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The mid-Pliocene Warm Period (mPWP, 3.3–3.0 Ma) was characterised by an atmospheric CO2 concentration exceeding 400 ppmv with minor changes in continental and orbital configurations. Simulations of this past climate state have improved with newer models but still show some substantial differences from proxy reconstructions. There is little information about atmospheric aerosol concentrations during the Pliocene, but previous work suggests that it could have been quite different from the modern period. Here we apply idealised aerosol scenario experiments to examine the importance of aerosol forcing on mPWP tropical precipitation and the possibility of aerosol uncertainty explaining the mismatch between reconstructions and simulations. The absence of industrial pollutants leads to further warming, especially in the Northern Hemisphere. The Intertropical Convergence Zone (ITCZ) becomes narrower and stronger and shifts northward after removal of anthropogenic aerosols. Though not affecting the location of monsoon domain boundary, removal of anthropogenic aerosol alters the amount of rainfall within the domain, increasing summer rain rate over eastern and southern Asia and western Africa. This work demonstrates that uncertainty in aerosol forcing could be the dominant driver in tropical precipitation changes during the mid-Pliocene: causing larger impacts than the changes in topography and greenhouse gases.

During the mid-Pliocene warm period (mPWP; 3.264–3.025 Ma), atmospheric CO2 concentrations were approximately 400 ppm, and the Antarctic Ice Sheet was substantially reduced compared to today. Antarctica is surrounded by the Southern Ocean, which plays a crucial role in the global oceanic circulation and climate regulation. Using results from the Pliocene Model Intercomparison Project (PlioMIP2), we investigate Southern Ocean conditions during the mPWP with respect to the pre-industrial period. We find that the mean sea surface temperature (SST) warming in the Southern Ocean is 2.8 °C, while global mean SST warming is 2.4 °C. The enhanced warming is strongly tied to a dramatic decrease in sea ice cover over the mPWP Southern Ocean. We also see a freshening of the ocean (sub)surface, driven by an increase in precipitation over the Southern Ocean and Antarctica. The warmer and fresher surface leads to a highly stratified Southern Ocean that can be related to weakening of the deep abyssal overturning circulation. Sensitivity simulations show that the decrease in sea ice cover and enhanced warming is largely a consequence of the reduction in the Antarctic Ice Sheet. In addition, the mPWP geographic boundary conditions are responsible for approximately half of the increase in mPWP SST warming, sea ice loss, precipitation, and stratification increase over the Southern Ocean. From these results, we conclude that a strongly reduced Antarctic Ice Sheet during the mPWP has a substantial influence on the state of the Southern Ocean and exacerbates the changes that are induced by a higher CO2 concentration alone. This is relevant for the long-term future of the Southern Ocean, as we expect melting of the western Antarctic Ice Sheet in the future, an effect that is not currently taken into account in future projections by Coupled Model Intercomparison Project (CMIP) ensembles.

Autism spectrum disorder (ASD) is characterized by social difficulties and often accompanied by internalizing and externalizing problems, which are frequently overlooked. Here, we examined and compared fractional anisotropy (FA) between 79 children with ASD (aged 4-7.8 years) and 70 age-, gender-, and handedness- matched typically developing controls (TDCs, aged 3-7.2 years). We aimed to explore the relationship among social difficulties, internalizing and externalizing problems, and brain structural foundation (characterized by white matter integrity). Compared with the TDCs, the children with ASD exhibited more severe internalizing and externalizing problems, which were positively correlated with social difficulties. Reduced FA values were observed in specific white matter tracts that integrate a fronto-temporal-occipital circuit. In particular, the FA values within this circuit were negatively correlated with internalizing problems and SRS-TOTAL scores. Mediation analysis revealed that internalizing problems mediated the relationship between the FA values in the left middle longitudinal fasciculus (L-MdLF) and corpus callosum forceps major (CCM) and social difficulties in children with ASD. These findings contribute to our understanding of social difficulties, internalizing and externalizing problems, and white matter integrity in children with ASD and highlight internalizing problems as a mediator between social difficulties and white matter integrity., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The DNA demethylating therapy with azacitidine (AZA) is a promising therapeutic strategy for elderly patients with acute myeloid leukemia (AML). AZA primarily inhibits DNA methylation, promotes cell differentiation and apoptosis in AML. However, as a cytosine nucleoside analog, AZA also has the potential to be incorporated into RNA molecules. To assess the impact of AZA on RNA m5C methylation during demethylating therapy, we conducted Nanopore direct-RNA sequencing on samples from three AML patients pre and after demethylating therapy, as well as on HL-60 cells pretreated with AZA. We performed an integrated analysis of the transcriptome and the m5C methylome, contrasting the states of complete remission with those of active disease (AML). Our results revealed an extensive demethylation effect at the RNA level attributable to AZA and found that mRNA m5C modification may play a pivotal role in the progression of AML. Additionally, S100P was identified as a biomarker with significant prognostic implications. We also conducted a conjoint analysis of the transcriptome and the m5C methylome of the full-length transcripts, uncovering several dysregulated mRNA isoforms. Collectively, our findings indicate that mRNA m5C methylation is implicated during AML progression, and AZA exhibits an overall suppressive effect on this process., (© 2024 The Author(s). Molecular Carcinogenesis published by Wiley Periodicals LLC.)

Aggregation-induced electrochemiluminescence (AIECL) provides a new approach for the development of novel electrochemiluminescence (ECL) strategies. Herein, a biosensor was constructed by incorporating 1,1,2,2-tetra(4-carboxylphenyl)ethylene (H 4 TCPE) into a mesoporous silica nanosphere (MSN) to obtain a highly organized AIECL luminophore of (MSN-H 4 TCPE) for signal antibody (Ab 2 ) labeling and using Pd nanocube (NC)-loaded Co 3 O 4 nanosheets (NSs) (PdNCs/Co 3 O 4 NSs) as a novel coreaction accelerator. The confinement of H 4 TCPE molecules in the MSN restricted the intramolecular rotation and thus enhanced the radiation transition of H 4 TCPE. In addition, the PdNCs/Co 3 O 4 NSs exhibited efficient mutual conversion of the Co 2+ /Co 3+ redox couple with the perfect catalytic performance of PdNCs and facilitated the decomposition of the coreactant, leading to a substantial enhancement in ECL signal. Subsequently, the localization and fixation strategy with HWRGWVC (HWR) heptapeptides as a specific antibody immobilization agent was introduced, which further maintained the biological activity of the antibody on the PdNCs/Co 3 O 4 NSs and MSN-H 4 TCPE surface and significantly improved the incubation performance. Benefiting from the perfect sensing strategy, the obtained ECL immunosensor revealed an admirable manifestation for the precise detection of neuron-specific enolase (NSE) with a broad concentration range of 1 fg/mL to 5 ng/mL and a detection limit of 0.33 fg/mL.

Background: Large language models (LLMs), such as ChatGPT, excel at interpreting unstructured data from public sources, yet are limited when responding to queries on private repositories, such as electronic health records (EHRs). We hypothesized that prompt engineering could enhance the accuracy of LLMs for interpreting EHR data without requiring domain knowledge, thus expanding their utility for patients and personalized diagnostics., Methods: We designed and systematically tested prompt engineering techniques to improve the ability of LLMs to interpret EHRs for nuanced diagnostic questions, referenced to a panel of medical experts. In 490 full-text EHR notes from 125 patients with prior life-threatening heart rhythm disorders, we asked GPT-4-turbo to identify recurrent arrhythmias distinct from prior events and tested 220 563 queries. To provide context, results were compared with rule-based natural language processing and BERT-based language models. Experiments were repeated for 2 additional LLMs., Results: In an independent hold-out set of 389 notes, GPT-4-turbo had a balanced accuracy of 64.3%±4.7% out-of-the-box at baseline. This increased when asking GPT-4-turbo to provide a rationale for its answers, requiring a structured data output, and providing in-context exemplars, rose to a balanced accuracy of 91.4%±3.8% ( P <0.05). This surpassed the traditional logic-based natural language processing and BERT-based models ( P <0.05). Results were consistent for GPT-3.5-turbo and Jurassic-2 LLMs., Conclusions: The use of prompt engineering strategies enables LLMs to identify clinical end points from EHRs with an accuracy that surpassed natural language processing and approximated experts, yet without the need for expert knowledge. These approaches could be applied to LLM queries for other domains, to facilitate automated analysis of nuanced data sets with high accuracy by nonexperts.

