, limitations and prospects.

The need for environmental sustainability while increasing the quantity, quality, and the rate of waste treatment to generate high-value environmental friendly fertilizer products is highly in demand. Vermicomposting is a good technology for the valorisation of industrial, domestic, municipal and agricultural wastes. Various vermicomposting technologies have been in use from time past to present. These technologies range from windrow, small - scale batch vermicomposting to large - scale continuous flow systems. Each of these processes has its own merits and demerits, necessitating advancement in the technology for efficient treatment of wastes. This work explores the hypothesis that the use of a continuous flow vermireactor system of a composite frame structure performs better than batch, windrow and other continuous systems operated in a single container. Following an in-depth review of the literature on vermicomposting technologies, treatment techniques, and reactor materials used, to explore the hypothesis, it was found that vermireactors operating in continuous flow fashion perform better in waste bioconversion than the batch and windrow techniques. Overall, the study concludes that batch techniques using plastic vermireactors predominate over the other reactor systems. However, the use of frame compartmentalized composite vermireactors performs considerably better in waste valorisation.

Recent Advances of Polyphenol Oxidases in Plants.

Polyphenol oxidase (PPO) is present in most higher plants, but also in animals and fungi. PPO in plants had been summarized several years ago. However, recent advances in studies of PPO in plants are lacking. This review concludes new researches on PPO distribution, structure, molecular weights, optimal temperature, pH, and substrates. And, the transformation of PPO from latent to active state was also discussed. This state shift is a vital reason for elevating PPO activity, but the activation mechanism in plants has not been elucidated. PPO has an important role in plant stress resistance and physiological metabolism. However, the enzymatic browning reaction induced by PPO is a major problem in the production, processing, and storage of fruits and vegetables. Meanwhile, we summarized various new methods that had been invented to decrease enzymatic browning by inhibiting PPO activity. In addition, our manuscript included information on several important biological functions and the transcriptional regulation of PPO in plants. Furthermore, we also prospect some future research areas of PPO and hope they will be useful for future research in plants.