Search

Several studies have linked branched-chain amino acid (BCAA) metabolism disorders with autism spectrum disorder (ASD), but the results have been inconsistent. The purpose of this study was to explore the association between BCAA concentrations and the risk of ASD. A total of 313 participants were recruited from two tertiary referral hospitals from May 2018 to July 2021. Concentrations of BCAAs in dried blood spots were analyzed using liquid chromatography-tandem mass spectrometry-based analysis. Multivariate analyses and restricted cubic spline models were used to identify the association between BCAAs and the risk of ASD, and a nomogram was developed by using multivariate logistic regression and the risk was determined by receiver operating characteristic curve analysis and calibration curve analysis. Concentrations of total BCAA, valine, and leucine/isoleucine were higher in the ASD group, and all of them were positively and non-linearly associated with the risk of ASD even after adjusting for potential confounding factors such as age, gender, body mass index, and concentrations of BCAAs (P < 0.05). The nomogram integrating total BCAA and valine showed a good discriminant AUC value of 0.756 (95% CI 0.676-0.835). The model could yield net benefits across a reasonable range of risk thresholds. In the stratified analysis, the diagnostic ability of the model was more pronounced in children older than 3 years. We provide evidence that increased levels of BCAAs are associated with the risk of ASD, and the nomogram model of BCAAs presented here can serve as a marker for the early diagnosis of ASD., (© 2024. The Author(s).)

During developmental processes such as embryogenesis, how a group of cells fold into specific structures, is a central question in biology. However, it remains a major challenge to understand and predict the behavior of every cell within the living tissue over time during such intricate processes. Here we present a geometric deep-learning model that can accurately capture the highly convoluted interactions among cells. We demonstrate that multicellular data can be represented with both granular and foam-like physical pictures through a unified graph data structure, considering both cellular interactions and cell junction networks. Using this model, we achieve interpretable 4-D morphological sequence alignment, and predicting cell rearrangements before they occur at single-cell resolution. Furthermore, using neural activation map and ablation studies, we demonstrate cell geometries and cell junction networks together regulate morphogenesis at single-cell precision. This approach offers a pathway toward a unified dynamic atlas for a variety of developmental processes.

Background: Increasing evidence suggests a robust correlation between the gut microbiome and alopecia areata. In light of the extensive diversity of gut microbiota, this study aims to utilize state-of-the-art and comprehensive data to explore the causative association between gut microbiota and alopecia areata., Objective: We conducted a Mendelian randomization (MR)-based two-sample study to elucidate the causal relationship between gut microbiota and alopecia areata., Method: Summary information on Ncase = 767 and Ncontrol = 394,105 cases of alopecia areata was obtained from the FinnGen study. A total of 473 gut microbial taxa were summarized from the genome-wide association study (GWAS) catalog. The study comprised a forward Mendelian randomization (MR) analysis with the gut microbiome as the exposure factor and alopecia areata as the outcome, as well as a reverse MR analysis with alopecia areata as the exposure factor and the gut microbiome as the outcome. Various analytical methods including inverse variance weighting (IVW), Weighted Median, MR-Egger, Weighted Mode, and Simple Mode were employed. Subsequently, sensitivity analysis was conducted to ensure the robustness of our research findings., Result: This study has established a causal relationship between gut microbiota and alopecia areata. Forward causal analysis revealed causality relationships between 16 gut microbial taxa and alopecia areata, while reverse causal analysis found that there may be a causal relationship between alopecia areata and 16 gut microbial taxa (not statistically significant)., Conclusion: Our study findings suggest a causal relationship between gut microbiota and alopecia areata, providing potential guidance for future clinical trials., Competing Interests: 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., (Copyright © 2024 Bi, Tey, Yao, Cao, Qian, Shi and Guo.)

Many critical biological processes, like wound healing, require densely packed cell monolayers/tissues to transition from a jammed solid-like to a fluid-like state. Although numerical studies anticipate changes in the cell shape alone can lead to unjamming, experimental support for this prediction is not definitive because, in living systems, fluidization due to density changes cannot be ruled out. Additionally, a cell's ability to modulate its motility only compounds difficulties since even in assemblies of rigid active particles, changing the nature of self-propulsion has non-trivial effects on the dynamics. Here, we design and assemble a monolayer of synthetic cell-mimics and examine their collective behaviour. By systematically increasing the persistence time of self-propulsion, we discovered a cell shape-driven, density-independent, re-entrant jamming transition. Notably, we observed cell shape and shape variability were mutually constrained in the confluent limit and followed the same universal scaling as that observed in confluent epithelia. Dynamical heterogeneities, however, did not conform to this scaling, with the fast cells showing suppressed shape variability, which our simulations revealed is due to a transient confinement effect of these cells by their slower neighbors. Our experiments unequivocally establish a morphodynamic link, demonstrating that geometric constraints alone can dictate epithelial jamming/unjamming., (© 2024. The Author(s).)

