Rh-Catalyzed α-Arylation of Cyclic 1,3-Dicarbonyls with Benzocyclobutenols Enabled by a Cyclic Iodonium Ylide Strategy.

To date, the general and catalytic α-arylation of cyclic 1,3-dicarbonyls remains elusive. We now report the first Rh-catalyzed α-arylation of cyclic 1,3-dicarbonyls with benzocyclobutenols through a cyclic iodonium ylide strategy. Our strategy represents a good solution for the previously challenging α-arylation of cyclic 1,3-dicarbonyls with sterically demanding aryl partners, which is especially appropriate for structurally unique heteroaromatic 1,3-dicarbonyls. Our approach features mild conditions, readily available starting materials, high yields, excellent functional group-tolerance, and simple operation, providing expedient access toward medically important 2-aryl (hetero)cyclic 1,3-dicarbonyls. The practicality of this approach is demonstrated by the gram-scale synthesis, one-pot synthesis, and numerous downstream transformations.

Analysis of Bladder Cancer Staging Prediction Using Deep Residual Neural Network, Radiomics, and RNA-Seq from High-Definition CT Images.

Bladder cancer has recently seen an alarming increase in global diagnoses, ascending as a predominant cause of cancer-related mortalities. Given this pressing scenario, there is a burgeoning need to identify effective biomarkers for both the diagnosis and therapeutic guidance of bladder cancer. This study focuses on evaluating the potential of high-definition computed tomography (CT) imagery coupled with RNA-sequencing analysis to accurately predict bladder tumor stages, utilizing deep residual networks. Data for this study, including CT images and RNA-Seq datasets for 82 high-grade bladder cancer patients, were sourced from the TCIA and TCGA databases. We employed Cox and lasso regression analyses to determine radiomics and gene signatures, leading to the identification of a three-factor radiomics signature and a four-gene signature in our bladder cancer cohort. ROC curve analyses underscored the strong predictive capacities of both these signatures. Furthermore, we formulated a nomogram integrating clinical features, radiomics, and gene signatures. This nomogram's AUC scores stood at 0.870, 0.873, and 0.971 for 1-year, 3-year, and 5-year predictions, respectively. Our model, leveraging radiomics and gene signatures, presents significant promise for enhancing diagnostic precision in bladder cancer prognosis, advocating for its clinical adoption.

Advancements in Solid-State Hydrogen Storage: A Review on the Glass Microspheres.

Glass microspheres, with their unique internal structure and chemical stability, offer a promising solution for the challenges of hydrogen storage and transmission, potentially advancing the utility of hydrogen as a safe and efficient energy source. In this review, we systematically evaluate various treatment and modification strategies, including fusion, sol-gel, and chemical vapor deposition (CVD), and compare the performance of different types of glass microspheres. Our synthesis of current research findings reveals that specific low-cost and environmentally friendly modification techniques can significantly enhance the hydrogen storage efficiency of glass microspheres, with some methods increasing storage capacity by up to 32% under certain conditions. Through a detailed life-cycle and cost-benefit assessment, our study highlights the economic and sustainability advantages of using modified glass microspheres. For example, selected alternative materials used in lightweight vehicles have been shown to reduce density by approximately 10% while reducing costs. This review not only underscores the contributions of modified glass microspheres to overcoming the limitations of current hydrogen storage technologies but also provides a systematic framework for improving their performance in hydrogen storage applications. Our research suggests that modified glass microspheres could help to make hydrogen energy more commercially viable and environmentally friendly.

High-quality faba bean reference transcripts generated using PacBio and Illumina RNA-seq data.

The genome of faba bean was first published in 2023. To promote future molecular breeding studies, we improved the quality of the faba genome based on high-density genetic maps and the Illumina and Pacbio RNA-seq datasets. Two high-density genetic maps were used to conduct the scaffold ordering and orientation of faba bean, culminating in an increased length (i.e., 14.28 Mbp) of chromosomes and a decrease in the number of scaffolds by 45. In gene model mining and optimisation, the PacBio and Illumina RNA-seq datasets from 37 samples allowed for the identification and correction 121,606 transcripts, and the data facilitated a prediction of 15,640 alternative splicing events, 2,148 lncRNAs, and 1,752 fusion transcripts, thus allowing for a clearer understanding of the gene structures underlying the faba genome. Moreover, a total of 38,850 new genes including 56,188 transcripts were identified compared with the reference genome. Finally, the genetic data of the reference genome was integrated and a comprehensive and complete faba bean transcriptome sequence of 103,267 transcripts derived from 54,753 uni-genes was formed.

