Single-cell atlas of the human brain vasculature across development, adulthood and disease.

A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood1. Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict substantial endothelial-to-perivascular cell ligand-receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies.

Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers.

BACKGROUND: The incidence of early-stage lung adenocarcinoma (ES-LUAD) is steadily increasing among non-smokers. Previous research has identified dysbiosis in the gut microbiota of patients with lung cancer. However, the local microbial profile of non-smokers with ES-LUAD remains largely unknown. In this study, we systematically characterized the local microbial community and its associated features to enable early intervention. METHODS: A prospective collection of ES-LUAD samples (46 cases) and their corresponding normal tissues adjacent to the tumor (41 cases), along with normal lung tissue samples adjacent to pulmonary bullae in patients with spontaneous pneumothorax (42 cases), were subjected to ultra-deep metagenomic sequencing, host transcriptomic sequencing, and proteomic sequencing. The obtained omics data were subjected to both individual and integrated analysis using Spearman correlation coefficients. RESULTS: We concurrently detected the presence of bacteria, fungi, and viruses in the lung tissues. The microbial profile of ES-LUAD exhibited similarities to NAT but demonstrated significant differences from the healthy controls (HCs), characterized by an overall reduction in species diversity. Patients with ES-LUAD exhibited local microbial dysbiosis, suggesting the potential pathogenicity of certain microbial species. Through multi-omics correlations, intricate local crosstalk between the host and local microbial communities was observed. Additionally, we identified a significant positive correlation (rho > 0.6) between Methyloversatilis discipulorum and GOLM1 at both the transcriptional and protein levels using multi-omics data. This correlated axis may be associated with prognosis. Finally, a diagnostic model composed of six bacterial markers successfully achieved precise differentiation between patients with ES-LUAD and HCs. CONCLUSIONS: Our study depicts the microbial spectrum in patients with ES-LUAD and provides evidence of alterations in lung microbiota and their interplay with the host, enhancing comprehension of the pathogenic mechanisms that underlie ES-LUAD. The specific model incorporating lung microbiota can serve as a potential diagnostic tool for distinguishing between ES-LUAD and HCs.

Ring-Contracted Artemisinin Derivatives as Novel CDK 4/6 Inhibitors: Synthesis and Anti-Breast Cancer Evaluation.

The endoperoxide group of artemisinins is universally accepted an essential group for their anti-cancer effects. In this study, a series of D-ring-contracted artemisinin derivatives were constructed by combining ring-contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty-six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H-NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 µM and 9.97±1.44 µM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 µM, and its activity was approximately 1/3 of the positive control Palbociclib.

Soil organic matter and total nitrogen as key driving factors promoting the assessment of acid-base buffering characteristics in a tea (Camellia sinensis) plantation habitat.

The issue of soil acidification in tea plantations has become a critical concern due to its potential impact on tea quality and plant health. Understanding the factors contributing to soil acidification is essential for implementing effective soil management strategies in tea-growing regions. In this study, a field study was conducted to investigate the effects of tea plantations on soil acidification and the associated acid-base buffering capacity (pHBC). We assessed acidification, pHBC, nutrient concentrations, and cation contents in the top 0-20 cm layer of soil across forty tea gardens of varying stand ages (0-5, 5-10, 10-20, and 20-40 years old) in Anji County, Zhejiang Province, China. The results revealed evident soil acidification due to tea plantation activities, with the lowest soil pH observed in tea gardens aged 10-20 and 20-40 years. Higher levels of soil organic matter (SOM), total nitrogen (TN), Olsen phosphorus (Olsen-P), available iron (Fe), and exchangeable hydrogen (H+) were notably recorded in 10-20 and 20-40 years old tea garden soils, suggesting an increased risk of soil acidification with prolonged tea cultivation. Furthermore, prolonged tea cultivation correlated with increased pHBC, which amplified with tea stand ages. The investigation of the relationship between soil pHBC and various parameters highlighted significant influences from soil pH, SOM, cation exchange capacity, TN, available potassium, Olsen-P, exchangeable acids (including H+ and aluminum), available Fe, and available zinc. Consequently, these findings underscore a substantial risk of soil acidification in tea gardens within the monitored region, with SOM and TN content being key driving factors influencing pHBC.

Bimetallic Cage-Based Metal-Organic Frameworks for Electrochemical Hydrogen Evolution Reaction with Enhanced Activity.

