Search

The current research on the damage-based strength reduction factor has been completely based on the inelastic single-degree-of-freedom systems that are more suitable for two-dimensional analyses. Therefore, it is necessary to construct damage-based strength reduction factor spectra for systems subjected to bidirectional ground motions. In this study, an inelastic single-mass bi-degree-of-freedom (SMBDOF) system subjected to the orthogonal bidirectional ground motions with the hysteretic property of two-dimensional yield-surface plasticity function is presented, and the x -component of the system is used to construct the damage-based strength reduction factor spectra of the system (R b spectra). The Park-Ang damage model is used to determine the constant damage index of the R b spectra. In addition, 178 ground motion records for site classes C, D, and E are considered as ground excitations of the SMBDOF system to construct the mean R b spectra with the format of R b - D - T for a given ductility capacity and R b - μ u - T for a given damage level. The R b spectra of the SMBDOF system is compared with the corresponding R spectra of the SDOF system. Statistical analysis considering different values of the natural period, ductility capacity, damage index, period ratio, and site condition is conducted. Analysis results show that the coupling of two-component responses of an inelastic system could increase the strength demand of the system in certain cases; the trend of the R b spectra presented in this study is approximately consistent for different site classes, but the spectral values have the characteristic of site conditions. Therefore, the influence of the period ratio should be considered because a large period difference between two components of the SMBDOF system could aggravate seismic damage in certain situations. Based on the statistical analysis, the expression of R b spectra curves with a period ratio γ = 1 is derived using the regression analysis, and the correction expression is obtained considering the influence of the period ratio on the R b spectra. Then, the construction procedure of the R b spectra is introduced. The predicted R b spectra obtained by the proposed procedure is compared with the actual mean spectra, and comparison results indicate a good match. [ABSTRACT FROM AUTHOR]

Plateau-Rayleigh instability─a macroscopic phenomenon describing the volume-constant breakup of one-dimensional continuous fluids─has now been widely observed in adatoms, liquids, polymers, and liquid metals. This instability enables controlled wetting-dewetting behavior at fluid-solid interfaces and, thereby, the self-limited patterning into ordered structures. However, it has yet to be observed in conventional inorganic solids, as the rigid lattices restrict their "fluidity". Here, we report the general fluid-like Plateau-Rayleigh instability of silver-based chalcogenide semiconductors featuring soft-lattice ionic crystals. It enables postsynthetic morphing from conformal core-shell nanowires to periodically coaxial ones. We reveal that such self-limited reconstruction is thermodynamically driven by the surface energy and interface energy and kinetically favored by the high ionic diffusion coefficients of subnanoscale soft-lattice shells. The resulting periodic heterostructures can be topotactically transformed for epitaxial combinations of functional semiconductors free from the lattice-matching rule. This fluid-like behavior in soft inorganic solids thus offers routes toward sophisticated nanostructures and controllable patterning at all-inorganic solid-solid interfaces.

Haptophyta represents a major taxonomic group, with plastids derived from the primary plastids of red algae. Here, we elucidated the cryoelectron microscopy structure of the photosystem I-light-harvesting complex I (PSI-LHCI) supercomplex from the haptophyte Isochrysis galbana . The PSI core comprises 12 subunits, which have evolved differently from red algae and cryptophytes by losing the PsaO subunit while incorporating the PsaK subunit, which is absent in diatoms and dinoflagellates. The PSI core is encircled by 22 fucoxanthin-chlorophyll a / c -binding light-harvesting antenna proteins (iFCPIs) that form a trilayered antenna arrangement. Moreover, a pigment-binding subunit, L iFP , which has not been identified in any other previously characterized PSI-LHCI supercomplexes, was determined in I. galbana PSI-iFCPI, presumably facilitating the interactions and energy transfer between peripheral iFCPIs and the PSI core. Calculation of excitation energy transfer rates by computational simulations revealed that the intricate pigment network formed within PSI-iFCPI ensures efficient transfer of excitation energy. Overall, our study provides a solid structural foundation for understanding the light-harvesting and energy transfer mechanisms in haptophyte PSI-iFCPI and provides insights into the evolution and structural variations of red-lineage PSI-LHCIs., Competing Interests: Competing interests statement:The authors declare no competing interest.

Brown algae, constituting the second largest group of marine macroalgae, fix significant amounts of inorganic carbon into alginate, the most abundant polysaccharide found in their cell walls. Alginate serves as an important macromolecular carbon source for marine bacteria. The catabolism of alginate by bacteria is an important step in the marine carbon cycle, and this area of research has attracted growing interests over the past decade. Here, we provide an overview of the recent advances in our understanding of marine bacterial alginate catabolic systems, both in individual organisms and within bacterial consortia, discuss the possibility of additional alginate metabolic pathways in light of the present findings, and highlight the future research foci., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Atropisomers with multiple stereogenic axes have attracted much attention due to their increasing significance in the fields of natural products, chiral materials, and drug discoveries. However, the catalytic stereoselective construction of axially chiral ring scaffolds with more than two axes on a single benzene ring remains a challenging task. Herein, we present an efficient method for synthesizing triaxially chiral polysubstituted naphthalene scaffolds via sequential Ni(II)-catalyzed Diels-Alder reaction of isobenzofurans and TfOH-promoted dehydrative aromatization reaction. Using 1,3-biarylisobenzofurans and β-aryl-substituted α,β-unsaturated N-acyl pyrazoles as modular reaction partners, a series of naphthalenes with 1,3,4-triaxes were synthesized with excellent enantioselectivities and diastereoselectivities. Furthermore, by attaching two pyrene chromophores to this novel triaxially chiral ring scaffold, a circularly polarized luminescence (CPL)-active dye exhibiting a remarkable luminescence dissymmetry factor (glum = ‒0.019) and high fluorescence quantum efficiency (ØFL = 0.29) was obtained, highlighting the potential applications of atropisomers with multiple stereogenic axes in the design of chiroptical organic materials., (© 2024 Wiley‐VCH GmbH.)