Ru(II)-Catalyzed Carboamination of Olefins with α-Carbonyl Sulfoxonium Ylides.

The first ruthenium-catalyzed carboamination of olefins with α-carbonyl sulfoxonium ylides is reported. The utilization of an inexpensive ruthenium catalyst enables the concise synthesis of pharmaceutically important isoindolin-1-ones, which possess both a stereogenic center and ß-carbonyl side chain. This method is mild, efficient, and scalable and allows for the coupling of a wide range of aryl-, heteroaryl-, alkenyl-, and alkyl-substituted sulfoxonium ylides. Moreover, the carbonyl side chain in the resulting product provides a good handle for downstream transformations. For mechanistic studies, a ruthacyle complex is obtained and proven to be the key intermediate in both catalytic and stoichiometric reactions.

Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery: A systematic review and meta-analysis.

BACKGROUND: Colorectal cancer is a major global health challenge that predominantly affects older people. Surgical management, despite advancements, requires careful consideration of preoperative patient status for optimal outcomes. AIM: To summarize existing evidence on the association of frailty with short-term postoperative outcomes in patients undergoing colorectal cancer surgery. METHODS: A literature search was conducted using PubMed, EMBASE and Scopus databases for observational studies in adult patients aged ≥ 18 years undergoing planned or elective colorectal surgery for primary carcinoma and/or secondary metastasis. Only studies that conducted frailty assessment using recognized frailty assessment tools and had a comparator group, comprising nonfrail patients, were included. Pooled effect sizes were reported as weighted mean difference or relative risk (RR) with 95% confidence intervals (CIs). RESULTS: A total of 24 studies were included. Compared with nonfrail patients, frailty was associated with an increased risk of mortality at 30 d (RR: 1.99, 95%CI: 1.47-2.69), at 90 d (RR: 4.76, 95%CI: 1.56-14.6) and at 1 year (RR: 5.73, 95%CI: 2.74-12.0) of follow up. Frail patients had an increased risk of any complications (RR: 1.81, 95%CI: 1.57-2.10) as well as major complications (Clavien-Dindo classification grade ≥ III) (RR: 2.87, 95%CI: 1.65-4.99) compared with the control group. The risk of reoperation (RR: 1.18, 95%CI: 1.07-1.31), readmission (RR: 1.70, 95%CI: 1.36-2.12), need for blood transfusion (RR: 1.67, 95%CI: 1.52-1.85), wound complications (RR: 1.49, 95%CI: 1.11-1.99), delirium (RR: 4.60, 95%CI: 2.31-9.16), risk of prolonged hospitalization (RR: 2.09, 95%CI: 1.22-3.60) and discharge to a skilled nursing facility or rehabilitation center (RR: 3.19, 95%CI: 2.0-5.08) was all higher in frail patients. CONCLUSION: Frailty in colorectal cancer surgery patients was associated with more complications, longer hospital stays, higher reoperation risk, and increased mortality. Integrating frailty assessment appears crucial for tailored surgical management.

Transcriptome Analysis Reveals Key Genes Involved in Trichome Formation in Pepper (Capsicum annuum L.).

Trichomes are specialized organs located in the plant epidermis that play important defense roles against biotic and abiotic stresses. However, the mechanisms regulating the development of pepper epidermal trichomes and the related regulatory genes at the molecular level are not clear. Therefore, we performed transcriptome analyses of A114 (less trichome) and A115 (more trichome) to dig deeper into the genes involved in the regulatory mechanisms of epidermal trichome development in peppers. In this study, the epidermal trichome density of A115 was found to be higher by phenotypic observation and was highest in the leaves at the flowering stage. A total of 39,261 genes were quantified by RNA-Seq, including 11,939 genes not annotated in the previous genome analysis and 18,833 differentially expressed genes. Based on KEGG functional enrichment, it was found that DEGs were mainly concentrated in three pathways: plant-pathogen interaction, MAPK signaling pathway-plant, and plant hormone signal transduction. We further screened the DEGs associated with the development of epidermal trichomes in peppers, and the expression of the plant signaling genes GID1B-like (Capana03g003488) and PR-6 (Capana09g001847), the transcription factors MYB108 (Capana05g002225) and ABR1-like (Capana04g001261), and the plant resistance genes PGIP-like (Capana09g002077) and At5g49770 (Capana08g001721) in the DEGs were higher at A115 compared to A114, and were highly expressed in leaves at the flowering stage. In addition, based on the WGCNA results and the establishment of co-expression networks showed that the above genes were highly positively correlated with each other. The transcriptomic data and analysis of this study provide a basis for the study of the regulatory mechanisms of pepper epidermal trichomes.

