"Fluorescence-wavelength" label-free POCT tandem with "fluorescence-photothermal" nanobody-immunosensor for detecting BSA and ß-lactoglobulin.

Two carbon dots (CDs) (λEm = 525 nm, G-CDs and λEm = 640 nm, R-CDs) were synthesized from citric acid and urea. The bovine serum albumin (BSA) responsiveness of the R-CDs was used to develop a "fluorescence-wavelength" label-free point of care testing (POCT) for the detection of the milk quality marker BSA with the detection limit (LOD) of 4.89 µg/mL for fluorescence mode and 3.38 µg/mL for wavelength mode. In addition, R-CDs were found to have hydroxyl radical (·OH)-dependent fluorescence quenching properties, and a "fluorescence-photothermal" immunosensor based on nanobodies was constructed by introducing the fluorescence signal of R-CDs@BSA and the photothermal signal of oxTMB for the detection of ß-lactoglobulin (ß-LG) with the LOD of 0.034 ng/mL for fluorescence mode and 0.075 ng/mL for photothermal mode. The tandem detection of POCT and immunosensor enables the simultaneous and highly sensitive detection of BSA and ß-LG after only simple dilution of less than 5 µL of sample.

An in-situ blocking strategy for improved anti-interference inspection of AFB1 based on hollow covalent organic framework capsules with commodious and undisturbed microenvironment.

This work proposed an in-situ blocking strategy for improved anti-interference and signal-amplified inspection of hazards via constructing hollow covalent organic framework (HCOF) capsules. An aptamer-FRET nanoprobe integrated with carbon dots and CuS was introduced into the micro-capsule as signal indicator to demonstrate the proof-of-concept. The HCOF was successfully prepared by removing the metal-organic frameworks (MOF) core from the MOF@COF that had been preloaded with the nanoprobes under mild conditions. Meanwhile, the hydrophobic surface of HCOF enhanced the adsorption and penetration of aflatoxin B1 (AFB1) into the capsule to interact with the nanoprobes. This strategy was applied to detect AFB1 in food samples, achieving a linear response of 1-300 nM along with a detection limit of 0.3 nM. Selectivity test verified that the prepared sensing platform could specifically recognize AFB1 without complex sample pretreatment. This study provides new ideas for improved anti-interference inspection of hazards against complex sample matrix.

Comprehensive insight on protein modification by V-type agent: A chemical proteomic approach employing bioorthogonal reaction.

Organophosphorus compounds (OPs) such as chemical agents and pesticides are posing critical threats to civilians due to their irreversible phosphonylation of diverse amino acids residues forming different protein adducts. However, traditional analytical approaches are quite limited in capturing the myriad of post-translational events that affect protein functions, especially in identifying the low-abundance OP adducts. Herein a systematic proteomic strategy based on a typical click-enrich-release-identify bioorthogonal operation was firstly developed by employing an alkynyl-tagged V-type agent probe (AVP) and a biotin-based azido-enrichment linker (BTP-N3 ). AVP targeting peptides from human serum albumin (HSA) or plasma were captured by BTP-N3 via CuAAC click reaction, enriched by streptavidin beads, released by selective alkaline hydrolysis of phenacyl ester bond, and subsequently sequenced by LC-MS/MS. This strategy has helped identifying 1115 unique OP adduction sites on 163 proteins in human plasma, and covers lots of OP adducts that cannot be achieved by traditional detection methods. The comprehensive coverage of novel OP substrates provided a general and sensitive approach to retrospective verification and/or dose assessment of toxic OPs.

Cobalt nanoparticles-catalyzed aerobic oxygenation and esterification of alkynes via C≡C bonds cleavage.