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, often accompanied by impaired vascular endothelial function in the lower limbs. This dysfunction is characterized by a reduced vasodilatory response, leading to decreased blood flow in the lower limbs and ultimately contributing to the development of diabetic peripheral neuropathy. To delve deeper into this pathological process, the study employed bioinformatics to identify and analyze genes highly active in DPN. The investigation revealed that Membrane metallo-endopeptidase (MME) was effectively mitigated by its antagonist. Male Sprague-Dawley (SD) rats served as the model to systematically explore the intrinsic connection among the nociceptible/orphanin FQ-N/OFQ receptor (N/OFQ-NOP) system, femoral artery blood flow in the lower extremities, MME, and DPN. The rats were randomized into two groups: a control group and a DPN group induced by a single intraperitoneal injection of 55 mg/kg streptozotocin (STZ), with 6 rats in each group. The findings indicated that compared to the control group, the DPN group exhibited a significant reduction in femoral artery blood flow. This was accompanied by a notable increase in serum N/OFQ concentration, heightened expression of opioid-related nociceptive protein receptor 1 (OPRL1) and MME in femoral artery tissues of the lower limbs, and an elevated sciatic nerve stimulation threshold. These results suggest that the serum N/OFQ level in DPN rats is increased, which may promote the occurrence of peripheral neuropathy by up regulating MME and reducing peripheral flow distribution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To construct and validate a new thyroid imaging reporting and data system (TI-RADS) based on radiating blood flow and grayscale US features., Materials and Methods: This study enrolled patients from 4 hospitals from January 2018 to November 2023 retrospectively and prospectively. All US features associated with malignant thyroid nodules were assessed by multivariable logistic regression to construct baseline US TI-RADS (BUS TI-RADS), which was tested with internal validation set, external validation set and prospective validation set. Additionally, its potential of reducing biopsy was assessed., Results: There were 2932 patients (2153 female, age: 42.83 ± 11.71; 779 male, age: 42.36 ± 11.78) with 3940 nodules (2831 malignant nodules and 1109 benign nodules). Independent predictive factors included composition, echogenicity, shape, margin, suspicious extrathyroidal extension, punctate echogenic foci, and radiating blood flow. Compared with American College of Radiology (ACR) TI-RADS and Chinese TI-RADS (C-TIRADS), the BUS TI-RADS had higher AUCs of 0.96 (95 % CI: [0.95, 0.97]; P < 0.001), 0.93 ([0.90, 0.97]; P < 0.001), 0.91 ([0.86, 0.96]; P < 0.003) and 0.95 ([0.93, 0.97]; P < 0.001) for the training set, internal validation set, external validation set and prospective validation set respectively. Decision curve analysis demonstrated higher net benefit for the BUS TI-RADS. And the BUS TI-RADS (4.1 %; 18.1 %) had lower percentage of biopsy and false negative rate compared with the ACR TI-RADS (31.2 %; 20.9 %) and C-TIRADS(33.1 %; 58.5 %)., Conclusion: BUS TI-RADS was created according to the simplified regression coefficients of radiating blood flow and grayscale ultrasonography features with excellent diagnostic performance and could reduce unnecessary biopsy with lower missed malignancy., 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.)

Fucoidan, the main polysaccharide in various species of brown seaweed, has a high annual production. It is an important source of marine organic carbon and exhibits diverse biological activities and significant application potential. Rhodopirellula sp. P2, a novel marine bacterium of the phylum Planctomycetota, was isolated from intertidal algae samples collected from the Weihai coast, the Yellow Sea, China. The strain P2 is a Gram-negative, aerobic, and pear-shaped bacterium. Here, we report the complete genome sequence of Rhodopirellula sp. P2. The genome of strain P2 consists of a single circular chromosome with 7,291,416 bp and a GC content of 57.38 %, including 5462 protein-coding genes, 2 rRNA genes, and 48 tRNA genes. Genomic analysis revealed that strain P2 possessed 173 CAZymes and 106 sulfatases, indicating that strain P2 has the potential ability to utilize multiple polysaccharides, especially hydrolyze fucoidan to fucose. The genome of strain P2 also encodes a gene cluster related to bacterial microcompartment, suggesting the ability of strain P2 to metabolize fucose. These results enhance the understanding of the diversity and ecological functions of Planctomycetota, and also facilitate the exploitation of Planctomycetota and enzyme resources to utilize fucoidan. This study provides genetic insights into fucoidan catabolism by Planctomycetota, expanding our understanding of fucoidan-degrading microbial groups., 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.)

Objectives: Individuals infected with extensively-drug-resistant (XDR) Acinetobacter baumannii are difficult to cure and have a high mortality rate. This study compared the genomic and phenotypic differences between XDR and non-multi-drug-resistant (MDR) A. baumannii, and further characterized hypervirulent XDR A. baumannii., Methods: In total, 1403 acinetobacter isolates were collected from patients with bacteraemia between 1997 and 2015. Antimicrobial susceptibility tests were performed to categorize isolates into non-MDR, MDR and XDR groups. The presence of selected virulence-associated genes was determined by polymerase chain reaction. Bacterial phenotypes, including iron acquisition, biofilm formation, capsule production, and virulence to larvae and mice, were determined., Results: Multi-locus sequence typing revealed a high prevalence of sequence type (ST) 2 (81.6%) and ST129 (18.4%) among 49 XDR isolates, and the STs of 18 non-MDR isolates were more diverse. Virulence-associated phenotypic assays showed that XDR isolates had higher iron acquisition ability, greater capsule production, and virulence to Galleria mellonella larvae. However, their ability to form biofilm was lower compared with that of non-MDR isolates. XDR isolates were more likely to have virulence genes (tonB, hemO, abaI and ptk), while non-MDR isolates were more likely to have pld and ompA genes. Twenty-one XDR isolates that had a <20% larvae survival rate after 7 days post-infection were defined as hypervirulent XDR isolates. Among them, isolates 1677 (ST129) and 929-1 (ST2) caused the death of all infected mice within 2 days., Conclusion: Some subpopulations of highly-drug-resistant ST2 isolates exhibit high virulence. As such, it is of utmost importance to continue monitoring the spread of hypervirulent XDR A. baumannii isolates., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Interleukin 3 (IL-3) plays an important role in hematopoiesis and immune regulation, brain IL-3/IL-3R signaling has been shown to involve in the physiological and pathological processes of a variety of neurodegenerative diseases, but its role in prion diseases is rarely described. Here, the changes of IL-3/IL-3R and its downstream signaling pathways in a scrapie-infected cell line and in the brains of several scrapie-infected rodent models were evaluated by various methods. Markedly decreased IL-3Rα were observed in the brains of scrapie-infected rodents at terminal stage and in the prion-infected cell model, which showed increased in the brain samples collected at early and middle stage of infection. The IL-3 levels were almost unchanged in the brains of scrapie-infected mice and in the prion-infected cell line. Morphological assays identified close co-localization of the increased IL-3Rα signals with NeuN- and Iba1-positive cells, whereas co-localization of IL-3 signals with NeuN- and GFAP-positive cells in the scrapie-infected brain tissues. Some downstream components of IL-3/IL-3R pathways, including JAK2-STAT5 and PI3K/AKT/mTOR pathways, were downregulated in the brains of scrapie-infected rodents at terminal stage and in the prion-infected cells. Stimulation of recombinant IL-3 on the cultured cells showed prion that the prion-infected cells displayed markedly more reluctant responses of JAK2-STAT5 and PI3K/AKT/mTOR pathways than the normal partner cells. These data suggest that although prion infection or PrP Sc accumulation in brain tissues does not affect IL-3 expression, it significantly downregulates IL-3R levels, thereby inhibiting the downstream pathways of IL-3/IL-3R and blocking the neuroregulatory and neuroprotective activities of IL-3., Competing Interests: Declarations. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflict of Interest: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mitochondrial dysfunction is one of the hallmarks in the pathophysiology of prion disease and other neurodegenerative diseases. Various metabolic dysfunctions are identified and considered to contribute to the progression of some types of neurodegenerative diseases. In this study, we evaluated the status of glycolysis pathway in prion-infected rodent and cell models. The levels of the key enzymes, hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) were significantly increased, accompanying with markedly downregulated mitochondrial complexes. Double-stained IFAs revealed that the increased HK2 and PFK distributed widely in GFAP-, Iba1-, and NeuN-positive cells. We also identified increased levels of AMP-activated protein kinase (AMPK) and the downstream signaling. Changes of AMPK activity in prion-infected cells by the AMPK-specific inhibitor or activator induced the corresponding alterations not only in the downstream signaling, but also the expressions of three key kinases in glycolysis pathway and the mitochondrial complexes. Transient removal or complete clearance of prion propagation in the prion-infected cells partially but significantly reversed the increases of the key enzymes in glycolysis, the upregulation of AMPK signaling pathway, and the decreases of the mitochondrial complexes. Measurements of the cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) showed lower OCR and higher ECAR in prion-infected cell line, which were sufficiently reversed by clearance of prion propagation. Those data indicate a metabolic reprogramming from oxidative phosphorylation to glycolysis in the brains during the progression of prion disease. Accumulation of PrP Sc is critical for the switch to glycolysis, largely via activating AMPK pathway., Competing Interests: Declarations. Ethics Approval: This study was performed in line with the principles of the Chinese Laboratory Animal Management. Approval was granted by the Research Ethics Committee of the National Institute for Viral Disease Control and Prevention, China CDC. Consent to Participate: Informed consent was obtained from all individual participants included in the study. Consent for Publication: The authors affirm that human research participants provided informed consent for publication of the images in figures. Competing Interests: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Four previously undescribed caryophyllene sesquiterpenoids (1-4) along with one known drimane sesquiterpenoid (5) were isolated from the fermentation products of the mushroom Hypholoma capnoides 819. The structures of 1-4 with rare tricyclic skeleton (6/5/4) or bicyclic skeletons (9/4) were determined on the basis of comprehensive spectroscopic data analysis, calculated NMR, ORD data, and their biosynthetic pathways. Compounds 1-5 only showed very weak cytotoxicity toward mouse microglial cells (BV2), breast cancer cells (MCF-7), and human lung cancer cells (A549) at 40 µM. In addition, none of the compounds demonstrated antibacterial activity against Staphylococcus aureus or Escherichia coli at 128 µg/mL., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Intracellular compartmentalization enhances biological reactions, crucial for cellular function and survival. An example is the carboxysome, a bacterial microcompartment for CO 2 fixation. The carboxysome uses a polyhedral protein shell made of hexamers, pentamers, and trimers to encapsulate Rubisco, increasing CO 2 levels near Rubisco to enhance carboxylation. Despite their role in the global carbon cycle, the molecular mechanisms behind carboxysome shell assembly remain unclear. Here, we present a structural characterization of α-carboxysome shells generated from recombinant systems, which contain all shell proteins and the scaffolding protein CsoS2. Atomic-resolution cryo-electron microscopy of the shell assemblies, with a maximal size of 54 nm, unveil diverse assembly interfaces between shell proteins, detailed interactions of CsoS2 with shell proteins to drive shell assembly, and the formation of heterohexamers and heteropentamers by different shell protein paralogs, facilitating the assembly of larger empty shells. Our findings provide mechanistic insights into the construction principles of α-carboxysome shells and the role of CsoS2 in governing α-carboxysome assembly and functionality.