T-cell acute lymphoblastic leukaemia (T-ALL) is a heterogeneous malignant disease with high relapse and mortality rates. To characterise the multiomics features of T-ALL, we conducted integrative analyses using single-cell RNA, TCR and chromatin accessibility sequencing on pre- and post-treatment peripheral blood and bone marrow samples of the same patients. We found that there is transcriptional rewiring of gene regulatory networks in T-ALL cells. Some transcription factors, such as TCF3 and KLF3, showed differences in activity and expression levels between T-ALL and normal T cells and were associated with the prognosis of T-ALL patients. Furthermore, we identified multiple malignant TCR clonotypes among the T-ALL cells, where the clonotypes consisted of distinct combinations of the same TCR α and β chain per patient. The T-ALL cells displayed clonotype-specific immature thymocyte cellular characteristics and response to chemotherapy. Remarkably, T-ALL cells with an orphan TCRβ chain displayed the strongest stemness and resistance to chemotherapy. Our study provided transcriptome and epigenome characterisation of T-ALL cells categorised by TCR clonotypes, which may be helpful for the development of novel predictive markers to evaluate treatment effectiveness for T-ALL., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

The research compared the combined effect of ultrasound (160 W, 2 min), oleic acid (15%, 11 h), and moist-heat treatment (HMT, 25% moisture content, 110 °C, 2 h) with their individual treatment on rice grains. The results showed that ultrasound treatment created pores and cracks in the rice grains, facilitating an easier penetration for oleic acid to develop amylose-oleic acid complex during HMT. Compared to native raw rice (NR), both single and combined treatments significantly altered the morphology, reduced swelling power and solubility, enhanced hydrophilicity, thus changing the moisture distribution, thermal and pasting characteristics. Notably, the combined treatment of three techniques significantly increased the relative crystallinity, accompanied by the highest digestive resistance, and the content of resistant starch was increased from 20.53% in NR to 31.75%, much higher than the other treatments. These findings provide potential for the manufacturers to rationally and flexibly employ this low digestible rice in health food products., Competing Interests: Declaration of competing interest The authors have no any conflict of interests or personal relationship that might influenced the work related to this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Meralgia paresthetica (MP) is a neuropathic condition marked by pain, tingling, and numbness in the anterolateral thigh, primarily caused by compression of the lateral femoral cutaneous nerve (LFCN). Although compression often occurs beneath the inguinal ligament, anatomical variations can lead to different entrapment sites. Treatments range from conservative measures to surgical decompression, depending on symptom severity. This study provides an anatomical review of the LFCN and presents a unique case of MP where the LFCN was compressed by the sartorius fascia rather than the typical site beneath the inguinal ligament. The study also explores the use of the Synaptive Modus X robotic exoscope for surgical decompression., Methods: This article presents a case study of a man in his 40s with a 15-year history of chronic MP symptoms, where the LFCN was atypically compressed by the sartorius fascia. Surgical decompression was performed using the robotic exoscope, a device offering high-definition, 3-dimensional visualization., Results: At 13 weeks postoperatively, the patient experienced improvement in thigh sensation and no pain. He returned to baseline ambulation with no complications. The exoscope allowed precise identification of the LFCN's anatomy and compression site, proving effective in enhancing surgical precision., Conclusions: This is the first report of primary LFCN decompression using the Synaptive Modus X exoscope. The device provides excellent visualization, ergonomic benefits, and educational advantages, making it a valuable alternative to traditional microscopes and loupes in nerve decompression and other microsurgical procedures. Further studies are needed to assess its cost-effectiveness and broader applications in plastic surgery., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Polycystic ovary syndrome (PCOS) is a prevalent yet complex reproductive endocrine disorder affecting 11-13% of women worldwide. Its main symptoms include elevated androgen levels, irregular menstrual cycles, and long-term metabolic and offspring health implications. Despite the disease's multifaceted nature involving genetic, epigenetic, and environmental factors, the role of alternative splicing in ovarian granulosa cells remains relatively unexplored. This study aims to investigate the transcriptional and alternative splicing characteristics of granulosa cells in PCOS patients and to elucidate the potential functional consequences of these changes. Analysis of previous published transcriptome sequencing data identified 491 upregulated and 401 downregulated genes in granulosa cells of PCOS patients, significantly involved in immune-related processes. Additionally, 1250 differential splicing events, predominantly involving exon skipping and affecting 947 genes, were detected. These genes with alternative splicing patterns were found to be enriched in endoplasmic reticulum stress and protein post-translational modification processes, suggesting their role in PCOS pathology. Moreover, the study highlighted that the utilization of different splice isoforms of the YAP1 gene may impact its interaction in the Hippo signaling pathway, influencing the pathogenesis of PCOS. These findings underscore substantial alterations in alternative splicing in granulosa cells of PCOS patients, providing a novel viewpoint for comprehending the molecular underpinnings of PCOS and suggesting potential avenues for therapeutic intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chiral hybrid metal halides have received considerable attention in circularly polarized luminescence and spintronics due to their structural diversity, ease of synthesis, and chemical versatility. However, only a limited number of chiral metal halides have been utilized in piezoelectric energy harvesters and motion sensors. Furthermore, the exploration of 0D chiral piezoelectric materials is still in their early stage, offering substantial potential for further development. Herein, a pair of enantiomorphic hybrid metal halide piezoelectrics, R-(1-2-NEA)2CdCl4 and S-(1-2-NEA)2CdCl4 (1-2-NEA+ = 1-(2-naphthyl) ethylamine cation), were synthesized and structurally characterized. In addition, the devices comprising R-(1-2-NEA)2CdCl4/PDMS or S-(1-2-NEA)2CdCl4/PDMS (PDMS = polydimethylsiloxane) composite films were fabricated, and the energy harvesting performance of the devices with varying halide contents was explored. The results demonstrate that the devices comprising 10 wt% R-(1-2-NEA)2CdCl4/PDMS or S-(1-2-NEA)2CdCl4/PDMS exhibit significant energy harvesting capabilities, with an open-circuit voltage and a short-circuit current up to 8.24 V and 0.72 μA, respectively. Furthermore, the devices display exceptional mechanical durability after 4500 cycles and demonstrate excellent sensitivity in detecting various human body movements, such as walking, elbow bending, and finger bending. This study highlights the considerable potential of chiral hybrid metal halides for use in energy harvesting and wearable sensors., (© 2024 Wiley‐VCH GmbH.)

Background: The clinical characteristics and time-to-onset of thromboembolic events (TEEs) associated with combined oral contraceptives (COCs) remain unclear, our current study was committed to providing more data for risk evaluation and management of COCs treatment., Research Design and Methods: This pharmacovigilance study was conducted in the FAERS database. We evaluated significant pharmacovigilance signals by using disproportionality analysis. The Weibull shape parameter test was used to analyze the time-to-onset of TEEs., Results: A total of 25,080 adverse events were involved in this study. Overall COCs were significantly related to venous thromboembolism (VTE) events. Levonorgestrel, desogestrel, and drospirenone containing COCs were significantly associated with arterial thromboembolism (ATE) besides norethisterone containing COCs. Drospirenone containing COCs associated with TEEs had the highest reporting frequencies ( n  = 22868, 91.18%). The most-mentioned PT was pulmonary embolism ( n  = 9244, 36.86%). The median time-to-onset of all TEEs was 264 days, the median time-to-onset of VTE was 258.0 days, shorter than ATE (344.0 days). The Weibull shape parameter test results showed that all of the disproportionality signals had early failure-type features., Conclusions: This study found an increased risk of TEEs treated with COCs, particularly with drospirenone. We should pay close attention to risk monitor on the treatment of early stages.

