Establishment of replication-competent vesicular stomatitis virus recapitulating SADS-CoV entry.

Zoonotic coronaviruses pose a continuous threat to human health, with newly identified bat-borne viruses like swine acute diarrhea syndrome coronavirus (SADS-CoV) causing high mortality in piglets. In vitro studies indicate that SADS-CoV can infect cell lines from diverse species, including humans, highlighting its potential risk to human health. However, the lack of tools to study viral entry, along with the absence of vaccines or antiviral therapies, perpetuates this threat. To address this, we engineered an infectious molecular clone of Vesicular Stomatitis Virus (VSV), replacing its native glycoprotein (G) with SADS-CoV spike (S) and inserting a Venus reporter at the 3' leader region to generate a replication-competent rVSV-Venus-SADS S virus. Serial passages of rVSV-Venus-SADS S led to the identification of an 11-amino-acid truncation in the cytoplasmic tail of the S protein, which allowed more efficient viral propagation due to increased cell membrane anchoring of the S protein. The S protein was integrated into rVSV-Venus-SADS SΔ11 particles, susceptible to neutralization by sera from SADS-CoV S1 protein-immunized rabbits. Additionally, we found that TMPRSS2 promotes SADS-CoV spike-mediated cell entry. Furthermore, we assessed the serum-neutralizing ability of mice vaccinated with rVSV-Venus-SADS SΔ11 using a prime-boost immunization strategy, revealing effective neutralizing antibodies against SADS-CoV infection. In conclusion, we have developed a safe and practical tool for studying SADS-CoV entry and exploring the potential of a recombinant VSV-vectored SADS-CoV vaccine.IMPORTANCEZoonotic coronaviruses, like swine acute diarrhea syndrome coronavirus (SADS-CoV), pose a continual threat to human and animal health. To combat this, we engineered a safe and efficient tool by modifying the Vesicular Stomatitis Virus (VSV), creating a replication-competent rVSV-Venus-SADS S virus. Through serial passages, we optimized the virus for enhanced membrane anchoring, a key factor in viral propagation. This modified virus, rVSV-Venus-SADS SΔ11, proved susceptible to neutralization, opening avenues for potential vaccines. Additionally, our study revealed the role of TMPRSS2 in SADS-CoV entry. Mice vaccinated with rVSV-Venus-SADS SΔ11 developed potent neutralizing antibodies against SADS-CoV. In conclusion, our work presents a secure and practical tool for studying SADS-CoV entry and explores the promise of a recombinant VSV-vectored SADS-CoV vaccine.

Enhanced protein-metabolite correlation analysis: To investigate the association between Staphylococcus aureus mastitis and metabolic immune pathways.

Mastitis is a disease characterized by congestion, swelling, and inflammation of the mammary gland and usually caused by infection with pathogenic microorganisms. Furthermore, the development of mastitis is closely linked to the exogenous pathway of the gastrointestinal tract. However, the regulatory mechanisms governing the gut-metabolism-mammary axis remain incompletely understood. The present study revealed alterations in the gut microbiota of mastitis rats characterized by an increased abundance of the Proteobacteria phylum. Plasma analysis revealed significantly higher levels of L-isoleucine and cholic acid along with 7-ketodeoxycholic acid. Mammary tissue showed elevated levels of arachidonic acid metabolites and norlithocholic acid. Proteomic analysis showed increased levels of IFIH1, Tnfaip8l2, IRGM, and IRF5 in mastitis rats, which suggests that mastitis triggers an inflammatory response and immune stress. Follistatin (Fst) and progesterone receptor (Pgr) were significantly downregulated, raising the risk of breast cancer. Extracellular matrix (ECM) receptors and focal adhesion signaling pathways were downregulated, while blood-milk barrier integrity was disrupted. Analysis of protein-metabolic network regulation revealed that necroptosis, protein digestion and absorption, and arachidonic acid metabolism were the principal regulatory pathways involved in the development of mastitis. In short, the onset of mastitis leads to changes in the microbiota and alterations in the metabolic profiles of various biological samples, including colonic contents, plasma, and mammary tissue. Key manifestations include disturbances in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism. At the same time, the integrity of the blood-milk barrier is compromised while inflammation is promoted, thereby reducing cell adhesion in the mammary glands. These findings contribute to a more comprehensive understanding of the metabolic status of mastitis and provide new insights into its impact on the immune system.