The dual inhibition of histone lysine-specific demethylase 1 (LSD1) and histone deacetylase (HDAC) has emerged as a promising strategy for cancer therapy. In this study, we report the discovery of novel 5-cyano-3-phenylindole-based LSD1/HDAC dual inhibitors, evaluated through both in vitro and in vivo assays. Among these inhibitors, compound 20c was identified as particularly potent, exhibiting high inhibitory activity against LSD1 (IC 50 = 39.0 nM) and HDAC1/2/3/6/8 (IC 50 = 1.4, 1.0, 1.3, 2.9, and 16.0 nM, respectively). Compound 20c effectively modulated the expression of biomarkers associated with LSD1 and HDAC inhibition and demonstrated superior antiproliferative activity compared to SAHA and 4SC-202 across multiple colorectal cancer cell lines. Following pharmacokinetic studies, 20c was further assessed in HCT-116 and HT-29 xenograft mouse models. It demonstrated significantly enhanced antitumor efficacy compared to SAHA, without causing observable toxicity. These findings highlight the potential of LSD1/HDAC dual inhibitors for the treatment of malignant cancers.

Background: The primary adverse effect of chemotherapy drugs is the induction of spermatogenic disorders. Schisandra chinensis (Turcz) Baill. have been preliminarily shown to have a significant ameliorative in spermatogenic disorders. Nevertheless, there are relatively few studies on non-medicinal parts such as stems of S. chinensis, which have good therapeutic potential for side effects caused by cisplatin. Up to now, a total of 238 compounds have been isolated and identified from the vine stem of S. chinensi. The main components are lignans, polysaccharides, volatile oils, and organic acids. Therefore, the development of S. chinensis stem as a source of a novel chemotherapy drug protector is of great significance., Methods: In the present study, we explored the protective effect of the stem extract of S. chinensis (SCE) against cisplatin-induced spermatogenic disorders and its possible molecular mechanisms in vitro and in vivo. The network pharmacology was used to predict the targets that may act on spermatogenic disorders. Mice were injected intraperitoneally with cisplatin at 2 mg/kg for 7 days to induce spermatogenic disorders. SCE (75, 150, and 300 mg/kg) was administered to mice by gavage for 21 days. TM3 cells were treated with Schisandrol B (Sol B) (0.5, 1, and 2 µM) in the presence or absence of cisplatin (40 µM), and then cell viability, oxidative stress, apoptosis, and mitochondrial function were evaluated., Results: 16 constituents and target proteins were predicted to have possible effects on spermatogenic disorders by network pharmacology. Both in vivo and in vitro experiments showed a favorable protective effect of SCE against cisplatin-induced spermatogenic disorders. Sol B might as the major chemical component is responsibility for the protective effect. The mechanism may involve the regulation of Nrf2\HO-1 protein, PI3K\Akt, apoptosis, and MAPK signaling pathway to modulate 17βHSD, cycp450, Star and other crucial proteins in the testosterone synthesis pathway. Ultimately, this regulatory process aims to ameliorate the disruption of sex hormone secretion by cisplatin., Conclusion: These results indicated that the lignans in SCE could effectively improve the spermatogenesis barrier caused by cisplatin. These findings provided a theoretical basis for the development of non-medicinal parts of S. chinensis, and laid a foundation for improving spermatogenesis disorders caused by chemotherapy drugs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Vibrio vulnificus is a significant opportunistic pathogen with the highest fatality rate among foodborne microbes. However, due to a lack of comprehensive surveillance, the characteristics of isolates in China remain poorly understood. This study analyzed 60 strains of V. vulnificus isolated from diverse sources in Shanghai, including shellfish, crabs, shrimps, throat swabs of migratory birds, as well as seafood farming water and seawater. Identification of the genotypes was performed using PCR, and cytotoxicity was determined using an LDH assay. DNA was sequenced using Illumina NovaSeq followed by a bioinformatic analysis. The results demonstrated that a majority of the strains belonged to the 16S rRNA B- vcg C genotype. All strains carried five antibiotic resistance genes (ARGs), with some strains carrying over ten ARGs, mediating resistance to multiple antibiotics. Five strains possessed a highly abundant effector delivery system, which further investigations revealed to be a type III secretion system II (T3SS2), marking the first description of T3SS2 in V. vulnificus . Phylogenetic analysis indicated that it belonged to a different genetic lineage from T3SS2α and T3SS2β of V. parahaemolyticus . Bacteria with T3SS2 sequences were concentrated in coastal areas and mostly within the genus Vibrio in the global prevalence survey. Our study provides essential baseline information for non-clinical V. vulnificus and discovers the existence of T3SS2 in several strains which may be more virulent, thereby posing a new threat to human health.