Background and Aims: There is a need to consolidate reporting guidance for nutrition randomised controlled trial (RCT) protocols. The reporting completeness in nutrition RCT protocols and study characteristics associated with adherence to SPIRIT and TIDieR reporting guidelines are unknown. We, therefore, assessed reporting completeness and its potential predictors in a random sample of published nutrition and diet-related RCT protocols., Methods: We conducted a meta-research study of 200 nutrition and diet-related RCT protocols published in 2019 and 2021 (aiming to consider periods before and after the start of the COVID pandemic). Data extraction included bibliometric information, general study characteristics, compliance with 122 questions corresponding to items and subitems in the SPIRIT and TIDieR checklists combined, and mention to these reporting guidelines in the publications. We calculated the proportion of protocols reporting each item and the frequency of items reported for each protocol. We investigated associations between selected publication aspects and reporting completeness using linear regression analysis., Results: The majority of protocols included adults and elderly as their study population (n = 73; 36.5%), supplementation as intervention (n = 96; 48.0%), placebo as comparator (n = 89; 44.5%), and evaluated clinical status as the outcome (n = 80; 40.0%). Most protocols described a parallel RCT (n = 188; 94.0%) with a superiority framework (n = 141; 70.5%). Overall reporting completeness was 52.0% (SD = 10.8%). Adherence to SPIRIT items ranged from 0% (n = 0) (data collection methods) to 98.5% (n = 197) (eligibility criteria). Adherence to TIDieR items ranged from 5.5% (n = 11) (materials used in the intervention) to 98.5% (n = 197) (description of the intervention). The multivariable regression analysis suggests that a higher number of authors [β = 0.53 (95%CI: 0.28-0.78)], most recent published protocols [β = 3.19 (95%CI: 0.24-6.14)], request of reporting guideline checklist during the submission process by the journal [β = 6.50 (95%CI: 2.56-10.43)] and mention of SPIRIT by the authors [β = 5.15 (95%CI: 2.44-7.86)] are related to higher reporting completeness scores., Conclusions: Reporting completeness in a random sample of 200 diet or nutrition-related RCT protocols was low. Number of authors, year of publication, self-reported adherence to SPIRIT, and journals' endorsement of reporting guidelines seem to be positively associated with reporting completeness in nutrition and diet-related RCT protocols., Competing Interests: Conflicts of interest Flávia Moraes Silva received a postdoctoral fellowship from COPPETEC Foundation. Michael Maia Schlussel, Shona Kirtley, Jennifer A de Beyer and Gary Collins are funded by Cancer Research UK (grant C49297/A27294). Matthew J Page is supported by an Australian Research Council Discovery Early Career Researcher Award (DE200101618). Colby Vorland has received honoraria from The Obesity Society and the Alliance for Potato Research and Education, and his university has received funds to support his research from: National Cattlemen's Beef Association; Alliance for Potato Research and Education; the Gordon and Betty Moore Foundation; and NIH. All authors work directly or have collaborations with the EQUATOR Network, an international initiative that seeks to improve the reliability and value of published health research literature by promoting transparent and accurate reporting and wider use of robust reporting guidelines., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The primary obesity surgery endoluminal (POSE) procedure is an innovative incision-less endoscopic bariatric procedure that is increasingly used. However, variable weight loss response and recurrence post-endoscopic bariatric procedures have at times necessitated laparoscopic bariatric conversion. The safety and approach of conversion to laparoscopic sleeve gastrectomy (LSG) or Roux-en-Y gastric bypass (RYGB), however, have been an active point of discussion within revisional bariatric surgery., Methods: This retrospective review of four consecutive patients is the largest description of medium-term postoperative outcomes and technical highlights of a laparoscopic conversion of POSE to RYGB. Chart review was completed to evaluate patients' post-POSE clinical course and perioperative outcomes after surgical conversion., Results: Early data suggests varied weight loss trajectory with POSE and marked improvement in weight response after surgical conversion. Qualitative review reveals successful single-staged conversions contrary to previous smaller case series describing staged conversions involving endoscopic removal of plications followed by RYGB. Review additionally reveals key perioperative considerations for successful conversions to include intraoperative endoscopy, upper gastrointestinal fluoroscopic studies, and at times computed tomography. The latter study and laparoscopic view of the post-POSE stomach challenge the prior notion that distal POSE allows for easy revision to LSG., Conclusions: Our case series underscores the complex multifactorial nature of metabolic disease and the increasing importance of a conscientious approach to conversion bariatric surgery as the adoption of POSE and the bariatric patient population continues to grow., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Traditional lipid nanoparticles (LNPs) suffer from low drug loading capacity (DLC), weak stability, and lack of responsiveness. Conventional approaches to address these issues involve the synthesis of lipid-prodrug by incorporating responsive covalent linkers. However, such approaches often result in suboptimal sensitivity for drug release and undermine therapeutic effectiveness. Herein, the study reports a fundamentally different concept for designing lipid-like prodrugs through boron-nitrogen (B-N) coordination and dynamic covalent interaction. The 5-fluorouracil-based lipid-like prodrugs, featuring a borate ester consisting of a glycerophosphoryl choline head and a boronic acid-modified 5Fu/dodecanamine complex tail, are used to prepare pH/H 2 O 2 cascade-responsive LNPs (5Fu-LNPs). The 5Fu-LNPs exhibit enhanced DLC and stability in a neutral physiological environment due to the B-N coordination and enhanced hydrophobicity. In tumors, acidic pH triggers the dissociation of B-N coordination to release prodrugs, which further responds to low H 2 O 2 concentrations to release drugs, showcasing a potent pH/H 2 O 2 -cascade-responsive property. Importantly, 5Fu-LNPs demonstrate greater antitumor efficiency and lower toxicity compared to the commercial 5Fu. These results highlight 5Fu-LNPs as a safer and more effective alternative to chemotherapy. This work presents a unique LNP fabrication strategy that can overcome the limitations of conventional LNPs and broaden the range of intelligent nanomaterial preparation techniques., (© 2024 Wiley‐VCH GmbH.)

Purpose: Glucagon-like receptor agonists (GLP1-RAs) have raised peri-procedural concerns due to their potential to delay gastric emptying. The American Association of Anesthesiologists has advised pausing a single dose before elective endoscopy. However, a subsequent directive from multiple gastroenterology societies underscored the need for further assessment to substantiate this practice. We aimed to evaluate the frequency of serious adverse events and retained gastric products during endoscopic sleeve gastroplasty (ESG) with uninterrupted GLP1-RA use., Materials and Methods: We conducted a retrospective evaluation of all patients undergoing ESG while on GLP1-RAs at three centers from August 2022 to February 2024. Per standard protocol, all patients had refrained from solid foods for at least 24 h and maintained nil per os for 12 h preceding their ESG. Records were reviewed for patient characteristics and medication type and doses. Primary outcomes included serious adverse events and retained gastric products based on patient records, procedure reports, and procedural videos., Results: Fifty-seven consecutive adults (89.5% women, mean age of 44 ± 9 years, mean BMI of 40.1 ± 8.1 kg/m 2 , 35.1% with T2DM, and 26.3% with pre-T2DM) underwent ESG without stopping GLP1-RAs, which included semaglutide (45.6%), liraglutide (19.3%), dulaglutide (22.8%), and tirzepatide (12.3%). During intubation, endoscopy, and recovery, there were no instances of retained gastric solids, pulmonary aspiration, gastroesophageal regurgitation, or hypoxia., Conclusion: A ≥ 24-h pre-endoscopy liquid-only diet with ≥ 12-h pre-endoscopy fast may negate the need for GLP1-RA interruption for routine upper endoscopy in adults with native gastric anatomy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sulfonamide antibiotics (SAs) widely used have potentially negative effects on human beings and ecosystems. Adsorption and advanced oxidation methods have been extensively applied in SAs wastewater treatment. In this study, compared with Al 3+ @BC500 and Fe 3+ @BC500, La 3+ @BC500 for activating persulfate (S 2 O 8 2- ) had the best effect removal performance of sulfadiazine (SDZ) and sulfamethoxazole (SMX). Morphology, acidity, oxygen-containing functional groups, and loading of La 3+ @BC500 were analyzed by techniques, including EA, BET, XRD, XPS, FT-IR. XRD results show that with the increase of La 3+ loading, the surface characteristics of biochar gradually changed from CaCO 3 to LaCO 3 OH. Through EPR technology, it is proved that LaCO 3 OH on the surface of La 3+ @BC500 can not only activate S 2 O 8 2- to generate SO 4 - •, but also to produce •OH. In the optimization experiment, the optimal dosage of La 3+ is between 0.05 and 0.2 (mol/L)/g. SDZ had a good removal effect at pH (5-9), but SMX had a good removal effect only at pH=3. Zeta potential also proves that the material is more stable under acidic conditions. The removal process of SDZ is more in accord with pseudo-first-order kinetics (R 2 =0.9869), while SMX is more in line with pseudo-second order kinetics (R 2 =0.9926)., 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 article., (Copyright © 2023. Published by Elsevier B.V.)

