Chlorophyll to zeaxanthin energy transfer in nonphotochemical quenching: An exciton annihilation-free transient absorption study.

Zeaxanthin (Zea) is a key component in the energy-dependent, rapidly reversible, nonphotochemical quenching process (qE) that regulates photosynthetic light harvesting. Previous transient absorption (TA) studies suggested that Zea can participate in direct quenching via chlorophyll (Chl) to Zea energy transfer. However, the contamination of intrinsic exciton-exciton annihilation (EEA) makes the assignment of TA signal ambiguous. In this study, we present EEA-free TA data using Nicotiana benthamiana thylakoid membranes, including the wild type and three NPQ mutants (npq1, npq4, and lut2) generated by CRISPR/Cas9 mutagenesis. The results show a strong correlation between excitation energy transfer from excited Chl Qy to Zea S1 and the xanthophyll cycle during qE activation. Notably, a Lut S1 signal is absent in the npq1 thylakoids which lack zeaxanthin. Additionally, the fifth-order response analysis shows a reduction in the exciton diffusion length (LD) from 62 ± 6 nm to 43 ± 3 nm under high light illumination, consistent with the reduced range of exciton motion being a key aspect of plants' response to excess light.

Targeted Protein O-GlcNAcylation Using Bifunctional Small Molecules.

Protein O-linked ß-N-acetylglucosamine modification (O-GlcNAcylation) plays a crucial role in regulating essential cellular processes. The disruption of the homeostasis of O-GlcNAcylation has been linked to various human diseases, including cancer, diabetes, and neurodegeneration. However, there are limited chemical tools for protein- and site-specific O-GlcNAc modification, rendering the precise study of the O-GlcNAcylation challenging. To address this, we have developed heterobifunctional small molecules, named O-GlcNAcylation TArgeting Chimeras (OGTACs), which enable protein-specific O-GlcNAcylation in living cells. OGTACs promote O-GlcNAcylation of proteins such as BRD4, CK2α, and EZH2 in cellulo by recruiting FKBP12F36V-fused O-GlcNAc transferase (OGT), with temporal, magnitude, and reversible control. Overall, the OGTACs represent a promising approach for inducing protein-specific O-GlcNAcylation, thus enabling functional dissection and offering new directions for O-GlcNAc-targeting therapeutic development.

On the use of tandem mass spectra acquired from samples of evolutionarily distant organisms to validate methods for false discovery rate estimation.

Estimating the false discovery rate (FDR) of peptide identifications is a key step in proteomics data analysis, and many methods have been proposed for this purpose. Recently, an entrapment-inspired protocol to validate methods for FDR estimation appeared in articles showcasing new spectral library search tools. That validation approach involves generating incorrect spectral matches by searching spectra from evolutionarily distant organisms (entrapment queries) against the original target search space. Although this approach may appear similar to the solutions using entrapment databases, it represents a distinct conceptual framework whose correctness has not been verified yet. In this viewpoint, we first discussed the background of the entrapment-based validation protocols and then conducted a few simple computational experiments to verify the assumptions behind them. The results reveal that entrapment databases may, in some implementations, be a reasonable choice for validation, while the assumptions underpinning validation protocols based on entrapment queries are likely to be violated in practice. This article also highlights the need for well-designed frameworks for validating FDR estimation methods in proteomics.

Merging Full-Spectrum and Fragment Ion Intensity Predictions from Deep Learning for High-Quality Spectral Libraries.

Spectral libraries are useful resources in proteomic data analysis. Recent advances in deep learning allow tandem mass spectra of peptides to be predicted from their amino acid sequences. This enables predicted spectral libraries to be compiled, and searching against such libraries has been shown to improve the sensitivity in peptide identification over conventional sequence database searching. However, current prediction models lack support for longer peptides, and thus far, predicted library searching has only been demonstrated for backbone ion-only spectrum prediction methods. Here, we propose a deep learning-based full-spectrum prediction method to generate predicted spectral libraries for peptide identification. We demonstrated the superiority of using full-spectrum libraries over backbone ion-only prediction approaches in spectral library searching. Furthermore, merging spectra from different prediction models, as a form of ensemble learning, can produce improved spectral libraries, in terms of identification sensitivity. We also show that a hybrid library combining predicted and experimental spectra can lead to 20% more confident identifications over experimental library searching or sequence database searching.