Therapeutic drug monitoring (TDM) of imatinib (IM) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. There was a significant correlation between unbound concentration and clinical response and toxicity, compared with total plasma concentrations, and the quantification of unbound IM and its metabolite, N-desmethyl imatinib (NDI) are of interest for TDM. However, traditional unbound drug separation methods have shortcomings, especially are susceptible to non-specific binding (NSB) of drugs to the polymer-constructed components of filter membranes, which are difficult to avoid at present. Hence it is necessary to developed a reliable separation method for the analysis of the unbound fraction of IM and NDI in TDM. We developed and validated an hollow fiber solid phase microextraction (HF-SPME) method coupled with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) that to measure unbound IM and NDI concentration in human plasma. It used the NSB phenomenon and solve the NSB problem. The preparation procedure only involves a common vortex and ultrasonication without dilution of samples and modification of membrane. A total of 50 chronic myeloid leukemia (CML) patients were enrolled in our study. The relationship between the unbound and total concentrations for IM and NDI, as well as the concentration ratios of NDI to IM in 50 clinical plasma samples were investigated. The extraction recovery is high to 95.5-106 % with validation parameters for the methodological results were all excellent. There were both a poor linear relationship between the unbound and total concentrations for IM (r 2 =0.504) and NDI (r 2 =0.201) in 50 clinical plasma samples. The unbound concentration ratios of NDI to IM varied widely in CML patients. The determination of unbound IM and NDI concentration is meaningful and necessary. The developed HF-SPME method is simple, accurate and precise that could be used to measure unbound IM and NDI concentration in clinical TDM., 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.)

To investigate the spatial and temporal distribution characteristics and assess the ecological risks associated with emerging contaminants （ECs） in the Beijiang drinking water source, non-targeted screening was conducted using the ultra-high performance liquid chromatography-mass spectrometry technique （UPLC-MS） for one year （June 2022 to May 2023）. This study also involved the quantitative detection of eight typical ECs. The results showed that through the non-targeted screening, a total of 346 pollutants were identified, with industrial materials, pharmaceuticals, and pesticides being the predominant pollutants, collectively accounting for 88.2%. Concentrations of eight representative ECs ranged from n.d （undetected） to 180 ng·L -1 , with detection rates exceeding 80% for six of them. Notably, higher concentrations were found in endocrine disruptors such as bisphenol A （BPA） and 4-nonylphenol （4-NP）, along with the pesticides atrazine （ATZ） and propisochlor （PPS）, with median concentrations ranging from 8.12 to 35.58 ng·L -1 . The concentrations of ATZ, PPS, roxithromycin （ROX）, and ibuprofen （IBU） were significantly higher in the spring season compared to those in other seasons （ P &lt;0.05）. Elevated ecological risk levels （RQ&gt;1） were observed at sampling point 1 （S1） and sampling point 3 （S3） for ATZ and Lomefloxacin （LOM）, while for 4-NP, it was determined to be high only at sampling site 2 （S2）. Given their high detection rates and ecotoxicity, particular attention should be paid to ATZ and 4-NP. The concentration level of ATZ exhibited significant seasonal variation due to its agricultural origin, so it is recommended to strengthen control during spring. Overall, this research provides critical insights into a comprehensive understanding of the presence and impact of ECs in this specific region.

Acute myeloid leukemia (AML) is a malignant cancer characterized by abnormal differentiation of hematopoietic stem and progenitor cells (HSPCs). While chimeric antigen receptor T (CAR-T) cell immunotherapies target AML cells, they often induce severe on-target/off-tumor toxicity by attacking normal cells expressing the same antigen. Here, we used base editors (BEs) and a prime editor (PE) to modify the epitope of CD123 on HSPCs, protecting healthy cells from CAR-T-induced cytotoxicity while maintaining their normal function. Although BE effectively edits epitopes, complex bystander products are a concern. To enhance precision, we optimized prime editing, increasing the editing efficiency from 5.9% to 78.9% in HSPCs. Epitope-modified cells were resistant to CAR-T lysis while retaining normal differentiation and function. Furthermore, BE- or PE-edited HSPCs infused into humanized mice endowed myeloid lineages with selective resistance to CAR-T immunotherapy, demonstrating a proof-of-concept strategy for treating relapsed AML., Competing Interests: Declaration of interests Y.Z., G.-H.C., and R.-J.J. filed a PCT patent related to this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dynamic molecules with tunable chemical and physical properties in response to external stimuli hold great potential for applications in various fields such as information storage, smart molecular machines, and biomimetics. Among them, supramolecular springs and spin-crossover (SCO) complexes can both undergo visible macroscopic changes under heat or light stimulation. In this study, we synthesized a unique trinuclear Fe(II)-SCO complex, [(R-L)Fe II {Au(CN) 2 } 2 ] (R 1), using a chiral chelating ligand decorated with rotatable benzyl rings. The [FeAu 2 ] trinuclear molecules form a 2 1 -helical supramolecular chain via elastic Au ⋯ ${\cdots }$ Au contacts. Interestingly, the synergy between the multiple dynamic factors (SCO event, rotation of the rings, and flexibility in Au ⋯ ${\cdots }$ Au distance) endows the complex with multiple switchings in both magnetism and structure, as well as the most intriguing characteristic of giant and anisotropic "breathing" feature in thermal expansion within two distinct temperature regimes. Specifically, complex R 1 undergoes two hysteretic magnetic transitions: a non-spin transition between 360 and 380 K and an unsymmetric SCO transition in the region of 160-280 K, associated with a symmetry-breaking event between the non-polar and polar space groups (P2 1 2 1 2 1 ↔P2 1 ). Both transitions are triggered/accompanied by the rotation (inward vs. outward) of the benzyl rings. Correspondingly, reversible spring-like motions of the helical chains with the helical pitches varying from 11.345 140 K to 12.509 280 K then back to 11.630 380 K  Å are observed in the two distinct temperature regimes. This work demonstrates a significant success in incorporating both SCO and spring-like motion in one system, paving the way for designing multifunctional dynamic materials for future devices., (© 2024 Wiley-VCH GmbH.)

Oxford Nanopore Technologies (ONT) offers ultrahigh-throughput multi-sample sequencing but only provides barcode kits that enable up to 96-sample multiplexing. We present TDFPS-Designer, a new toolkit for nanopore sequencing barcode design, which creates significantly more barcodes: 137 with a length of 20 base pairs, 410 at 24 bp, and 1779 at 30 bp, far surpassing ONT's offerings. It includes GPU-based acceleration for ultra-fast demultiplexing and designs robust barcodes suitable for high-error ONT data. TDFPS-Designer outperforms current methods, improving the demultiplexing recall rate by 20% relative to Guppy, without a reduction in precision., (© 2024. The Author(s).)

