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Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which macrophages produce cytokines that enhance inflammation and contribute to the destruction of cartilage and bone. Additive Sishen decoction (ASSD) is a widely used traditional Chinese medicine for the treatment of RA; however, its active ingredients and the mechanism of its therapeutic effects remain unclear., Methods: To predict the ingredients and key targets of ASSD, we constructed "drug-ingredient-target-disease" and protein-protein interaction networks. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the potential mechanism. The activity of the predicted key ingredients was verified in lipopolysaccharide-stimulated macrophages. The binding mode between the key ingredients and key targets was elucidated using molecular docking and molecular dynamics simulation., Results: In all, 75 ASSD active ingredients and 1258 RA targets were analyzed, of which kaempferol, luteolin, and quercetin were considered key components that mainly act through inflammation-related pathways, such as the PI3K-AKT, TNF, and IL-17 signaling pathways, to ameliorate RA. Transcriptome sequencing suggested that kaempferol-, luteolin-, and quercetin-mediated inhibition of glycolysis reduced the lipopolysaccharide-induced production of proinflammatory factors. In vitro experiments indicated that kaempferol, luteolin, and quercetin decreased Glut1 and LDHA expression by diminishing PI3K-AKT signaling to inhibit glycolysis. Molecular dynamic simulation revealed that kaempferol, luteolin, and quercetin stably occupied the hydrophobic pocket of PI3Kδ., Conclusion: Our results show that the PI3Kδ-mediated anti-inflammatory responses elicited by kaempferol, luteolin, and quercetin are crucial for the therapeutic efficacy of ASSD against RA., Competing Interests: The authors have declared no conflicts of interest in this work., (© 2025 Ren et al.)

Environmental stressors, including pathogens, substantially affect the growth of host plants. However, how non-adapted bacteria influence nonhost plants has not been reported. Here, we reveal that infection of Arabidopsis flowers by Xanthomonas oryzae pv. oryzae PXO99A, a bacterial pathogen causing rice blight disease, suppresses ovule initiation and reduces seed number without causing visible disease symptoms. TleB, secreted by the type VI secretion system (T6SS), interacts with plant E3 ligase PUB14 and disrupts the function of the PUB14-BZR1 module, leading to decreased ovule initiation and seed yield. On the other site, PUB14 concurrently promotes TleB's degradation. Our findings indicate that bacterial infections in nonhost plants directly repress offspring production. The regulatory mechanism by effectors PUB14-BZR1 is widely present, suggesting that plants may balance reproduction and defense and produce fewer offspring to conserve resources, thus enabling them to remain in a standby mode prepared for enhanced resistance.

Previous studies illustrated that two banana GA20 oxidase2 (MaGA20ox2) genes, Ma04g15900 and Ma08g32850 , are implicated in controlling banana growth and development; however, the biological function of each gene remains unknown. Ma04g15900 protein (termed MaGA20ox2f in this article) is the closest homolog to the Rice SD1 (encoded by 'green revolution gene', OsSD1 ) in the banana genome. The expression of MaGA20ox2f is confined to leaves, peduncles, fruit peels, and pulp. Knockout of MaGA20ox2f by CRISPR/Cas9 led to late flowering and low-yielding phenotypes. The flowering time of ΔMaGA20ox2f #1 and ∆MaGA20ox2f #2 lines was delayed approximately by 61 and 58 days, respectively, while fruit yield decreased by 81.13% and 76.23% compared to wild type under normal conditions. The endogenous levels of downstream products of GA20 oxidase, GA15 and GA20, were significantly reduced in ∆MaGA20ox2f mutant shoots and fruits, but bioactive GA1 was only significantly reduced in the mutant fruits. Quantitative proteomics analysis identified 118 up-regulated proteins and 309 down-regulated proteins in both ΔMaGA20ox2f #1 and ∆MaGA20ox2f #2 lines, compared to wild type, with the down-regulated proteins primarily associated with photosynthesis, porphyrin and chlorophyll metabolism. The decreased chlorophyll contents in ΔMaGA20ox2f #1 and ∆MaGA20ox2f #2 lines corroborated the findings of the proteomics data. We propose that photosynthesis inhibition caused by lower chlorophyll contents in ΔMaGA20ox2f mutant leaves and GA1 deficiency in ΔMaGA20ox2f mutant fruits may be the two critical reasons contributing to the late flowering and low-yielding phenotypes of ΔMaGA20ox2f mutants., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01523-3., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In order to investigate the influence of ultrasonic vibration (UV) on microstructural evaluation of amorphous coating, the Fe-based amorphous (Fe 41.5 Co 12.2 Cr 7.4 Mo 37.3 C 0.3 B 0.5 Y 0.4 Al 0.4 ) coatings with and without UV were fabricated by laser cladding technology. The microstructure and corrosion resistance of the coatings were studied in detail to understand the mechanism of the UV on amorphous coatings. It can be found that the cavitation effect generated by UV refines and breaks the columnar crystals at the interface. Compared to the coatings without UV, the average length of columnar crystals of coatings with UV decreases by 57.52 %, reducing from 25.26 ± 5.89 μm to 10.73 ± 3.91 μm. In addition, the sound pressure gradient drives the accelerated flow of the molten pool, resulting in a flow velocity of up to 0.134 m/s. The acoustic streaming effect of UV promotes the uniform distribution of elements and inhibits the segregation of the intermetallic compounds, which increases the amorphous content from 68.5 % to 75.3 %. The acoustic streaming and cavitation effects refine the microstructure and increase the amorphous content by using of UV, which contributes to improve the corrosion resistance., 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.)

We are rapidly approaching the midpoint of the period set by the UN Agenda 2030 for transforming our activities on the planet Earth. Yet, many of the global issues we have begun with stand still while some of them took a much more severe course. The Sustainable Development Goals (SDGs) are unambiguous. What is unclear is the way to propel our socio-economic organizations into the desired performances. Regarding performance control, the built environment is arguably the most critical system. Every year, we add more urbanized land to the face of the planet without clearly envisioning its environmental effects and social outgrowth. As a result, we frequently find ourselves struggling with unpleasant consequences and unpredicted side effects. In our body of knowledge, there is a missing link between urban structure and performance. This paper offers a systemic breakdown of urban structural parameters and a coherent reading of its performance indicators intending to create a City Information Modelling (CIM) tool. The objective is to formulate the reciprocal relationship between the components of the built environment (as the designer's toolbox) and the system's outcome. To do so, this article moves from the Integrated Modification Methodology (IMM), exploring it through the lens of an Entity-Relationship (ER) schema, delving into its systemic approach to model the built environment as a Complex Adaptive System (CAS). IMM elucidates the intricate structure/performance relationships inherent in the complexity of the built environment. Building upon the successful IMM application in numerous urban transformation projects and retrofitting procedures, our focus is now on streamlining operational processes and accelerating workflow efficiency. Specifically, we seek to optimize the rapid assessment of correlations between structural changes and performance outcomes within the IMM framework. This work aims to operationalize the Agenda 2030, enabling a practical methodological interpretation of targets and indicators in SDG11., 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.)