Mediterranean diet related to 3-year incidence of cognitive decline: results from a cohort study in Chinese rural elders.

OBJECTIVE: This study aims to examine the effect of the Mediterranean diet (MeDi) on cognitive decline among the Chinese elderly with a 3-year follow-up. METHODS: This study is divided into two waves: wave-1 January 2019 to June 2019 (n = 2313); wave-2 January 2022 to March 2022 (n = 1648). MeDi scores were calculated from the Mediterranean Diet Adherence Screener (MEDAS), with the scoring of low compliance (0-6 points) and high compliance (7-14 points). The Mini-Mental State Examination (MMSE) was used to assess cognitive function. An MMSE score dropping ≥ 2 points from baseline was defined as cognitive decline. The relationships between MeDi score and cognitive decline were analyzed by linear regression models or Binary logistic regression. RESULTS: During the 3-year follow-up, 23.8% of patients exhibited cognitive decline. The study revealed a significant difference in MMSE score changes between low and high MeDi adherence groups (p < 0.001). MeDi score was negatively correlated with cognitive deterioration (ß = -0.020, p = 0.026). MeDi score was only negatively associated with cognitive decline in the female subgroup aged ≥65 years (ß = -0.034, p = 0.033). The food beans (OR = 0.65, 95%CI:0.51, 0.84), fish (OR = 0.72, 95%CI:0.54, 0.97), and cooked vegetables (OR = 0.68, 95%CI:0.53, 0.84) were protective factors for cognitive decline. CONCLUSIONS: This study suggests that greater adherence to the MeDi is linked to a reduced risk of cognitive decline in elderly people. However, this is found only in women who are 65 years old or older. It also found long-term adherence to beans, fish, and vegetables are more effective in improving cognitive function.

Steering sp-Carbon Content in Graphdiynes for Enhanced Two-Electron Oxygen Reduction to Hydrogen Peroxide.

Compared to sp2-hybridized graphene, graphdiynes (GDYs) composed of sp and sp2 carbon are highly promising as efficient catalysts for electrocatalytic oxygen reduction into oxygen peroxide because of the high catalytic reactivity of the electron-rich sp-carbon atoms. The desired catalytic capacity of GDY, such as catalytic selectivity and efficiency, can theoretically be achieved by strategically steering the sp-carbon contents or the topological arrangement of the acetylenic linkages and aromatic bonds. Herein, we successfully tuned the electrocatalytic activity of GDYs by regulating the sp-to-sp2 carbon ratios with different organic monomer precursors. As the active sp-carbon atoms possess electron-sufficient π orbitals, they can donate electrons to the lowest unoccupied molecular orbital (LUMO) orbitals of O2 molecules and initiate subsequent O2 reduction, GDY with the high sp-carbon content of 50 at% exhibits excellent capability of catalyzing O2 reduction into H2O2. It demonstrates exceptional H2O2 selectivity of over 95.0% and impressive performance in practical H2O2 production, Faraday efficiency (FE) exceeding 99.0%, and a yield of 83.3 nmol s-1 cm-2. Our work holds significant importance in effectively steering the inherent properties of GDYs by purposefully adjusting the sp-to-sp2 carbon ratio and highlights their immense potential for research and applications in catalysis and other fields.

Light-induced giant enhancement of nonreciprocal transport at KTaO3-based interfaces.

Nonlinear transport is a unique functionality of noncentrosymmetric systems, which reflects profound physics, such as spin-orbit interaction, superconductivity and band geometry. However, it remains highly challenging to enhance the nonreciprocal transport for promising rectification devices. Here, we observe a light-induced giant enhancement of nonreciprocal transport at the superconducting and epitaxial CaZrO3/KTaO3 (111) interfaces. The nonreciprocal transport coefficient undergoes a giant increase with three orders of magnitude up to 105 A-1 T-1. Furthermore, a strong Rashba spin-orbit coupling effective field of 14.7 T is achieved with abundant high-mobility photocarriers under ultraviolet illumination, which accounts for the giant enhancement of nonreciprocal transport coefficient. Our first-principles calculations further disclose the stronger Rashba spin-orbit coupling strength and the longer relaxation time in the photocarrier excitation process, bridging the light-property quantitative relationship. Our work provides an alternative pathway to boost nonreciprocal transport in noncentrosymmetric systems and facilitates the promising applications in opto-rectification devices and spin-orbitronic devices.