The carboxysome is a natural proteinaceous organelle for carbon fixation in cyanobacteria and chemoautotrophs. It comprises hundreds of protein homologs that self-assemble to form a polyhedral shell structure to sequester cargo enzymes, ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), and carbonic anhydrases. How these protein components assemble to construct a functional carboxysome is a central question in not only understanding carboxysome structure and function but also synthetic engineering of carboxysomes for biotechnological applications. Here, we determined the structure of the chaperone protein CcmS, which has recently been identified to be involved in β-carboxysome assembly, and its interactions with β-carboxysome proteins. The crystal structure at 1.99 Å resolution reveals CcmS from Nostoc sp. PCC 7120 forms a homodimer, and each CcmS monomer consists of five α-helices and four β-sheets. Biochemical assays indicate that CcmS specifically interacts with the C-terminal extension of the carboxysome shell protein CcmK1, but not the shell protein homolog CcmK2 or the carboxysome scaffolding protein CcmM. Moreover, we solved the structure of a stable complex of CcmS and the C-terminus of CcmK1 at 1.67 Å resolution and unveiled how the CcmS dimer interacts with the C-terminus of CcmK1. These findings allowed us to propose a model to illustrate CcmS-mediated β-carboxysome assembly by interacting with CcmK1 at the outer shell surface. Collectively, our study provides detailed insights into the accessory factors that drive and regulate carboxysome assembly, thereby improving our knowledge of carboxysome structure, function, and bioengineering., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Several studies have observed renal cell ferroptosis during cisplatin-induced acute kidney injury (AKI). However, the mechanism is not completely clear. In this study, oxidized arachidonic acid (AA) metabolites are increased in cisplatin-treated HK-2 cells. Targeted metabolomics showed that the end product of pyrimidine biosynthesis is decreased and the initiating substrate of pyrimidine biosynthesis is increased in cisplatin-treated mouse kidneys. Mitochondrial DHODH, a key enzyme for pyrimidine synthesis, and its downstream product CoQH 2 , are downregulated. DHODH overexpression attenuated but DHODH silence exacerbated cisplatin-induced CoQH 2 depletion and lipid peroxidation. Mechanistically, renal DHODH acetylation is elevated in cisplatin-exposed mice. Mitochondrial SIRT3 is reduced in cisplatin-treated mouse kidneys and HK-2 cells. Both in vitro SIRT3 overexpression and in vivo NMN supplementation attenuated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis. By contrast, Sirt3 knockout aggravated cisplatin-induced mitochondrial DHODH acetylation and renal cell ferroptosis, which can not be attenuated by NMN. Additional experiments showed that cisplatin caused mitochondrial dysfunction and SIRT3 SUMOylation. Pretreatment with mitochondria-target antioxidant MitoQ alleviated cisplatin-caused mitochondrial dysfunction, SIRT3 SUMOylation, and DHODH acetylation. MitoQ pretreatment protected against cisplatin-caused AKI and renal cell ferroptosis. Taken together, these results suggest that mitochondrial dysfunction-evoked DHODH acetylation partially contributes to renal cell ferroptosis during cisplatin-induced AKI., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Cases of fetal volvulus without malrotation are extremely uncommon and pose a life-threatening condition of acute abdomen. In cases of inadequate intestinal rotation, the narrowing of the attachment of the mesenteric root can easily cause intestinal torsion and consequent local blood circulation disorders within the intestinal tract, leading to aseptic necrosis and simultaneous intestinal perforation, resulting in meconium peritonitis, ascites, anemia, and potentially fetal death. In ultrasound examinations, it may be the preferred examination method for this disease. Ultrasound physicians should improve their understanding of this disease in prenatal diagnosis, as it has important clinical value for obstetric management and neonatal treatment, thereby potentially improving adverse pregnancy outcomes., 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.)

Dimethylsulfoniopropionate (DMSP) is one of Earth's most abundant organosulfur compounds with important roles in stress tolerance, chemotaxis, global carbon and sulfur cycling, and climate-active gas production. Diverse marine prokaryotes and eukaryotes produce DMSP via three known pathways (methylation, transamination, and decarboxylation) and metabolize DMSP via three further pathways (demethylation, cleavage, and oxidation). Over 20 key enzymes from these pathways have been identified that demonstrate the biodiversity and importance of DMSP cycling. The last dozen years have seen significant changes in our understanding of the enzymology and molecular mechanisms of these DMSP cycling enzymes through the application of biochemistry and structural biology. This has yielded more than 10 crystal structures and, in many cases, detailed explanations as to how and why organisms synthesis and metabolize DMSP. In this review, we describe recent progress in biochemical and mechanistic understandings of DMSP synthesis and metabolism, highlighting the important knowledge gleaned and current challenges that warrant further exploration.

The spread of antibiotic resistance genes (ARGs), particularly those carried on plasmids, poses a major risk to global health. However, the extent and frequency of ARGs transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a novel fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer. It combines CRISPR/Cas9 fluorescence tagging, fluorescence-activated cell sorting, 16S rRNA gene sequencing, and microbial community analysis. CRISPR-AMRtracker integrates a fluorescent tag immediately downstream of ARGs, enabling the tracking of ARG transfer without compromising the host cell's antibiotic susceptibility, fitness, conjugation, and transposition. Notably, our experiments demonstrate that sfGFP-tagged plasmid-borne mcr-1 can transfer across diverse bacterial species within fecal samples. This innovative approach holds the potential to illuminate the dynamics of ARG dissemination and provide valuable insights to shape effective strategies in mitigating the escalating threat of antibiotic 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 Ltd. All rights reserved.)