Background: Trimethylamine N-oxide (TMAO) has been widely explored and considered as a biomarker for adverse cardiovascular events. However, the relationships between TMAO adverse cardiovascular events are inconsistent in patients. Therefore, this meta-analysis aimed to estimate association between TMAO levels and the prognosis of patients with myocardial infarction (MI)., Methods: We searched PubMed, EMBASE, the Cochrane Library, and Web of Science from inception to July 2, 2023, to retrieve all relevant clinical trials. Associations between TMAO levels, major adverse cardiovascular events (MACE), all-cause mortality, recurrent MI, stroke, etc., were systematically addressed. Outcomes included MACE, all-cause mortality, recurrent MI, rehospitalization caused by heart failure, stroke, revascularization, SYNTAX score, and multivessel disease. A fixed/random-effects model should be adopted to calculate the pooled estimates. Besides, funnel plot, Begg's test and Egger' test were used to test publication bias., Results: A total of nine studies were included in our meta-analysis. Our results indicated that higher TMAO levels were associated with greater risk of MACE (RR = 1.94; 95% CI = 1.39 to 2.73), all-cause mortality (RR = 1.56; 95% CI = 1.00 to 2.44), and MI (RR = 1.21; 95% CI = 1.01 to 1.45). No significant association was found in stroke, SYNTAX, and multivessel disease. Besides, our results reported that the association between TMAO levels and MACE after MI was not affected by the geographic localization., Conclusion: This study was the first meta-analysis that showed a significant positive association of TMAO levels with MACE, all-cause mortality, and recurrent MI in patients with MI., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=460400, PROSPERO (CRD42023460400)., 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 Li, Wang, Xu, Luo and Dong.)

This paper addresses the tracking control problem of nonlinear discrete-time multi-agent systems (MASs). First, a local neighborhood error system (LNES) is constructed. Then, a novel tracking algorithm based on asynchronous iterative Q-learning (AIQL) is developed, which can transform the tracking problem into the optimal regulation of LNES. The AIQL-based algorithm has two Q values Q i A and Q i B for each agent i, where Q i A is used for improving the control policy and Q i B is used for evaluating the value of the control policy. Moreover, the convergence of LNES is given. It is shown that the LNES converges to 0 and the tracking problem is solved. A neural network-based actor-critic framework is used to implement AIQL. The critic network of AIQL is composed of two neural networks, which are used for approximating Q i A and Q i B respectively. Finally, simulation results are given to verify the performance of the developed algorithm. It is shown that the AIQL-based tracking algorithm has a lower cost value and faster convergence speed than the IQL-based tracking algorithm., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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

Incidental identification of foreign body (FB) during daily screening endoscopy is not rare. The patients may have unspecific symptoms and do not report a history of FB ingestion at presentation. Although these FBs mostly pass through the gastrointestinal tract uneventfully, a certain proportion could be impacted and cause complications. Lack of a definite history of FB ingestion could make diagnosis difficult and delay treatment when FB presents with deceiving endoscopic appearances. We report a duodenal FB mimicking erosion found in screening upper endoscopy.

Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papilloma virus infection. Although it is generally seen in the genital and perianal regions, anal canal and rectum sometimes could be involved. It has been reported to be associated with higher risk of intraepithelial neoplasia and cancer. Surgery excision and fulguration are the primary treatment, while high local recurrence rate of CA remains bothering. We presented a case of CA that detected via colonoscopy and successfully treated with endoscopic submucosal dissection.

Sepsis-induced acute lung injury (ALI) is prevalent in patients with sepsis and has a high mortality rate. Peptidyl arginine deiminase 2 (PADI2) and PADI4 play crucial roles in mediating the host's immune response in sepsis, but their specific functions remain unclear. Our study shows that Padi2-/- Padi4-/- double KO (DKO) improved survival, reduced lung injury, and decreased bacterial load in Pseudomonas aeruginosa (PA) pneumonia-induced sepsis mice. Using single-cell RNA-Seq (scRNA-Seq), we found that the deletion of Padi2 and Padi4 reduced the Nlrp3+ proinflammatory macrophages and fostered Chil3+ myeloid cell differentiation into antiinflammatory macrophages. Additionally, we observed the regulatory role of the NLRP3/Ym1 axis upon DKO, confirmed by Chil3 knockdown and Nlrp3-KO experiments. Thus, eliminating Padi2 and Padi4 enhanced the polarization of Ym1+ M2 macrophages by suppressing NLRP3, aiding in inflammation resolution and lung tissue repair. This study unveils the PADIs/NLRP3/Ym1 pathway as a potential target in treatment of sepsis-induced ALI.

Drought is one of the most serious abiotic stresses, and emerging evidence suggest plant microbiome affects plant drought tolerance. However, there is a lack of genetic evidence regarding whether and how plants orchestrate the dynamic assembly of the microbiome upon drought. By utilizing mutants with enhanced or decreased root hair densities, we find that root hair regulators also affect drought induced root microbiome changes. Rhizobiaceae is a key biomarker taxa affected by root hair related mutants. We isolated and sequenced 1479 root associated microbes, and confirmed that several Rhizobium strains presented stress-alleviating activities. Metagenome, root transcriptome and root metabolome studies further reveal the multi-omic changes upon drought stress. We knocked out an ornithine cyclodeaminase (ocd) gene in Rhizobium sp. 4F10, which significantly dampens its stress alleviating ability. Our genetic and integrated multi-omics studies confirm the involvement of host genetic effects in reshaping a stress-alleviating root microbiome during drought, and provide mechanistic insights into Rhizobiaceae mediated abiotic stress protection., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Lateral flow immunoassay (LFIA) is valued for its simplicity and rapidity for on-site screening, however, it experienced false negatives in real sample analysis due to low sensitivity. Although many signal amplification techniques can improve the sensitivity, they usually require additional complicated steps. To address these issues, taking Treponema pallidum ( T. pallidum ) antibodies as a model detecting target, herein, we report an all-in-one LFIA (AIO-LFIA) with triple-step signal amplification to significantly improve sensitivity while maintaining simplicity. This LFIA utilizes a biotin-streptavidin system for initial signal amplification, followed by introducing a release controller with a specific imprinted structure for timed multicomponent release, which avoids the extra steps when adding components in traditional LFIA. Particularly, a 3D-printed programmed metal in situ growth (MISG) device is integrated to localize signal enhancement at specific sites, overcoming limitations of traditional MISG and substantially reducing reagent usage and assay time, and the nitrocellulose membrane surface was much cleaner than the conventional approach, which facilitates signal readout. After optimization, the proposed AIO-LFIA is capable of visual detection down to 1 pg/mL T. pallidum antibodies in 15 min, 1000-fold lower than the gold nanoparticle-based LFIA. In clinical testing of 152 samples, the AIO-LFIA can distinguish all positive samples, outperforming commercial LFIA which missed those positive samples with relatively low antibody levels. Thus, this study presents a universal ultrasensitive and reliable AIO-LFIA strategy for infectious diseases self-testing, providing an effective promising prospect to address the challenge over emerging infectious diseases in the future.