Overcoming the Blood-Brain Tumor Barrier with Docetaxel-Loaded Mesoporous Silica Nanoparticles for Treatment of Temozolomide-Resistant Glioblastoma.

While temozolomide (TMZ) has been a cornerstone in the treatment of newly diagnosed glioblastoma (GBM), a significant challenge has been the emergence of resistance to TMZ, which compromises its clinical benefits. Additionally, the nonspecificity of TMZ can lead to detrimental side effects. Although TMZ is capable of penetrating the blood-brain barrier (BBB), our research addresses the need for targeted therapy to circumvent resistance mechanisms and reduce off-target effects. This study introduces the use of PEGylated mesoporous silica nanoparticles (MSN) with octyl group modifications (C8-MSN) as a nanocarrier system for the delivery of docetaxel (DTX), providing a novel approach for treating TMZ-resistant GBM. Our findings reveal that C8-MSN is biocompatible in vitro, and DTX@C8-MSN shows no hemolytic activity at therapeutic concentrations, maintaining efficacy against GBM cells. Crucially, in vivo imaging demonstrates preferential accumulation of C8-MSN within the tumor region, suggesting enhanced permeability across the blood-brain tumor barrier (BBTB). When administered to orthotopic glioma mouse models, DTX@C8-MSN notably prolongs survival by over 50%, significantly reduces tumor volume, and decreases side effects compared to free DTX, indicating a targeted and effective approach to treatment. The apoptotic pathways activated by DTX@C8-MSN, evidenced by the increased levels of cleaved caspase-3 and PARP, point to a potent therapeutic mechanism. Collectively, the results advocate DTX@C8-MSN as a promising candidate for targeted therapy in TMZ-resistant GBM, optimizing drug delivery and bioavailability to overcome current therapeutic limitations.

Enhanced visible light photo-Fenton catalysis by Fe-doping oligo-layer natural molybdenite with efficient carrier spatial-driven Fe3+/Fe2+ cycle.

Developing cost-effective and efficient photo-Fenton catalysts is crucial for advancing photo-Fenton technology. MoS2 is a representative transition metal disulfide with attractive photoresponsiveness, making it ideal for preparing composite photo-Fenton catalysts. In this study, natural molybdenite was innovatively utilized as a source of MoS2 (OM) to synthesize a low-cost and efficient Fe@MoS2 (OMF) composite photo-Fenton catalyst by comminution and adsorption, which was then applied to the remediation of antibiotic-contaminated water. The OMF composites exhibited significant catalytic activity, with a kinetic rate constant of 0.022 min-1, which was 3.1 times higher than that of the original OM (0.007 min-1), indicating a 3% increase. This was attributed to the synergistic effect of many photogenerated electrons and reversible Mo4+/Mo6+ redox pairs, which accelerated the regeneration of Fe2+. After three cyclic tests, the concentrations of dissolved Fe2+ and Mo2+ ions remained below 0.38 mg/L and 0.17 mg/L, respectively. This indicates the high reusability of the catalyst in cyclic experiments. Ultimately, the main active species, •OH and •O2 -, were generated during the photo-Fenton process, contributing significantly to TC degradation. This study may serve as a reference for the development and application of natural mineral composite photo-Fenton catalysts in the treatment of organic wastewater.

[Acute heart failure in a neonate]. / æ–°ç”Ÿå„¿æ€¥æ€§å¿ƒåŠŸèƒ½ä¸å ¨1例.

The male patient, one day old, was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth. The patient had transient hypoglycemia early after birth, and acute heart failure suddenly occurred on the eighth day after birth. Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol, and pituitary magnetic resonance imaging was normal. Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene (c.917-2A>G+c.608C>T), inherited respectively from the parents. The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene. Upon initiating hydrocortisone replacement therapy, cardiac function rapidly returned to normal. After being discharged, the patient continued with the hydrocortisone replacement therapy. By the 18-month follow-up, the patient was growing and developing well. In neonates, unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases, and timely cortisol testing and genetic testing should be conducted.