The heterogeneity and suboptimal efficacy of biological treatments and small molecule drugs necessitate their precise selection based on biomarkers that predict therapeutic responses in inflammatory bowel disease. Recent studies have identified numerous novel biomarkers predictive of responses to biologics and small molecule modulators, utilizing a variety of omics approaches in inflammatory bowel disease. In this review, we systematically examine baseline omics biomarkers that predict responses to biological therapies and small molecule drugs, drawing on literature from PubMed. Our analysis spans multiple omics disciplines, including genomics, transcriptomics (both bulk RNA and single-cell RNA sequencing), proteomics, microbiomics, and metabolomics, with particular emphasis on the impact of models integrating multiple omics datasets. Additionally, to further the field of precision medicine, we evaluated specific biomarkers that may exhibit distinct effects on responses to multiple therapeutic interventions., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Multi-level non-volatile ferroelectric memories are emerging as promising candidates for data storage and neuromorphic computing applications, due to the enhancement of storage density and the reduction of energy and space consumption. Traditional multi-level operations are achieved by utilizing intermediary polarization states, which exhibit an unpredictable ferroelectric domain switching nature, leading to unstable multi-level memory. In this study, a unique approach of composition-graded ferroelectric ScAlN to achieve tunable operating voltage in a wide range and attain precise control of domain switching and stable multi-level memory is proposed. This non-volatile memory supports multi-level storage up to 7-bit capacities, and exhibits enhanced performance compared to the uniform composition device, showing one order of magnitude higher ON/OFF ratio, 30% reduced working voltage, and up to 50% enhanced tuning window of operating voltage. Finally, the emulation of long-term plasticity and linear weight update akin to biological synapse with high uniformity and reliability are demonstrated. The proposed composition-grading architecture offers new opportunities for next-generation multi-level ferroelectric memories, paving the way for advanced hybrid integration in multifunctional computing systems., (© 2024 Wiley‐VCH GmbH.)

The black soldier fly larvae (BSFL) is a highly valued resource insect, renowned for its efficient and eco-friendly approach to the treatment of organic waste. A crucial matter that demands clarification is whether the heavy metals are eliminated or remain within BSFL bodies. Our research focused on the toxicokinetic and the dynamic tissue changes of cadmium (Cd) in BSFL exposed to low (50 mg/kg), moderate (300 mg/kg), and high levels (700 mg/kg) of Cd stress, with the goal of offering a novel perspective on this matter. Our results demonstrated a negative correlation with the BAF kinetic and a positive correlation with the BAF as Cd concentrations increased. BSFL exhibited significant rates of Cd uptake, with values for Cd 50, Cd 300 , and Cd 700 being K 1 = 1.3998, 0.9794, and 0.9023 g substrate g larvae -1 day -1 , respectively. Across all treatments, BSFL were capable of excreting Cd, with a DT 50 less than 2 days. The gut, particularly the midgut, was identified as the primary tissue for Cd enrichment. The anterior midgut played a pivotal role as a critical organ during high Cd exposure, while the middle midgut served as a stable storage organ. The posterior midgut was the preferred tissue for Cd accumulation. Following bioconversion by BSFL, the concentration and bioavailability of Cd in the resulting residue were altered. In conclusion, BSFL possess significant potential for swiftly mitigating high-concentration Cd pollution. Moreover, the application of a 2-day short-term elimination feeding strategy can significantly elevate the food safety and safety for animal consumption of BSFL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Urban resilience is crucial for sustainable development and resident safety in a changing environment with potential risks. Given China's rapid urbanization, constructing resilient cities that anticipate risks, mitigate disaster impacts, and swiftly recover from crises is paramount. This study explores a key area of urban construction: building safety. We apply the dynamic nonhomogeneous grey model (DNMGM(1,1)) to simulate the building death toll and use a traffic accident death toll dataset for validation. Unlike traditional models, DNMGM(1,1) can integrate and respond to new data points in real-time, thus producing accurate predictions when facing new trends or fluctuations in the data. The research findings indicate that with a dataset size of 6, the DNMGM(1,1) model achieves average relative errors of 9.26% and 7.29% when predicting fatalities in both construction and traffic accidents. This performance demonstrates superior prediction accuracy compared to traditional grey models. This method uses prediction models to support the construction of elastic cities, providing strong data support and decision-making tools for planning and resource allocation. Specific interventions and policy frameworks based on this study by urban planners and policymakers can promote resilient urban development. Future efforts should strive to enhance its robustness and adaptability in different fields., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A novel dicyanoisophorone-based colorimetric fluorescent probe 3 has been prepared for recognizing peroxynitrite in aqueous conditions. A large bathochromic shift of the absorption band is observed upon titration with ONOO - , inducing a clearly visible solution color change from yellow to pale pink, which makes "naked-eye" detection possible. Moreover, probe 3 can react instantly with ONOO - and is accompanied by a significant fluorescence enhancement at 621 nm while the detection limit is as low as 37 nM. Most importantly, probe 3 exhibits high selectivity and sensitivity towards ONOO - in the presence of other competitive ions in aqueous solution. Probe 3 has also been successfully applied in living MCF-7 cells, and the results suggest that probe 3 could be applied as a potential candidate for the detection of ONOO - .

The increase in atmospheric methane (CH 4 ) level directly contributes to approximately one-fifth of global mean temperature rise since preindustrial era, only next to CO 2 . Global anthropogenic CH 4 emissions has augmented by nearly three-fifths during the past five decades; due to climate change, natural CH 4 emissions are plausibly projected to increase in the foreseeable future. Thereby, examining and projecting long-term natural and anthropogenic CH 4 emissions and sinks are imperative. According to peer-reviewed literatures as information sources for this compendium, we recapitulate natural and anthropogenic CH 4 emissions, summarize available abatement approaches and their mitigation potentials, and investigate and encapsulate economic costs and social benefits of reductions. We list current challenges in realizing CH 4 emissions reductions and suggest possible technical pathways for future mitigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Importance: Regulatory guidance and standardization of disease outcome measures are essential to improve cutaneous lupus erythematosus (CLE) trial design and enhance the diversity of trial participants., Objective: To assess variability in erythema presentation across CLE subtypes and among race and ethnicity groups to determine whether these potential differences affect patient eligibility for erythema trials., Design, Setting, and Participants: This cross-sectional study included 377 patients with CLE enrolled in the University of Pennsylvania Cutaneous Lupus Erythematosus Database from January 2007 to December 2023. Data analyses were performed from December 2023 to February 2024., Exposure: Race and CLE subtype., Main Outcomes and Measures: Mean erythema calculated per the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-Activity total score divided by areas affected; then, the result was categorized as pink (1.00-1.49) or red (≥1.50) as surrogate estimates of scores per the Cutaneous Lupus Activity Investigator Global Assessment (CLA-IGA)., Results: The total study cohort included 377 adult patients with CLE (mean [SD; range] age, 45.2 [14.8; 18.4-88.8] years; 305 females [80.9%] and 72 males [19.1%]; 115 Black [30.5%], 228 White [60.5%], 34 patients of other races [9.0%; Asian, multiple races, Native American/Pacific Islander, or unknown], and 11 of Hispanic/Latino ethnicity [2.9%]). The most common CLE subtype was chronic CLE (CCLE), affecting 243 patients (64.5%), followed by subacute CLE (SCLE) in 103 patients (27.3%) and acute CLE (ACLE) in 31 patients (8.2%). Significant differences were observed in average erythema across subtypes, with mean (SD) SCLE of 1.62 (0.39) and hypertrophic CCLE of 1.78 (0.25) as the only subtypes routinely classified as red. Significant differences were also observed by race and ethnicity: mean (SD) erythema score in White patients was red (1.58 [0.45]) more frequently than in Black patients (1.36 [0.40]) and patients of other races (1.30 [0.39]), in whom, on average, it was scored as pink. Importantly, among patients who would meet typical CLASI entry criteria (score ≥8) for clinical trials, erythema in more Black patients than in White patients was classified as pink (42% [96 patients] vs 24% [28 patients]), which suggests exclusion from trial participation when a baseline of red lesions is required., Conclusions and Relevance: The findings of this cross-sectional study suggest that using average erythema scores per the CLA-IGA scale imposes substantial limitations on trial eligibility, specifically by race and subtype. Given the critical need to standardize CLE trial outcome measures and increase diverse representation in clinical trials, our findings support the use of the CLASI as the primary scoring tool to determine erythema trial eligibility.