An unprecedented efficient protocol is developed for the oxidative cleavage of C≡C bonds in alkynes to produce structure-diverse esters using heterogeneous cobalt nanoparticles as catalyst with molecular oxygen as the oxidant. A diverse set of mono- and multisubstituted aromatic and aliphatic alkynes can be effectively cleaved and converted into the corresponding esters. Characterization analysis and control experiments indicate high surface area and pore volume, as well as nanostructured nitrogen-doped graphene-layer coated cobalt nanoparticles are possibly responsible for excellent catalytic activity. Mechanistic studies reveal that ketones derived from alkynes under oxidative conditions are formed as intermediates, which subsequently are converted to esters through a tandem sequential process. The catalyst can be recycled up to five times without significant loss of activity.

Synthetic exploration of electrophilic xanthylation via powerful N-xanthylphthalimides.

Organic xanthates are broadly applied as synthetic intermediates and bioactive molecules in synthetic chemistry. Electrophilic xanthylation represents a promising approach but has rarely been explored mainly due to the lack of powerful electrophilic reagents. Herein, synthetic exploration of electrophilic xanthylation via powerful N-xanthylphthalimides was investigated. This strategy might provide a new avenue to less-concerned but meaningful electrophilic xanthylation in organic synthesis. With the help of these powerful reagents, electrophilic xanthylation of a wide range of substrates including aryl/alkenyl boronic acids, ß-keto esters, 2-oxindole, and alkyl amines, as well as previously inaccessible phenols (first report) was achieved under mild reaction conditions. Notably, this simple electrophilic xanthylation of alkyl amine substrates will occur in the desulfuration reaction, consistent with the previously reported methods. Similarly, xanthamide and thioxanthate groups could also be transformed into desired nucleophiles via this electrophilic reagent strategy. The broad substrate scope, excellent functional group compatibility and late-stage functionalization of bioactive or functional molecules made them very attractive as general reagents which will allow rapid incorporation of SC(S)R (R = OEt, Oalkyl, NEt2 and SEt) into the target molecules.

High-quality reference genome assemblies for two Australimusa bananas provide insights into genetic diversity of the Musaceae family and regulatory mechanisms of superior fiber properties.

Bananas (Musa spp.) are the monocotyledonous plants with high genetic diversity from the Musaceae family, which are mostly cultivated in tropical and subtropical countries. The fruits are popular consumed and the plants have diverse uses in people's livelihood. Four genetic groups (genomes) have been predicted to contribute to the current banana cultivars, viz., Musa acuminata (A-genome), Musa balbisiana (B-genome), Musa schizocarpa (S-genome) and species of the Australimusa section (T-genome). However, the T-genome has not been effectively explored. Here we presented the high-quality TT genomes of two representative accessions, 'Abaca' (Musa textilis) with high quality natural fiber, and 'Utafun' (Musa troglodytarum, Fe'i group) with abundant ß-carotene, both of which possess ten pseudochromosomes with a total size of 613 Mb and 619 Mb, respectively. Comparative genome analysis revealed that the larger size of T-genome is likely attributable to rapid expansion and slow removal of transposon. Compared with Musa AA or BB accessions, or sisal (Agava sisalana), Abaca's fibers exhibited superior mechanical properties, mainly due to its thicker cell wall with higher compositions of cellulose, lignin and hemicellulose. The expression of cellulose-synthesis gene MusaCesAs peaked earlier in Abaca than in AA or BB accessions during plant development, possibly causing an earlier accumulation of cellulose in secondary cell wall (SCW) formation. The Abaca-specific expressed gene MusaMYB26, which is directly regulated by MusaMYB61, may be an important regulator to promote precocious expression of SCW MusaCesAs. Furthermore, MusaWRKY2 and MusaNAC68 which could be involved in regulating expression of MusaLAC and MusaCAD, may at least partially elucidate the high accumulation of lignin in Abaca. This work contributes to better understanding of banana domestication and diverse genetic resources in Musaceae family and provide resources for Musa genetic improvement.

Treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs.

Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication is available to provide potential clinical benefits. However, drug resistance is a big obstacle to obtain desired clinical prognosis. In this review, we provide a summary of treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs, including pancreatic cancer, gastric adenocarcinoma, colorectal adenocarcinoma, lung adenocarcinoma, and prostate cancer. Although the underlying molecular mechanisms involved in drug resistance of adenocarcinoma vary from one organ to the other, there are several targets that are universal for drug resistance in adenocarcinoma, and targeting these molecules could potentially reverse drug resistance in the treatment of adenocarcinomas.