Imidacloprid reduces the mating success of males in bumblebees.

Bumblebees play a vital role in both natural and agricultural environments, but there has been a noticeable decline in their populations. Pesticides, particularly neonicotinoids, are widely regarded as a substantial contributing factor to the decline in bumblebee populations, as evidenced by the detrimental impacts documented across many stages of their life cycle. Mating is vital for the population maintenance of bumblebees. Nevertheless, there is a scarcity of research conducted on the effects of pesticides on the mating process. In this study, we individually examined the impact of imidacloprid on the mating behavior of bumblebee males and queens. A competitive mating experiment was conducted to evaluate the effect on the competitive prowess of male individuals and the mate selection behavior of female individuals. The study revealed that the mating rate of bumblebees exposed to a concentration of 10 ppb of imidacloprid was 3 %. This finding demonstrated a statistically significant impact when compared to the control group, which exhibited a mating rate of 58 % in the normal mating experiment. Furthermore, in the competitive mating experiment, we found that the competitive mating success rate of treated males (1 %) was significantly lower than that of untreated males (35 %). Hence, it provides evidence that neonicotinoid imidacloprid negatively affects bumblebee mating success and cautions us to protect bumblebees from pesticide exposure to prevent a severe impact on their populations.

Hyperspectral imaging combined with blood oxygen saturation for in vivo analysis of small intestinal necrosis tissue.

Acute mesenteric ischemia (AMI) is a clinically significant vascular and gastrointestinal condition, which is closely related to the blood supply of the small intestine. Unfortunately, it is still challenging to properly discriminate small intestinal tissues with different degrees of ischemia. In this study, hyperspectral imaging (HSI) was used to construct pseudo-color images of oxygen saturation about small intestinal tissues and to discriminate different degrees of ischemia. First, several small intestine tissue models of New Zealand white rabbits were prepared and collected their hyperspectral data. Then, a set of isosbestic points were used to linearly transform the measurement data twice to match the reference spectra of oxyhemoglobin and deoxyhemoglobin, respectively. The oxygen saturation was measured at the characteristic peak band of oxyhemoglobin (560 nm). Ultimately, using the oxygenated hemoglobin reflectance spectrum as the benchmark, we obtained the relative amount of median oxygen saturation in normal tissues was 70.0 %, the IQR was 10.1 %, the relative amount of median oxygen saturation in ischemic tissues was 49.6 %, and the IQR was 14.6 %. The results demonstrate that HSI combined with the oxygen saturation computation method can efficiently differentiate between normal and ischemic regions of the small intestinal tissues. This technique provides a powerful support for internist to discriminate small bowel tissues with different degrees of ischemia, and also provides a new way of thinking for the diagnosis of AMI.

3'-Deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

JOURNAL/nrgr/04.03/01300535-202410000-00028/figure1/v/2024-02-06T055622Z/r/image-tiff Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome. 3'-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3'-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3'-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3'-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3'-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3'-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3'-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3'-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

Protein disulfide isomerase 1 is required for RodA assembling-based conidial hydrophobicity of Aspergillus fumigatus.

The hydrophobic layer of Aspergillus conidia, composed of RodA, plays a crucial role in conidia transfer and immune evasion. It self-assembles into hydrophobic rodlets through intramolecular disulfide bonds. However, the secretory process of RodA and its regulatory elements remain unknown. Since protein disulfide isomerase (PDI) is essential for the secretion of many disulfide-bonded proteins, we investigated whether PDI is also involved in RodA secretion and assembly. By gene knockout and phenotypic analysis, we found that Pdi1, one of the four PDI-related proteins of Aspergillus fumigatus, determines the hydrophobicity and integrity of the rodlet layer of the conidia. Preservation of the thioredoxin-active domain of Pdi1 was sufficient to maintain conidial hydrophobicity, suggesting that Pdi1 mediates RodA assembly through its disulfide isomerase activity. In the absence of Pdi1, the disulfide mismatch of RodA in conidia may prevent its delivery from the inner to the outer layer of the cell wall for rodlet assembly. This was demonstrated using a strain expressing a key cysteine-mutated RodA. The dormant conidia of the Pdi1-deficient strain (Δpdi) elicited an immune response, suggesting that the defective conidia surface in the absence of Pdi1 exposes internal immunogenic sources. In conclusion, Pdi1 ensures the correct folding of RodA in the inner layer of conidia, facilitating its secretion into the outer layer of the cell wall and allowing self-assembly of the hydrophobic layer. This study has identified a regulatory element for conidia rodlet assembly.IMPORTANCEAspergillus fumigatus is the major cause of invasive aspergillosis, which is mainly transmitted by the inhalation of conidia. The spread of conidia is largely dependent on their hydrophobicity, which is primarily attributed to the self-assembly of the hydrophobic protein RodA on the cell wall. However, the mechanisms underlying RodA secretion and transport to the outermost layer of the cell wall are still unclear. Our study identified a critical role for Pdi1, a fungal protein disulfide isomerase found in regulating RodA secretion and assembly. Inhibition of Pdi1 prevents the formation of correct S-S bonds in the inner RodA, creating a barrier to RodA delivery and resulting in a defective hydrophobic layer. Our findings provided insight into the formation of the conidial hydrophobic layer and suggested potential drug targets to inhibit A. fumigatus infections by limiting conidial dispersal and altering their immune inertia.