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with the decrease and functional impairment of regulatory T cells (Tregs). In the current study, we explored the interplay of miR-155 and suppressor of cytokine signaling 1 (SOCS1) in regulating Treg function and stability in SLE., Methods: Clinical samples from healthy subjects and SLE patients were collected, and a mouse model of SLE was established to profile the expression pattern of miR-155 and SCOS1 in Tregs. Tregs isolated from mouse spleen were stimulated by inflammatory cytokines to confirm involvement of miR-155/SOCS1 axis in dictating Treg stability and function. We also administrated synthetic miR-155 inhibitor in SLE animal model to evaluate the potential effect on rescuing Treg function and alleviating SLE progression., Results: Tregs from SLE patients and SLE-induced mice exhibited a downregulation of SOCS1 and an upregulation of miR-155. In Tregs stimulated by inflammatory cytokines, Nuclear factor kappa B (NF-κB) signaling activation was required for the change of SOCS1 and miR-155 expression. miR-155 served as a negative regulator to dampen SOCS1 expression in inflammation-stimulated Tregs. The transfection of miR-155 mimic impaired the suppressive function and differentiation of Tregs through targeting SOCS1. In contrast, miR-155 inhibition improved Treg function under inflammatory stimulation and alleviated SLE conditions in the mouse model., Conclusion: Inflammation-induced miR-155 impairs Treg stability and function in SLE through decreasing SOCS1 expression. Targeting miR-155 might be developed as an intervention to mitigate SLE conditions., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

To investigate the impact of different H 2 O 2 concentrations on the Fenton-like systems of H 2 O 2 /biochar, this study examined the mechanism of the physical structure and environmental persistent free radicals (EPFRs) of biochar during diethyl phthalate (DEP) removal by the Fenton-like system. The peak-splitting method was utilized to differentiate EPFRs types in cotton stalk biochar produced at different temperatures. High-temperature environments promote π-electron delocalization, which facilitates phenyl π free radicals and σ-π oxygen-containing free radicals. By analyzing relationships between the removal rate K 1 and removal constant K obs of DEP with the structural properties of biochar, it was discovered that EPFRs concentrations in biochar had a significant positive correlation with K 1 (r = 0.92) and K obs (r = 0.97). Different H 2 O 2 concentrations added to the biochar removal system resulted in varied DEP removal efficiency. Among them, CS 500 , CS 550 , and CS 600 exhibited superior DEP removal efficiency when H 2 O 2 concentration was 5 mM., 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.)

Objective: This study revealed a core regulator and common upstream mechanisms for the multifaceted pathological processes of age-related macular degeneration (AMD) and provided proof-of-concept for this new therapeutic target., Methods: Comprehensive gene expression analysis was performed using RNA sequencing of eye cup from old mice as well as laser-induced choroidal neovascularization (CNV) mouse model. Through integrative analysis and protein-protein interaction (PPI) analysis, common pathways and key transcription factor was identified simultaneously engaged in age-related retinal degeneration and CNV, the two typical pathological process of AMD. Subsequently, the expression changes of Spi1 , the key regulator, as well as the alternation of the downstream mechanisms were validated in both models through qRT-PCR, Elisa, flow cytometry and immunofluorescence. Further, we assessed the impact of Spi1 knockdown in vitro and in vivo using gene intervention vectors carried by adeno-associated virus or lentivirus to test its potential as a therapeutic target., Results: Compared to corresponding controls, we found 1,939 and 1,319 genes differentially expressed in eye cups of old and CNV mice respectively. The integrative analysis identified a total of 275 overlapping DEGs, of which 150 genes were co-upregulated. PPI analysis verified a central transcription factor, SPI1. The significant upregulation of Spi1 expression was then validated in both models, accompanied by macrophage polarization towards the M1 phenotype. Finally, SPI1 suppression significantly inhibited M1 polarization of BMDMs and attenuated neovascularization in CNV mice., Conclusion: This study demonstrates that SPI1 exerts a pivotal role in AMD by regulation of macrophage polarization and innate immune response, offering promise as an innovative target for treating AMD., Competing Interests: 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., (Copyright © 2024 Qi, Zhang, Kong, Bi, Kong, Zhang and Zhao.)

Cell competition in epithelial tissue eliminates transformed cells expressing activated oncoproteins to maintain epithelial homeostasis. Although the process is now understood to be of mechanochemical origin, direct mechanical characterization and associated biochemical underpinnings are lacking. Here, we employ tissue-scale stress and compressibility measurements and theoretical modeling to unveil a mechanical imbalance between normal and transformed cells, which drives cell competition. In the mouse intestinal epithelium and epithelial monolayer, transformed cells get compacted during competition. Stress microscopy reveals an emergent compressive stress at the transformed loci leading to this compaction. A cell-based self-propelled Voronoi model predicts that this compressive stress originates from a difference in the collective compressibility of the competing populations. A new collective compressibility measurement technique named gel compression microscopy then elucidates a two-fold higher compressibility of the transformed population than the normal population. Mechanistically, weakened cell-cell adhesions due to reduced junctional abundance of E-cadherin in the transformed cells render them collectively more compressible than normal cells. Taken together, our findings unveil a mechanical basis for epithelial homeostasis against oncogenic transformations with implications in epithelial defense against cancer., Competing Interests: Competing interests The authors declare no competing interests.

Lipid nanoparticle (LNP) remains the most advanced platform for messenger RNA (mRNA) delivery. To date, mRNA LNPs synthesis is mostly performed by mixing lipids and mRNA with microfluidics. In this study, a cost-effective microfluidic setup for synthesizing mRNA LNPs is developed. It allows to fine-tune the LNPs characteristics without compromising LNP properties. It is compared with a commercial device (NanoAssemblr) and ethanol injection and the influence of manufacturing conditions on the performance of mRNA LNPs is investigated. LNPs prepared by ethanol injection exhibit broader size distributions and more inhomogeneous internal structure (e.g., bleb-like substructures), while other LNPs show uniform structure with dense cores. Small angel X-ray scattering (SAXS) data indicate a tighter interaction between mRNA and lipids within LNPs synthesized by custom device, compared to LNPs produced by NanoAssemblr. Interestingly, the better transfection efficiency of polysarcosine (pSar)-modified LNPs correlates with a higher surface roughness than that of PEGylated ones. The manufacturing approach, however, shows modest influence on mRNA expression in vivo. In summary, the home-developed cost-effective microfluidic device can synthesize LNPs and represents a potent alternative to NanoAssemblr. The preparation methods show notable effect on LNPs' structure but a minor influence on mRNA delivery in vitro and in vivo., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background: Early diagnosis and treatment of HPV persistent infection and cervical intraepithelial neoplasia, which have yet to be thoroughly characterized in Guangxi, Southwestern China, are the key preventative measures for the development of cervical cancer in women, particularly in HIV-infected women., Methods: A retrospective study of 181 patients with HPV infection or cervical intraepithelial neoplasia who received surgical excision of lesions and were prospectively enrolled at the Fourth People's Hospital of Nanning between January 2018 and February 2023 was performed. HPV-infected patients were divided into two subgroups: HIV-infected and HIV/HPV-coinfected patients and compare differences between these groups., Results: HPV16, 18, 52, and 58 were the most prevalent HPV genotypes. High-risk HPV was significantly co-infected with multiple genotypes (P = 0.0332). HIV-infected women were predisposed to HPV infection (P < 0.0001), and the development of cervical cancer at a young age (P = 0.0336) compared to HIV-uninfected women and the loop electrosurgical excision procedure (P = 0.0480) is preferred for the treatment., Conclusions: HIV infection may increase HPV prevalence and lead to cervical cancer development at a young age. The loop electrosurgical excision procedure is an efficient evaluation and treatment strategy for HIV-infected women suffering from cervical intraepithelial neoplasia., (© 2024. The Author(s).)