Orthogroup and phylotranscriptomic analyses identify transcription factors involved in plant cold response: a case study of Arabidopsis BBX29.

C-repeat binding factors (CBFs) are well-known transcription factors (TFs) in regulating plant cold acclimation. Increasing RNA-seq data from different species provides opportunities to determine other TFs involved in cold response; however, the task is challenging since gene gain/loss led to an intertwined community of co-orthologs and in-paralogs between and within species. Here, using orthogroup (closely-related homologs) analysis, we identified 10,549 orthogroups in five representative eudicots. Based on phylotranscriptomic analysis of cold-treated seedlings of the eudicots, we further determined 35 high-confidence Conserved Cold-responsive transcription Factor orthogroups (CoCoFos), including many well-known cold-responsive regulators (CBFs, HSFC1, ZAT6/10, CZF1, etc.). Moreover, we selected Arabidopsis BBX29 for experimental validation. Expression and genetic analyses showed that cold-induction of BBX29 is CBFs- and ABA-independent and BBX29 plays a negative role in cold tolerance. Integrative RNA-seq and CUT&Tag-seq analyses revealed that BBX29 represses a set of cold-induced TFs (ZAT12, PRR9, RVE1, MYB96, etc.). Altogether, our analysis yields a library of eudicot CoCoFos and demonstrates a negative regulator of Arabidopsis BBX29 in cold tolerance.

Regulation of gut microbiota and alleviation of DSS-induced colitis by vitexin.

PURPOSE: Vitexin is one of the flavonoids in millet and has a variety of biological activities. However, the function of vitexin on colitis is not clear. This research studied the regulation of vitexin on colitis and investigated the possible mechanisms. METHODS: An in vitro fermentation model was used to evaluate the regulation of vitexin on gut microbiota of patients with inflammatory bowel disease (IBD). At the same time, an acute colitis mice model induced by dextran sodium sulfate (DSS) was used to evaluate the effects of vitexin on intestinal inflammation, barrier and gut microbiota. RESULTS: In this study, it was found that vitexin altered the structure of gut microbiota by decreasing harmful bacteria, such as Veillonella, Terrisporobacter, Klebsiella, Paeniclostridium, and increasing beneficial bacteria, such as Parabacteroides, Flavonifractor, Blautia after in vitro fermentation with the feces of colitis patients. Further, DSS-induced colitis mice models revealed that vitexin treatment significantly improved colitis symptoms, maintained intestinal barrier and down-regulated the expression of inflammatory factors, such as IL-1ß and TNF-α. In addition, vitexin also improved the diversity of gut microbiota of colitis mice by decreasing the abundance of harmful bacteria. CONCLUSION: This research suggested that vitexin could alleviate colitis by regulating gut microbiota and attenuated gut inflammation.

Bioinformatics led discovery of biomarkers related to immune infiltration in diabetes nephropathy.

BACKGROUND: The leading cause of end-stage renal disease is diabetic nephropathy (DN). A key factor in DN is immune cell infiltration (ICI). It has been shown that immune-related genes play a significant role in inflammation and immune cell recruitment. However, neither the underlying mechanisms nor immune-related biomarkers have been identified in DNs. Using bioinformatics, this study investigated biomarkers associated with immunity in DN. METHODS: Using bioinformatic methods, this study aimed to identify biomarkers and immune infiltration associated with DN. Gene expression profiles (GSE30528, GSE47183, and GSE104948) were selected from the Gene Expression Omnibus database. First, we identified 23 differentially expressed immune-related genes and 7 signature genes, LYZ, CCL5, ALB, IGF1, CXCL2, NR4A2, and RBP4. Subsequently, protein-protein interaction networks were created, and functional enrichment analysis and genome enrichment analysis were performed using the gene ontology and Kyoto Encyclopedia of Genes and Genome databases. In the R software, the ConsensusClusterPlus package identified 2 different immune modes (cluster A and cluster B) following the consistent clustering method. The infiltration of immune cells between the 2 clusters was analyzed by applying the CIBERSORT method. And preliminarily verified the characteristic genes through in vitro experiments. RESULTS: In this study, the samples of diabetes nephropathy were classified based on immune related genes, and the Hub genes LYZ, CCL5, ALB, IGF1, CXCL2, NR4A2 and RBP4 related to immune infiltration of diabetes nephropathy were obtained through the analysis of gene expression differences between different subtypes. CONCLUSIONS: This study was based on bioinformatics technology to analyze the biomarkers of immune related genes in diabetes nephropathy. To analyze the pathogenesis of diabetes nephropathy at the RNA level, and ultimately provide guidance for disease diagnosis, treatment, and prognosis.