Integrated transcriptome and metabolome analysis reveals anthocyanin biosynthesis mechanisms in pepper (Capsicum annuum L.) leaves under continuous blue light irradiation.

BACKGROUND: Different metabolic compounds give pepper leaves and fruits their diverse colors. Anthocyanin accumulation is the main cause of the purple color of pepper leaves. The light environment is a critical factor affecting anthocyanin biosynthesis. It is essential that we understand how to use light to regulate anthocyanin biosynthesis in plants. RESULT: Pepper leaves were significantly blue-purple only in continuous blue light or white light (with a blue light component) irradiation treatments, and the anthocyanin content of pepper leaves increased significantly after continuous blue light irradiation. This green-to-purple phenotype change in pepper leaves was due to the expression of different genes. We found that the anthocyanin synthesis precursor-related genes PAL and 4CL, as well as the structural genes F3H, DFR, ANS, BZ1, and F3'5'H in the anthocyanin synthesis pathway, had high expression under continuous blue light irradiation. Similarly, the expression of transcription factors MYB1R1-like, MYB48, MYB4-like isoform X1, bHLH143-like, and bHLH92-like isoform X3, and circadian rhythm-related genes LHY and COP1, were significantly increased after continuous blue light irradiation. A correlation network analysis revealed that these transcription factors and circadian rhythm-related genes were positively correlated with structural genes in the anthocyanin synthesis pathway. Metabolomic analysis showed that delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside were significantly higher under continuous blue light irradiation relative to other light treatments. We selected 12 genes involved in anthocyanin synthesis in pepper leaves for qRT-PCR analysis, and the accuracy of the RNA-seq results was confirmed. CONCLUSIONS: In this study, we found that blue light and 24-hour irradiation together induced the expression of key genes and the accumulation of metabolites in the anthocyanin synthesis pathway, thus promoting anthocyanin biosynthesis in pepper leaves. These results provide a basis for future study of the mechanisms of light quality and photoperiod in anthocyanin synthesis and metabolism, and our study may serve as a valuable reference for screening light ratios that regulate anthocyanin biosynthesis in plants.

Combined Photothermal Therapy and Cancer Immunotherapy by Immunogenic Hollow Mesoporous Silicon-Shelled Gold Nanorods.

Hyperthermia can be integrated with tumor-killing chemotherapy, radiotherapy and immunotherapy to give rise to an anti-tumor response. To this end, a nano-delivery system is built, which can connect hyperthermia and immunotherapy. On this basis, the impact of such a combination on the immune function of dendritic cells (DCs) is explored. The core of this system is the photothermal material gold nanorod (GNR), and its surface is covered with a silica shell. Additionally, it also forms a hollow mesoporous structure using the thermal etching approach, followed by modification of targeted molecule folic acid (FA) on its surface, and eventually forms a hollow mesoporous silica gold nanorod (GNR@void@mSiO2) modified by FA. GNR@void@mSiO2-PEG-FA (GVS-FA) performs well in photothermal properties, drug carriage and release and tumor targeting performance. Furthermore, the thermotherapy of tumor cells through in vitro NIR irradiation can directly kill tumor cells by inhibiting proliferation and inducing apoptosis. GVS-FA loaded with imiquimod (R837) can be used as a adjuvant to enhance the immune function of DCs through hyperthermia.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants.

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS.

N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, has not been previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells and asthmatic patients and that it influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid-liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules. Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and interleukin-1ß secretion leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation.

Graphitic Armor: A Natural Molecular Sieve for Robust Hydrogen Electroxidation.