Living objects are able to consume chemical energy and process information independently from others. However, living objects can coordinate to form ordered groups such as schools of fish. This work considers these complex groups as living materials and presents imaging-based experiments of laboratory schools of fish to understand how activity, which is a non-equilibrium feature, affects the structure and dynamics of a group. We use spatial confinement to control the motion and structure of fish within quasi-2D shoals of fish and use image analysis techniques to make quantitative observations of the structures, their spatial heterogeneity, and their temporal fluctuations. Furthermore, we utilize Monte Carlo simulations to replicate the experimentally observed data which provides insight into the effective interactions between fish and confirms the presence of a confinement-based behavioral preference transition. In addition, unlike in short-range interacting systems, here structural heterogeneity and dynamic activities are positively correlated as a result of complex interplay between spatial arrangement and behavioral dynamics in fish collectives., (© 2024. The Author(s).)

Biological tissues transform between solid- and liquidlike states in many fundamental physiological events. Recent experimental observations further suggest that in two-dimensional epithelial tissues these solid-liquid transformations can happen via intermediate states akin to the intermediate hexatic phases observed in equilibrium two-dimensional melting. The hexatic phase is characterized by quasi-long-range (power-law) orientational order but no translational order, thus endowing some structure to an otherwise structureless fluid. While it has been shown that hexatic order in tissue models can be induced by motility and thermal fluctuations, the role of cell division and apoptosis (birth and death) has remained poorly understood, despite its fundamental biological role. Here we study the effect of cell division and apoptosis on global hexatic order within the framework of the self-propelled Voronoi model of tissue. Although cell division naively destroys order and active motility facilitates deformations, we show that their combined action drives a liquid-hexatic-liquid transformation as the motility increases. The hexatic phase is accessed by the delicate balance of dislocation defect generation from cell division and the active binding of disclination-antidisclination pairs from motility. We formulate a mean-field model to elucidate this competition between cell division and motility and the consequent development of hexatic order.

Background: Early and precise diagnosis of bronchopulmonary dysplasia (BPD) is essential to improve the prognosis of preterm infants with BPD. Studying ferroptosis-related genes for diagnostic markers of BPD was the objective of this study., Methods: Using the GEO database and the FerrDb database, we obtained the GSE32472 dataset and screened the ferroptosis-related differentially expressed mRNAs (FRDE-mRNAs). By using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), possible biological functions and pathways were identified for FRDE-mRNAs. Three machine learning algorithms (LASSO, SVM-RFE, Random Forest) were used to recognize hub genes, as well as CIBERSORT for exploring the immune landscape of BPD and controls. Functional predictions for hub genes were made using single-gene gene set enrichment analysis (GSEA)., Results: Twenty three FRDE-mRNAs were obtained and were mainly involved in autophagy, fatty acid metabolism and ferroptosis. The four hub genes (LPIN1, ACADSB, WIPI1 and SLC7A11) screened were utilized to construct a diagnostic nomogram. The receiver operating characteristic (ROC) curves and calibration curves demonstrateld that the nomogram exhibited good predictive performance. Eight types of immune cell markers differed significantly between BPD and controls., Conclusion: We developed a diagnostic model for BPD, which could facilitate the early diagnosis and timely intervention of BPD., Impact: The role of ferroptosis in bronchopulmonary dysplasia is rarely reported. The ferroptosis-related genes (LPIN1, ACADSB, WIPI1 and SLC7A11) we identified could serve as early diagnostic biomarkers for BPD. Immune cell infiltration features in BPD and signaling pathways associated with marker genes give new insight into the disease process and provide a basis for further research., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Introduction and Aims: This study aimed to explore the perspectives and experiences of mothers of school-age children with asthma in care., Methods: A phenomenological study was conducted using qualitative research methods from August 2021 to November 2021. Mothers (from Sichuan, China) of school-aged children with asthma who sought outpatient care at the pediatric asthma clinic were purposively sampled based on their occupation, education level, and duration of their child's illness. Semi-structured face-to-face interviews were conducted in consultation room A07 of the pediatric asthma clinic. The interviews were audio-recorded, transcribed verbatim, and analyzed thematically., Results: 23 mothers expressed interest, but data saturation was reached after recruiting 15 mothers.Four main themes encompassing ten sub-themes emerged from the analysis: (1) Negative psychological burden, with sub-themes including anxiety shock, fear of death, guilt, and stigma. (2) Family dysfunction, with sub-themes including impaired quality of life, family emotional crisis, and heavy economic burden. (3) Difficulty in seeking medical treatment. (4) Active response, with sub-themes including emotional adjustment, family empowerment, and social support., Conclusions: In this sample, the caregiving experience of mothers of school-age children with asthma is diverse and complex, reflected not only in personal psychological aspects but also in family functioning and social support. Taking into account various factors, such as addressing psychological well-being, emphasizing family and social support, and promoting the sharing of positive experiences, may result in more effective alleviation of caregiving stress for mothers of school-age children with asthma.

Arsenic (As), a common environmental pollutant, has become a hot topic in recent years due to its potentially harmful effects. Liver damage being a central clinical feature of chronic arsenic poisoning. However, the underlying mechanisms remain unclear. We demonstrated that arsenic can lead to oxidative stress in the liver and result in structural and functional liver damage, significantly correlated with the expression of AUF1, Dicer1, and miR-155 in the liver. Interestingly, knockdown AUF1 promoted the up-regulatory effects of arsenic on Dicer1 and miR-155 and the inhibitory effects on SOD1, which exacerbated oxidative damage in rat liver. However, overexpression of AUF1 reversed the up-regulatory effects of arsenic on Dicer1 and miR-155, restored arsenic-induced SOD1 depletion, and attenuated liver oxidative stress injury. Further, we verified the mechanism and targets of miR-155 in regulating SOD1 by knockdown/overexpression of miR-155 and nonsense mutant SOD1 3'UTR experiments. In conclusion, these results powerfully demonstrate that arsenic inhibits AUF1 protein expression, which in turn reduces the inhibitory effect on Dicer1 expression, which promotes miR-155 to act on the SOD1 3'UTR region after high expression, thus inhibiting SOD1 protein expression and enzyme activity, and inducing liver injury. This finding provides a new perspective for the mechanism research and targeted prevention of arsenic poisoning, as well as scientific evidence for formulating strategies to prevent and control environmental arsenic pollution., 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 B.V.)