Spectroscape enables real-time query and visualization of a spectral archive in proteomics.

In proteomics, spectral archives organize the enormous amounts of publicly available peptide tandem mass spectra by similarity, offering opportunities for error correction and novel discoveries. Here we adapt an indexing algorithm developed by Facebook for organizing online multimedia resources to tandem mass spectra and achieve practically instantaneous retrieval and clustering of approximate nearest neighbors in a large spectral archive. An interactive web-based graphical user interface enables the user to view a query spectrum in its clustered neighborhood, which facilitates contextual validation of peptide identifications and exploration of the dark proteome.

metaSpectraST: an unsupervised and database-independent analysis workflow for metaproteomic MS/MS data using spectrum clustering.

BACKGROUND: The high diversity and complexity of the microbial community make it a formidable challenge to identify and quantify the large number of proteins expressed in the community. Conventional metaproteomics approaches largely rely on accurate identification of the MS/MS spectra to their corresponding short peptides in the digested samples, followed by protein inference and subsequent taxonomic and functional analysis of the detected proteins. These approaches are dependent on the availability of protein sequence databases derived either from sample-specific metagenomic data or from public repositories. Due to the incompleteness and imperfections of these protein sequence databases, and the preponderance of homologous proteins expressed by different bacterial species in the community, this computational process of peptide identification and protein inference is challenging and error-prone, which hinders the comparison of metaproteomes across multiple samples. RESULTS: We developed metaSpectraST, an unsupervised and database-independent metaproteomics workflow, which quantitatively profiles and compares metaproteomics samples by clustering experimentally observed MS/MS spectra based on their spectral similarity. We applied metaSpectraST to fecal samples collected from littermates of two different mother mice right after weaning. Quantitative proteome profiles of the microbial communities of different mice were obtained without any peptide-spectrum identification and used to evaluate the overall similarity between samples and highlight any differentiating markers. Compared to the conventional database-dependent metaproteomics analysis, metaSpectraST is more successful in classifying the samples and detecting the subtle microbiome changes of mouse gut microbiomes post-weaning. metaSpectraST could also be used as a tool to select the suitable biological replicates from samples with wide inter-individual variation. CONCLUSIONS: metaSpectraST enables rapid profiling of metaproteomic samples quantitatively, without the need for constructing the protein sequence database or identification of the MS/MS spectra. It maximally preserves information contained in the experimental MS/MS spectra by clustering all of them first and thus is able to better profile the complex microbial communities and highlight their functional changes, as compared with conventional approaches. tag the videobyte in this section as ESM4 Video Abstract.

Mechanistic Insight into the Inhibitory Activity of Elasnin-Based Coating against Early Marine Biofilms.

Marine biofilms are multispecies microbial communities on surfaces that are crucial to the marine environment. They cause marine corrosion, biofouling, and transmission of marine pathogens and thus pose a great threat to public health and the maritime industry. To control marine biofilms, effective and environmentally friendly antibiofilm compounds are highly needed. Elasnin is a potent antibiofilm compound that exhibits high efficiency in inhibiting marine biofilms and biofouling, but its mode of action remains unclear. In the present study, multiomic analysis combined with quorum-sensing assays and in silico study revealed that elasnin acted as a signaling molecule in the microbial community. Elasnin promoted the growth of dominant species in the biofilm but deprived their ability of sensing and responding to environmental changes by disturbing their regulations of the two-component system, i.e., the ATP-binding cassette transport system and the bacterial secretion system. Consequently, biofilm maturation and subsequent biofouler settlement were inhibited. Elasnin also exhibited higher antibiofilm efficiency than dichlorooctylisothiazolinone and had low toxicity potential on the embryos and adults of marine medaka fish. Overall, this study provided molecular and ecological insights into elasnin's mode of action, highlighting its application potential in controlling marine biofilms and the feasibility and advantages of using signal molecules to develop eco-friendly technologies.