The crucial relationship between miRNA-27 and CSE/H2S, and the mechanism of action of GLP-1 in myocardial hypertrophy.

Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H2S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H2S signaling. We established a model of cardiac hypertrophy by obtaining hypertrophic tissue from mice subjected to transverse aortic constriction (TAC) and from cells treated with angiotensin-II. Molecular alterations in the myocardium were quantified using quantitative real time PCR (qRT-PCR), Western blotting, and ELISA. Morphological changes were characterized by hematoxylin and eosin (HE) staining and Masson's trichrome staining. Functional myocardial changes were assessed using echocardiography. Our results demonstrated that miR-27a levels were elevated, while H2S levels were reduced in TAC mice and myocardial hypertrophy. Further luciferase and target scan assays confirmed that cystathionine-γ-lyase (CSE) was a direct target of miR-27a and was negatively regulated by it. Notably, enhancement of H2S expression in the heart was observed in mice injected with recombinant adeno-associated virus vector 9 (rAAV9)-anti-miR-27a and in cells transfected with a miR-27a inhibitor during cardiac hypertrophy. However, this effect was abolished by co-transfection with CSE siRNA and the miR-27a inhibitor. Conversely, injecting rAAV9-miR-27a yielded opposite results. Interestingly, our findings demonstrated that glucagon-like peptide-1 (GLP-1) agonists could mitigate myocardial damage by down-regulating miR-27a and up-regulating CSE. In summary, our study suggests that inhibition of miR-27a holds therapeutic promise for the treatment of cardiac hypertrophy by increasing H2S levels. Furthermore, our findings unveil a novel mechanism of GLP-1 agonists involving the miR-27a/H2S pathway in the management of cardiac hypertrophy.

Genome comparisons reveal accessory genes crucial for the evolution of apple Glomerella leaf spot pathogenicity in Colletotrichum fungi.

Apple Glomerella leaf spot (GLS) is an emerging fungal disease caused by Colletotrichum fructicola and other Colletotrichum species. These species are polyphyletic and it is currently unknown how these pathogens convergently evolved to infect apple. We generated chromosome-level genome assemblies of a GLS-adapted isolate and a non-adapted isolate in C. fructicola using long-read sequencing. Additionally, we resequenced 17 C. fructicola and C. aenigma isolates varying in GLS pathogenicity using short-read sequencing. Genome comparisons revealed a conserved bipartite genome architecture involving minichromosomes (accessory chromosomes) shared by C. fructicola and other closely related species within the C. gloeosporioides species complex. Moreover, two repeat-rich genomic regions (1.61 Mb in total) were specifically conserved among GLS-pathogenic isolates in C. fructicola and C. aenigma. Single-gene deletion of 10 accessory genes within the GLS-specific regions of C. fructicola identified three that were essential for GLS pathogenicity. These genes encoded a putative non-ribosomal peptide synthetase, a flavin-binding monooxygenase and a small protein with unknown function. These results highlight the crucial role accessory genes play in the evolution of Colletotrichum pathogenicity and imply the significance of an unidentified secondary metabolite in GLS pathogenesis.

National genomic epidemiology investigation revealed the spread of carbapenem-resistant Escherichia coli in healthy populations and the impact on public health.