To clarify the key role of oxygen vacancy defects on enhancing the oxidative activity of the catalysts, metal-organic frameworks (MOFs) derived MnO X catalysts with different morphologies and oxygen vacancy defects were successfully prepared using a facile in-situ self-assembly strategy with different alkali moderators. The obtained morphologies included three-dimensional (3D) triangular cone stacked MnO X hollow sphere (MnO X -H) and 3D nanoparticle stacked MnO X nanosphere (MnO X -N). Compared to MnO X -N, MnO X -H exhibited higher activity for the oxidation of toluene (T 90  = 226 °C). This was mainly due to the large number of oxygen vacancy defects and Mn 4+ species in the MnO X -H catalyst. In addition, the hollow structure of MnO X -H not only facilitated toluene adsorption and activation of toluene and also provided more active sites for toluene oxidation. Reaction mechanism studies showed that the conversion of toluene to benzoate could be realized over MnO X -H catalyst during toluene adsorption at room temperature. In addition, abundant oxygen vacancy defects can accelerate the activated oxidation of toluene and the formation of oxidation products during toluene oxidation., 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 Inc. All rights reserved.)

The trihelix transcription factor (GT) gene family members play vital roles in plant growth and development, responses to abiotic or biotic stress, and fruit ripening. However, its role in banana fruit ripening remains unclear. Here, 59 MaGT gene members were identified in banana and clustered into five subfamilies, namely GT1, GT2, GTγ, SIP1, and SH4. This classification is completely supported by their gene structures and conserved motif analysis. Transcriptome data analysis indicated that MaGT14, MaGT21, and MaGT27 demonstrated significant differential expression during fruit ripening. Quantitative real-time PCR analysis revealed that these three genes were highly induced by ethylene treatment, responded to cold and heat stress, and had a high expression abundance in ripe fruit. Subcellular localization demonstrated that MaGT21 and MaGT27 functioned as nuclear proteins, while MaGT14 functioned as a nuclear and cell membrane protein. Further investigation indicated MaGT21 could positively stimulate the transcription of the key ethylene biosynthesis gene MaACO1 by directly targeting the GT motif in the promoter. MaGT21 transient overexpression in banana fruit upregulated MaACO1 and accelerated fruit ripening. Our findings provide comprehensive and valuable information for further functional studies of MaGT genes in banana, help to understand the roles of MaGTs during banana fruit ripening., 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 Masson SAS. All rights reserved.)

The past decade has witnessed an increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) owing to robust evidence of its benefits in type 2 diabetes and obesity. However, delay gastric emptying effect of GLP-1RAs has raised concerns for risk of gastric food retention and pneumonia aspiration during upper endoscopy. There have been observation studies reporting an increased incidence of gastric food retention among patients on GLP-1RAs, especially long-acting one like semaglutide. But the association between GLP-1RAs use and pneumonia aspiration during EGD remains unclear due to lack of high-level evidence. We report a case of pulmonary aspiration during EGD in a patient prescribed semaglutide.

Utilizing ultrafast light-matter interaction to manipulate electronic states of quantum materials is an emerging area of research in condensed matter physics. It has significant implications for the development of future ultrafast electronic devices. However, the ability to induce long-lasting metastable electronic states in a fully reversible manner is a long-standing challenge. Here, by using ultrafast laser excitations, we demonstrate the capability to manipulate the electronic polar states in the charge-density-wave material EuTe 4 in a non-volatile manner. The process is completely reversible and is achieved at room temperature with an all-optical approach. Each induced non-volatile state brings about modifications to the electrical resistance and second harmonic generation intensity. The results point to layer-specific phase inversion dynamics by which photoexcitation mediates the stacking polar order of the system. Our findings extend the scope of non-volatile all-optical control of electronic states to ambient conditions, and highlight a distinct role of layer-dependent phase manipulation in quasi-two-dimensional systems with inherent sublayer stacking orders., (© 2024. The Author(s).)

Background: Extracellular vesicles (EVs) are cell-secreted membrane vesicles that have become a promising, natural nanoparticle system for delivering either naturally carried or exogenously loaded therapeutic molecules. Among reported cell sources for EV manufacture, human induced pluripotent stem cells (hiPSCs) offer numerous advantages. However, hiPSC-EVs only have a moderate ability for brain delivery. Herein, we sought to develop a stable hiPSC line for producing EVs with substantially enhanced brain targeting by genetic engineering to overexpress rabies viral glycoprotein (RVG) peptide fused to the N terminus of lysosomal associated membrane protein 2B (RVG-Lamp2B) which has been shown capable of boosting the brain delivery of EVs via the nicotinic acetylcholine receptor., Methods: An RVG-Lamp2B-HA expression cassette was knocked into the AAVS1 safe harbor locus of a control hiPSC line using the CRISPR/Cas9-assisted homologous recombination. Western blot was used to detect the expression of RVG-Lamp2B-HA in RVG-edited hiPSCs as well as EVs derived from RVG-edited hiPSCs. Uptake of EVs by SH-SY5Y cells in the presence of various endocytic inhibitors was analyzed using flow cytometry. Biodistribution and brain delivery of intravenously injected control and RVG-modified EVs in wild-type mice were examined using ex vivo fluorescent imaging., Results: Here we report that an RVG-Lamp2B-HA expression cassette was knocked into the AAVS1 safe harbor locus of a control hiPSC line using the CRISPR/Cas9-assisted homologous recombination. The RVG-edited iPSCs have normal karyotype, express pluripotency markers, and have differentiation potential. Expression of RVG-Lamp2B-HA was detected in total cell extracts as well as EVs derived from RVG-edited (vs. control) hiPSCs. The RVG-modified EVs enter neuronal cells via distinct endocytic pathways, compared with control EVs. The biodistribution study confirmed that EVs derived from RVG-edited hiPSCs possess higher brain delivery efficiency., Conclusion: Taken together, we have established stable, genetically engineered hiPSCs for producing EVs with RVG expression, offering the improved ability for brain-targeted drug delivery., (© 2024. The Author(s).)