Pseudoalteromonas are abundant in the oceans and possess great potential in the synthesis of bioactive natural products. Although many secondary metabolite biosynthetic gene clusters have been identified from Pseudoalteromonas genomes, most of their products have not been characterized. In this study, endogenous constitutive promoters with high transcriptional activity were obtained from Pseudoalteromonas flavipulchra S16 through RNA-seq and a fluorescence assay of luciferase gene expression. Through in situ promoter replacement two silent biosynthetic gene clusters (BGCs) were successfully activated, leading to production of intramolecular cyclized alteramides and two novel ureido-containing linear peptides, alteropeptilides. This study provides a feasible approach for the activation of silent BGCs and the mining of novel compounds from marine bacteria.

The delivery vehicles based on protein-polysaccharide-polyphenol are promising methods to encapsulate bioactive components with the aim of improving their solubility and bioavailability. In this study, we used Flammulina velutipes protein (FVP) and Flammulina velutipes soluble polysaccharides (FVSP) as raw materials and prepared FVP-FVSP and FVP-FVSP-TP composite particles loaded with tea polyphenols (TP), the high internal phase Pickering emulsions stabilized by FVP-FVSP and FVP-FVSP-TP for the delivery of β-carotene (BC) were created. FVP-FVSP-TP has more promise as Pickering emulsion stabilizer than FVP-FVSP because of the smaller particle size, proper contact angle, and lower surface tension. The optimal preparation conditions of the emulsion were 4 % particle concentration and 80 % oil phase volume fraction. The emulsions stabilized by FVP-FVSP and FVP-FVSP-TP were o/w emulsions. Compared to the emulsion stabilized by FVP-FVSP, the FVP-FVSP-TP stabilized emulsion had higher G', G″ values and viscosity and showed better thermal, centrifugal, storage and oil oxidation stability. Moreover, FVP-FVSP-TP stabilized emulsions could further enhance the retention rate and bioaccessibility of TP and β-carotene. This study provides a theoretical basis for the application of FVP and FVSP in Pickering emulsions, and a reference for the fabrication of delivery vehicles to improve the stability and bioaccessibility of bioactive substances., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the progressive loss of motor neurons. Recent insights into ALS pathogenesis underscore the pivotal role of the gut microbiome, prompting an investigation into the potential therapeutic impact of fecal microbiota transplantation (FMT) on sporadic ALS patients., Methods: Conducted as a double-blind, placebo-controlled, parallel-group, randomized clinical trial, the study enrolled 27 participants from October 2022 to April 2023. The participants were followed up for 6 months from February 2023 to October 2023, during in-person visits at baseline, week 15, week 23, and week 35. The participants, evenly randomized, received either healthy donor FMT (FMT, n = 14) or a mixture of 0.9% saline and food coloring (E150c) as sham transplantation (placebo, n = 13). The primary outcome measured the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score from baseline to week 35. Secondary outcomes included changes in gastrointestinal and respiratory functions, muscle strength, autonomic function, cognition, quality of life, intestinal microbiome composition, and plasm neurofilament light chain protein (NFL). Efficacy and safety outcomes were assessed in the intention-to-treat population., Results: A total of 27 randomized patients (47% women; mean age, 67.2 years), 24 participants completed the entire study. Notably, ALSFRS-R score changes exhibited no significant differences between FMT (6.1 [SD, 3.11]) and placebo (6.41[SD, 2.73]) groups from baseline to week 35. Secondary efficacy outcomes, encompassing respiratory function, muscle strength, autonomic function, cognition, quality of life, and plasm NFL, showed no significant differences. Nevertheless, the FMT group exhibited improvements in constipation, depression, and anxiety symptoms. FMT induced a shift in gut microbiome community composition, marked by increased abundance of Bifidobacterium, which persisted until week 15 (95% CI, 0.04 to 0.28; p = 0.01). Gastrointestinal adverse events were the primary manifestations of FMT-related side effects., Conclusions: In this clinical trial involving 27 sporadic ALS patients, FMT did not significantly slow the decline in ALSFRS-R score. Larger multicenter trials are needed to confirm the efficacy of FMT in sporadic ALS patients and to explore the underlying biological mechanisms., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR 2200064504., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was obtained from the Institutional Ethics Committees of the First Affiliated Hospital of Zhengzhou University (2021-KY-0385–002). Participants gave informed consent to participate before being enrolled. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Electroreduction of CO 2 into multi-carbon (C2+) products (e.g. C2+ alcohols) offers a promising way for CO 2 utilization. Use of strong alkaline electrolytes is favorable to producing C2+ products. However, CO 2 can react with hydroxide to form carbonate/bicarbonate, which results in low carbon utilization efficiency and poor stability. Using acidic electrolyte is an efficient way to solve the problems, but it is a challenge to achieve high selectivity of C2+ products. Here we report that the amine modified copper nanoparticles exhibit high selectivity of C2+ products and carbon utilization at acidic condition. The Faradaic efficiency (FE) of C2+ products reach up to 81.8 % at acidic media (pH=2) with a total current density of 410 mA cm -2 over n-butylamine modified Cu. Especially the FE of C2+ alcohols is 52.6 %, which is higher than those reported for CO 2 electroreduction at acidic condition. In addition, the single-pass carbon efficiency towards C2+ production reach up to 60 %. Detailed studies demonstrate that the amine molecule on the surface of Cu cannot only enhance the formation, adsorption and coverage of *CO, but also provide a hydrophobic environment, which result in the high selectivity of C2+ alcohols at acidic condition., (© 2024 Wiley-VCH GmbH.)

Objectives: Low-dose interleukin 2 (Ld-IL2) is increasingly being explored as an immune-modulating treatment for autoimmune diseases which mainly affect T cell subsets. This study investigates the metabolic effects of Ld-IL2 therapy in patients with primary Sjögren's syndrome (pSS)., Method: A total of 60 patients were recruited to conduct a double-blind, randomized clinical trial. Of these patients, 50% (30/60) received Ld-IL2 therapy along with standard treatment for 12 weeks, followed by 12 weeks of follow-up. The effectiveness was evaluated by Sjögren's Tool for Assessing Response (STAR). An untargeted analysis was performed to profile hydrophilic metabolites., Results: Metabolic profiling revealed significant alterations post-treatment, notably in metabolites like acetyl-CoA, ascorbic acid, and glutathione, which are beneficial in managing autoimmune diseases. In addition, the levels of metabolite accumulation were correlated with variations in immune cell subsets (p < 0.05), particularly Tregs. Moreover, patients exhibiting a specific metabolic profile, including lower serum levels of isoleucine, ADP, Thymidine 5'-triphosphate, and other metabolites, had a high response rate (91.7%-98.6%), as indicated by the receiver operating characteristic (ROC) curve., Conclusions: These findings suggest that Ld-IL2 therapy influences metabolic pathways in pSS, offering insights into the systemic effects of Ld-IL2 therapy beyond immune modulation., Trial Registration Number: ClinicalTrials.gov number, NCT02464319. Key Points • Metabolic alteration in pSS is significantly associated with Ld-IL2 therapy. • Metabolic changes correlate with variations in immune cell subsets, particularly Tregs. • Metabolic profiling could be a valuable tool in guiding Ld-IL2 therapy choices for pSS patients., Competing Interests: Declarations. Ethics statements: This study involves human participants and was approved by the Human Ethics Committee of Peking University People’s Hospital (Beijing, China) (2020PHB359-01). Participants gave informed consent to participate in the study before taking part. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s).)