Clinical, neuroimaging, and behavioural risk factors for neurocognitive impairment in Chinese patients with haemophilia: A multicentre study.

BACKGROUND: Few studies have evaluated the impact of subclinical microstructural changes and psychosocial factors on cognitive function in patients with haemophilia. OBJECTIVES: To determine the prevalence and characteristics of cognitive impairment in patients with haemophilia, and identify associated risk factors. METHODS: We recruited haemophilia A or B patients who were aged ≥10 years old from three public hospitals in Hong Kong. A neurocognitive battery was administered to evaluate their attention, memory, processing speed and cognitive flexibility performances. They also underwent magnetic resonance imaging to identify cerebral microbleeds. Validated self-reported questionnaires were administered to assess their mental health status and adherence to prophylactic treatment. General linear modelling was used to investigate the association of neurocognitive outcomes with risks factors, adjusting for age and education attainment. RESULTS: Forty-two patients were recruited (median age 32.0 years; 78.6% haemophilia A; 80.9% moderate-to-severe disease). Six patients (14.3%) had developed cerebral microbleeds. A subgroup of patients demonstrated impairments in cognitive flexibility (30.9%) and motor processing speed (26.2%). Hemarthrosis in the previous year was associated with worse attention (Estimate = 7.62, 95% CI: 1.92-15.33; p = .049) and cognitive flexibility (Estimate = 8.64, 95% CI: 2.52-13.29; p = .043). Depressive (Estimate = 0.22, 95% CI: 0.10-0.55; p = .023) and anxiety (Estimate = 0.26, 95% CI: 0.19-0.41; p = .0069) symptoms were associated with inattentiveness. Among patients receiving prophylactic treatment (71.4%), medication adherence was positively correlated with cognitive flexibility (p = .037). CONCLUSION: A substantial proportion of patients with haemophilia demonstrated cognitive impairment, particularly higher-order thinking skills. Screening for cognitive deficits should be incorporated into routine care. Future studies should evaluate the association of neurocognitive outcomes with occupational/vocational outcomes.

Topical corticosteroids for the prevention of severe radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: Radiation dermatitis (RD) is a frequently occurring adverse reaction during radiotherapy in cancer patients. While the use of topical corticosteroids (TCs) is common for the treatment of RD, its role in preventing severe reactions remains unclear. This systematic review and meta-analysis aim to evaluate the evidence on the use of TCs as prophylaxis of RD. METHODS: A systematic search was conducted using OVID MedLine, Embase, and Cochrane databases (between 1946 and 2023) to identify studies examining TC use in the prevention of severe RD. Statistical analysis was completed using RevMan 5.4 to calculate pooled effect sizes and 95% confidence intervals. Forest plots were then developed using a random effects model. RESULTS: Ten RCTs with a total of 1041 patients met the inclusion criteria. Six studies reported on mometasone furoate (MF) and four studies reported on betamethasone. Both TCs were associated with a significant improvement in the prevention of moist desquamation [OR = 0.34, 95% CI [0.25, 0.47], p < 0.00001], but betamethasone was found to be more effective than MF [OR = 0.29, 95% CI [0.18, 0.46], p < 0.00001 and OR = 0.39, 95% CI [0.25, 0.61], p < 0.0001, respectively]. A similar finding was seen in reducing the development of grade 2 or higher RD according to the Radiation Therapy Oncology Group scale. CONCLUSIONS: The current evidence supports the use of TCs in preventing severe reactions of RD. Both MF and betamethasone were found to be effective; however, betamethasone, a higher potency TC, is more effective despite MF being more commonly reported in literature.