Background: Endoscopic resection (ER) of gastric submucosal tumors (G-SMTs) is challenging due to the difficulty of exposure. Traction-assisted ER has been shown to provide better outcomes than traditional endoscopic operation by exposing the dissection plane. In this study, we investigated the efficacy and safety of the snare traction-assisted method in ER of G-SMTs., Method: From May 2021 to March 2023, we used snare traction-assisted method to treat 24 patients with 24 G-SMTs in our department. Clinical characteristics and the outcomes of ER were recorded., Result: The mean tumor diameter was 1.8±0.9 cm. Six G-SMTs underwent endoscopic submucosal dissection (ESD), and 18 underwent endoscopic full-thickness resection (EFTR). En bloc resection and R0 resection was achieved in all the 24 lesions. The average procedure time was 45.4 ± 23.4 minutes. The patients were discharged in 5.0 days after procedures, without delayed bleeding or other adverse events., Conclusion: Snare traction-assisted method provides an effective traction for endoscopic resection of G-SMTs even if the tumor is difficult to remove. While further studies comparing the snare traction-assisted method with the conventional procedure are necessary.

Background: Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by a CAG/CTG repeat expansion at the PPP2R2B locus., Objective: We investigated how the CAG repeat expansion within the PPP2R2B 7B7D transcript influences the expression of Bβ1 and a potential protein containing a long polyserine tract., Methods: Transcript and protein expression were measured using quantitative PCR (qPCR) and Western blot, respectively, in an SK-N-MC cell model that overexpresses the full-length PPP2R2B 7B7D transcript. The apoptotic effect of a protein containing a long polyserine tract on SK-N-MC cells was evaluated using caspase 3/7 activity., Results: The CAG repeat expansion increases the expression of the PPP2R2B 7B7D transcript, as well as Bβ1 protein, in an SK-N-MC cell model in which the full-length PPP2R2B 7B7D transcript is overexpressed. The CAG repeat expansion within the 7B7D transcript is translated into a long polyserine tract that triggers apoptosis in SK-N-MC cells., Conclusions: The SCA12 mutation leads to overexpression of PPP2R2B Bβ1 and to expression of a protein containing a long polyserine tract; both these effects potentially contribute to SCA12 pathogenesis. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

Pseudomonas aeruginosa (PA) infection can cause pneumonia and sepsis by activating peptidyl-arginine deiminase (PAD) and triggering the formation of neutrophil extracellular traps (NETs). Our previous research has elucidated the crucial role of PAD2 in regulating CitH3 production and NETosis signaling following bacterial infection. Therefore, targeting PAD2 with selective inhibitors holds promise for treating PA-induced sepsis. Here, we compare the structure and function of two PAD2 inhibitors, AFM32a and AFM41a, and investigate their biological effects in mice subjected with PA. We analyze their impact on PAD2 inhibition, macrophage polarization, and other host defense mechanisms against PA-induced sepsis utilizing both in vivo and in vitro approaches. Our findings demonstrate that both PAD2 inhibitors (AFM32a and AFM41a) and Pad2 deficiency substantially enhance protection against PA-induced sepsis, with AFM41a showing superior efficacy over AFM32a. This protective effect is marked by improved survival rates, reduced bacterial growth in mice subjected to PA infection, and the promotion of M2 macrophage polarization coupled with enhanced autophagic activity. Our results advocate for targeting PAD2 as an effective strategy to bolster host defenses against PA infection. Utilizing AFM41a to promote M2 macrophage polarization and autophagy offers promising avenues for the treatment of PA infection and the improvement of sepsis outcomes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Breast cancer is the second leading cause of death in women, with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) as the two most common forms of invasive breast cancer. While estrogen receptor positive (ER+) IDC and ILC are treated similarly, the multifocality of ILC presents challenges in detection and treatment, worsening long-term clinical outcomes in patients. With increasing documentation of chemoresistance in ILC, additional treatment options are needed. Oncolytic adenoviral therapy may be a promising option, but cancer cells must express the coxsackievirus & adenovirus receptor (CAR) for adenoviral therapy to be effective. The present study aims to evaluate the extent to which CAR expression is observed in ILC in comparison to IDC, and how the levels of CAR expression correlate with adenovirus transduction efficiency. The effect of liposome encapsulation on transduction efficiency is also assessed., Methods: To characterize CAR expression in invasive breast carcinoma, 36 formalin-fixed paraffin-embedded (FFPE) human breast tumor samples were assayed by CAR immunohistochemistry (IHC). Localization of CAR in comparison to other junctional proteins was performed using a multiplex immunofluorescence panel consisting of CAR, p120-catenin, and E-cadherin. ILC and IDC primary tumors and cell lines were transduced with E1- and E3-deleted adenovirus type 5 inserted with a GFP transgene (Ad-GFP) and DOTAP liposome encapsulated Ad-GFP (DfAd-GFP) at various multiplicities of infection (MOIs). Transduction efficiency was measured using a fluorescence plate reader. CAR expression in the human primary breast carcinomas and cell lines was also evaluated by IHC., Results: We observed membranous CAR, p120-catenin and E-cadherin expression in IDC. In ILC, we observed cytoplasmic expression of CAR and p120-catenin, with absent E-cadherin. Adenovirus effectively transduced high-CAR IDC cell lines, at MOIs as low as 12.5. Ad-GFP showed similar transduction as DfAd-GFP in high-CAR IDC cell lines. Conversely, Ad-GFP transduction of ILC cell lines was observed only at MOIs of 50 and 100. Furthermore, Ad-GFP did not transduce CAR-negative IDC cell lines even at MOIs greater than 100. Liposome encapsulation (DfAd-GFP) improved transduction efficiency 4-fold in ILC and 17-fold in CAR-negative IDC cell lines., Conclusion: The present study demonstrates that oncolytic adenoviral therapy is less effective in ILC than IDC due to differences in spatial CAR expression. Liposome-enhanced delivery may be beneficial for patients with ILC and tumors with low or negative CAR expression to improve adenoviral therapeutic effectiveness., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Prophylactic defect closure has been considered to prevent delayed bleeding after polypectomy. However, recent evidence has demonstrated its beneficial effect is limited to those ≥20 mm proximal nonpedunculated lesions. Despite this, prophylactic defect closure is widely performed in clinical practice after colonic endoscopic submucosal dissection (ESD). We present a rare complication of prophylactical clip closure after colonic ESD.