Membranous nephropathy (MN) is an autoimmune disease that is caused by the production of autoantibody against glomerular podocyte antigens by immune cells due to the lack of self-tolerance mechanisms. Similar to many autoimmune diseases, the pathogenesis of MN is still vague and many experiments are being conducted to detect the antigens and genetic reasons for MN illness. Recently, new antigens, such as exotosin 1/exotosin 2, neural EGF-like-1, semaphorin 3B, and protocadherin 7 have been identified in MN patients who did not have presence of antiphospholipase A2 receptor antigen. What is more, cytokines, which are molecules that regulate immune responses, have been found to have harmful effects in various autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and MN. The role of cytokines and treatment strategies in MN patients is discussed in this article. As the understanding of the disease improves, targeted therapies that focus on specific antigens or cytokines may be developed to effectively manage MN.

Background: Cinnabaris, as a commonly used mineral drugs, is a classic sedative medicine. Shang-Ke-Jie-Gu tablet is a famous Chinese patent medicine with Cinnabaris, However, the function of Cin in the prescription hasn't been clarified., Purpose: Our study evaluated the toxicity of Shang-Ke-Jie-Gu tablet (SK) with or without Cinnabaris, and illuminate the related mechanisms that why cinnabaris is necessary., Methods: The toxicity of SK and Cin free Shang-Ke-Jie-Gu tablet (CFSK) was evaluated by physical and behavioral tests and histological examinations. The detoxificaion mechanism of Cin on Strychni Semen (SS)-induced neurotoxicity in SK was performed based on the analysis of intestinal absorption, liver metabolism, serum metabolomics, and gut microbiota. The mercury accumulation of SK was assayed using human hair by ICP-MS., Results: Cin was found to inhibit the neurotoxicity of SS in SK. Our study shows that Cin could inhibit SS's absorption in small intestine and promote its metabolism in the liver. A serum metabolomics study showed that taurine and hypotaurine metabolism and retrograde endocannabinoid signaling pathway were associated with Cin attenuation. Association analysis with gut microbiota suggested that Cin could downregulate four key metabolites, including 12‑hydroxy arachidonic acid, GM4(d18:1/18:0), C16 sphinganine, and LysoPC(18:1(11Z)/0:0), by downregulating Lachnospiraceae&#95;NK4A136 and upregulating Prevotella to inhibit the toxic effects of SS. In addition, the danger of mercury poisoning in a longer time administration of SK was evaluated using human hair, and no visible increase in mercury was observed., Conclusion: As a new discovery in compatibility, Cin was proved to be capable of inhibiting the neurotoxicity not only in SK but also in Cin-SS combination, displaying vital roles in Traditional Chinese Medicines., Competing Interests: Declaration of competing interest The authors (Na Han, Taotao Wang, Sheng Chang, Rong Gao, Yuanyuan Wen, Zhihui Liu, Haoying Xi, Jianxiu Zhai, Ruimao Feng, Sikai Li, Jun Yin) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All data were generated inhouse, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy., (Copyright © 2024. Published by Elsevier GmbH.)

Chitosan, as a kind of naturally occurring green and degradable material for the preservation of perishable foods, was investigated in this study with the objective of enhancing its preservation performances. Herein, lignin was modified using the solvent fractionation method (modified lignin, ML, including ML1-ML3), while natural clinoptilolite zeolite was modified using the alkali modification method (modified clinoptilolite zeolite, MCZ, including MCZ1-MCZ5). After optimizing the conditions, it was discovered that incorporating both ML3 and MCZ3 into pure chitosan-based membranes might be conducive to fabricate chitosan-based composite membranes for the preservation of perishable foods. As-prepared composite membranes possessed better visible light transmittance, antioxidant activity, and carbon dioxide/oxygen selectivity, resulting in improved preservation effects on the model perishable foods such as bananas, cherry tomatoes, and cheeses. These findings might indicate promising applications for chitosan-based composite membranes with modified lignin and zeolite in the field of eco-friendly degradable materials for the preservation of perishable foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, a novel dextrin-based micelle (OSAD-SH), dual-modified with octenyl succinic anhydride (OSA) and cysteamine, was developed to address the acid instability issues of micelle modified only by OSA and designed for curcumin delivery. Three amphiphilic OSAD-SH polymers with different free sulfhydryl content were first synthesized. The study demonstrated that OSAD-SH micelles exhibited strong self-assembly properties, appearing as spheres with diameters ranging from 92.41 to 194.20 nm. Blank micelles showed good dilution resistance, as well as stability against acid, thermal, and ionic strength. The curcumin encapsulated by the micelles was in an amorphous state. In vitro release experiment demonstrated that curcumin released from OSAD-SH micelles exhibited pH responsiveness. The Ritger-Peppas model effectively predicted the release behavior of curcumin, which followed a super case-II transport. The OSAD-SH micelle will be a promising nanocarrier for improving the physicochemical properties of curcumin in food fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The amygdala, known for its functional heterogeneity, plays a critical role in the neural mechanism of adolescent major depressive disorder (aMDD). However, changes in its subregional functional networks in relation to stressful factors remain unclear. We recruited 78 comorbidity-free, medication-naive aMDD patients and 40 matched healthy controls (HC) to explore changes in resting-state functional connectivity (FC) across four amygdala subregions: the centromedial nucleus (CM), the basolateral nucleus (LB), the superficial nucleus (SF), and the amygdalostriatal transition area (Astr). Then, we performed partial correlation analysis to investigate the relationship between amygdala subregional FC and stressful factors as measured by the Chinese Version of Family Environment Scale (FES-CV) and the Adolescent Self-Rated Life Events Scale (ASLEC). Compared to HC, aMDD patients demonstrated significantly decreased functional connectivity between the left CM and left precentral gyrus, as well as between left SF and left precentral gyrus, and between left LB and posterior cingulate gyrus (PCC)/precuneus. In aMDD group, left CM-precentral gyrus FC exhibited negative correlation with interpersonal relationship and punishment, and positive correlation with family cohesion and expressiveness. This study reveals distinct patterns of abnormal functional connectivity among amygdala subregions in aMDD. Our findings suggest that the CM network, in particular, may be involved in stress-related factors in aMDD, which provide a potential target for the prevention and treatment of adolescent depression., Competing Interests: Declarations. Ethical approval: This research was approved by the Ethics Committee of the Third People’s Hospital of Mianyang, and it is all done in accordance with the ethical standards set out in the 1964 Declaration of Helsinki and its subsequent amendments. Informed consent: Not applicable Competing interests: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

A variety of animals can be infected by encephalomyocarditis virus (EMCV). EMCV is the established causative agent of myocarditis and encephalitis in some animals. EMCV causes high fatality in suckling and weaning piglets, making pigs the most susceptible domestic animal species. Importantly, EMCV has zoonotic potential to infect the human population. The ability of the pathogen to avoid and undermine the initial defence mechanism of the host contributes to its virulence and pathogenicity. A large body of literature highlights the intricate strategies employed by EMCV to escape the innate immune machinery to suit its "pathogenic needs." Here, we also provide examples on how EMCV interacts with certain host proteins to dampen the infection process. Hence, this concise review aims to summarize these findings in a compendium of decades of research on this exciting yet underappreciated topic.

Competing Interests: Conflicts of interest Dr Werth has grants from Pfizer, Biogen, Gilead, Corbus Pharmaceuticals, AstraZeneca, Amgen, Regeneron, CSL Behring, BMS, Horizon, Rome Pharmaceuticals, Priovant, Ventus, Viela and consults for Janssen, Lilly, Pfizer, Biogen, BMS, Gilead, Amgen, Nektar, EMD Sorona, CSL Behring, Crisalis, Viela Bio, Argenx, Kwoya Kirin, Regeneron, AstraZeneca, Abbvie, GSK, Cugene, UCB, Rome Pharmaceuticals, Horizon, Merck, Sanofi, Calyx, Cabaletta Bio, Nuvig Pharmaceuticals, Takeda, Immunovant, Anaptysbio, Evommune, Innovaderm, Alpine Immune Sciences, Caribou, Xencor, Ventus. The University of Pennsylvania owns the copyright for the CLASI. Drs Gomes, Eldaboush, Feng, and Authors Xie, Stone, and Ricco have no conflicts of interest to declare.