MASCC clinical practice guidelines for the prevention and management of acute radiation dermatitis: part 1) systematic review.

Acute radiation dermatitis (ARD) commonly develops in cancer patients undergoing radiotherapy and is often characterized by erythema, desquamation, and pain. A systematic review was conducted to summarize the current evidence on interventions for the prevention and management of ARD. Databases were searched from 1946 to September 2020 to identify all original studies that evaluated an intervention for the prevention or management of ARD, with an updated search conducted in January 2023. A total of 235 original studies were included in this review, including 149 randomized controlled trials (RCTs). Most interventions could not be recommended due to a low quality of evidence, lack of supporting evidence, or conflicting findings across multiple trials. Photobiomodulation therapy, Mepitel® film, mometasone furoate, betamethasone, olive oil, and oral enzyme mixtures showed promising results across multiple RCTs. Recommendations could not be made solely based on the published evidence due to limited high-quality evidence. As such, Delphi consensus recommendations will be reported in a separate publication.

Comparative proteomic analysis reveals the different hepatotoxic mechanisms of human hepatocytes exposed to silver nanoparticles.

Silver nanoparticles (AgNPs), which have been used extensively in consuming products and eventually released into the natural environment, have aroused concerns recently because of their potentially harmful effects on human beings following various routes of exposure. As the liver is one of the largest accumulation and deposition sites of circulatory AgNPs, it is important to evaluate the hepatotoxicity induced by AgNPs. However, the acting mechanisms of AgNPs-induced hepatotoxicity are still elusive to a great extent. Herein, we investigated the hepatotoxic effects of AgNPs using a comparative proteomics approach. First, we evaluated the cytotoxicity of different-sized AgNPs and found that the cancerous liver cells were generally more sensitive than the normal liver cells. Next, proteomics results suggested that HepG2 and L02 cells showed distinct adaptive responses upon AgNPs exposure. HepG2 cells respond to stresses by adapting energy metabolism, upregulating metallothionein expression and increasing the expression of antioxidants, while L02 cells protect themselves by increasing DNA repair and macro-autophagy. Besides, mitochondrial ROS has been identified as one of the causes of AgNPs-induced hepatotoxicity. Collectively, our results revealed that hepatic cancer cells and normal cells cope with AgNPs in notably different pathways, providing new insights into mechanisms underlying AgNPs-induced hepatotoxicity. DATA AVAILABILITY: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (Deutsch et al. (2020)) via the PRIDE (Perez-Riverol et al. (2019)) partner repository with the dataset identifier PXD029511.

Prevention of radiation dermatitis with skin hygiene and washing: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aims to evaluate the effects of washing in patients receiving radiotherapy (RT) on radiation dermatitis (RD) severity. METHODS: A literature search was performed using Ovid MEDLINE, Embase, and Cochrane databases between January 1, 1946, and January 31, 2023. Four randomized controlled trials (RCTs) studying the effects of washing with or without soap on RD were identified. A meta-analysis was conducted for clinician-reported outcomes using RevMan 5.4 and a narrative synthesis for patient-reported outcomes due to a lack of reported data amenable to quantitative comparison in accordance with the Synthesis Without Meta-analysis (SWiM) guidelines. The Cochrane Risk of bias (RoB2) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria were used to assess risk of bias and certainty of evidence, respectively. RESULTS: Two RCTs met the inclusion criteria for meta-analysis. Washing with or without soap significantly reduced the incidence of severe RD (OR: 0.32, 95% CI: 0.19-0.55, p < 0.01) and moist desquamation (OR: 0.25, 95% CI: 0.12-0.52, p < 0.01). Two of four trials found an association between washing and reduced itching score (p = 0.38). Pain score was not found to be significantly different with or without washing in any of the four studies (p = 0.07). The two studies that assessed burn scores did not detect any difference between the washing group versus no washing group (p = 0.25). Washing was associated with improved quality of life (QoL) measures in one study. CONCLUSION: Washing with or without soap during RT resulted in less severe RD and less moist desquamation. Given the QoL benefits of washing, it should be advocated as part of routine skin care during RT.