While it is known that cells with differential adhesion tend to segregate and preferentially sort, the physical forces governing sorting and invasion in heterogeneous tumors remain poorly understood. To investigate this, we tune matrix confinement, mimicking changes in the stiffness and confinement of the tumor microenvironment, to explore how physical confinement influences individual and collective cell migration in 3D spheroids. High levels of confinement lead to cell sorting while reducing matrix confinement triggers the collective fluidization of cell motion. Cell sorting, which depends on cell-cell adhesion, is crucial to this phenomenon. Burst-like migration does not occur for spheroids that have not undergone sorting, regardless of the degree of matrix confinement. Using computational Self-Propelled Voronoi modeling, we show that spheroid sorting and invasion into the matrix depend on the balance between cell-generated forces and matrix resistance. The findings support a model where matrix confinement modulates 3D spheroid sorting and unjamming in an adhesion-dependent manner, providing insights into the mechanisms of cell sorting and migration in the primary tumor and toward distant metastatic sites. STATEMENT OF SIGNIFICANCE: The mechanical properties of the tumor microenvironment significantly influence cancer cell migration within the primary tumor, yet how these properties affect intercellular interactions in heterogeneous tumors is not well understood. By utilizing calcium and calcium chelators, we dynamically alter collagen-alginate hydrogel stiffness and investigate tumor cell behavior within co-culture spheroids in response to varying degrees of matrix confinement. High confinement is found to trigger cell sorting while reducing confinement for sorted spheroids facilitates collective cell invasion. Notably, without prior sorting, spheroids do not exhibit burst-like migration, regardless of confinement levels. This work establishes that matrix confinement and intercellular adhesion regulate 3D spheroid dynamics, offering insights into cellular organization and migration within the primary tumor., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The growth of environmentally sensitive complex-shaped electronic devices (ECEDs) has led to a surging demand for flexible electromagnetic wave (EMW) absorbers. Herein, the water loss property of hydrogel was ingeniously applied for the flexible encapsulation (FE) of ECEDs. To be specific, saturated state (SGT) hydrogels were prepared by chemical cross-linking, and the hydrogen bond dissipation network promoted FE. Additionally, SGT has an effective absorption bandwidth (EAB) of 6.04 GHz at 1.65 mm due to the presence of dipole polarization. With the loss of water, SGT transitions to its natural state (NGT), and the decreasing conductivity leads to better impedance matching. NGT exhibited a broader EAB (9.20 GHz at 2.65 mm) and also strength and lightness (density of 0.3 g cm -3 ). Furthermore, the semi-automatic reversible cyclic transformation between SGT and NGT gels further broadens application scenarios. GT gel combines self-encapsulation and self-optimized performance as a potential EMW absorber for FE., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Objective: This study was conducted to explore the risk factors for the prognosis and recurrence of ureteropelvic junction obstruction (UPJO)., Methods: The correlation of these variables with the prognosis and recurrence risks was analyzed by binary and multivariate logistic regression. Besides, a nomogram was constructed based on the multivariate logistic regression calculation. After the model was verified by the C-statistic, the ROC curve was plotted to evaluate the sensitivity of the model. Finally, the decision curve analysis (DCA) was conducted to estimate the clinical benefits and losses of intervention measures under a series of risk thresholds., Results: Preoperative automated peritoneal dialysis (APD), preoperative urinary tract infection (UTI), preoperative renal parenchymal thickness (RPT), Mayo adhesive probability (MAP) score, and surgeon proficiency were the high-risk factors for the prognosis and recurrence of UPJO. In addition, a nomogram was constructed based on the above 5 variables. The area under the curve (AUC) was 0.8831 after self cross-validation, which validated that the specificity of the model was favorable., Conclusion: The column chart constructed by five factors has good predictive ability for the prognosis and recurrence of UPJO, which may provide more reasonable guidance for the clinical diagnosis and treatment of this disease., Competing Interests: 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 Ma, Gao, Chang, Lu, Li, Ding, Bi and Sun.)

Acupuncture was studied to investigate the mechanism of its effect on protease vitality and free radical damage in Type I CIA rats induced by type II collagen. The study divided rats into a control group (injected with physiological saline, n = 10), a model group (injected with type II collagen, n = 10), and an intervention group (injected with type II collagen + acupuncture ST36 and GB39, 3 times a week, for a total of 4 weeks, n = 10) based on the different injected drugs. Then, various indicators of the mice were experimentally tested using joint index scoring, H&E histological staining, protein blotting, and immunohistochemistry staining methods. Acupuncture ST36 and GB39 can reduce arthritis scores, histological staining scores, and increase MVD in CIA rats. And reduce protease levels, alleviate inflammation, synovial hyperplasia, and angiogenesis. In addition, the intervention group TNF-α, IL-1β and IL-6 mRNA were reduced, and the clearance rates of hydrogen peroxide free radicals and nitric oxide free radicals were increased. The expression levels of ROS and MDA decrease, while the expression levels of SOD increase It has been proved that acupuncture at ST36 and GB39 can inhibit the release of ROS, reduce protease activity, inflammation, synovial hyperplasia, angiogenesis and free radical damage, thus reducing the severity of CIA (Collagen-Induced Arthritis) in rats., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Conductive hydrogels have shown promising application prospects in the field of flexible sensors, but they often suffer from poor mechanical properties, low sensitivity, and lack of frost resistance. Herein, we report a tough, highly sensitive, and antifreeze strain sensor assembled from a conductive organohydrogel composed of a dual-cross-linked polyacrylamide and poly(vinyl alcohol) (PVA) network, as well as MXene nanosheets as nanofillers and poly(3,4-ethylenedioxythiophene)-doped poly(styrenesulfonate) (PEDOT/PSS) as the main conducting component (PPMP-OH organohydrogel). The tensile strength and toughness of PPMP-OH had been greatly enhanced by MXene nanosheets due to the mechanical reinforcement of MXene nanosheets, as well as various strong noncovalent interactions formed in the organohydrogels. The PPM 1 P-OH organohydrogels showed a tensile strength of 1.48 MPa at 772% and a toughness of 5.59 MJ/m 3 . Moreover, the conductivity and strain-sensing performance of PPMP-OH were significantly improved by PEDOT/PSS, which can form hydrogen bonds with PVA and electrostatic interactions with MXene. This was greatly beneficial for constructing a uniformly distributed and stable 3D conductive network and helped to obtain strain-dependent resistance of PPMP-OH. The strain sensors assembled from PPMP 1 -OH exhibited a high sensitivity of 5.16, a wide range of detectable strains up to 500%, and a short response time of 122 ms, which can effectively detect various physiological activities of the human body with high stability. In addition, the corresponding pressure sensor array also showed high sensitivity in identifying pressure magnitude and position.

Tin-lead (Sn-Pb) mixed perovskites is beneficial to a single-junction or all-perovskite tandem device. However, the poor quality of the perovskite surface resulting from Sn 2+ oxidation and uncontrollable crystallization degrades device performance and stability. Herein, based on interface engineering, a novel biguanide derivative of PZBGACl is employed that integrates different types of N-related groups to reconstruct the surface/grain boundaries of Sn-Pb perovskite. Combined with the microcorrosion effect of isopropanol solvent, PZBGACl can induce surface recrystallization of perovskite, and passivate various types of defects via hydrogen bond or Lewis acid-base interaction, leading to an excellent perovskite film with reduced stress, larger grain size, and more n-type surface. As a result, the obtained Sn-Pb solar cell achieves a power conversion efficiency of 22.0%, and exhibits excellent N 2 storage/operation stability., (© 2023 Wiley‐VCH GmbH.)