Background: Fatty acid metabolism constitutes a significant and intricate biochemical process within microorganisms. Cytochrome P450 (CYP450) enzymes are found in most organisms and occupy a pivotal position in the metabolism of fatty acids. However, the role of CYP450 enzyme mediated fatty acid metabolism in the pathogenicity of pathogenic fungi remains unclear., Methods: In this study, a CYP450 enzyme-encoding gene, SsCYP86 , was identified in the sugarcane smut fungus Sporisorium scitamineum and its functions were characterized using a target gene homologous recombination strategy and metabonomics., Results: We found that the expression of SsCYP86 was induced by or sugarcane wax or under the condition of mating/filamentation. Sexual reproduction assay demonstrated that the SsCYP86 deletion mutant was defective in mating/filamentation and significantly reduced its pathogenicity. Further fatty acid metabolomic analysis unravelled the levels of fatty acid metabolites were reduced in the SsCYP86 deletion mutant. Exogenous addition of fatty acid metabolites cis-11-eicosenoic acid (C20:1N9), pentadecanoic acid (C15:0), and linolenic acid (C18:3N3) partially restored the mating/filamentation ability of the SsCYP86 deletion mutant and restored the transcriptional level of the SsPRF1 , a pheromone response transcription factor that is typically down-regulated in the absence of SsCYP86 . Moreover, the constitutive expression of SsPRF1 in the SsCYP86 deletion mutant restored its mating/filamentation., Conclusion: Our results indicated that SsCyp86 modulates the SsPRF1 transcription by fatty acid metabolism, and thereby regulate the sexual reproduction of S. scitamineum . These findings provide insights into how CYPs regulate sexual reproduction in S. scitamineum .

In pathogenic fungi, calcium-calmodulin-dependent serine-threonine-specific phosphatase calcineurin is involved in morphogenesis and virulence. Therefore, calcineurin and its tightly related protein complexes are attractive antifungal drug targets. However, there is limited knowledge available on the relationship between in vivo Ca 2+ -binding sites of calmodulin (CaM) and its functions in regulating stress responses, morphogenesis, and pathogenesis. In the current study, we demonstrated that calmodulin is required for hyphal growth, conidiation, and virulence in the human fungal pathogen, Aspergillus fumigatus . Site-directed mutations of calmodulin revealed that a single Ca 2+ -binding site mutation had no significant effect on A. fumigatus hyphal development, but multiple Ca 2+ -binding site mutations exhibited synergistic effects, especially when cultured at 42 °C, indicating that calmodulin function in response to temperature stress depends on its Ca 2+ -binding sites. Western blotting implied that mutations in Ca 2+ -binding sites caused highly degraded calmodulin fragments, suggesting that the loss of Ca 2+ -binding sites results in reduced protein stability. Moreover, normal intracellular calcium homeostasis and the nuclear translocation of the transcriptional factor CrzA are dependent on Ca 2+ -binding sites of Af CaM, demonstrating that Ca 2+ -binding sites of calmodulin are required for calcium signalling and its major transcription factor CrzA. Importantly, in situ mutations for four Ca 2+ -binding sites of calmodulin resulted in an almost complete loss of virulence in the Galleria mellonella wax moth model. This study shed more light on the functional characterization of putative calcium-binding sites of calmodulin in the morphogenesis and virulence of A. fumigatus , which enhances our understanding of calmodulin biological functions in cells of opportunistic fungal pathogens.

Competing Interests: The authors declare that they have no conflict of interest.

Because of its extreme toxicity and health risks, hexavalent chromium [Cr(VI)] has been identified as a major environmental contaminant. Bioreduction is considered as one of effective techniques for cleaning up Cr(VI)-contaminated sites, but the remediation efficiency needs to be enhanced. Here, a novel immobilized microbial agent was produced by immobilizing Bacillus cereus ZY-2009 with sodium alginate (SA) using polyvinyl alcohol (PVA) and activated carbon (AC). To evaluate the decrease of Cr(VI) by immobilized bacterial agents, batch tests were conducted with varying immobilization conditions, immobilization carriers, and dosages of medication. The removal of Cr(VI) by the agent prepared by the composite immobilization method was better than that by the adsorption and encapsulation methods. The optimal preparation conditions were the fraction of magnetic PVA was 5.00%, the fraction of SA was 4.00%, the fraction of CaCl 2 was 4.00%, and the calcification time was 12 h. The experimental results indicated that PVA/SA/AC agents accelerated the reduction rate of Cr(VI). The removal rate of Cr(VI) by immobilized cells (90.5%) under ideal conditions was substantially higher than that of free cells (11.0%). This novel agent had a large specific surface area and a rich pore structure, accounting for its high reduction rate. The results suggest that the PVA/SA/AC immobilized Bacillus cereus ZY-2009 agent has great potential to remove Cr(VI) from wastewater treatment systems.

Trihelix transcription factors (TF) are photoresponsive proteins featuring a characteristic three-helix structure (helix-loop-helix-loop-helix) and contain the Myb/SANT-LIKE (MSL) domain. They perform crucial functions in the development and stress-response of plants. However, the function of the Trihelix TF in potato ( Solanum tuberosum L.) remains unknown. In the present study, forty-three StMSL s were characterized in the potato genome and named StMSL1 to StMSL43 . Structural domain analysis revealed that motifs 1 and 2 may play a central role in the implementation of trihelix gene functions, and motifs 4 and 9 may be related to specific functions of StMSL. Phylogenetic analysis divided the StMSLs into six groups (SIP1, GT1, GT2, GTγ, SH4 and GT3). The GT3 group, which is rarely identified in the Trihelix TF family, contained three StMSLs. The 43 StMSLs were unevenly distributed on 12 chromosomes in potato and comprised two pairs of tandem duplication and five pairs of segmental duplication genes. Additionally, RNA-Seq analysis found that 36 out of the 43 StMSLs were expressed in at least one of the 12 tissues, with some exhibiting tissue-specific expression patterns. Trihelix transcriptional regulation network analysis identified 387 genes as potential targets of the 36 StMSL genes, and these genes have a wide variety of functions. Furthermore, RNA-Seq analysis revealed that at least 18 StMSLs were upregulated in response to osmotic stress. The induced pattern of eight StMSLs was subsequently validated using qRT-PCR. This study provides a detailed insight into the StMSLs of the potato and lays the foundation for further analysis of the functions of the Trihelix gene in plant development., Competing Interests: The authors declare that they have no competing interests., (© 2024 Mei et al.)

Background: Increased epicardial adipose tissue (EAT) has adverse effects in cardiovascular diseases, independent of body mass index (BMI). Estrogen levels may impact EAT accumulation. Little is known about the predictors and potential impact of EAT in PAH., Research Question: Is EAT associated with estrogen levels, disease severity, and mortality in PAH?, Study Design and Methods: We conducted a retrospective cohort study of patients with PAH enrolled in the Penn Pulmonary Hypertension registry and used chest computed tomography (CT) scans to quantify EAT. We also measured serum estrone and estradiol levels., Results: 221 patients were included in the analysis, with median follow-up of 88 months. Mean age was 55.1 years, 74.7% were female, mean BMI was 27.20 kg/m 2 , and the most common PAH etiology was connective tissue disease-associated PAH (43.0%) followed by idiopathic/heritable PAH (35.3%). Median EAT volume was 52.1 mL/m 2 . Of the 102 patients with a follow-up chest CT, EAT increased over time in 74 (71.8%). High EAT volume (HR 2.62, 95% CI 1.62-4.24, p<0.001) and greater accumulation of EAT over time (HR 1.09, 95% CI 1.01 - 1.17, p=0.03) were both independently associated with worse survival. Patients with high EAT volume had lower serum estrone (13.70 versus 30.60 pg/mL, p=0.009) and estradiol (6.05 versus 19.40 pg/mL, p=0.002) levels compared to those with low EAT volume., Interpretation: In patients with PAH, high EAT and a greater rate of accumulation of EAT volume were independently associated with worse survival. Higher EAT volume was also associated with lower estrogen levels. The association of EAT volume with survival was independent of BMI and disease severity, suggesting that EAT may be a marker for a unique PAH phenotype. Future research should investigate the role of EAT-modifying therapies in PAH and consider incorporating EAT into PAH risk models., (Copyright © 2024. Published by Elsevier Inc.)