Modeling Lower-Order Statistics to Enable Decoy-Free FDR Estimation in Proteomics.

One of the chief objectives in mass spectrometry-based peptide identification in proteomics is the statistical validation of top-scoring peptide-spectrum matches (PSMs) in the form of false discovery rate (FDR) estimation. Existing methods construct a null model that captures the characteristics of incorrect target PSMs to estimate the FDR, most often with the help of decoys. Decoy-based methods, however, increase the computational cost and rely on the difficult-to-verify assumption that decoy PSMs constitute a sufficient and representative sample of the population of possible incorrect target PSMs. On the other hand, the possibility of FDR estimation assisted by the plentiful non-top-scoring PSMs, which are almost always incorrect, has been scarcely explored. In this work, we propose a novel decoy-free procedure for developing null models for top-scoring PSMs using the transformed e-value (TEV) score and the distributions of non-top-scoring target PSMs. The method relies on a theoretically derivable relationship between the parameters of the distributions of lower-order statistics of the TEV score and a necessary empirical optimization to fit a single parameter to actual data. The framework was tested on multiple different data sets and two search engines. We present evidence that our method is comparable to and occasionally outperforms popular decoy-free and decoy-based methods in FDR estimation.

The effect of antiperspirant and deodorant use on acute radiation dermatitis in breast cancer patients during radiotherapy: a systematic review and meta-analysis.

PURPOSE: While some authors have investigated the impact of antiperspirant /deodorant on the development of acute radiation dermatitis (RD) among patients undergoing radiotherapy (RT) for breast cancer, recommendations supporting the use of antiperspirant/deodorant during breast RT remain highly variable. This systematic review and meta-analysis aims to evaluate the evidence investigating the effect of antiperspirant/deodorant on the development of acute RD during post-operative breast RT. METHODS: A literature search has been performed using OVID MedLine, Embase, and Cochrane databases (1946 to September 2020) to identify randomized controlled trials (RCTs) that have investigated deodorant/antiperspirant use during RT. The meta-analysis was conducted using RevMan 5.4 to calculate pooled effect sizes and 95% confidence intervals (CI). RESULTS: Five RCTs met the inclusion criteria. The use of antiperspirant/deodorant did not significantly affect the incidence of grade (G) 1 + RD (OR 0.81, 95% CI 0.54-1.21, p = 0.31). Prohibition of deodorant use did not significantly prevent the occurrence of G2 + acute RD (OR 0.90, 95%, CI 0.65-1.25, p = 0.53). No significant effect was reported in preventing G3 RD between the antiperspirant/deodorant and control groups (OR 0.54, 95%, CI 0.26-1.12, p = 0.10). There was no significant difference in pruritus and pain between patients undergoing skin care protocols with or without antiperspirant/deodorant (OR 0.73, 95% CI 0.29, 1.81, p = 0.50, and OR 1.05, 95% CI 0.43-2.52, p = 0.92, respectively). CONCLUSIONS: The use of antiperspirant/deodorant during breast RT does not significantly affect the incidence of acute RD, pruritus, and pain. As such, the current evidence does not support recommendation against antiperspirant/deodorant use during RT.

