Cathelicidin peptide analogues inhibit EV71 infection through blocking viral entry and uncoating.

Given the serious neurological complications and deaths associated with enterovirus 71 (EV71) infection, there is an urgent need to develop effective antivirals against this viral infection. In this study, we demonstrated that two Cathelicidin-derived peptides, LL-18 and FF-18 were more potent against EV71 infection than the parent peptide LL-37, which is the mature and processed form of Cathelicidin. These peptides could directly bind to the EV71 virus particles, but not to coxsackievirus, indicative of their high specificity. The binding of peptides with the virus surface occupied the viral canyon region in a way that could block virus-receptor interactions and inhibit viral uncoating. In addition, these peptide analogues could also relieve the deleterious effect of EV71 infection in vivo. Therefore, Cathelicidin-derived peptides might be excellent candidates for further development of antivirals to treat EV71 infection.

Coordination-Directed Self-Assembly of Functional Polynuclear Lanthanide Supramolecular Architectures.

Lanthanide supramolecular chemistry is a fast growing and intriguing research field due to the unique photophysical, magnetic, and coordination properties of lanthanide ions (LnIII). Compared with the intensively investigated mononuclear Ln-complexes, polymetallic lanthanide supramolecular assemblies offer more structural superiority and functional advantages. In recent decades, significant progress has been made in polynuclear lanthanide supramolecules, varying from structural evolution to luminescent and magnetic functional materials. This review summarizes the design principles in ligand-induced coordination-driven self-assembly of polynuclear Ln-structures and intends to offer guidance for the construction of more elegant Ln-based architectures and optimization of their functional performances. Design principles concerning the water solubility and chirality of the lanthanide-organic assemblies that are vital in extending their applications are emphasized. The strategies for improving the luminescent properties and the applications in up-conversion, host-guest chemistry, luminescent sensing, and catalysis have been summarized. Magnetic materials based on supramolecular assembled lanthanide architectures are given in an individual section and are classified based on their structural features. Challenges remaining and perspective directions in this field are also briefly discussed.

USP7 reduction leads to developmental failure of mouse early embryos.

As a member of Ubiquitin-specific protease subfamily, ubiquitin specific protease 7 (USP7) has been reported to participate in a variety of cellular processes, including cell cycle, apoptosis, DNA damage response, and epigenetic modification. However, its function in preimplantation embryos is still obscure. To investigate the functions of USP7 during preimplantation embryo development, we used siRNA to degrade endogenous USP7 messenger RNA. We found that USP7 knockdown significantly decreased the development rate of mouse early embryos. Moreover, depletion of USP7 induced the accumulation of the DNA lesions and apoptotic blastomeres in early embryos. In addition, USP7 knockdown caused an abnormal H3K27me3 modification in 2-cell embryos. Overall, our results indicate that USP7 maintains genome stability perhaps via regulating H3K27me3 and DNA damage, consequently controlling the embryo quality.

Subhealth Status of Nursing Staff and Its Influencing Factors in Shaanxi Province.

Background: The concept of subhealth, defined as a state between health and illness characterized by diminished vitality and adaptability, is emerging as a significant concern, particularly among nursing staff. In Shaanxi Province, there is a notable prevalence of subhealth conditions among nurses, influenced by various factors, including lifestyle, work environment, and psychological stress. Purpose: This study aims to investigate the level of subhealth status among nursing staff in Shaanxi hospitals, identify the primary causes and risk factors affecting their subhealth, and propose relevant countermeasures. The goal is to provide a scientific basis for developing strategies to enhance nursing staff's physical and mental well-being. Methods: A comprehensive questionnaire survey was conducted among 1068 nursing staff members from different hospitals in Shaanxi Province. The survey assessed various dimensions of subhealth, including physical, psychological, and social aspects. Data were analyzed to determine the relationships between subhealth status and factors like exercise frequency, dietary habits, smoking and alcohol consumption, occupational injuries, work situation, and stress levels. Results: Most respondents were female, aged between 21 and 40 years. The study found no significant gender-related differences in subhealth scores. Key factors affecting subhealth included physical exercise, dietary habits, occupational stress, and work conditions. The data revealed higher physical subhealth but lower psychological subhealth among nursing staff compared to regional norms. Notable relationships were observed between lifestyle choices, work-related factors, and the subhealth status of nursing staff. Conclusion: The subhealth status of nursing staff in Shaanxi hospitals is influenced by a combination of lifestyle, occupational, and psychological factors. The study underscores the need for targeted interventions focusing on lifestyle modifications, stress management, and improved work conditions to enhance the overall health status of nursing staff. This research provides valuable insights for healthcare policymakers and administrators to develop effective strategies for managing subhealth conditions among nursing professionals.