Neuroinflammation is a common pathological feature in a number of neurodegenerative diseases, which is mediated primarily by the activated glial cells. Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome-associated neuroinflammatory response is mostly considered. To investigate the situation of the NLRP3-related inflammation in prion disease, we assessed the levels of the main components of NLRP3 inflammasome and its downstream biomarkers in the scrapie-infected rodent brain tissues. The results showed that the transcriptional and expressional levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein (ASC) in the brains of scrapie-infected rodents were significantly increased at terminal stage. The increased NLPR3 overlapped morphologically well with the proliferated GFAP-positive astrocytes, but little with microglia and neurons. Using the brain samples collected at the different time-points after infection, we found the NLRP3 signals increased in a time-dependent manner, which were coincidental with the increase of GFAP. Two main downstream cytokines, IL-1β and IL-18, were also upregulated in the brains of prion-infected mice. Moreover, the gasdermin D (GSDMD) levels, particularly the levels of GSDMD-NT, in the prion-infected brain tissues were remarkably increased, indicating activation of cell pyroptosis. The GSDMD not only co-localized well with the astrocytes but also with neurons at terminal stage, also showing a time-dependent increase after infection. Those data indicate that NLRP3 inflammasomes were remarkably activated in the infected brains, which is largely mediated by the proliferated astrocytes. Both astrocytes and neurons probably undergo a pyroptosis process, which may help the astrocytes to release inflammatory factors and contribute to neuron death during prion infection., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To assess the diagnostic utility of clinical magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in distinguishing between histological grading and isocitrate dehydrogenase ( IDH ) classification in adult diffuse gliomas., Methods: A retrospective analysis was conducted on 247 patients diagnosed with adult diffuse glioma. Experienced radiologists evaluated DWI and MRS images. The Kruskal-Wallis test examined differences in DWI and MRS-related parameters across histological grades, while the Mann-Whitney U test assessed molecular classification. Receiver Operating Characteristic (ROC) curves evaluated parameter effectiveness. Survival curves, stratified by histological grade and IDH classification, were constructed using the Kaplan-Meier test., Results: The cohort comprised 141 males and 106 females, with ages ranging from 19 to 85 years. The Kruskal-Wallis test revealed significant differences in ADC mean, Cho/NAA, and Cho/Cr concerning glioma histological grade ( P  < .01). Subsequent application of Dunn's test showed significant differences in ADC mean among each histological grade ( P  < .01). Notably, Cho/NAA exhibited a marked distinction between grade 2 and grade 3/4 gliomas ( P  < .01). The Mann-Whitney U test indicated that only ADC mean showed statistical significance for IDH molecular classification ( P  < .01). ROC curves were constructed to demonstrate the effectiveness of the specified parameters. Survival curves were also delineated to portray survival outcomes categorized by histological grade and IDH classification. Conclusions: Clinical MRS demonstrates efficacy in glioma histological grading but faces challenges in IDH classification. Clinical DWI's ADC mean parameter shows significant distinctions in both histological grade and IDH classification., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Monozygotic (MZ) twins cannot be distinguished using conventional forensic STR typing because they present identical STR genotypings. However, MZ twins do not always live in the same environment and often have different dietary and other lifestyle habits. Metabolic profiles are deyermined by individual characteristics and are also influenced by the environment in which they live. Therefore, they are potential markers capable of identifying MZ twins. Moreover, the production of proteins varies from organism to organism and is influenced by both the physiological state of the body and the external environment. Hence, we used metabolomics and proteomics to identify metabolites and proteins in peripheral blood to discriminate MZ twins. We identified 1749 known metabolites and 622 proteins in proteomic analysis. The metabolic profiles of four pairs of MZ twins revealed minor differences in intra-MZ twins and major differences in inter-MZ twins. Each pair of MZ twins exhibited distinct characteristics, and four metabolites-methyl picolinate, acesulfame, paraxanthine, and phenylbenzimidazole sulfonic acid-were observed in all four MZ twin pairs. These four differential exogenous metabolites conincidently show that the different external environments and life styles can be well distinguished by metabolites, considering that twins do not all have the same eating habits and living environments. Moreover, MZ twins showed different protein profiles in serum but not in whole blood. Thus, our results indicate that differential metabolites provide potential biomarkers for the personal identification of MZ twins in forensic medicine., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: As the population ages and technology advances, lateral lumbar intervertebral fusion (LLIF) is gaining popularity for the treatment of degenerative lumbar scoliosis (DLS). This study investigated the feasibility, minimally invasive concept, and benefits of LLIF for the treatment of DLS by observing and assessing the clinical efficacy, imaging changes, and complications following the procedure., Methods: A retrospective analysis was performed for 52 DLS patients (12 men and 40 women, aged 65.84 ± 9.873 years) who underwent LLIF from January 2019 to January 2023. The operation time, blood loss, complications, clinical efficacy indicators (visual analogue scale [VAS], Oswestry disability index [ODI], and 36-Item Short Form Survey), and imaging indicators (coronal position: Cobb angle and center sacral vertical line-C7 plumbline [CSVL-C7PL]; and sagittal position: sagittal vertical axis [SVA], lumbar lordosis [LL], pelvic incidence angle [PI], and thoracic kyphosis angle [TK] were measured). All patients were followed up. The above clinical evaluation indexes and imaging outcomes of patients postoperatively and at last follow-up were compared to their preoperative results., Results: Compared to the preoperative values, the Cobb angle and LL angle were significantly improved after surgery (p < 0.001). Meanwhile, CSVL-C7PL, SVA, and TK did not change much after surgery (p > 0.05) but improved significantly at follow-up (p < 0.001). There was no significant change in PI at either the postoperative or follow-up timepoint. The operation took 283.90 ± 81.62 min and resulted in a total blood loss of 257.27 ± 213.44 mL. No significant complications occurred. Patients were followed up for to 21.7 ± 9.8 months. VAS, ODI, and SF-36 scores improved considerably at postoperative and final follow-up compared to preoperative levels (p < 0.001). After surgery, the Cobb angle and LL angle had improved significantly compared to preoperative values (p < 0.001). CSVL-C7PL, SVA, and TK were stable after surgery (p > 0.05) but considerably improved during follow-up (p < 0.001). PI showed no significant change at either the postoperative or follow-up timepoints., Conclusion: Lateral lumbar intervertebral fusion treatment of DLS significantly improved sagittal and coronal balance of the lumbar spine, as well as compensatory thoracic scoliosis, with good clinical and radiological findings. Furthermore, there was less blood, less trauma, and quicker recovery from surgery., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Designing solid polymer electrolytes (SPEs) with high ionic conductivity for room-temperature operation is essential for advancing flexible all-solid-state energy storage devices. Innovative strategies are urgently required to develop SPEs that are safe, stable, and high-performing. In this work, we introduce photoexcitation-modulated heterojunctions as catalytically active fillers within SPEs, guided by photocatalytic design principles, and meanwhile employ natural bacterial cellulose to improve the compatibility with poly(ethylene oxide), improve the coordination environment of lithium salts, and optimize both ion transport and mechanical properties. In situ photothermal experiments and theoretical calculations reveal that the strong photogenerated electric field produced by trace heterojunctions within poly(ethylene oxide) electrolytes under photoexcitation significantly enhances lithium salt dissociation, increasing the concentration of mobile Li + . This results in a substantial increase in ionic conductivity, reaching 0.135 mS cm -1 at 25 °C, with a Li + transference number as high as 0.46. The flexible all-solid-state lithium-metal pouch cells exhibit an impressive discharge capacity of 178.8 mAh g -1 even after repeated bending and folding, and demonstrate exceptional long-term cycling stability, retaining 86.7 % of their initial capacity after 250 cycles at 1 C (25 °C). This research offers a novel approach to developing high-performance flexible lithium-metal batteries., (© 2024 Wiley-VCH GmbH.)

Alginate oligosaccharides (AOs), derived from alginate degradation, exhibit diverse biological activities and hold significant promise in various fields. The enzymatic preparation of AOs relies on alginate lyases, which offers distinct advantages. In contrast to the conventional use of sodium alginate derived from brown algae as the substrate for the enzymatic preparation of AOs, AO preparation directly from brown algae is more appealing due to its time and energy efficiency. Thus, the identification of potent alginate lyases and cost-effective brown algae substrates is crucial for optimizing AO production. Herein, we identified and characterized an alginate lyase, AlyP18, capable of efficiently decomposing algae, from a marine bacterium Pseudoalteromonas agarivorans A3 based on secretome analysis. AlyP18 is a mesothermal, endo-type and bifunctional alginate lyase with high enzymatic activity. Two brown algae substrates, Laminaria japonica roots and Macrocystis pyrifera , were used for the AO preparation by AlyP18. Upon optimization of AlyP18 hydrolysis parameters, the substrate degradation efficiency and AO production reached 53% and ~32% for L. japonica roots, respectively, and 77% and ~46.5% for M. pyrifera . The generated AOs primarily consisted of dimers to pentamers, with trimers and tetramers being dominant. This study provides an efficient alginate lyase and alternative brown algal feedstock for the bioconversion of high-value AOs from brown algae.