Background: Mechanical circulatory support may facilitate high-risk percutaneous coronary intervention (PCI). This study aimed to assess the feasibility, safety and effectiveness of high-risk PCI under the support of venoarterial extracorporeal membrane oxygenation (VA-ECMO) combined with intra-aortic balloon pump (IABP)., Methods: We enrolled patients who received VA-ECMO plus IABP-assisted PCI procedures at our center from April 2012 to June 2018. Major adverse cardiac events (MACEs) included all-cause death, myocardial infarction, and target vessel revascularization., Results: A total of 10 patients were included, with a mean age of 71 years, EuroSCORE II of 19.9%, and SYNTAX score of 39.8. Procedural success was achieved in nine (90%) patients. The mean duration of ECMO support was 1.5 hours, and 2.6 stents were implanted per patient. Major complications included contrast-induced nephropathy needing hemodialysis in one (10%) patient, significant hemoglobin drop requiring blood transfusion in two (20%) patients, pulmonary infection in one (10%) patient, and local surgical incision infection in one (10%) patient. The accumulative mortality rates for the nine patients with procedural success were 0, 22.2%, and 44.4% at 1, 3, and 5 years follow-up, respectively. However, cardiac death occurred in only one (11.1%) patient. In addition, two patients received repeat PCI or coronary artery bypass grafting within two years following the index procedure. The overall incidence rates of MACEs were 11.1%, 44.4%, and 66.7% at 1, 3, and 5 years follow-up, respectively., Conclusions: VA-ECMO plus IABP-assisted high-risk PCI was feasible in patients with complex coronary disease, with a high procedural success rate and acceptable mid-term clinical outcomes., Competing Interests: All the authors declare no conflict of interest.

Phase-change memory (PCM) is a novel type of nonvolatile memory and is suitable for artificial neural synapses. This article investigates the Lagrange global exponential stability (LGES) of a class of PCNNs with mixed time delays. First, based on the conductivity characteristics of PCM, a piecewise equation is established to describe the electrical conductivity of PCM. By using the proposed piecewise equation to simulate the neural synapses, a novel PCNN with discrete and distributed time delays is proposed. Then, using comparative theory and fundamental inequalities, the LGES conditions based on the M -matrix are proposed in the sense of Filippov, and the exponential attractive set (EAS) is obtained based on M -matrix and external input. Moreover, the Lyapunov global exponential stability (GES) conditions of PCNNs without external input are obtained by using the inequality technique and eigenvalue theory, which is a form of M -matrix. Finally, two simulation examples are given to verify the validity of the obtained results.

Background: The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized., Methods: To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development., Results: We identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups., Conclusion: The novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology., (© 2024. The Author(s).)

Depression is one of the most common mental disorders and is mainly characterized by low mood or lack of interest and pleasure. It can be accompanied by varying degrees of cognitive and behavioral changes and may lead to suicide risk in severe cases. Due to the subjectivity of diagnostic methods and the complexity of patients' conditions, the diagnosis of major depressive disorder (MDD) has always been a difficult problem in psychiatry. With the discovery of more diagnostic biomarkers associated with MDD in recent years, especially emerging non-coding RNAs (ncRNAs), it is possible to quantify the condition of patients with mental illness based on biomarker levels. Point-of-care biosensors have emerged due to their advantages of convenient sampling, rapid detection, miniaturization, and portability. After summarizing the pathogenesis of MDD, representative biomarkers, including proteins, hormones, and RNAs, are discussed. Furthermore, we analyzed recent advances in biosensors for detecting various types of biomarkers of MDD, highlighting representative electrochemical sensors. Future trends in terms of new biomarkers, new sample processing methods, and new detection modalities are expected to provide a complete reference for psychiatrists and biomedical engineers., 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.)

Optical nonlinearities are one of the most fascinating properties of two-dimensional (2D) materials. While tremendous efforts have been made to find and optimize the second-order optical nonlinearity in enormous 2D materials, opportunities to explore higher-order ones are elusive because of the much lower efficiency. Here, we report the giant high odd-order optical nonlinearities in centrosymmetric correlated van der Waals insulator manganese phosphorus triselenide. When illuminated by two near-infrared femtosecond lasers, the sample generates a series of profound four- and six-wave mixing outputs. The near-infrared third-order nonlinear susceptibility reaches near the highest record values of 2D materials. Comparative measurements to other prototypical nonlinear optical materials [lithium niobate, gallium(II) selenide, and tungsten disulfide] reveal its extraordinary wave mixing efficiency. The wave mixing processes are further used for nonlinear optical waveguide with multicolor emission. Our work highlights the promising prospect for future research of the nonlinear light-matter interactions in the correlated 2D system and for potential nonlinear photonic applications.

Cardiovascular diseases (CVDs), especially chronic heart failure, threaten many patients' lives worldwide. Because of its slow course and complex causes, its clinical screening, diagnosis, and prognosis are essential challenges. Clinical biomarkers and biosensor technologies can rapidly screen and diagnose. Multiple types of biomarkers are employed for screening purposes, precise diagnosis, and treatment follow-up. This article provides an up-to-date overview of the biomarkers associated with the six main heart failure etiology pathways. Plasma natriuretic peptides (BNP and NT-proBNP) and cardiac troponins (cTnT, cTnl) are still analyzed as gold-standard markers for heart failure. Other complementary biomarkers include growth differentiation factor 15 (GDF-15), circulating Galactose Lectin 3 (Gal-3), soluble interleukin (sST2), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). For these biomarkers, the electrochemical biosensors have exhibited sufficient sensitivity, detection limit, and specificity. This review systematically summarizes the latest molecular biomarkers and sensors for heart failure, which will provide comprehensive and cutting-edge authoritative scientific information for biomedical and electronic-sensing researchers in the field of heart failure, as well as patients. In addition, our proposed future outlook may provide new research ideas for researchers., 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.)