Adverse event reporting attitude and its individual and organizational predictors among nursing staff: A multisite study in Chinese nursing homes.

This study explored the status of adverse event reporting attitudes and its predictors among nursing staff in Chinese nursing homes. A cross-sectional study was conducted with 475 nursing staff, and they completed sociodemographic and facility-related questionnaire, Incident Reporting Attitude Scale, Adverse Event Reporting Awareness Scale, and Nursing Home Survey on Patient Safety Culture. Univariate analysis and multiple linear regression models were performed. The mean score for adverse event reporting attitude was 125.87 (SD=15.35). The predictors included individual variables, such as education level (ß=0.129, p = 0.001) and working years (ß=-0.102, p = 0.007), and organizational variables, such as patient safety culture (ß=0.503, p < 0.001) and adverse event reporting awareness (ß=0.261, p < 0.001). These factors explained 35.3 % of total variance. Managers in nursing homes should strengthen team-targeted education and training for nursing staff with longer working years and lower educational backgrounds. Meanwhile, a simplified and non-punitive reporting system should be established to create positive safety management climate.

N-Acetyltransferase 8 Promotes Viral Replication by Increasing the Stability of Enterovirus 71 Nonstructural Proteins.

Enterovirus 71 (EV71) is deemed a reemergent pathogen, with recent outbreaks worldwide. EV71 infection causes hand, foot, and mouth disease (HFMD) and has been associated with severe cardiac and central nervous system complications and even death. Viruses need host factors to complete their life cycle; therefore, the identification of the host factors for EV71 infection is pivotal to new antiviral research. Emerging evidence has highlighted the importance of protein acetylation during infection by various human viruses. The endoplasmic reticulum (ER), as the prominent organelle of EV71 replication, also has a unique acetylation regulation mechanism. However, the pathogenesis of EV71 and its relationship with the ER-based acetylation machinery are not fully understood. In this study, we demonstrated for the first time that the ER-resident acetyltransferase N-acetyltransferase 8 (NAT8) is a host factor for EV71 infection. Inhibiting NAT8 with CRISPR or a small compound significantly suppressed EV71 infection in SK-N-SH cells. NAT8 promoted EV71 replication in an acetyltransferase-activity-dependent manner. Additionally, we found that NAT8 facilitates EV71 infection by interacting with EV71 2B, 3AB, and 3C proteins and increasing the stability of these proteins. These results uncovered a novel function of NAT8 and elucidated a new mechanism underlying the regulation of EV71 replication. IMPORTANCE EV71 is one of the most common pathogens causing HFMD in young children, and some patients experience severe or fatal neurological consequences. To ensure efficient replication, the virus must hijack multiple host factors for its own benefit. Here, we show that the ER-resident acetyltransferase NAT8 is a host factor for EV71 infection. EV71 fails to complete its infection in various cells in the absence of NAT8. We further show that NAT8 benefits EV71 replication in an acetyltransferase-activity-dependent manner. Finally, we show that NAT8 facilitates EV71 infection by interacting with EV71 2B, 3AB, and 3C proteins and increasing the stability of these proteins. These results uncovered a novel function of NAT8 in EV71 infection and elucidated a new mechanism underlying the regulation of EV71 replication.

Spike protein mediated membrane fusion during SARS-CoV-2 infection.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to public health and has quickly become a global concern. The infection of SARS-CoV-2 begins with the binding of its spike protein to the receptor-angiotensin-converting enzyme 2 (ACE2), which, after a series of conformation changes, results in the fusion of viral-cell membranes and the release of the viral RNA genome into the cytoplasm. In addition, infected host cells can express spike protein on their cell surface, which will interact with ACE2 on neighboring cells, leading to cell membrane fusion and the formation of multinucleated cells or syncytia. Both viral entry and syncytia formation are mediated by spike-ACE2 interaction and share some common mechanisms of membrane fusion. Here in this review, we will summarize our current understanding of spike-mediated membrane fusion, which may shed light on future broad-spectrum antiviral development.