The aims of this study were to analyze the morphological changes of the mandibular angle after orthognathic surgery for mandibular setback and investigate related factors. This retrospective study included patients from January 2017 to December 2021 diagnosed with skeletal class III deformity who underwent BSSRO (Group I) or bimaxillary surgery (Group II). Preoperative (T0), within 1 month postoperatively (T1), and 6 months postoperatively (T2) CT scans were collected from 61 patients to three-dimensionally analyze the proximal segment displacement, the linear and angular changes of the mandibular angle. The gonion points moved posteriorly and laterally (P < 0.001), while the inferior movement was not significant (P = 1.000, P = 0.274). The intergonial width increased by 3.32 ± 1.87 mm and 2.34 ± 1.77 mm as revealed by T2 CTs, respectively, in Group I and Group II. Mandibular angle decreased in both groups and by 1.41 ± 2.95° in Group I and 1.37 ± 3.41° in Group II. The increase in intergonial width between T1 and T0 was negatively correlated with the preoperative mandibular angle (P = 0.003) and positively correlated with the transverse outward movement of the proximal segment (P < 0.001). After surgery, the intergonial width increased and the inferior and posterior border of the proximal segment flared outward. The changes in intergonial width and mandibular angle were mainly related to the rotation of the proximal segment, which has a certain impact on the aesthetics of the lower face. Therefore, controlling the position of the proximal segment is of vital importance to lessen the changes in the mandibular angle area.Level of Evidence III. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Under global change scenarios, the sea surface temperature is increasing steadily along with other changes to oceanic environments. Consequently, marine diatoms are influenced by multiple ocean global change drivers. We hypothesized that temperature rise mediates the responses of polar and temperate diatoms to UV radiation (UVR) to different extents, and exposed the temperate centric diatoms, Thalassiosira weissflogii and Skeletonema costatum, and a polar pennate diatom Entomoneis sp., to warming (+5°C) for 10 days, then performed short-term incubations under different radiation treatments with or without UVR. The effective quantum yields of the three diatoms were stable during exposure to PAR, but decreased when exposed to PAR + UVR, leading to significant UV-induced inhibition, which was 3% and 9%, respectively, for T. weissflogii and S. costatum under ambient temperature but increased to 12% and 17%, respectively, in the cells acclimated to the warming treatment. In contrast, UVR induced much higher inhibition, by about 45%, in the polar diatom Entomoneis sp. at ambient temperature, and the warming treatment alleviated the UV-induced inhibition, which dropped to 36%. The growth rates were significantly inhibited by UVR in S. costatum under the warming treatment and in Entomoneis sp. under ambient temperature, while there was no significant effect for T. weissflogii. Our results indicate that the polar diatom was more sensitive to UVR though warming could alleviate its impact, whereas the temperate diatoms were less sensitive to UVR but warming exacerbated its impacts, implying that diatoms living in different regions may exhibit differential responses to global changes., (© 2023 American Society for Photobiology.)

In cell clusters, the prominent factors at play encompass contractility-based enhanced tissue surface tension and cell unjamming transition. The former effect pertains to the boundary effect, while the latter constitutes a bulk effect. Both effects share outcomes of inducing significant elongation in cells. This elongation is so substantial that it surpasses the limits of linear elasticity, thereby giving rise to additional effects. To investigate these effects, we employ atomic force microscopy (AFM) to analyze how the mechanical properties of individual cells change under such considerable elongation. Our selection of cell lines includes MCF-10A, chosen for its pronounced demonstration of the extended differential adhesion hypothesis (eDAH), and MDA-MB-436, selected due to its manifestation of cell unjamming behavior. In the AFM analyses, we observe a common trend in both cases: as elongation increases, both cell lines exhibit strain stiffening. Notably, this effect is more prominent in MCF-10A compared to MDA-MB-436. Subsequently, we employ AFM on a dynamic range of 1-200 Hz to probe the mechanical characteristics of cell spheroids, focusing on both surface and bulk mechanics. Our findings align with the results from single cell investigations. Specifically, MCF-10A cells, characterized by strong contractile tissue tension, exhibit the greatest stiffness on their surface. Conversely, MDA-MB-436 cells, which experience significant elongation, showcase their highest stiffness within the bulk region. Consequently, the concept of single cell strain stiffening emerges as a crucial element in understanding the mechanics of multicellular spheroids (MCSs), even in the case of MDA-MB-436 cells, which are comparatively softer in nature.

Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of unknown, individual-specific effectors in F. nucleatum-dependent carcinogenesis. Here, we identify that F. nucleatum is enriched preferentially in KRAS p.G12D mutant CRC tumor tissues and contributes to colorectal tumorigenesis in Villin-Cre/Kras G12D+/- mice. Additionally, Parabacteroides distasonis (P. distasonis) competes with F. nucleatum in the G12D mouse model and human CRC tissues with the KRAS mutation. Orally gavaged P. distasonis in mice alleviates the F. nucleatum-dependent CRC progression. F. nucleatum invades intestinal epithelial cells and binds to DHX15, a protein of RNA helicase family expressed on CRC tumor cells, mechanistically involving ERK/STAT3 signaling. Knock out of Dhx15 in Villin-Cre/Kras G12D+/- mice attenuates the CRC phenotype. These findings reveal that the oncogenic effect of F. nucleatum depends on somatic genetics and gut microbial ecology and indicate that personalized modulation of the gut microbiota may provide a more targeted strategy for CRC treatment., (© 2024. The Author(s).)

Phytoplankton face numerous pressures resulting from chemical and physical stressors, primarily induced by human activities. This study focuses on investigating the interactive effects of widely used antifouling agent Irgarol 1051 and UV radiation on the photo-physiology of marine diatoms from diverse latitudes, within the context of global warming. Our findings clearly shown that both Irgarol and UV radiation have a significant inhibitory impact on the photochemical performance of the three diatoms examined, with Irgarol treatment exhibiting more pronounced effects. In the case of the two temperate zone diatoms, we observed a decrease in the inhibition induced by Irgarol 1051 and UVR as the temperature increased up to 25°C. Similarly, for the subarctic species, an increase in temperature resulted in a reduction in the inhibition caused by Irgarol and UVR. These results suggest that elevated temperatures can mitigate the short-term inhibitory effects of both Irgarol and UVR on diatoms. Furthermore, our data indicate that increased temperature could significantly interact with UVR or Irgarol for temperate diatoms, while this was not the case for cold water diatoms, indicating temperate and subarctic diatoms may respond differentially under global warming., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bi 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.)

The complement system is increasingly recognized as a key player in the synapse loss and cognitive impairments observed in Alzheimer's disease (AD). In particular, the process of complement-dependent synaptic pruning through phagocytosis is over-activated in AD brains, driving detrimental excessive synapse elimination and contributing to synapse loss, which is the strongest neurobiological correlate of cognitive impairments in AD. Herein we review recent advances in characterizing complement-mediated synapse loss in AD, summarize the underlying mechanisms, and discuss the possible involvement of AD risk factors such as aging and various risk genes. We conclude with an overview of key questions that remain to be addressed., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Colloidal gels exhibit solid-like behavior at vanishingly small fractions of solids, owing to ramified space-spanning networks that form due to particle-particle interactions. These networks give the gel its rigidity, and with stronger attractions the elasticity grows as well. The emergence of rigidity can be described through a mean field approach; nonetheless, fundamental understanding of how rigidity varies in gels of different attractions is lacking. Moreover, recovering an accurate gelation phase diagram based on the system's variables has been an extremely challenging task. Understanding the nature of colloidal clusters, and how rigidity emerges from their connections is key to controlling and designing gels with desirable properties. Here, we employ network analysis tools to interrogate and characterize the colloidal structures. We construct a particle-level network, having all the spatial coordinates of colloids with different attraction levels, and also identify polydisperse rigid fractal clusters using a Gaussian mixture model, to form a coarse-grained cluster network that distinctly shows main physical features of the colloidal gels. A simple mass-spring model then is used to recover quantitatively the elasticity of colloidal gels from these cluster networks. Interrogating the resilience of these gel networks shows that the elasticity of a gel (a dynamic property) is directly correlated to its cluster network's resilience (a static measure). Finally, we use the resilience investigations to devise [and experimentally validate] a fully resolved phase diagram for colloidal gelation, with a clear solid-liquid phase boundary using a single volume fraction of particles well beyond this phase boundary., Competing Interests: Competing interests statement:The authors declare no competing interest.