Comprehensive Social Trait Judgments From Faces in Autism Spectrum Disorder.

Processing social information from faces is difficult for individuals with autism spectrum disorder (ASD). However, it remains unclear whether individuals with ASD make high-level social trait judgments from faces in the same way as neurotypical individuals. Here, we comprehensively addressed this question using naturalistic face images and representatively sampled traits. Despite similar underlying dimensional structures across traits, online adult participants with self-reported ASD showed different judgments and reduced specificity within each trait compared with neurotypical individuals. Deep neural networks revealed that these group differences were driven by specific types of faces and differential utilization of features within a face. Our results were replicated in well-characterized in-lab participants and partially generalized to more controlled face images (a preregistered study). By investigating social trait judgments in a broader population, including individuals with neurodevelopmental variations, we found important theoretical implications for the fundamental dimensions, variations, and potential behavioral consequences of social cognition.

A deep generative framework with embedded vector arithmetic and classifier for sample generation, label transfer, and clustering of single-cell data.

Multiple-source single-cell datasets have accumulated quickly and need computational methods to integrate and decompose into meaningful components. Here, we present inClust (integrated clustering), a flexible deep generative framework that enables embedding auxiliary information, latent space vector arithmetic, and clustering. All functional parts are relatively modular, independent in implementation but interrelated at runtime, resulting in an all-in general framework that could work in supervised, semi-supervised, or unsupervised mode. We show that inClust is superior to most data integration methods in benchmark datasets. Then, we demonstrate the capability of inClust in the tasks of conditional out-of-distribution generation in supervised mode, label transfer in semi-supervised mode, and spatial domain identification in unsupervised mode. In these examples, inClust could accurately express the effect of each covariate, distinguish the query-specific cell types, or segment spatial domains. The results support that inClust is an excellent general framework for multiple-task harmonization and data decomposition.

Magnetic-fluorescent immunosensing platform applying AuNPs heterogeneous MIL-53(Al) composite for efficient detection of zearalenone.

Rapid, sensitive, specific and stable detection of mycotoxin in food remains an extremely crucial issue. Herein, a magnetic-fluorescent immunosensing platform for the detection of zearalenone (ZEN) was proposed. The platform utilized Au nanoparticles (AuNPs) heterogeneous fluorescent metal-organic framework (MIL-53(Al)@AuNPs) labeled with ZEN-bovine serum albumin (ZEN-BSA) as signal probe and ZEN mono-antibodies coupled with magnetic NPs (MNPs-mAbs) as capture probe. Specifically, the heterogenization of AuNPs on the MIL-53(Al) surface improved its biocompatibility, and facilitated the loading of ZEN-BSA conjugates. The MNPs-mAbs could rapidly capture the target ZEN, simplify the immunoassay process and further improve the detection efficiency. The established competitive magnetic-fluorescent immunosensing platform had a wider linear response to ZEN in the range of 0.001-100 ng/mL with a lower limit of detection (LOD) at 0.0035 ng/mL, and could finish the whole detection process within 20 min, showing great potential for rapid and sensitive detection of food contaminants.