BACKGROUND: Carbapenem-resistant Escherichia coli (CREC) has been considered as WHO priority pathogens, causing a great public health concern globally. While CREC from patients has been thoroughly investigated, the prevalence and underlying risks of CREC in healthy populations have been overlooked. Systematic research on the prevalence of CREC in healthy individuals was conducted here. We aimed to characterize CREC collected from healthy populations in China between 2020 and 2022 and to compare the genomes of CREC isolates isolated from healthy individuals and clinical patients. METHODS: We present a nationwide investigation of CREC isolates among healthy populations in China, employing robust molecular and genomic analyses. Antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatics were utilized to analyze a cohort of CREC isolates (n = 113) obtained from fecal samples of 5 064 healthy individuals. Representative plasmids were extracted for third-generation nanopore sequencing. We previously collected 113 non-duplicate CREC isolates (59 in 2018, 54 in 2020) collected from ICU patients in 15 provinces and municipalities in China, and these clinical isolates were used to compare with the isolates in this study. Furthermore, we employ comparative genomics approaches to elucidate molecular variations and potential correlations between clinical and non-clinical CREC isolates. RESULTS: A total of 147 CREC isolates were identified from 5 064 samples collected across 11 provinces in China. These isolates were classified into 64 known sequence types (STs), but no dominant STs were observed. In total, seven carbapenemase genes were detected with blaNDM-5 (n = 116) being the most prevalent one. Genetic environments and plasmid backbones of blaNDM were conserved in CREC isolated from healthy individuals. Furthermore, we compared clinical and healthy human-originated CRECs, revealing noteworthy distinctions in 23 resistance genes, including blaNDM-1, blaNDM-5, and blaKPC (χ2 test, p < 0.05). Clinical isolates contained more virulence factors associated with iron uptake, adhesion, and invasion than those obtained from healthy individuals. Notably, CREC isolates generally found healthy people are detected in hospitalized patients. CONCLUSIONS: Our findings underscore the significance of healthy populations-derived CRECs as a crucial reservoir of antibiotic resistance genes (ARGs). This highlights the need for ongoing monitoring of CREC isolates in healthy populations to accurately assess the potential risks posed by clinical CREC isolates.

Distinguish MnO2/Mn2+ Conversion/ Zn2+ Intercalation/ H+ Conversion Chemistries at Different Potentials in Aqueous Zn||MnO2 Batteries.

The rechargeable aqueous Zn||MnO2 chemistry has been extensively explored, but its electrochemical reaction mechanisms, especially in the context of MnO2/Mn2+ conversion and Zn2+/H+ intercalation chemistry, remain not fully understood. Here, we designed an amphiphilic hydrogel electrolyte, which distinguished the MnO2/Mn2+ conversion, Zn2+ intercalation, and H+ intercalation and conversion processes at three distinct discharge plateaus of an aqueous Zn||MnO2 battery. The amphiphilic hydrogel electrolyte is featured with an extended electrochemical stability window up to 3.0 V, high ionic conductivity, Zn2+-selective ion tunnels, and hydrophobic associations with cathode materials. This specifically designed electrolyte allows the MnO2/Mn2+ conversion reaction at a discharge plateau of 1.75 V. More interesting, the discharge plateaus of ~1.33 V, previously assigned as the co-intercalation of Zn2+ and H+ ions in the MnO2 cathode, are specified as the exclusive intercalation of Zn2+ ions, leading to an ultra-flat voltage plateau. Furthermore, with a distinct three-step electrochemical energy storage process, a high areal capacity of 1.8 mAh cm-2 and high specific energy of 0.858 Wh cm-2, even at a low MnO2 loading mass of 0.5 mg cm-2 are achieved. To our knowledge, this is the first report to fully distinguish different mechanisms at different potentials in aqueous Zn||MnO2 batteries.

Observation of giant non-reciprocal charge transport from quantum Hall states in a topological insulator.

Symmetry breaking in quantum materials is of great importance and can lead to non-reciprocal charge transport. Topological insulators provide a unique platform to study non-reciprocal charge transport due to their surface states, especially quantum Hall states under an external magnetic field. Here we report the observation of non-reciprocal charge transport mediated by quantum Hall states in devices composed of the intrinsic topological insulator Sn-Bi1.1Sb0.9Te2S, which is attributed to asymmetric scattering between quantum Hall states and Dirac surface states. A giant non-reciprocal coefficient of up to 2.26 × 105 A-1 is found. Our work not only reveals the properties of non-reciprocal charge transport of quantum Hall states in topological insulators but also paves the way for future electronic devices.

Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study.

BACKGROUND: With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them. METHODS: In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases. RESULTS: We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins. CONCLUSION: We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

L-shaped association between lean body mass to visceral fat mass ratio with hyperuricemia: a cross-sectional study.