Photobiomodulation therapy for the prevention of acute radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: Approximately 95% of patients undergoing radiotherapy (RT) experience radiation dermatitis (RD). Evidence has suggested that photobiomodulation therapy (PBMT) can stimulate skin renewal and minimize RD. The aim of the present paper was to investigate the efficacy of PBMT in RD prevention through a comprehensive literature review. METHODS: A literature search of Ovid MEDLINE, Embase, and Cochrane databases was conducted from 1980 to March 2021 to identify RCT on the use of PBMT for RD prevention. Forest plots were developed using RevMan software to quantitatively compare data between studies. RESULTS: Five papers were identified: four in breast and one in head and neck cancer patients. Patients receiving PBMT experienced less severe RD than the control groups after 40 Gray (Gy) of RT (grade 3 toxicity: Odds Ratio (OR): 0.57, 95% CI 0.14-2.22, p = 0.42) and at the end of RT (grade 0 + 1 vs. 2 + 3 toxicity: OR: 0.28, 95% CI 0.15-0.53, p < 0.0001). RT interruptions due to RD severity were more frequent in the control group (OR: 0.81, 95% CI 0.10-6.58, p = 0.85). CONCLUSION: Preventive PBMT may be protective against the development of severe grades of RD and reduce the frequency of RT interruptions. Larger sample sizes and other cancer sites at-risk of RD should be evaluated in future studies to confirm the true efficacy of PBMT, also in preventing the onset of RD and to finalize a standardized protocol to optimize the technique. At present, starting PBMT when RT starts is recommendable, as well as performing 2 to 3 laser sessions weekly.

Natural and miscellaneous agents for the prevention of acute radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the available literature describing the efficacy of natural and miscellaneous agents in preventing acute radiation dermatitis (RD) in cancer patients. METHODS: OVID MedLine, Embase, and Cochrane literature databases were searched from 1946 to January 2023 for randomized controlled trials studying the use of natural and miscellaneous agents to prevent RD. RevMan 5.4 was used for the meta-analysis to calculate the pooled effect sizes and 95% confidence intervals (CI) using the random effects analysis. RESULTS: For the systematic review and meta-analysis, 19 and 16 studies were included, respectively. Of the five studied natural products (aloe vera, oral enzymes, olive oil, calendula, and curcumin), only oral enzymes and olive oil significantly reduced the incidence of Radiation Therapy Oncology Group grade 2+ (RR: 0.42, 95%CI 0.30-0.58, p < 0.00001, RR: 0.66, 95% CI 0.51-0.85, p = 0.001, resp.). The oral enzymes also reduced the grade 3+ RD incidence (RR: 0.18, 95%CI 0.06-0.55, p = 0.003). The other agents demonstrated no significant effect. CONCLUSION: This review and meta-analysis on natural and miscellaneous agents in preventing RD in cancer patients demonstrated that oral enzymes and olive oil prevented RD severity. However, evidence supporting natural agents to prevent RD is inconsistent, mainly because of low studies numbers, low-quality study designs, and small sample sizes. Therefore, concrete conclusions cannot be made. Research on (new) natural or miscellaneous agents should focus on a randomized controlled double-blinded study design with a large patient population, a higher consistency in research methods, and clinician- and patient-reported outcomes.

Topical non-steroidal agents for the prevention of radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: Radiation dermatitis (RD) is a common side effect of radiation therapy, affecting a majority of breast and head and neck cancer patients with a negative impact on quality of life. Currently, no consensus exists regarding the prevention of RD. METHODS: PubMed, Embase and Cochrane databases (1946 to December 2022) were searched using PRISMA guidelines to identify randomized controlled trials (RCTs) that investigated the use of topical non-steroidal agents in the prevention of RD in patients undergoing radiotherapy. RESULTS: A total of six RCTs were included, comprising 627 patients. Among the topical non-steroidal agents analyzed, only the use of Biafine® in breast cancer patients was significant in preventing grade 4 and 3 + RD as classified by the Radiation Therapy Oncology group (RTOG) scale (OR = 0.07, 95% CI 0.01-0.63, p = 0.02, and OR 0.11, 95% CI 0.03-0.41, p < 0.01, respectively). The remaining agents (trolamine alone and hyaluronic acid/hyaluronan) did not significantly prevent the occurrence of RD. CONCLUSION: The results of this systematic review and meta-analysis indicate that Biafine® can prevent grade 3 + RD in breast cancer patients. The use of trolamine and hyaluronic acid does not significantly affect the incidence of RD.