Background: Azvudine (FNC) is a novel small molecule antiviral drug for treating COVID-19 that is available only on the Chinese market. Despite being recommended for treating COVID-19 by the Chinese guidelines, its efficacy and safety are still unclear. This study aimed to evaluate the protective effect of FNC on COVID-19 outcomes and its safety., Methods: We followed the PRISMA 2020 guidelines and searched the PubMed, Embase, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI) databases to evaluate studies on the effectiveness of FNC in treating COVID-19 in China, focusing on mortality and overall outcomes. Additionally, its impact on the length of hospital stay (LOHS), time to first nucleic acid negative conversion (T-FNANC), and adverse events was evaluated. The inclusion criterion was that the studies were published from July 2021 to April 10, 2024. This study uses the ROBINS-I tool to assess bias risk and employs the GRADE approach to evaluate the certainty of the evidence., Results: The meta-analysis included 24 retrospective studies involving a total of 11 830 patients. Low-certainty evidence revealed no significant difference in mortality (OR = 0.91, 95% CI: 0.76-1.08) or LOHS (WMD = -0.24, 95% CI: -0.83 to 0.35) between FNC and Paxlovid in COVID-19 patients. Low-certainty evidence shows that the T-FNANC was longer (WMD = 1.95, 95% CI: 0.36-3.53). Compared with the Paxlovid group, low-certainty evidence shows the FNC group exhibited a worse composite outcome (OR = 0.77, 95% CI: 0.63-0.95) and fewer adverse events (OR = 0.63, 95% CI: 0.46-0.85). Compared with supportive treatment, low certainty shows FNC significantly reduced the mortality rate in COVID-19 patients (OR = 0.61, 95% CI: 0.51-0.74) and decreased the composite outcome (OR = 0.67, 95% CI: 0.50-0.91), and very low certainty evidence shows significantly decreased the T-FNANC (WMD = -4.62, 95% CI: -8.08 to -1.15). However, in very low certainty, there was no significant difference in LOHS (WMD = -0.70, 95% CI: -3.32 to 1.91) or adverse events (OR = 1.97, 95% CI: 0.48-8.17)., Conclusions: FNC appears to be a safe and potentially effective treatment for COVID-19 in China, but further research with larger, high-quality studies is necessary to confirm these findings. Due to the certainty of the evidence and the specific context of the studies conducted in China, caution should be exercised when considering whether the results are applicable worldwide., Trial Registration: PROSPERO number: CRD42024520565., (© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

We herein describe the preparation and application of a new bispentafluoroethylated organocuprate [Ph 4 P] + [Cu(CF 2 CF 3 ) 2 ] - . This complex has demonstrated a remarkable range of reactivities towards carboxylic acids, diazonium salts, organic halides, boronic esters, terminal alkynes and (hetero)arenes as a versatile pentafluoroethylating reagent. The construction of C(sp 3 )-/C(sp 2 )-/C(sp)-CF 2 CF 3 bonds can therefore be achieved using a single reagent., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The global spread of monkeypox has become a worldwide public healthcare issue. Therefore, there is an urgent need for accurate and sensitive detection methods to effectively control its spreading. Herein, we screened by phage display two peptides M4 (sequence: DPCGERICSIAL) and M6 (sequence: SCSSFLCSLKVG) with good affinity and specificity to monkeypox virus (MPXV) B21R protein. To simulate the state of the peptide in the phage and to avoid spatial obstacles of the peptide, GGGSK was added at the C terminus of M4 and named as M4a. Molecular docking shows that peptide M4a and peptide M6 are bound to different epitopes of B21R by hydrogen bonds and salt-bridge interactions, respectively. Then, peptide M4a was selected as the capture probe, phage M6 as the detection probe, and carbonized polymer dots (CPDs) as the fluorescent probe, and a colorimetric and fluorescent double-signal capture peptide/antigen/signal peptide-displayed phage sandwich ELISA triggered by horseradish peroxidase (HRP) through a simple internal filtration effect (IFE) was constructed. HRP catalyzes H 2 O 2 to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to generate blue oxidized TMB, which can further quench the fluorescence of CPDs through IFE, enabling to detect MPXV B21R in colorimetric and fluorescent modes. The proposed simple immunoassay platform shows good sensitivity and reliability in MPXV B21R detection. The limit of detection for colorimetric and fluorescent modes was 27.8 and 9.14 pg/mL MPXV B21R, respectively. Thus, the established double-peptide sandwich-based dual-signal immunoassay provides guidance for the development of reliable and sensitive antigen detection capable of mutual confirmation, which also has great potential for exploring various analytical strategies for other respiratory virus surveillance.

Neonicotinoid insecticides (NNIs) have attracted global concern due to its extensive use in agricultural activities and their potential risks to the animal and human health, however, there is limited knowledge on the regional traits and ecological risks of NNIs in the aquatic environments. We herein investigated the occurrence of NNIs within the midsection of Yangtze River in China, offering the inaugural comprehensive report on NNIs within this region. In this study, eleven NNIs were analyzed in 108 river water and sediment samples from three seasons (normal, dry and wet season). We detected a minimum of seven NNIs in the water and four NNIs in the sediment, with total concentrations ranging from 12.33 to 100.5 ng/L in water and 0.08-5.68 ng/g in sediment. The levels of NNIs in both river water and sediment were primarily influenced by the extent of agricultural activities. The estimated annual load of NNIs within the midsection of Yangtze River totaled 40.27 tons, April was a critical contamination period. Relative potency factor (RPF) analysis of the human exposure risk revealed that infants faced the greatest exposure risk, with an estimated daily intake of 11.27 ng kg -1 ∙bw∙d -1 . We established the acute and chronic thresholds for aquatic organisms by employing the Species Sensitive Distribution (SSD) method (acute: 384.1 ng/L; chronic: 168.9 ng/L). Based on the findings from this study, 33% of the river water samples exceeded the chronic ecological risks thresholds, indicating the urgent need for intervention programs to guarantee the safety of the river for aquatic life in the Yangtze River Basin., 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.)

Spinocerebellar ataxia type 12 (SCA12) is caused by a CAG expansion mutation in PPP2R2B, a gene encoding brain-specific regulatory units of protein phosphatase 2A (PP2A); while normal alleles carry 4 to 31 triplets, the disease alleles carry 43 to 78 triplets. Here, by CRISPR/Cas9n genome editing, we have generated a human heterozygous SCA12 iPSC line with 73 triplets for the mutant allele. The heterozygous SCA12 iPSCs have normal karyotype, express pluripotency markers and are able to differentiate into the three germ layers., 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.)