BACKGROUND: Insufficient attention has been given to examining the correlation between body composition and hyperuricemia, leading to inconsistent findings. The primary objective of this research is to explore the association between lean body mass index (LMI), visceral fat mass index (VFMI), and hyperuricemia. A specific emphasis will be placed on assessing the link between the ratio of lean body mass to visceral fat mass (LMI/VFMI) and hyperuricemia. METHODS: The present study employed a cross-sectional design and involved a total of 9,646 individuals who participated in the National Health and Nutrition Examination Survey (NHANES). To explore the associations among the variables, logistic and linear regressions were employed. Additionally, subgroup analyses and sensitivity analyses were conducted based on various characteristics. RESULTS: The results showed that LMI was positively associated with hyperuricemia (for Per-SD: OR = 1.88, 95%CI: 1.75, 2.01; for quartiles [Q4:Q1]: OR = 5.37, 95%CI: 4.31, 6.69). Meanwhile, VFMI showed a positive association with hyperuricemia (for Per-SD: OR = 2.02, 95%CI: 1.88, 2.16; for quartiles [Q4:Q1]: OR =8.37, 95%CI: 6.70, 10.47). When considering the effects of In LMI/VFMI, an L-shaped negative association with hyperuricemia was observed (for Per-SD: OR = 0.45, 95%CI: 0.42, 0.49; for quartiles [Q4:Q1]: OR = 0.16, 95%CI: 0.13, 0.20). Subgroup and sensitivity analyses demonstrated the robustness of this association across different subgroups. Additionally, the segmented regression analysis indicated a saturation effect of 5.64 for the In LMI/VFMI with hyperuricemia (OR = 0.20, 95%CI: 0.17, 0.24). For every 2.72-fold increase of In LMI/VFMI, the risk of hyperuricemia was reduced by 80%. CONCLUSION: The LMI/VFMI ratio is non-linearly associated with serum uric acid. Whether this association is causal needs to be confirmed in further longitudinal studies or Mendelian randomization.

Multiomics analysis investigating the impact of a high-fat diet in female Sprague-Dawley rats: alterations in plasma, intestinal metabolism, and microbial composition.

Introduction: With improvements in living conditions, modern individuals exhibit a pronounced inclination towards a high-fat diet, largely because of its distinctive gustatory appeal. However, the association between high-fat diets and metabolic complications has largely been ignored, and metabolic diseases such as obesity and non-alcoholic fatty liver disease now constitute a major public health concern. Because high-fat diets increase the risk of metabolic diseases, a thorough investigation into the impact of high-fat diets on gut microbiota and metabolism is required. Methods: We utilize 16S rRNA sequencing and untargeted metabolomics analysis to demonstrate that SD rats fed a high-fat diet exhibited marked alterations in gut microbiota and plasma, intestinal metabolism. Results: Changes in gut microbiota included a decreased abundance at phylum level for Verrucomicrobiota, and a decreased abundance at genus level for Akkermansia, Ralstonia, Bacteroides, and Faecalibacterium. Additionally, significant changes were observed in both intestinal and plasma metabolite levels, including an upregulation of bile acid metabolism, an upregulation of glucose-lipid metabolism, and increased levels of metabolites such as norlithocholic acid, cholic acid, D-fructose, D-mannose, fructose lactate, and glycerophosphocholine. We also investigated the correlations between microbial communities and metabolites, revealing a significant negative correlation between Akkermansia bacteria and cholic acid. Discussion: Overall, our findings shed light on the relationship between symbiotic bacteria associated with high-fat diets and metabolic biomarkers, and they provide insights for identifying novel therapeutic approaches to mitigate disease risks associated with a high-fat diet.

Chiral Iridium-Based TLD-1433 Analogues: Exploration of Enantiomer-Dependent Behavior in Photodynamic Cancer Therapy.

Metallodrug-based photodynamic therapy (PDT) agents have demonstrated significant superiority against cancers, while their different chirality-induced biological activities remain largely unexplored. In this work, we successfully developed a pair of enantiopure mononuclear Ir(III)-based TLD-1433 analogues, Δ-Ir-3T and Λ-Ir-3T, and their enantiomer-dependent anticancer behaviors were investigated. Photophysical measurements revealed that they display high photostability and chemical stability, strong absorption at 400 nm with high molar extinction coefficients (ε = 5.03 × 104 M-1 cm-1), and good 1O2 relative quantum yields (ΦΔ ≈ 47%). Δ- and Λ-Ir-3T showed potent efficacy against MCF-7 cancer cells, with a photocytotoxicity index of ≤44 238. This impressive result, to the best of our knowledge, represents the highest value among reported mononuclear Ir(III)-based PDT agents. Remarkably, Λ-Ir-3T tended to be more potent than Δ-Ir-3T when tested against SK-MEL-28, HepG2, and LO2 cells, with consistent results across multiple test repetitions.