Prion diseases are fatal neurodegenerative disorders characterized by neuron damage and loss. Growth-associated protein 43 (GAP43) functions in neuronal plasticity and synaptic function, but its role in prion diseases is not fully elucidated. In this study, we investigated the changes of GAP43 in the central nerve system (CNS) of several prion-infected rodent models and explored the potential relationship of GAP43 with PrP Sc deposit and neuron loss using various methods. We found that GAP43 levels were significantly decreased in the brain tissues of scrapie-infected rodent models at the terminal stage of the disease. Immunohistochemical analysis showed that GAP43 colocalized with NeuN-positive cells morphologically, indicating the presence of GAP43 in mature neurons. On contrary, the levels of GAP43 and p-GAP43 increased in a prion-infected cell line SMB-S15 in vitro, accompanying with the increase of intracellular calcium. Stimulation of lipopolysaccharide (LPS) upregulated while removal of PrP Sc propagation downregulated the level of GAP43 in SMB-S15 cells. Morphological colocalization and molecular interaction between GAP43 and PrP Sc have been addressed in the brains of prion-infected rodents and prion-infected cell line. Histological assays of the serial sections of the whole brains of prion-infected mice proposed that the reduced GAP43 level correlated with large amount of PrP Sc deposits and notable neuron damage and loss showing cell crumpled and nuclear pyknosis. The impairment of GAP43 signaling and disturbance of calcium homeostasis by aberrance of brain GAP43/p-GAP43 not only reflect but also likely contribute to the pathology of severe neuron loss at the end of prion disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Astragalus , a group of legume plants, has a pronounced rhizosphere effect. Many species of Astragalus with limited resource reserves are distributed in the high-altitude area of northern Yunnan, China. Although some of these plants have high medicinal value, the recognition of them is still at a low level. The aim of this research is to explore the species diversity of cultivable rhizofungi derived from Astragalus acaulis , A. forrestii and A. ernestii growing in a special high-cold environment of northwest Yunnan and discover anti-infective components from these fungi. A total of 93 fungal strains belonging to 38 species in 18 genera were isolated and identified. Antibacterial and antimalarial screening yielded 10 target strains. Among them, the ethyl acetate crude extract of the fermented substrate of the rhizofungus Aspergillus calidoustus AA12 derived from the plant A. acaulis showed broad-spectrum antibacterial activity and the best antimalarial activity. Further chemical investigation led to the first discovery of seven compounds from the species A. calidoustus , including sesterterpine 6-epi-ophiobolin G; three sesquiterpenes, penicisochroman A, pergillin and 7-methyl-2-(1-methylethylethlidene)-furo [3,2-H]isoquinoline-3-one; and three polyketides, trypacidin, 1,2-seco-trypacidin and questin. Among them, the compound 6-epi-ophiobolin G exhibited moderate to strong antibacterial activity against six Gram-positive pathogens with the minimum inhibitory concentration (MIC) ranging from 25 to 6.25 μg/mL and a prominent inhibitory effect on the biofilm of Streptococcus agalactiae at an MIC value of 3.125 μg/mL. This compound also displayed potent antimalarial activity against Plasmodium falciparum strains 3D7 and chloroquine-resistant Dd2 at the half-maximal inhibitory concentration (IC 50 ) values of 3.319 and 4.340 µmol/L at 72 h, respectively. This study contributed to our understanding of the cultivable rhizofungi from characteristic Astragalus plants in special high-cold environments and further increased the library of fungi available for natural anti-infectious product screening.

Background: The optimal glycosylated hemoglobin (HbA1c) target in type 2 diabetes mellitus (T2DM) patients remains controversial, especially in patients with concomitant coronary heart disease (CHD). This study aimed to investigate the correlation between baseline HbA1c and long-term prognosis in CHD patients with T2DM., Methods: The study enrolled 6,839 CHD patients with T2DM and measured HbA1c at admission in a multicenter prospective observational cohort. Patients were divided into two groups according to baseline HbA1c levels: optimal glycemic control group (HbA1c < 7.0 %, n = 3023) and poor glycemic control group (HbA1c ≥ 7.0 %, n = 3816). The study endpoints were all-cause death and major adverse cardiac and cerebrovascular events (MACCEs)., Results: The median follow-up period was 2.1 years. During this period, 229 (3.3 %) all-cause deaths, 165 (2.4 %) cardiac deaths, and 759 (11.1 %) MACCEs occurred. Unadjusted Kaplan-Meier analysis showed that the incidences of all-cause death, cardiac death, non-fatal MI, unplanned revascularization, and MACCEs were significantly lower in the HbA1c < 7.0 % group than in the HbA1c ≥ 7.0 % group (P < 0.05). Multivariate Cox hazard analysis indicated that the incidences of all-cause death, cardiac death and MACCEs were significantly lower in the HbA1c < 7.0 % group compared to the HbA1c ≥ 7.0 % group [all-cause death: hazard ratio (HR) 1.969, 95 % confidence interval (CI) 1.421-2.729; cardiac death: HR 2.515, 95 % CI 1.647-3.839; MACCEs: HR 1.345, 95 % CI 1.150-1.573; P < 0.001]., Conclusions: Baseline HbA1c level was associated with all-cause death, cardiac death, and MACCEs in CHD patients with T2DM., Competing Interests: The authors declare that the study has no competing interests., (© 2024 Published by Elsevier Ltd.)

To investigate the effect of gamma irradiation on the volatile compounds of edible oils. Three types of oilseeds, including peanut, sesame, and flaxseed, were subjected to 8 kGy gamma irradiation, followed by cold pressing to extract their oils. The volatile compounds of the oils were isolated by simultaneous distillation extraction and analyzed by gas chromatography-mass spectrometry. A total of 91 volatile compounds were identified, which can be grouped into eight categories: hydrocarbons, aldehydes, ketones, alcohols, acids, esters, furans, and benzene derivatives. Irradiation treatment resulted in a significant increase in the levels of hydrocarbons, aldehydes, and ketones in all oil samples (p < 0.05), with the greatest increase observed in hydrocarbons (4-14 times). In contrast, changes in alcohols, acids, esters, furans, and benzene derivatives were related to oilseed type. The increased hydrocarbons mainly originated from the degradation of palmitic, stearic, oleic, and linoleic acids. The irradiation resistance of the three oilseeds varied considerably, in the order: flaxseed > sesame > peanut. Based on the odor activity value, 11 key aroma compounds were selected, and (E)-2-decenal (tallow, oily, and orange), 1-octanol (soapy and oily), and 1-nonanol (floral and soapy) were only detected in the irradiated samples. Principal component analysis revealed that the oil samples of the three oilseeds could be well classified based on their key aroma compounds, and that the irradiation treatment had no remarkable effect on their intrinsic aroma., (© 2024 Institute of Food Technologists.)

Aims: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), and its level is genetically determined. Although guidelines and consensuses in various cardiovascular fields have emphasized the importance of Lp(a), screening for Lp(a) in China has not been well studied., Methods: A cross-sectional study was conducted using a random sample of 30,000 medical examiners from each of the five health check-up centres. The distribution of Lp(a) was described for those who completed Lp(a) testing, and logistic regression modelling was used to evaluate the relationship between Lp(a) levels and vascular structure and function in the population who underwent carotid ultrasound and brachial‒ankle pulse wave velocity (baPWV) measurements., Results: Lp(a) was measured in only 4400 (3.02%) of the 150,000 participants. Among those tested for Lp(a), the median concentration was 15.85 mg/dL. The proportion of participants with Lp(a) levels ≥ 30 mg/dL was 15.00%. Multiple logistic regression analysis revealed a significant correlation between Lp(a) and cIMT ≥ 1.0 mm (OR: 1.008, 95% CI: 1.001-1.014, P=0.020) and carotid artery plaques (OR: 1.010, 95% CI: 1.004-1.016, P=0.001) but no correlation with baPWV ≥ 1400 (OR: 0.999, 95% CI: 0.993-1.005, P=0.788) or baPWV ≥ 1800 (OR: 1.002, 95% CI: 0.993-1.011, P=0.634)., Conclusions: The detection rate of Lp(a) at health checkups is low, and Lp(a) is positively associated with cervical vascular sclerosis and plaque but not with baPWV. Therefore, the testing rate of Lp(a) and the awareness of the risk of vascular structural changes due to Lp(a) should be further improved.