Guest-Driven Self-Assembly and Chiral Induction of Photofunctional Lanthanide Tetrahedral Cages.

Chiral luminescent lanthanide-organic cages have many potential applications in enantioselective recognition, sensing, and asymmetric catalysis. However, due to the paucity of structures and their limited cavities, host-guest chemistry with lanthanide-organic cages has remained elusive so far. Herein, we report a guest-driven self-assembly and chiral induction approach for the construction of otherwise inaccessible Ln4L4-type (Ln = lanthanide ions, i.e., EuIII, TbIII; L = ligand) tetrahedral hosts. Single crystal analyses on a series of host-guest complexes reveal remarkable guest-adaptive cavity breathing on the tetrahedral cages, reflecting the advantage of the variation tolerance on coordination geometry of the f-elements. Meanwhile, noncovalent confinement of pyrene within the lanthanide cage not only leads to diminishment of its excimer emission but also facilitates guest to host energy transfer, opening up a new sensitization window for the lanthanide luminescence on the cage. Moreover, stereoselective self-assembly of either Λ4- or Δ4- type Eu4L4 cages has been realized via chiral induction with R/S-BINOL or R/S-SPOL templates, as confirmed by NMR, circular dichroism (CD), and circularly polarized luminescence (CPL) with high dissymmetry factors (glum) up to ±0.125.

Stereocontrolled Self-Assembly of Ln(III)-Pt(II) Heterometallic Cages with Temperature-Dependent Luminescence.

Structurally well-defined discrete d/f heterometallic complexes show diverse application potential in electrooptic and magnetic materials. However, precise control of the component and topology of such heterometallic compounds with fine-tuned photophysical properties is still challenging. Herein, we report the stereocontrolled syntheses of a series of LnIII-PtII heterometallic cages through coordination-driven self-assembly of enantiopure alkynylplatinum-based metalloligands (L1R/S, L2R/S) with lanthanide ions (Ln = EuIII, YbIII, NdIII, LuIII). Taking advantage of the metal-to-ligand charge transfer (MLCT) excited state on the designed alkynylplatinum ligands, the excitation window for the sensitized near-infrared (NIR) luminescence on the YbIII- and NdIII-containing cages can be extended to the visible region (up to 500 nm). Linear temperature-dependent red and NIR emissions observed on the Ln4(L2R/S)6 (LnIII = EuIII and YbIII, respectively) complexes suggest their potential applications as luminescent temperature sensors, with sensitivities of -0.54% (LnIII = EuIII, 77-250 K) and -0.17% (LnIII = YbIII, 77-300 K) per K achieved. This work not only offers a good strategy to prepare new d/f heterometallic supramolecular cages but also paves the way for the design of stimuli-responsive luminescent materials.

Coordination-Assembly of Lanthanide Supramolecular Hydrogels with Luminescent Multi-stimulus Response.

Luminescent supramolecular hydrogels have shown extensive potential for a variety of applications due to their unique optical properties and biocompatibility. Coordination self-assembly provides a promising strategy for the preparation of supramolecular hydrogels. In this contribution, a series of luminescent lanthanide (Ln) supramolecular hydrogels HG-Ln2nL3n1/2 are synthesized by coordination self-assembly of Ln ions and V shaped bis-tetradentate ligands (H4L1 and H4L2) with different bent angles (∠B). Two rigid conjugated ligands H4L1 and H4L2 with bent angles (∠B ≈ 150°) featuring a 2,6-pyridine bitetrazolate chelating moiety were designed and synthesized, which generated hydrogels via the deprotonation self-assembly with lanthanide ions. Characteristic Eu3+ and Yb3+ emissions were realized in the corresponding hydrogels, with intriguing multi-stimulus response behaviors. The luminescence of the HG-Eu2nL3n1 hydrogel can be enhanced or quenched when stimulated by diverse metal ions, attributed to the replacement of the coordinated lanthanide ions and changes in the intersystem crossing efficiency of the ligand. Furthermore, pH-responsive emission of the HG-Eu2nL3n1 hydrogel has also been observed. Our work provides potential strategies for the design of next-generation smart responsive hydrogel materials with variable structures.