Activation of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome complex is an essential innate immune signaling mechanism. To reveal how human NLRP3 inflammasome assembly and activation are controlled, in particular by components of the ubiquitin system, proximity labeling, affinity purification, and RNAi screening approaches were performed. Our study provides an intricate time-resolved molecular map of different phases of NLRP3 inflammasome activation. Also, we show that ubiquitin C-terminal hydrolase 1 (UCH-L1) interacts with the NACHT domain of NLRP3. Downregulation of UCH-L1 decreases pro-interleukin-1β (IL-1β) levels. UCH-L1 chemical inhibition with small molecules interfered with NLRP3 puncta formation and ASC oligomerization, leading to altered IL-1β cleavage and secretion, particularly in microglia cells, which exhibited elevated UCH-L1 expression as compared to monocytes/macrophages. Altogether, we profiled NLRP3 inflammasome activation dynamics and highlight UCH-L1 as an important modulator of NLRP3-mediated IL-1β production, suggesting that a pharmacological inhibitor of UCH-L1 may decrease inflammation-associated pathologies., Competing Interests: Declaration of interests E.W.T. is a founder and shareholder in Myricx Pharma Ltd. and receives consultancy or research funding from Kura Oncology, Pfizer Ltd., Samsara Therapeutics, Myricx Pharma Ltd., MSD, Exscientia, and Daiichi Sankyo., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Valorization of algal biomass to fuels and chemicals frequently requires pretreatment to lyse cells and extract lipids, leaving behind an extracted solid residue as an underutilized intermediate. Mild oxidative treatment (MOT) is a promising route to simultaneously convert nitrogen contained in these residues to easily recyclable ammonium and to convert carbon in the same fraction to biofuel precursor carboxylates. We show that for a Nannochloropsis algae under certain oxidation conditions, nearly all the nitrogen in the residues can be converted to ammonium and recovered by cation exchange, while up to ∼20% of the carbon can be converted to short chain carboxylates. At the same time, we also show that soluble phosphorus in the form of phosphate can be selectively recovered by anion exchange, leaving a clean aqueous carbon stream for further upgrading., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Hydrodynamic dimension (HD) is the primary indicator of the size of bioconjugated particles and biomolecules. It is an important parameter in the study of solid-liquid two-phase dynamics. HD dynamic monitoring is crucial for precise and customized medical research as it enables the investigation of the continuous changes in the physicochemical characteristics of biomolecules in response to external stimuli. However, current HD measurements based on Brownian motion, such as dynamic light scattering (DLS), are inadequate for meeting the polydisperse sample demands of dynamic monitoring. In this paper, we propose MMQCM method samples of various types and HD dynamic monitoring. An alternating magnetic field of frequency ω m excites biomolecule-magnetic bead particles (bioMBs) to generate magnetization motion, and the quartz crystal microbalance (QCM) senses this motion to provide HD dynamic monitoring. Specifically, the magnetization motion is modulated onto the thickness-shear oscillation of the QCM at the frequency ω q . By analysis of the frequency spectrum of the QCM output signal, the ratio of the magnitudes of the real and imaginary parts of the components at frequency ω q ± 2ω m is extracted to characterize the particle size. Using the MMQCM approach, we successfully evaluated the size of bioMBs with different biomolecule concentrations. The 30 min HD dynamic monitoring was implemented. An increase of ∼10 nm in size was observed upon biomolecular structural stretching. Subsequently, the size of bioMBs gradually reduced due to the continuous dissociation of biomolecules, with a total reduction of 20∼40 nm. This HD dynamic monitoring demonstrates that the release of biomolecules can be regulated by controlling the duration of magnetic stimulation, providing valuable insights and guidance for controlled drug release in personalized precision medicine.

In order to prepare biomass-derived carbon materials with high specific capacitance at a low activation temperature (≤700 °C), nanoporous carbon materials were prepared from zanthoxylum bungeanum peels and seeds via the pyrolysis and KOH-activation processes. The results show that the optimal activation temperatures are 700 °C and 600 °C for peels and seeds. Benefiting from the hierarchical pore structure (micropores, mesopores, and macropores), the abundant heteroatoms (N, S, and O) containing functional groups, and plentiful electrochemical active sites, the PAC-700 and SAC-600 derive the large capacities of ~211.0 and ~219.7 F g -1 at 1.0 A g -1 in 6 M KOH within the three-electrode configuration. Furthermore, the symmetrical supercapacitors display a high energy density of 22.9 and 22.4 Wh kg -1 at 7500 W kg -1 assembled with PAC-700 and SAC-600, along with exceptional capacitance retention of 99.1% and 93.4% over 10,000 cycles at 1.0 A g -1 . More significantly, the contribution here will stimulate the extensive development of low-temperature activation processes and nanoporous carbon materials for electrochemical energy storage and beyond.

To enhance the postharvest quality of avocado (Persea americana Mill.) fruit, this study investigates alterations in cell wall metabolism and reactive oxygen species (ROS) metabolism during near-freezing temperature (NFT) storage, and explores their impact on fruit softening. The fruit was stored at 25 °C, 5 °C, 2 °C, and NFT, respectively. NFT storage retarded firmness loss and chilling injury in comparison with 25 °C, 5 °C, and 2 °C. NFT storage delayed the decrease of ionic-soluble pectin (ISP) and cellulose (CLL) contents by suppressing cell wall degradation enzyme activities. Correlation analysis showed that cell wall degradation enzyme activities were positively correlated to rates of ethylene release and respiration. Moreover, NFT storage maintained higher levels of DPPH and ABTS scavenging abilities, activities of superoxide dismutase, peroxidase, and catalase, as well as ascorbate-glutathione cycle (ascorbic acid, glutathione, glutathione disulfide, ascorbate peroxidase, cycle-related enzymes), thereby inhibited the increase of ROS content, malondialdehyde content, and cell membrane permeability. Fruit firmness and chilling injury were correlated with the contents of hydrogen (H 2 O 2 ), superoxide anion (O 2 .- ), ISP, and CLL. These results suggested that NFT could suppress fruit softening and chilling injury by inhibiting cell wall degradation through delaying respiration and ethylene production and suppressing ROS production via activation of antioxidant systems, thereby maintaining quality and prolonged storage life during avocado fruit storage., 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 Masson SAS. All rights reserved.)

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103 + T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61 + tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies., (© 2024. The Author(s).)