Biomass Separators as a"Lifesaver"for Safe and Long-Life Lithium Metal Batteries.

The growth of lithium dendrites and the shuttle of polysulfides in lithium metal batteries (LMBs) have hindered their development. In LMBs, the cathode and anode are separated by a separator, although this does not solve the battery's issues. The use of biomass materials is widespread for modifying the separator due to their porous structure and abundant functional groups. LMBs perform more electrochemically when lithium ions are deposited uniformly and polysulfide shuttling is reduced using biomass separators. In this review, we analyze the growth of lithium dendrite and the shuttle of polysulfide in LMBs, summarize the types of biomass separator materials and the mechanisms of action (providing mechanical barriers, promoting uniform deposition of metal ions, capturing polysulfides, shielding polysulfide). The prospect of developing new separator materials from the perspective of regulating ion transport and physical sieving efficiency as well as the application of advanced technologies such as synchrotron radiation to characterize the mechanism of action of biomass separators is also proposed.

A deep-learning system to help make the surgical planning of coil embolization for unruptured intracranial aneurysms.

BACKGROUND: Coil embolization is a common method for treating unruptured intracranial aneurysms (UIAs). To effectively perform coil embolization for UIAs, clinicians must undergo extensive training with the assistance of senior physicians over an extended period. This study aimed to establish a deep-learning system for measuring the morphological features of UIAs and help the surgical planning of coil embolization for UIAs. METHODS: Preoperative computational tomography angiography (CTA) data and surgical data from UIA patients receiving coil embolization in our medical institution were retrospectively reviewed. A convolutional neural network (CNN) model was trained on the preoperative CTA data, and the morphological features of UIAs were measured automatically using this CNN model. The intraclass correlation coefficient (ICC) was utilized to examine the similarity between the morphologies measured by the CNN model and those determined by experienced clinicians. A deep neural network model to determine the diameter of first coil was further established based on the CNN model within the derivation set (75% of all patients) using neural factorization machines (NFM) model and was validated using a validation set (25% of all patients). The general match ratio (the difference was within ± 1 mm) between the predicted diameter of first coil by model and that used in practical scenario was calculated. RESULTS: One-hundred fifty-three UIA patients were enrolled in this study. The CNN model could diagnose UIAs with an accuracy of 0.97. The performance of this CNN model in measuring the morphological features of UIAs (i.e., size, height, neck diameter, dome diameter, and volume) was comparable to the accuracy of senior clinicians (all ICC > 0.85). The diameter of first coil predicted by the model established based on CNN model and the diameter of first coil used actually exhibited a high general match ratio (0.90) within the derivation set. Moreover, the model performed well in recommending the diameter of first coil within the validation set (general match ratio as 0.91). CONCLUSION: This study presents a deep-learning system which can help to improve surgical planning of coil embolization for UIAs.

Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy.

Immunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response and boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable of triggering both pyroptosis and ferroptosis remains limited. Here we show the construction of a covalent organic framework (COF-919) from planar and twisted AIEgen-based motifs as a dual-inducer of pyroptosis and ferroptosis for efficient antitumor immunity. Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, and longer lifetime to favor the generation of reactive oxygen species (ROS) and photothermal conversion, triggering pyroptosis. Because of its good ROS production capability, it upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. Additionally, the induction of pyroptosis and ferroptosis by COF-919 effectively inhibits tumor metastasis and recurrence, resulting in over 90% tumor growth inhibition and cure rates exceeding 80%.

Monocarboxylate transporter 4 promotes the migration of non­cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis.