Boosting the Curie temperature of GaN monolayer through van der Waals heterostructures.

The pursuit of van der Waals (vdW) heterostructures with high Curie temperature and strong perpendicular magnetic anisotropy is vital to the advancement of next generation spintronic devices. First-principles calculations are used to study the electronic structures and magnetic characteristics of GaN/VS2vdW heterostructure under biaxial strain and electrostatic doping. Our findings show that a ferromagnetic ground state with a remarkable Curie temperature (477 K), much above room temperature, exists in GaN/VS2vdW heterostructure and 100% spin polarization efficiency. Additionally, GaN/VS2vdW heterostructure still maintains perpendicular magnetic anisotropy under biaxial strain, which is indispensable for high-density information storage. We further explore the electron, magnetic, and transport properties of VS2/GaN/VS2vdW sandwich heterostructure, where the magnetoresistivity can reach as high as 40%. Our research indicates that the heterostructure constructed by combining the ferromagnet VS2and the non-magnetic semiconductor GaN is a promising material for vdW spin valve devices at room temperature. .

Analysis of mild and severe neonatal enterovirus infections in a Chinese neonatal tertiary center: a retrospective case-control study.

PURPOSE: To compare the clinical characteristics, virus serotype, and outcome in cases of mild and severe enteroviral infection at a tertiary neonatal intensive care unit in China. METHODS: A retrospective analysis of cases hospitalized between June and August 2019. Samples (stool or throat swabs) were examined using reverse transcription polymerase chain reaction. Positive cases were divided into two groups: mild infection and severe infection. RESULTS: A total of 149 cases were assigned to one of two groups: mild infection (n = 104) and severe infection (n = 45). There were no significant differences between the groups in terms of sex, gestational age, birth weight, mode of delivery, and onset within 7 days. Clinical symptoms in both groups mostly resembled sepsis (fever, rash, poor feeding, and lethargy); however, there were significant variations in concomitant symptoms such as hepatitis, thrombocytopenia, encephalitis, coagulopathy, and myocarditis. Severe cases were more likely to have abnormal complete blood counts, biochemical parameters, and cerebrospinal fluid markers. The predominant serotypes implicated in neonatal enterovirus infections were echoviruses and Coxsackievirus B. Invasive ventilation, intravenous immunoglobulin, vasoactive medications, and blood product transfusions were often required, with high mortality rates among severe cases. CONCLUSION: We found significant differences between mild and severe cases of neonatal enterovirus infection with respect to complications, laboratory findings, and enterovirus serotypes. It is crucial to exercise caution when newborns exhibit symptoms of sepsis, during an enterovirus outbreak. Anemia, thrombocytopenia, abnormal liver function, and coagulation dysfunction should be monitored closely as they could indicate the presence of a severe enteroviral infection.

Quaternary Ammonium Assisted Synthesis of Melanin-like Poly(l-DOPA) Nanoparticles with a Boosted Photothermal Effect.

Poly(levodopa) nanoparticles (P(l-DOPA) NPs) are another kind of melanin mimetic besides well-established polydopamine nanoparticles (PDA NPs). Due to the presence of carboxyl groups, the oxidative polymerization of l-DOPA to obtain particles was not as efficient as that of dopamine. Several established methods toward P(l-DOPA) NP fabrication do not combine convenience, morphological regularity, size controllability, low cost, and adaptability to metal-free application scenarios. In this work, P(l-DOPA) NPs were successfully prepared in hot water with the assistant of organic quaternary ammonium, due to the extra physical cross-linking mediated by cations. The employed physical interactions could also be affected by quaternary ammonium structure (i.e., number of cation heads, length of alkyl chain) to achieve different polymerization acceleration effects. The obtained P(l-DOPA) NPs retained superior photothermal properties and outperformed PDA-based melanin materials. Furthermore, P(l-DOPA) NPs were used in photothermal tumor therapy and showed better efficacy. This study offers new insights into the synthesis of melanin-like materials, as well as new understanding of the interaction between quaternary ammonium and bioinspired polyphenolic materials.