Three undescribed hybrid flavan-chalcones, caesalpinflavans D-F, and an unreported normonoterpene-chalcone heterodimer, caesalpinnone B, along with three known biflavonoids were isolated from the twigs and leaves of Caesalpinia digyna. Their structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculations. Caesalpinflavan F was identified as a bis-(hybrid flavan-chalcone), its natural occurrence was supported by HPLC-IT-TOF-MS analysis. The condensation of caesalpinflavan B with acetone was possibly a key step in the biosynthesis of caesalpinflavan F. Caesalpinnone B represents an unprecedented meroterpenoid featuring a cyclobutane central framework, which was derived from chalcone and normonoterpenoid via a key [2 + 2] cyclization reaction. Biological evaluation revealed that compounds caesalpinflavan D, oxytrodiflavanone A, and caesalpinnone B exhibited moderate cytotoxicity against HL-60, SMMC-7721, SW480, A-549 and/or MDA-MB-231 cell lines with IC 50 values ranging from 8.051 ± 0.673 to 24.26 ± 0.61 μM. This study provided evidence for further research and possible utilization of C. digyna in the future., 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 © 2023 Elsevier Ltd. All rights reserved.)

During embryonic morphogenesis, tissues undergo dramatic deformations in order to form functional organs. Similarly, in adult animals, living cells and tissues are continually subjected to forces and deformations. Therefore, the success of embryonic development and the proper maintenance of physiological functions rely on the ability of cells to withstand mechanical stresses as well as their ability to flow in a collective manner. During these events, mechanical perturbations can originate from active processes at the single-cell level, competing with external stresses exerted by surrounding tissues and organs. However, the study of tissue mechanics has been somewhat limited to either the response to external forces or to intrinsic ones. In this work, we use an active vertex model of a 2D confluent tissue to study the interplay of external deformations that are applied globally to a tissue with internal active stresses that arise locally at the cellular level due to cell motility. We elucidate, in particular, the way in which this interplay between globally external and locally internal active driving determines the emergent mechanical properties of the tissue as a whole. For a tissue in the vicinity of a solid-fluid jamming or unjamming transition, we uncover a host of fascinating rheological phenomena, including yielding, shear thinning, continuous shear thickening, and discontinuous shear thickening. These model predictions provide a framework for understanding the recently observed nonlinear rheological behaviors in vivo .

As the roles of historical trials and real-world evidence in drug development have substantially increased, several approaches have been proposed to leverage external data and improve the design of clinical trials. While most of these approaches focus on methodology development for borrowing information during the analysis stage, there is a risk of inadequate or absent enrollment of concurrent control due to misspecification of heterogeneity from external data, which can result in unreliable estimates of treatment effect. In this study, we introduce a Bayesian hybrid design with flexible sample size adaptation (BEATS) that allows for adaptive borrowing of external data based on the level of heterogeneity to augment the control arm during both the design and interim analysis stages. Moreover, BEATS extends the Bayesian semiparametric meta-analytic predictive prior (BaSe-MAP) to incorporate time-to-event endpoints, enabling optimal borrowing performance. Initially, BEATS calibrates the expected sample size and initial randomization ratio based on heterogeneity among the external data. During the interim analysis, flexible sample size adaptation is performed to address conflicts between the concurrent and historical control, while also conducting futility analysis. At the final analysis, estimation is provided by incorporating the calibrated amount of external data. Therefore, our proposed design allows for an approximation of an ideal randomized controlled trial with an equal randomization ratio while controlling the size of the concurrent control to benefit patients and accelerate drug development. BEATS also offers optimal power and robust estimation through flexible sample size adaptation when conflicts arise between the concurrent control and external data., (© 2023 John Wiley & Sons Ltd.)

We introduce an active version of the recently proposed finite Voronoi model of epithelial tissue. The resultant Active Finite Voronoi (AFV) model enables the study of both confluent and non-confluent geometries and transitions between them, in the presence of active cells. Our study identifies six distinct phases, characterized by aggregation-segregation, dynamical jamming-unjamming, and epithelial-mesenchymal transitions (EMT), thereby extending the behavior beyond that observed in previously studied vertex-based models. The AFV model with rich phase diagram provides a cohesive framework that unifies the well-observed progression to collective motility via unjamming with the intricate dynamics enabled by EMT. This approach should prove useful for challenges in developmental biology systems as well as the complex context of cancer metastasis. The simulation code is also provided.

We investigate the rigidity transition associated with shear jamming in frictionless, as well as frictional, disk packings in the quasi-static regime and at low shear rates. For frictionless disks, the transition under quasi-static shear is discontinuous, with an instantaneous emergence of a system spanning rigid clusters at the jamming transition. For frictional systems, the transition appears continuous for finite shear rates, but becomes sharper for lower shear rates. In the quasi-static limit, it is discontinuous as in the frictionless case. Thus, our results show that the rigidity transition associated with shear jamming is discontinuous, as demonstrated in the past for isotropic jamming of frictionless particles, and therefore a unifying feature of the jamming transition in general.

Chronic kidney disease (CKD) is a progressive loss in kidney function. Early detection of patients who will progress to late-stage CKD is of paramount importance for patient care. To address this, we develop a pipeline to process longitudinal electronic heath records (EHRs) and construct recurrent neural network (RNN) models to predict CKD progression from stages II/III to stages IV/V. The RNN model generates predictions based on time-series records of patients, including repeated lab tests and other clinical variables. Our investigation reveals that using a single variable, the recorded estimated glomerular filtration rate (eGFR) over time, the RNN model achieves an average area under the receiver operating characteristic curve (AUROC) of 0.957 for predicting future CKD progression. When additional clinical variables, such as demographics, vital information, lab test results, and health behaviors, are incorporated, the average AUROC increases to 0.967. In both scenarios, the standard deviation of the AUROC across cross-validation trials is less than 0.01, indicating a stable and high prediction accuracy. Our analysis results demonstrate the proposed RNN model outperforms existing standard approaches, including static and dynamic Cox proportional hazards models, random forest, and LightGBM. The utilization of the RNN model and the time-series data of previous eGFR measurements underscores its potential as a straightforward and effective tool for assessing the clinical risk of CKD patients concerning their disease progression., (© 2023. The Author(s).)

Objective: Microscopy was used to characterize platelet- Plasmodium -infected erythrocyte interactions in patients infected with Plasmodium falciparum , Plasmodium vivax , Plasmodium ovale or Plasmodium malariae , and to investigate the relationship between platelet-associated parasite killing and parasite clearance., Methods: Data from 244 malaria patients admitted to the Fourth People's Hospital of Nanning between 1 January 2011 and 30 September 2022, and 45 healthy controls, were collected prospectively and assessed retrospectively. Characteristics of platelet-erythrocyte interactions were visualized by microscopy, and blood cell count and clinical profiles of these participants were obtained from the electronic medical records. ANOVA, contingency tables and Cox proportional hazards regression models were used to do statistical analysis on the subgroups., Results: Platelet enlargement and minor pseudopodia development were observed. Platelets were found directly attaching to parasitized erythrocytes by all Plasmodium species studied, especially mature stages, and lysis of parasitized erythrocytes was connected to platelet-mediated cytolysis. Platelet counts were correlated inversely with parasitaemia and duration of parasite clearance. Artemisinin combination therapy was more effective than artemisinin alone in clearing Plasmodium in patients with thrombocytopenia., Conclusions: Platelet-parasitized erythrocytes cell-to-cell contacts initiated platelet-associated parasite killing and helped to limit Plasmodium infection in cases of human malaria. The weakening platelet-associated parasite killing effects could be counteracted by artemisinin combination therapy in patients with thrombocytopenia.