Background: Inflammatory myofibroblastic tumor (IMT) is a rare intermediate-grade neoplasm. It presents a great challenge in diagnosis and treatment. This study aims to identify the clinicopathological characteristics of IMT., Methods: A retrospective study was conducted, enrolling patients with IMT at Peking Union Medical College Hospital from January 2013 to October 2023. Clinical information, treatments, and efficacy were analyzed., Results: A total of 72 patients were enrolled, including 38 men and 34 women, with a median age of 46.5 years. The most common primary site included the lung (n = 15, 20.8%), intestinal tract (n = 8, 11.1%), abdominal cavity (n = 7, 9.7%), and nasal sinus (n = 5, 6.9%). Thirty patients harbored anaplastic lymphoma kinase (ALK) fusion genes; Sixty-five (90.3%) patients underwent surgical resection, and 11 of them had postoperative recurrence. Thirty patients received systemic therapy, including nonsteroidal anti-inflammatory drugs (n = 1), steroids (n = 5), chemotherapy (n = 7), targeted therapy (n = 2), and immune checkpoint inhibitor (n = 1)., Conclusions: The most common site of IMT is the lung. Surgery is the main treatment for IMT, and postoperative adjuvant therapy for ALK-positive patients needs to be focused. The molecular testing is essential for all patients diagnosed with IMTs. Systemic treatment needs further research., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

The advancement of all-solid-state lithium metal batteries requires breakthroughs in solid-state electrolytes (SSEs) for the suppression of lithium dendrite growth at high current densities and high capacities (>3 mAh cm - 2 ) and innovation of SSEs in terms of crystal structure, ionic conductivity and rigidness. Here we report a superionic conducting, highly lithium-compatible and air-stable vacancy-rich β-Li 3 N SSE. This vacancy-rich β-Li 3 N SSE shows a high ionic conductivity of 2.14 × 10 -3  S cm -1 at 25 °C and surpasses almost all the reported nitride-based SSEs. A Li- and N-vacancy-mediated fast lithium-ion migration mechanism is unravelled regarding vacancy-triggered reduced activation energy and increased mobile lithium-ion population. All-solid-state lithium symmetric cells using vacancy-rich β-Li 3 N achieve breakthroughs in high critical current densities up to 45 mA cm - 2 and high capacities up to 7.5 mAh cm - 2 , and ultra-stable lithium stripping and plating processes over 2,000 cycles. The high lithium compatibility mechanism of vacancy-rich β-Li 3 N is unveiled as intrinsic stability to lithium metal. In addition, β-Li 3 N possesses excellent air stability through the formation of protection surfaces. All-solid-state lithium metal batteries using the vacancy-rich β-Li 3 N as SSE interlayers and lithium cobalt oxide (LCO) and Ni-rich LiNi 0.83 Co 0.11 Mn 0.06 O 2 (NCM83) cathodes exhibit excellent battery performance. Extremely stable cycling performance is demonstrated with high capacity retentions of 82.05% with 95.2 mAh g -1 over 5,000 cycles at 1.0 C for LCO and 92.5% with 153.6 mAh g -1 over 3,500 cycles at 1.0 C for NCM83. Utilizing the vacancy-rich β-Li 3 N SSE and NCM83 cathodes, the all-solid-state lithium metal batteries successfully accomplished mild rapid charge and discharge rates up to 5.0 C, retaining 60.47% of the capacity. Notably, these batteries exhibited a high areal capacity, registering approximately 5.0 mAh cm - 2 for the compact pellet-type cells and around 2.2 mAh cm - 2 for the all-solid-state lithium metal pouch cells., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Meningiomas are central nervous system tumors whose incidence increases with age. Benign meningioma pathogenesis involves germline or somatic mutation of target genes, such as NF2, leading to clonal expansion. We used an established cancer epidemiology model to investigate the number of rate-limiting steps sufficient for benign meningioma development., Methods: Incidence data was obtained from the Surveillance, Epidemiology and End Results Program (SEER) for nonmalignant meningioma from 2004 to 2020. Age-adjusted incidence rates per 100,000 person-years were divided into 5-year bands. This was repeated for vestibular schwannomas as a negative control. The Armitage-Doll methodology was applied. Mathematical solutions correcting for volatile tumor microenvironments were applied to fit higher-order models using polynomial regression when appropriate. A 75:25 training:test split was utilized for validation., Results: 222,509 cases of benign meningiomas were identified. We noted strong linear relationships between log-transformed incidence and age across the cohort and multiple subpopulations: male, white, black, Hispanic, Asian/Pacific Islander, and American Indian subpopulations all demonstrated R 2  = 0.99. Slopes were between 3.1 and 3.4, suggesting a four-step process for benign meningioma development. Female patients exhibited nonlinear deviations, but the corrected model demonstrated R 2  = 0.99 with a four-hit pathway. This model performed robustly on test data with R 2  = 0.99. Vestibular schwannomas demonstrated a slope of 2.1 with R 2  = 0.99, suggesting a separate three-step process., Conclusion: Four mutations are uniquely required for the development of benign meningiomas. Correcting for volatile tumor microenvironments reliably accounted for nonlinear deviations in behavior. Further studies are warranted to elucidate genomic findings suggestive of key mutations in this pathway., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant with adverse health consequences. Our previous studies showed that PFOS caused an increase in mitochondrial iron and accelerated the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), one classic executor in the ferroptosis pathway. As ACSL4 is located in the mitochondria-associated endoplasmic reticulum (ER) membranes, here, we intended to further explore the role of ACSL4 in the inter-organelle iron crosstalk between ER and mitochondria under PFOS exposure. We found that PFOS caused ER iron accumulation in mice liver and human hepatocytes L-02. Inhibition of solute carrier family 39 member 7 (SLC39A7/ZIP7), a potential ER iron efflux channel supposed by us, alleviated PFOS-induced mitochondrial iron overload and further elevated ER iron level. Knockdown of voltage-dependent anion channel 3 (VDAC3) or mitochondrial calcium uniporter (MCU), the respective potential mitochondrial iron influx channels in outer/inner mitochondrial membrane, reversed the mitochondrial iron overload and aggravated ER iron accumulation in the cells under PFOS treatment. ACSL4 interacted with both ZIP7 and VDAC3 in mice liver and L-02 cells after treatment with PFOS. Upon inhibition of ACSL4, the ZIP7-VDAC3 interaction was reduced, mitigating mitochondrial iron overload and exacerbating iron accumulation in ER. Inhibiting VDAC3 or ZIP7 reversed the overloaded cytosolic iron under PFOS treatment, however, we found no further decrease in cytosolic iron after simultaneous inhibiting VDAC3 and ZIP7 compared with respectively inhibiting VDAC3 or ZIP7 alone. Our study provides evidence and reveals the molecular mechanism underneath the ER-mitochondria iron crosstalk under PFOS exposure, providing new insights into and enriches the understanding of the iron network-regulating function of the ferroptosis executor ACSL4 and highlighting its role in PFOS toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study investigates the effects of hexagonal microtextured titanium sheets on fibroblast growth and collagen synthesis, crucial factors in anastomotic healing., Materials and Methods: Hexagonal titanium sheets were fabricated using a laser microtextured machine. Mouse fibroblastic embryonic stem cells (NIH/3T3) were cultured on these sheets. Cell proliferation was assessed using a CCK8 assay, and expression of TGF-β/Smad pathway-related genes and collagen types I and III was evaluated through qRT-PCR and western blot., Results: Hexagonal titanium sheets significantly enhanced fibroblast growth and collagen synthesis. The 50-30 group, with the smallest contact angle (48 ± 2.3°), exhibited the highest cell growth rates by CCK8 assay. Gene expression analysis revealed that TGF-β1, Smad2, Smad3, Smad4, and COL1A1 were significantly upregulated in the 50-30 group on day 7. Meanwhile, type I collagen expression was significantly increased in the 50-30 group on day 7 by western blot analysis., Conclusion: Our findings demonstrate that laser-fabricated hexagonal microtextured titanium sheets enhance hydrophilicity and promote fibroblast growth, activating the TGF-β/Smad pathway to facilitate collagen synthesis. These results have important implications for tissue repair and regeneration., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

An efficient nickel-catalyzed direct fluorosulfonylation of vinyl bromides and benzyl bromides under mild reaction conditions has been developed for sulfonyl fluorides utilizing Na 2 S 2 O 4 and NFSI as the sulfur dioxide and fluorine sources, respectively. This reaction system tolerates organic bromide compounds, such as β-styryl bromides, alkyl vinyl bromides, and benzyl bromides, to achieve corresponding sulfonyl fluorides in moderate to good yields, with convenient operation, mild conditions, broad substrate scope, good functional group compatibility, and excellent retention of configuration to vinyl bromides.