The deep marine sediments represent a major repository of organic matter whilst hosting a great number of uncultivated microbes. Microbial metabolism plays a key role in the recycling of organic matter in the deep marine sediments. D-amino acids (DAAs) and DAA-containing muropeptides, an important group of organic matter in the deep marine sediments, are primarily derived from bacterial peptidoglycan decomposition. Archaea are abundant in the deep ocean microbiome, yet their role in DAA metabolism remains poorly studied. Here, we report bioinformatic investigation and enzymatic characterization of deep marine sedimentary archaea involved in DAA metabolism. Our analyses suggest that a variety of archaea, particularly the Candidatus Bathyarchaeota and the Candidatus Lokiarchaeaota, can metabolize DAAs. DAAs are converted into L-amino acids via amino acid racemases (Ala racemase, Asp racemase and broad substrate specificity amino acid racemase), and converted into α-keto acid via d-serine ammonia-lyase, whereas DAA-containing di-/tri-muropeptides can be hydrolyzed by peptidases (dipeptidase and D-aminopeptidase). Overall, this study reveals the identity and activity of deep marine sedimentary archaea involved in DAA metabolism, shedding light on the mineralization and biogeochemical cycling of DAAs in the deep marine sediments., 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.)

The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H 2 O 2 -treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Cadmium (Cd) is a common environmental metal. Previous studies indicated that long-term respiratory Cd exposure caused lung injury and airway inflammation. The purpose of this study was to evaluate whether short-term respiratory Cd exposure induces pulmonary ferroptosis and NLRP3 inflammasome activation. Adult C57BL/6J mice were exposed to Cd by inhaling CdCl 2 aerosol (0, 10, or 100 ppm) for 5 days. Serum and lung Fe 2+ contents were elevated in Cd-exposed mice. Oxidized AA metabolites, the major oxidized lipids during ferroptosis, were upregulated in Cd-exposed mouse lungs. Pulmonary MDA content and 4-HNE-positive cells were increased in Cd-exposed mice. ACSL4 and COX-2, two lipoxygenases, were upregulated in Cd-exposed mouse lungs. Further analyses found that phosphorylated NF-kB p65 was elevated in Cd-exposed mouse lungs. Innate immune receptor protein NLRP3 and adapter protein ASC were upregulated in Cd-exposed mouse lungs. Caspase-1 was activated and IL-1β and IL-18 were upregulated in Cd-exposed mouse lungs. Fer-1, a specific inhibitor of ferroptosis, attenuated Cd-induced elevation of pulmonary NLRP3 and ASC, caspase-1 activation, and IL-1β and IL-18 upregulation. Finally, mitoquinone (MitoQ), a mitochondria-target antioxidant, suppressed Cd-caused ferroptosis and NLRP3 inflammasome activation. Our results demonstrate that ferroptosis might partially mediate Cd-evoked activation of NLRP3 inflammasome in the lungs., 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 Inc. All rights reserved.)

The reaction center-light-harvesting complex 1 (RC-LH1) plays an essential role in the primary reactions of bacterial photosynthesis. Here, we present high-resolution structures of native monomeric and dimeric RC-LH1 supercomplexes from Rhodobacter ( Rba. ) blasticus using cryo-electron microscopy. The RC-LH1 monomer is composed of an RC encircled by an open LH1 ring comprising 15 αβ heterodimers and a PufX transmembrane polypeptide. In the RC-LH1 dimer, two crossing PufX polypeptides mediate dimerization. Unlike Rhodabacter sphaeroides counterpart, Rba. blasticus RC-LH1 dimer has a less bent conformation, lacks the PufY subunit near the LH1 opening, and includes two extra LH1 αβ subunits, forming a more enclosed S-shaped LH1 ring. Spectroscopic assays reveal that these unique structural features are accompanied by changes in the kinetics of quinone/quinol trafficking between RC-LH1 and cytochrome bc 1 . Our findings reveal the assembly principles and structural variability of photosynthetic RC-LH1 supercomplexes, highlighting diverse strategies used by phototrophic bacteria to optimize light-harvesting and electron transfer in competitive environments.

Transformation between oxidation states is widespread in transition metal coordination chemistry and biochemistry, typically occurring in solution. However, air-induced oxidation in porous crystalline solids with retention of crystallinity is rare due to the dearth of materials with high structural stability that are inherently redox active. Herein, we report a new family of such materials, four isostructural cobalt-pyrazolate frameworks of face-centered cubic, fcu , topology, fcu-L-Co , that are sustained by Co 8 molecular building blocks (MBBs) and dipyrazolate ligands, L . fcu-L-Co were observed to spontaneously transform from Co(II) 8 to Co(III) 8 MBBs in air with retention of crystallinity, marking the first such instance in metal-organic frameworks (MOFs). This transformation can also be achieved through water vapor sorption cycling, heating, or chemical oxidation. The reverse reactions were conducted by exposure of fcu-L-Co(III) to aqueous hydrazine. fcu-L-Co(II) exhibited high gravimetric water vapor uptakes of 0.55-0.68 g g -1 at 30% relative humidity (RH), while in fcu-L-Co(III) the inflection point shifted to lower RH and framework stability improved. Insight into the transformation between fcu-L-Co(II) and fcu-L-Co(III) was gained from single crystal X-ray diffraction and in situ spectroscopy. Overall, the crystal engineering approach we adopted has afforded a new family of MOFs that exhibit cobalt redox chemistry in a confined space coupled with high porosity.

ATP-binding cassette (ABC) transporters hydrolyse ATP to transport various substrates. Previous studies have shown that ABC transporters are responsible for transporting plant hormones and heavy metals, thus contributing to plant immunity. Herein, we identified a wheat G-type ABC transporter, TaABCG2-5B, that responds to salicylic acid (SA) treatment and is induced by Fusarium graminearum, the primary pathogen causing Fusarium head blight (FHB). The loss-of-function mutation of TaABCG2-5B (ΔTaabcg2-5B) reduced SA accumulation and increased susceptibility to F. graminearum. Conversely, overexpression of TaABCG2-5B (OE-TaABCG2-5B) exerted the opposite effect. Quantification of intracellular SA in ΔTaabcg2-5B and OE-TaABCG2-5B protoplasts revealed that TaABCG2-5B acts as an importer, facilitating the transport of SA into the cytoplasm. This role was further confirmed by Cd 2+ absorption experiments in wheat roots, indicating that TaABCG2-5B also participates in Cd 2+ transport. Thus, TaABCG2-5B acts as an importer and is crucial for transporting multiple substrates. Notably, the homologous gene TaABCG2-5A also facilitated Cd 2+ uptake in wheat roots but did not significantly influence SA accumulation or FHB resistance. Therefore, TaABCG2 could be a valuable target for enhancing wheat tolerance to Cd 2+ and improving FHB resistance., (© 2024 The Author(s). Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Genomic sequences are traditionally represented as strings of characters: A (adenine), C (cytosine), G (guanine), and T (thymine). However, an alternative approach involves depicting sequence-related information through image representations, such as Chaos Game Representation (CGR) and read pileup images. With rapid advancements in deep learning (DL) methods within computer vision and natural language processing, there is growing interest in applying image-based DL methods to genomic sequence analysis. These methods involve encoding genomic information as images or integrating spatial information from images into the analytical process. In this review, we summarize three typical applications that use image processing with DL models for genome analysis. We examine the utilization and advantages of these image-based approaches., (© 2024. The Author(s).)