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

The determination of a treatment plan for a target patient with tumor is a difficult problem due to the existence of heterogeneity in patients' responses, incomplete information about tumor states, and asymmetric knowledge between doctors and patients, and so on. In this paper, a method for quantitative risk analysis of treatment plans for patients with tumor is proposed. To reduce the impacts of the heterogeneity in patients' responses on analysis results, the method conducts risk analysis by mining historical similar patients from Electronic Health Records (EHRs) in multiple hospitals using federated learning (FL). For this, the Recursive Feature Elimination based on the Support Vector Machine (SVM) and Deep Learning Important FeaTures (DeepLIFT) are extended into the FL framework to select key features and determine key feature weights for identifying historical similar patients. Then, in the database of each collaborative hospital, the similarities between the target patient and all historical patients are calculated, and the historical similar patients are determined. According to the statistics of tumor states and treatment outcomes of historical similar patients in all collaborative hospitals, the related data (including the probabilities of different tumor states and possible outcomes of different treatment plans) for risk analysis of the alternative treatment plans can be obtained, which can eliminate the asymmetric knowledge between doctors and patients. The related data are valuable for the doctor and patient to make their decisions. Experimental studies have been conducted to verify the feasibility and effectiveness of the proposed method., (© 2023 Society for Risk Analysis.)

Objectives: We aimed to investigate clinical uncertainties by characterizing the accuracy and utility of commercially available antibodies of Mycobacterium tuberculosis in the diagnostic assessment of suspected tuberculosis in high-burden countries., Methods: We conducted a retrospective, descriptive, cohort study among participants aged ≥ 18 years with suspected tuberculosis in Nanning, Guangxi, and China. Participants were tested for M. tuberculosis infection using commercially available antibodies against Mycobacterum tuberculosis . Specificity, sensitivity, negative and positive predictive values, and negative and positive likelihood ratios of the tests were determined. Sputum specimens and bronchoalveolar lavage fluid were sent for mycobacterial culture, Xpert MTB/RIF assay, and cell-free M. tuberculosis DNA or RNA assay. Blood samples were used for IGRAs, T-cell counts (CD3 + CD4+ and CD3 + CD8+), and antibodies to tuberculosis test., Results: Of the 1857 participants enrolled in this study, 1772 were included in the analyses, among which, 1311 were diagnosed with active tuberculosis. The specificity of antibody against 16kD for active tuberculosis was 92.7% (95% confidence interval [CI]: 89.3-95.4) with a positive likelihood ratio for active tuberculosis cases of 3.1 (95% CI: 2.1-4.7), which was higher than that of antibody to Rv1636 (90.5% [95% CI: 86.6-93.5]), antibody to 38kD (89.5% [95% CI: 85.5-92.7]), antibody against CFP-10 (82.6% [95% CI: 77.9-86.7]), and antibody against LAM (79.3% [95% CI: 74.3-83.7]). Sensitivity ranged from 15.8% (95% CI: 13.9-17.9) for antibody against Rv1636 to 32.9% (95% CI: 30.4-35.6) for antibody to LAM., Conclusions: Commercially available antibodies against to Mycobacterium tuberculosis do not have sufficient sensitivity for the diagnostic evaluation of active tuberculosis. However, antibody against Rv1636 and 16kD may have sufficiently high specificities, high positive likelihood ratios, and correspondingly high positive predictive values to facilitate the rule-in of active tuberculosis.

Background: One reason patients with cancer cannot benefit from immunotherapy is the lack of immune cell infiltration in tumor tissues. Cancer-associated fibroblasts (CAFs) are emerging as central players in immune regulation that shapes tumor microenvironment (TME). Earlier we reported that integrin α5 was enriched in CAFs in colorectal cancer (CRC), however, its role in TME and cancer immunotherapy remains unclear. Here, we aimed to investigate the role for integrin α5 in fibroblasts in modulating antitumor immunity and therapeutic efficacy combined with checkpoint blockade in CRC., Methods: We analyzed the CRC single-cell RNA sequencing (scRNA-seq) database to define the expression of ITGA5 in CRC tumor stroma. Experimentally, we carried out in vivo mouse tumor xenograft models to confirm the targeting efficacy of combined α5β1 inhibition and anti-Programmed death ligand 1 (PD-L1) blockade and in vitro cell-co-culture assay to investigate the role of α5 in fibroblasts in affecting T-cell activity. Clinically, we analyzed the association between α5 expression and infiltrating T cells and evaluated their correlation with patient survival and immunotherapy prognosis in CRC., Results: We revealed that ITGA5 was enriched in FAP -CAFs. Both ITGA5 knockout fibroblasts and therapeutic targeting of α5 improved response to anti-PD-L1 treatment in mouse subcutaneous tumor models. Mechanistically, these treatments led to increased tumor-infiltrating CD8 + T cells. Furthermore, we found that α5 in fibroblasts correlated with extracellular matrix (ECM)-related genes and affected ECM deposition in CRC tumor stroma. Both in vivo analysis and in vitro culture and cell killing experiment showed that ECM proteins and α5 expression in fibroblasts influence T-cell infiltration and activity. Clinically, we confirmed that high α5 expression was associated with fewer CD3 + T and CD8 + T cells, and tissues with low α5 and high CD3 + T levels correlated with better patient survival and immunotherapy response in a CRC cohort with 29 patients., Conclusions: Our study identified a role for integrin α5 in fibroblasts in modulating antitumor immunity by affecting ECM deposition and showed therapeutic efficacy for combined α5β1 inhibition and PD-L1 blockade in CRC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The stratum corneum (SC) and cell membrane are two major barriers that hinder the therapeutic outcomes of transdermal drug delivery for the treatment of skin diseases. While microneedles (MNs) can efficiently penetrate the SC to deliver nanomedicines, the optimization of physicochemical properties of nanomedicines in MNs to enhance their in vivo cellular delivery efficiency remains unclear. Here, how the size and surface charge of drug-loaded liposomes in MNs influence the retention time and cellular delivery in psoriatic skin is systematically investigated. The results indicate that while 100 nm negatively-charged liposomes in MNs show higher cellular uptake in vitro, 250 and 450 nm liposomes could enhance skin retention and the long-term in vivo cellular delivery efficiency of drugs. Moreover, 250 nm cationic liposomes with a stronger positive charge show an extraordinarily long skin retention time of 132 h and significantly higher in vivo cellular internalization. In the treatment study, dexamethasone (dex)-loaded cationic liposomes-integrated MNs show better therapeutic outcomes than dex-loaded anionic liposomes-integrated MNs in a psoriasis-like animal model. The design principles of liposomes in MN drug delivery systems explored in the study hold the potential for enhancing the therapeutic outcomes of psoriasis and are instrumental for successful translation., (© 2023 Wiley-VCH GmbH.)