Conversion of microalgae to renewable fuels and chemical co-products by pretreating and fractionation holds promise as an algal biorefinery concept, but a better understanding of the pretreatment performance as a function of algae strain and composition is necessary to de-risk algae conversion operations. Similarly, there are few examples of algae pretreatment at scales larger than the bench scale. This work aims to de-risk algal biorefinery operations by evaluating the pretreatment performance across nine different microalgae samples and five different pretreatment methods at small (5 mL) scale and further de-risk the operation by scaling pretreatment for one species to the 80 L scale. The pretreatment performance was evaluated by solubilization of feedstock carbon and nitrogen [as total organic carbon (TOC) and total nitrogen (TN)] into the aqueous hydrolysate and extractability of lipids [as fatty acid methyl esters (FAMEs)] from the pretreated solids. A range of responses was noted among the algae samples across pretreatments, with the current dilute Brønsted acid pretreatment using H 2 SO 4 being the most consistent and robust. This pretreatment produced TOC yields to the hydrolysate ranging from 27.7 to 51.1%, TN yields ranging from 12.3 to 76.2%, and FAME yields ranging from 57.9 to 89.9%. In contrast, the other explored pretreatments (other dilute acid pretreatments, dilute alkali pretreatment with NaOH, enzymatic pretreatment, and flash hydrolysis) produced lower or more variable yields across the three metrics. In light of the greater consistency across samples for dilute acid pretreatment, this method was scaled to 80 L to demonstrate scalability with microalgae feedstocks., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The crash severity analysis is of significant importance in traffic crash prevention and emergency resource allocation. A range of innovations offers potential traffic crash severity prediction models to improve road safety. However, the semantic information inherent in traffic crash data, which is crucial in enabling a deeper understanding of its underlying factors and impacts, has yet to be fully utilized. Moreover, traffic crash data are commonly characterized by a small sample size, which leads to sample imbalance problem resulting in prediction performance decline. To tackle these problems, we propose a semantic understanding-based data-enhanced double-layer stacking model, named EnLKtreeGBDT, for crash severity prediction. Specifically, to fully leverage the inherent semantic information within traffic crash data and analyze the factors influencing crashes, we design a semantic enhancement module for multi-dimensional feature extraction. This module aims to enhance the understanding of crash semantics and improve prediction accuracy. Then we introduce a data enhancement module that utilizes data denoising and migration techniques to address the challenge of data imbalance, reducing the prediction model's dependence on large sample crash data. Furthermore, we construct a two-layer stacking model that combines multiple linear and nonlinear classifiers. This model is designed to augment the capability of learning linear and nonlinear mixed relationships, thereby improving the accuracy of predicting the severity of crashes on complex urban roads. Experiments on historical datasets of UK road safety crashes validate the effectiveness of the proposed model, and superior performance of prediction precision is achieved compared with the state-of-the-arts. The ablation experiments on both semantic and data enhancement modules further confirm the indispensability of each module in the proposed model., Competing Interests: The authors declare no potential conflicts of interest with respect to the research., (© 2024 The Author(s).)

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

Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation., (© 2024. The Author(s).)

To explore contaminant concerns as a result of anthropogenic disturbance of the river system, this study provided the first extensive investigation of the contamination profiles, possible driving factors, and ecological risks of 40 target compounds including pharmaceuticals and personal care products (PPCPs), neonicotinoid pesticides (NNIs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) in sediments of the whole Yangtze River (the world's third longest river). Among these target compounds, PPCPs were the dominant contaminants with a total concentration (∑ 15 PPCPs) of 2.13-14.99 ng/g, followed by ∑ 7 PCBs (11 NNIs (7 PBDEs (

The increasing demand for sustainable aviation fuel (SAF) creates a need for innovative biomass and lipid sources with compositions that are compatible with refineries. Algae-derived oils present an opportunity to supply a process-compatible lipid feedstock at yields higher than those of conventional oilseed crops. With few documented reports on chemical composition, the process readiness remains elusive. We present data on extraction efficiency, yield, and purity of lipids from algae with and without the application of a low-concentration sulfuric acid pretreatment of the biomass. The pretreatment process increased the oil yield and positively impacted the quality of the extracted oils. Results from fatty acid and lipidomics analysis revealed that the low-lipid biomass sources extracted 70-80% of the available lipids, and the non-fatty acid co-extractants exceeded 40% of the extracted oils. For a high-lipid algae sample, derived from a genetically engineered strain, we show >90% extraction yield with >85% FAME purity. This work provides insights into the composition of algae-derived oils and quality metrics that are essential to determining the viability of lipid hydroprocessing to SAF., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Glioblastoma (GBM) is the most common malignant primary brain tumor. Despite comprehensive treatment with traditional surgery, radiotherapy, and chemotherapy, the median survival rate is <14.6% and the 5-year survival rate is only 5%. FBXO22, a substrate receptor of the SCF ubiquitin ligases, has been reported to play a promoting role in melanoma, liver cancer, cervical cancer, and other cancers. However, the function of FBXO22 in GBM has not been reported. In the present study, we demonstrate that FBXO22 is highly expressed in glioma and is positively correlated with worse pathological features and shorter survival of GBM patients. We revealed that FBXO22 promotes GBM cell proliferation, angiogenesis, migration, and tumorigenesis in vitro and in vivo. In terms of mechanism, we reveal that FBXO22 decreases VHL expression by directly mediating VHL ubiquitination degradation, which ultimately increases HIF-1α and VEGFA expression. In addition, our data confirm that there are positive correlations among FBXO22, HIF-1α, and VEGFA expression, and there is a negative correlation between FBXO22 and VHL protein expression in glioma patients. Our study strongly indicates that FBXO22 is a promising diagnostic marker and therapeutic target for glioma patients., (© 2024. The Author(s).)

Microplastic pollution, an emerging pollution issue, has become a significant environmental concern globally due to its ubiquitous, persistent, complex, toxic, and ever-increasing nature. As a multifaceted and diverse suite of small plastic particles with different physicochemical properties and associated matters such as absorbed chemicals and microbes, future research on microplastics will need to comprehensively consider their multidimensional attributes. Here, we introduce a novel, conceptual framework of the "microplastome", defined as the entirety of various plastic particles (<5 mm), and their associated matters such as chemicals and microbes, found within a sample and its overall environmental and toxicological impacts. As a novel concept, this paper aims to emphasize and call for a collective quantification and characterization of microplastics and for a more holistic understanding regarding the differences, connections, and effects of microplastics in different biotic and abiotic ecosystem compartments. Deriving from this lens, we present our insights and prospective trajectories for characterization, risk assessment, and source apportionment of microplastics. We hope this new paradigm can guide and propel microplastic research toward a more holistic era and contribute to an informed strategy for combating this globally important environmental pollution issue.