Itraconazole attenuates the stemness of nasopharyngeal carcinoma cells via triggering ferroptosis.

Radiotherapy is a common therapy method for nasopharyngeal carcinoma (NPC) treatment; however, radioresistance greatly limits the clinical efficiency and prognosis of NPC patients. Therefore, it is extremely urgent to reveal the underlying mechanism contributing to radioresistance and find possible diagnostic biomarkers. Here, we collected the spheroids formed by NPC cells, which had been confirmed to hold the stem cell-like traits, and found that these spheroids exhibited a certain degree of radioresistance. Additionally, NPC spheroids displayed a certain degree of ferroptosis resistance, as evident by the decrease of iron concentration in lysosomes and lipid peroxides oxygen, and increase of glutathione (GSH) level. Furthermore, we revealed that itraconazole triggered the ferroptosis of NPC spheroids, which is characterized as the increase of iron concentration and lipid peroxides oxygen, and decrease of GSH level, and decreased the cell viability of NPC spheroids. Notably, itraconazole partially reversed the radioresistance of NPC spheroids. Mechanistically, we found that itraconazole can sequester iron in lysosome and thus trigger ferroptosis; this is essential for itraconazole-mediated attenuation on NPC spheroid stemness. Therefore, this study provides evidences showing that itraconazole might be used for killing NPC stem cells and thus attenuate radioresistance.

Water-Soluble Organic Nanoparticles with Programable Intermolecular Charge Transfer for NIR-II Photothermal Anti-Bacterial Therapy.

Extensive recent efforts have been put on the design of high-performance organic near-infrared (NIR) photothermal agents (PTAs), especially over NIR-II bio-window (1000-1350 nm). So far, the development is mainly limited by the rarity of molecules with good NIR-II response. Here, we report organic nanoparticles of intermolecular charge-transfer complexes (CTCs) with easily programmable optical absorption. By employing different common donor and acceptor molecules to form CTC nanoparticles (CT NPs), absorption peaks of CT NPs can be controllably tuned from the NIR-I to NIR-II region. Notably, CT NPs formed with perylene and TCNQ have a considerably red-shifted absorption peak at 1040 nm and achieves a good photothermal conversion efficiency of 42 % under 1064 nm excitation. These nanoparticles were used for antibacterial application with effective activity towards both Gram-negative and Gram-positive bacteria. This work opens a new avenue into the development of efficient PTAs.

Coordination-Assembled Water-Soluble Anionic Lanthanide Organic Polyhedra for Luminescent Labeling and Magnetic Resonance Imaging.

Lanthanide-containing functional complexes have found a variety of applications in materials science and biomedicine because of their unique electroptical and magnetic properties. However, the poor stability and solubility in water of multicomponent lanthanide organic assemblies significantly limit their practical applications. We report here a series of water-stable anionic Ln2nL3n-type (n = 2, 3, 4, and 5) lanthanide organic polyhedra (LOPs) constructed by deprotonation self-assembly of three fully conjugated ligands (H4L1 and H4L2a/b) featuring a 2,6-pyridine bitetrazolate chelating moiety. The outcomes of the LOPs formation reactions were found to be very sensitive toward the reaction conditions including base, metal source, solvents, and concentrations as characterized by a combination of NMR, high-resolution ESI-MS and X-ray crystallography. Ligands H4L2a/b manifested an excellent sensitization toward lanthanide ions (Ln = EuIII and TbIII), with high luminescent quantum yields for Tb8L2a12 (Φ = 11.2% in water) and Eu8L2b12 (Φ = 76.8% in DMSO) measured in polar solvents. Furthermore, due to the giant molecular weight and rigidity of the polyhedral skeleton, Gd8L2b12 showed a very high longitudinal relaxivity (r1) of 400.53 mM-1S-1. The performance of Gd8L2b12 as potential magnetic resonance imaging contrast agents (CAs) in vivo was evaluated with much longer retention time in the tumor sites compared with the commercial GdIII-based CAs. Dual-modal imaging potential has also been demonstrated with the mixed Eu/Gd LOPs. Our results not only provide a new design route toward water-stable multinuclear lanthanide organic assemblies but also offer potential candidates of supramolecular-edifices for bioimaging and drug delivery.