Carbon coating layers have been found to improve the catalytic performance of transition metals, which is usually explained as an outcome of electronic synergistic effect. Herein we reveal that the defective graphitic carbon, with a unique interlayer gap of 0.342 nm, can be a highly selective natural molecular sieve. It allows efficient diffusion of hydrogen molecules or radicals both along the in-plane and out-of-plane direction, but sterically hinders the diffusion of molecules with larger kinetic diameter (e.g., CO and O2) along the in-plane direction. As a result, poisonous species lager than 0.342 nm are sieved out, even when their adsorption on the metal is thermodynamically strong; at the same time, the interaction between H2 and the metal is not affected. This natural molecular sieve provides a very chance for constructing robust metal catalysts for hydrogen-relevant processes, which are more tolerant to chemical or electrochemical oxidation or CO-relevant poisoning.

Aptamers combined with immune checkpoints for cancer detection and targeted therapy: A review.

In recent years, remarkable strides have been made in the field of immunotherapy, which has emerged as a standard treatment for many cancers. As a kind of immunotherapy drug, monoclonal antibodies employed in immune checkpoint therapy have proven beneficial for patients with diverse cancer types. However, owing to the extensive heterogeneity of clinical responses and the complexity and variability of the immune system and tumor microenvironment (TME), accurately predicting its efficacy remains a challenge. Recent advances in aptamers provide a promising approach for monitoring alterations within the immune system and TME, thereby facilitating targeted immunotherapy, particularly focused on immune checkpoint blockade, with enhanced antitumor efficiency. Aptamers have been widely used in tumor cell detection, biosensors, drug discovery, and biomarker screening due to their high specificity and high affinity with their targets. This review aims to comprehensively examine the research status and progress of aptamers in cancer diagnosis and immunotherapy, with a specific emphasis on those related to immune checkpoints. Additionally, we will discuss the future research directions and potential therapeutic targets for aptamer-based immune checkpoint therapy, aiming to provide a theoretical basis for targeting immunotherapy molecules and blocking tumor immune escape.

Protein Coronas Derived from Mucus Act as Both Spear and Shield to Regulate Transferrin Functionalized Nanoparticle Transcellular Transport in Enterocytes.

The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an "active PC" to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of "passive PCs" formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.

Measuring entanglement entropy and its topological signature for phononic systems.

Entanglement entropy is a fundamental concept with rising importance in various fields ranging from quantum information science, black holes to materials science. In complex materials and systems, entanglement entropy provides insight into the collective degrees of freedom that underlie the systems' complex behaviours. As well-known predictions, the entanglement entropy exhibits area laws for systems with gapped excitations, whereas it follows the Gioev-Klich-Widom scaling law in gapless fermion systems. However, many of these fundamental predictions have not yet been confirmed in experiments due to the difficulties in measuring entanglement entropy in physical systems. Here, we report the experimental verification of the above predictions by probing the nonlocal correlations in phononic systems. We obtain the entanglement entropy and entanglement spectrum for phononic systems with the fermion filling analog. With these measurements, we verify the Gioev-Klich-Widom scaling law. We further observe the salient signatures of topological phases in entanglement entropy and entanglement spectrum.

Stabilization of the Metastable Pre-Fusion Conformation of the SARS-CoV-2 Spike Glycoprotein through N-Linked Glycosylation of the S2 Subunit.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, represents a serious threat to public health. The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry into host cells and is heavily glycosylated. In this study, we systemically analyzed the roles of 22 putative N-linked glycans in SARS-CoV-2 S protein expression, membrane fusion, viral entry, and stability. Using the α-glycosidase inhibitors castanospermine and NB-DNJ, we confirmed that disruption of N-linked glycosylation blocked the maturation of the S protein, leading to the impairment of S protein-mediated membrane fusion. Single-amino-acid substitution of each of the 22 N-linked glycosylation sites with glutamine revealed that 9 out of the 22 N-linked glycosylation sites were critical for S protein folding and maturation. Thus, substitution at these sites resulted in reduced S protein-mediated cell-cell fusion and viral entry. Notably, the N1074Q mutation markedly affected S protein stability and induced significant receptor-independent syncytium (RIS) formation in HEK293T/hACE2-KO cells. Additionally, the removal of the furin cleavage site partially compensated for the instability induced by the N1074Q mutation. Although the corresponding mutation in the SARS-CoV S protein (N1056Q) did not induce RIS in HEK293T cells, the N669Q and N1080Q mutants exhibited increased fusogenic activity and did induce syncytium formation in HEK293T cells. Therefore, N-glycans on the SARS-CoV and SARS-CoV-2 S2 subunits are highly important for maintaining the pre-fusion state of the S protein. This study revealed the critical roles of N-glycans in S protein maturation and stability, information that has implications for the design of vaccines and antiviral strategies.