Realgar is a toxic mineral medicine containing arsenic that is present in many traditional Chinese medicines. It has been reported that the abuse of drugs containing realgar has potential neurotoxicity, but its mechanism of toxicity has not been fully clarified. In this study, we demonstrated that arsenic in realgar promoted mitochondrial fission via UBXD8-mediated DRP1 translocation to the mitochondria and activated mitophagy via PINK1-Parkin, resulting in mitochondrial dysfunction and nerve cell death in the rat cortex. We used PC12 cells and treated them with inorganic arsenic (iAs). Mdivi-1, a mitochondrial fission inhibitor, and the siRNA UBXD8 or PINK1 were used as interventions to verify the precise mechanism by which arsenic affects realgar-induced mitochondrial instability. The results revealed that the arsenic in realgar accumulated in the brain and led to neurobehavioral abnormalities in the rats. We demonstrated that arsenic in realgar-induced high expression of UBXD8 promoted the translocation of DRP1 to the mitochondria, where it underwent phosphorylation, which led to the over-fission of the mitochondria and mitochondria-mediated apoptosis. Moreover, the over-fission of the mitochondria activates mitophagy, which is self-protective but only partially alleviates apoptosis and mitochondria dysfunction. Our findings revealed the crosstalk between mitochondrial fission and mitophagy in realgar-induced neurotoxicity. These results highlight the role of the transposition of DRP1 by UBXD8 in realgar-induced mitochondrial dysfunction and provide new ideas and data for the study of the mechanism of realgar-induced neurotoxicity., Competing Interests: Declarations. Ethics Approval: All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of China Medical University (ethics committee approval numbers: CMU2021120). Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Spiroplasma eriocheiris is a pathogen in the Chinese mitten crab Eriocheir sinensis and is associated with tremor disease. S. eriocheiris infects virtually all artificially bred crustaceans, resulting in significant economic losses to the aquaculture industry in China. Recombinase polymerase amplification (RPA) is considered a promising technology for the rapid and sensitive detection of disease. For the rapid detection of S. eriocheiris, this study established basic RPA, RPA-EXO and RPA-LFD, which were visualised via agarose gel electrophoresis, SYBR Green I, fluorescence signals and test lines on lateral flow dipsticks. Specific primers and probes were designed based on the 16S ribosomal RNA sequence of S. eriocheiris. The optimal primer pairs for the basic RPA, RPA-EXO and RPA-LFD were RPA-F3/R3, RPA-F3/R3 and RPA-LFD-F3/R3, respectively. The optimal temperatures and times of basic RPA, RPA-EXO and RPA-LFD were 37°C for 25 min, 39°C for 30 min and 39°C for 10 min, respectively. The specificity test indicated that in addition to the positive test results for S. eriocheiris, the other five DNA templates tested negative, demonstrating strong specificity. The results of the sensitivity test revealed that the detection limits of RPA, RPA-EXO and RPA-LFD were 5.77 × 10 -2 , 5.77 × 10 -4 and 1.52 × 10 -6  ng/μL, respectively, indicating high sensitivity. This study established three methods for the detection of S. eriocheiris that are characterised by a constant temperature, rapid response, high sensitivity and strong specificity., (© 2024 John Wiley & Sons Ltd.)

Aqueous room-temperature phosphorescence (RTP) materials have garnered considerable attention for their significant potential across various applications such as bioimaging, sensing, and encryption. However, establishing a universally applicable method for achieving aqueous RTP remains a substantial challenge. Herein, we present a versatile supramolecular strategy to transition RTP from solid states to aqueous phases. By leveraging a cyclic peptide-based supramolecular scaffold, we have developed a noncovalent approach to molecularly disperse diverse organic phosphors within its rigid hydrophobic microdomain in water, yielding a series of aqueous RTP materials. Moreover, high-performance supramolecular phosphorescence resonance energy transfer (PRET) systems have been constructed. Through the facile co-assembly of a fluorescent acceptor with the existing RTP system, these PRET systems exhibit high energy transfer efficiencies (>80 %), red-shifted afterglow emission (520-790 nm), ultralarge Stokes shifts (up to 450 nm), and improved photoluminescence quantum yields (6.1-30.7 %). This study not only provides a general strategy for constructing aqueous RTP materials from existing phosphors, but also facilitates the creation of PRET systems featuring color-tunable afterglow emission., (© 2024 Wiley-VCH GmbH.)

Structural reconstruction of electrocatalysts plays a pivotal role in catalytic performances for CO 2 reduction reaction (CO 2 RR), whereas the behavior is by far superficially understood. Here, we report that CO 2 accessibility results in a universal self-adaptive structural reconstruction from Cu 2 O to Cu@Cu x O composites, ending with feeding gas-dependent microstructures and catalytic performances. The CO 2 -rich atmosphere favors reconstruction for CO 2 RR, whereas the CO 2 -deficient one prefers that for hydrogen evolution reaction. With the assistance of spectroscopic analysis and theoretical calculations, we uncover a CO 2 -induced passivation behavior by identifying a reduction-resistant but catalytic active Cu(I)-rich amorphous layer stabilized by *CO intermediates. Additionally, we find extra CO production is indispensable for the robust production of C 2 H 4 . An inverse correlation between durability and FE CO /FE C2H4 is disclosed, suggesting that the self-stabilization process involving the absorption of *CO intermediates on Cu(I) sites is essential for durable electrolysis. Guided by this insight, we design hollow Cu 2 O nanospheres for durable and selective CO 2 RR electrolysis in producing C 2 H 4 . Our work recognizes the previously overlooked passivation reconstruction and self-stabilizing behavior and highlights the critical role of the local atmosphere in modulating reconstruction and catalytic processes., Competing Interests: Declarations Conflict of Interest The authors declare no interest conflict. They have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Key Message: The gene regulating fruit pedicel length in wax gourd was finely mapped to a 211 kb region on chromosome 8. The major gene, Bch08G017310 (BhGA2ox3), was identified through forward genetics. Fruit pedicel length (FPL) is a crucial trait in wax gourd (Benincasa hispida) that affects fruit development and cultivation management. However, the key regulatory genes and mechanisms of FPL in wax gourds remain poorly understood. In this study, we constructed an F 2 population using wax gourd plants with long fruit pedicels (GF-7-1-1) and short fruit pedicels (YSB-1-1-2) as parents. Through BSA-seq, we initially localised the FPL candidate gene to an 8.4 Mb region on chromosome 8, which was further narrowed down to a 1.1 Mb region via linkage analysis. A large F 2 population of 2163 individuals was used to screen for recombinants, and the locus was ultimately narrowed to within a 211 kb (62,299,856-62,511,174 bp) region. Sequence and expression analyses showed that Bch08G017310 (named BhGA2ox3) is a strong candidate gene for FPL in wax gourds. It encodes gibberellin (GA) 2-beta-dioxygenase, a member of the GA 2-oxidase (GA2ox) family. Cytology showed that GA treatment significantly elongated the fruit pedicels and enlarged the cells in the plants with short fruit pedicels. Ectopic expression of BhGA2ox3 showed that BhGA2ox3 overexpression in Arabidopsis thaliana resulted in significantly shorter fruit pedicels. This study lays a theoretical foundation for the regulatory mechanism of FPL in wax gourds and molecular breeding., Competing Interests: Declarations Conflict of interests The authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)