Single-Photomolecular Nanotheranostics for Synergetic Near-Infrared Fluorescence and Photoacoustic Imaging-Guided Highly Effective Photothermal Ablation.

Multi-modality imaging-guided cancer therapy is considered as a powerful theranostic platform enabling simultaneous precise diagnosis and treatment of cancer. However, recently reported multifunctional systems with multiple components and sophisticate structures remain major obstacles for further clinical translation. In this work, a single-photomolecular theranostic nanoplatform is fabricated via a facile nanoprecipitation strategy. By encapsulating a semiconductor oligomer (IT-S) into an amphiphilic lipid, water-dispersible IT-S nanoparticles (IT-S NPs) are prepared. The obtained IT-S NPs have a very simple construction and possess ultra-stable near-infrared (NIR) fluorescence (FL)/photoacoustic (PA) dual-modal imaging and high photothermal conversion efficiency of 72.3%. Accurate spatiotemporal distribution profiles of IT-S NPs are successfully visualized by NIR FL/PA dual-modal imaging. With the comprehensive in vivo imaging information provided by IT-S NPs, tumor photothermal ablation is readily realized under precise manipulation of laser irradiation, which greatly improves the therapeutic efficacy without any obvious side effects. Therefore, the IT-S NPs allow high tumor therapeutic efficacy under the precise guidance of FL/PA imaging techniques and thus hold great potential as an effective theranostic platform for future clinical applications.

Self-Assembly of Lanthanide-Covalent Organic Polyhedra: Chameleonic Luminescence and Efficient Catalysis.

A series of multinuclear lanthanide-covalent organic polyhedra (LnCOPs), including pillar-typed triangular prisms 1-Ln3 and tetrahedra 2-Ln4 (Ln = LaIII, SmIII, EuIII), have been constructed for the first time, through either one-pot subcomponent self-assembly or postassembly metalation. In contrast to the known tetrahedral cages based on transition metals, the pillar-typed polyhedra were favored from the same organic components in the presence of lanthanides. Besides this, facile transmetalations between the 1-Ln3 polyhedra endow cascade chameleonic luminescence. Meanwhile, the open metal sites and pendent amine groups on 1-Ln3 enable these polyhedra to catalyze the Henry reaction efficiently.

Effects of dietary supplementation with herbal extract mixture on growth performance, organ weight and intestinal morphology in weaning piglets.

BACKGROUND: Many countries are increasingly prohibiting the addition of antibiotics in livestock diets. Therefore, herb extracts have gradually drawn attention to substitute antibiotics. Our present study aimed to determine the effects of herbal extract mixture (HEM) in dietary on growth performance, organ weight, intestinal morphology and intestinal nutrient transporters in weaned pigs. METHODS: 27 piglets (Duroc × [Landrace × Yorkshire]; Body Weight (BW) = 5.99 ± 0.13 kg) were weaned at day 21 and randomly divided into three groups (n = 9 piglets/group). All piglets received a basal diet containing similar amounts of nutrients for 14 days. The three groups were the control (no additive), the antibiotics (375 mg/kg chlortetracycline, 20%, 500 mg/kg enramycin, 4%, 1,500 mg/kg oxytetracycline calcium, 50%) and the HEM group (1000 mg/kg extract mixture of golden-and-silver honeysuckle, huangqi, duzhong leaves and dangshen). After 14 d of treatment, we collected tissue samples to measure organ weight, intestinal parameters, intestinal morphology, digestive enzyme activities and intestinal mRNA expression of nutrient transporters. RESULTS: The HEM group had no effects on growth performance and organ weight of weaned pigs. But compared with the control group, both HEM and antibiotics improved intestinal morphology, and HEM elevated the expression of nutrient transporters in ileum (SLC6A9, SLC15A1, and SLC5A1). HEM significantly decreased the activities of maltase in ileum and the ratio of small intestinal weight to BW than control group. CONCLUSIONS: These results indicate benefit effects of the supplementation of HEM in diet, including modulating intestinal morphology and increasing the mRNA expression of nutrients transporters. These findings suggest that HEM provides novel insights into a variety of herbal extract mixtures to replace antibiotics in animal production.