The tumor microenvironment (TME) and Warburg effect are critical for the regulation of tumor metastasis. The monocarboxylate transporter (MCT) family members, particularly MCT4, which is encoded by the solute carrier family 16 member 3 gene, play an important role in the regulation of the TME and mediation of the Warburg effect by transporting lactate out of cancer cells. Migration and invasion are two key features of metastasis. Few studies have investigated the mechanism by which MCT4 promotes cell migration, and the suggested mechanisms by which MCT4 promotes migration vary in different tumor cell models. The purpose of the present study was to use non-cancerous cells as a research model to investigate the specific mechanism underlying the promotion of migration by MCT4. In a previous study, murine L929 cells overexpressing human MCT4 (MCT4-L929 cells) were generated and MCT4 was demonstrated to promote the migration and invasion of these non-cancerous cells. In the present study, MCT4-L929 cells and control-L929 cells were used to investigate the potential pathways and mechanisms through which MCT4 promotes cell migration. RNA sequencing analysis revealed 872 differentially expressed genes, comprising 337 and 535 upregulated and downregulated genes, respectively, in the MCT4-L929 cells. Reverse transcription-quantitative analysis and western blotting revealed that MCT4 overexpression increased the transcription and protein levels of insulin-like growth factor 1 (IGF1). In a wound healing assay, the migration of exogenous mouse IGF1-treated control-L929 cells was similar to that of MCT4-L929 cells. Additionally, the inhibition of IGF1 receptor (IGF1R) or serum/glucocorticoid regulated kinase 1 (SGK1), a downstream protein in the IGF1 and phosphoinositide 3-kinase PI3K regulatory subunit 3 (PIK3R3) pathways, in MCT4-L929 cells mitigated the cell migration-promoting effect of MCT4. These novel findings suggest that MCT4 may promote the migration of L929 fibroblast cells via activation of the IGF1/IGF1R/PIK3R3/SGK1 axis.

Relationship between daytime napping with the occurrence and development of diabetes: a systematic review and meta-analysis.

OBJECTIVE: To determine the relationship of napping with incident diabetes risk and glycaemic control in people with diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE (PubMed), EMBASE, Web of Science and the Cochrane Library were searched for studies published from database inception to 9 May 2023. ELIGIBILITY CRITERIA: Observational studies reporting the relationship of napping with diabetes or glycaemic control in patients with diabetes in adult populations were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the literature, extracted data and assessed the quality of the included studies. The results were reported as ORs and 95% CIs, which were pooled by using fixed and random effects models, and subgroup analyses were performed. The Grading of Recommendations Assessment, Development and Evaluation method was used to assess the quality of the evidence. RESULTS: Forty studies were included in our review. Habitual napping was associated with an increased diabetes risk (OR 1.20, 95% CI 1.14 to 1.27) and poor glycaemic control in patients with diabetes (OR 2.05, 95% CI 1.55 to 2.73). Nap durations less than 30 min were unrelated to diabetes (OR 1.05, 95% CI 0.97 to 1.14). Nap durations of 30-60 min were associated with diabetes risk (OR 1.09, 95% CI 1.02 to 1.17), but there were differences in the subgroup analysis results. Nap durations of more than 60 min significantly increased the risk of diabetes (OR 1.31, 95% CI 1.20 to 1.44). CONCLUSIONS: Napping is associated with increased diabetes risk and poor glycaemic control, and future research will need to confirm whether there are sex and regional differences. Nap durations of more than 60 min significantly increases the risk of diabetes, and the relationship between nap duration and glycaemic control in patients with diabetes needs to be further explored in the future. PROSPERO REGISTRATION NUMBER: CRD42021292103.

Is constructed wetlands carbon source or carbon sink? Case analysis based on life cycle carbon emission accounting.

Constructed wetlands (CWs) are widely used to polish the effluent of wastewater treatment plants and micro-polluted river or lake water. However, the impact of large-scale applications of CWs on carbon emissions is unclear. In this study, the carbon footprints of two full-scale hybrid CWs were determined based on life cycle assessment (LCA). Results showed that the carbon emission of CW ranged from 0.10 to 0.14 kg CO2-eq/m3, and was significantly correlated with the influent chemical oxygen demand loads and electricity consumption. However, CW would approach carbon neutrality during the service period when taking plant carbon sequestration into consideration. Compared with other advanced wastewater treatment technologies, CWs showed significant low-carbon emission and cost-effective benefits. This study clarified the role of CWs in the carbon cycle and would provide guidance for the construction and management of CWs.