Physicochemical properties and energy content of yellow dent corn from different climatic origins in growing pigs.

OBJECTIVE: The objective of this study was to determine the digestible energy (DE) and metabolizable energy (ME) of yellow dent corn sourced from different meteorological origins fed to growing pigs and develop equations to predict the DE and ME of yellow dent corn from southwestern China. METHODS: Sixty crossbred barrows were allotted to 20 treatments in a triplicate 20×2 incomplete Latin square design with 3 replicated pigs per dietary treatment during 2 consecutive periods. Each period lasted for 12 days, and total feces and urine during the last 5 days of each period were collected to calculate the energy contents. RESULTS: On dry matter (DM) basis, the DE and ME in 20 corn grain samples ranged from 15.38 to 16.78 MJ/kg and from 14.93 to 16.16 MJ/kg, respectively. Selected best-fit prediction equations for DE and ME (MJ/kg DM basis) for yellow dent corn (n = 16) sourced from southwestern China were as follows: DE = 28.58-(0.12×% hemicellulose)+(0.35×% ether extract)-(0.83×MJ/kg gross energy)+(0.20×% crude protein)+(0.49×% ash); ME = 30.42- (0.11×% hemicellulose)+(0.31×% ether extract)-(0.81×MJ/kg gross energy). CONCLUSION: Our results indicated that the chemical compositions, but not the meteorological conditions or physical characteristics could explain the variation of energy contents in yellow dent corn sourced from southwestern China fed to growing pigs.

De novo transcriptome and phytochemical analyses reveal differentially expressed genes and characteristic secondary metabolites in the original oolong tea (Camellia sinensis) cultivar 'Tieguanyin' compared with cultivar 'Benshan'.

BACKGROUND: The two original plants of the oolong tea cultivar ('Tieguanyin') are "Wei shuo" 'Tieguanyin'-TGY (Wei) and "Wang shuo" 'Tieguanyin'-TGY (Wang). Another cultivar, 'Benshan' (BS), is similar to TGY in its aroma, taste, and genetic make-up, but it lacks the "Yin Rhyme" flavor. We aimed to identify differences in biochemical characteristics and gene expression among these tea plants. RESULTS: The results of spectrophotometric, high performance liquid chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS) analyses revealed that TGY (Wei) and TGY (Wang) had deeper purple-colored leaves and higher contents of anthocyanin, catechins, caffeine, and limonene compared with BS. Analyses of transcriptome data revealed 12,420 differentially expressed genes (DEGs) among the cultivars. According to a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the flavonoid, caffeine, and limonene metabolic pathways were highly enriched. The transcript levels of the genes involved in these three metabolic pathways were not significantly different between TGY (Wei) and TGY (Wang), except for two unigenes encoding IMPDH and SAMS, which are involved in caffeine metabolism. The comparison of TGY vs. BS revealed eight up-regulated genes (PAL, C4H, CHS, F3'H, F3H, DFR, ANS, and ANR) and two down-regulated genes (FLS and CCR) in flavonoid metabolism, four up-regulated genes (AMPD, IMPDH, SAMS, and 5'-Nase) and one down-regulated XDH gene in caffeine metabolism; and two down-regulated genes (ALDH and HIBADH) in limonene degradation. In addition, the expression levels of the transcription factor (TF) PAP1 were significantly higher in TGY than in BS. Therefore, high accumulation of flavonoids, caffeine, and limonene metabolites and the expression patterns of their related genes in TGY might be beneficial for the formation of the "Yin Rhyme" flavor. CONCLUSIONS: Transcriptomic, HPLC, and GC-MS analyses of TGY (Wei), TGY (Wang), and BS indicated that the expression levels of genes related to secondary metabolism and high contents of catechins, anthocyanin, caffeine, and limonene may contribute to the formation of the "Yin Rhyme" flavor in TGY. These findings provide new insights into the relationship between the accumulation of secondary metabolites and sensory quality, and the molecular mechanisms underlying the formation of the unique flavor "Yin Rhyme" in TGY.