A cage-based metal-organic framework (Ni-NKU-101) with biphenyl-3,3',5,5'-tetracarboxylic acid was synthesized via solvothermal method. Ni-NKU-101 contains two types of cages based on trinuclear and octa-nuclear nickel-clusters that are connected with each other by the 4-connected ligands, to form a 3D framework with a new topology. A mixed-metal strategy was used to synthesize isostructural bimetallic MOFs of Mx Ni1-x -NKU-101 (M=Mn, Co, Cu, Zn). The electrocatalytic studies showed that the hydrogen evolution reaction (HER) activity of Cux Ni1-x -NKU-101 is much higher than that of other Mx Ni1-x -NKU-101 catalysts in acidic aqueous solution, owing to the synergistic effect of the bimetallic centers. The optimized Cu0.19 Ni0.81 -NKU-101 has an overpotential of 324 mV at 10 mA cm-2 and a Tafel slope of 131 mV dec-1 . The mechanism of HER activity over these bimetallic MOF-based electrocatalysts are discussed in detail.

Review on the COVID-19 pandemic prevention and control system based on AI.

As a new technology, artificial intelligence (AI) has recently received increasing attention from researchers and has been successfully applied to many domains. Currently, the outbreak of the COVID-19 pandemic has not only put people's lives in jeopardy but has also interrupted social activities and stifled economic growth. Artificial intelligence, as the most cutting-edge science field, is critical in the fight against the pandemic. To respond scientifically to major emergencies like COVID-19, this article reviews the use of artificial intelligence in the combat against the pandemic from COVID-19 large data, intelligent devices and systems, and intelligent robots. This article's primary contributions are in two aspects: (1) we summarized the applications of AI in the pandemic, including virus spreading prediction, patient diagnosis, vaccine development, excluding potential virus carriers, telemedicine service, economic recovery, material distribution, disinfection, and health care. (2) We concluded the faced challenges during the AI-based pandemic prevention process, including multidimensional data, sub-intelligent algorithms, and unsystematic, and discussed corresponding solutions, such as 5G, cloud computing, and unsupervised learning algorithms. This article systematically surveyed the applications and challenges of AI technology during the pandemic, which is of great significance to promote the development of AI technology and can serve as a new reference for future emergencies.

Plasmon catalytic PATP coupling reaction on Ag-NPs/graphite studied via in situ electrochemical surface-enhanced Raman spectroscopy.

The p-aminothiophenol (PATP) coupling reaction on plasmon substrates such as Ag and Au nanoparticles has received extensive attention since the catalytic effect of the surface plasmon was found. Currently, in situ kinetic studies of this reaction are rare, especially those focusing on the specific role of the hot electron-hole carriers. Here, in situ electrochemical surface-enhanced Raman spectroscopy (SERS) is developed to study the plasmon catalytic reaction of PATP in a controlled aqueous environment involving the factors of O2, electron and hole carriers, and solution pH. Ag nanoparticles supported on graphite serve as a SERS substrate, which could separate hot electron-hole pairs effectively and is beneficial to study the effects of hot carriers on plasmon-driven reactions. In situ electrochemical SERS measurements reveal two reaction paths for the PATP coupling reaction. One is that plasmon-induced hot holes activate the dehydrogenation of PATP and then the radical coupling reaction to form p,p'-dimercaptoazobenzene (DMAB) under O2-free conditions. Another is likely to be that the surface Ag2O/AgOH, which is generated from Ag and 1O2/O2-, catalyzes the oxidation of PATP and then the coupling process under O2-rich conditions. Benefitting from the potential/atmosphere controlled measurements in situ, the intermediate species of PATP(NH)/PATP(N) are observed with vibrational bands at around 1056, 1202, 1253, 1395, 1514 and 1540 cm-1.

Finely Tuned Structure and Catalytic Performance of Cerium Oxides by a Continuous Samarium Doping from 0 to 100.

Cerium oxides are prevalent catalytic materials, and the lanthanide-doped ceria have attracted special interest since it is easy to tune the concentration of oxygen vacancies (VO) by changing the doping content. The presence of VO is generally believed to favor a catalytic reaction, but the formation of dopant-vacancy associations at a high doping concentration might produce an adverse effect. Herein, evolutions of the structural properties and catalytic performances in Sm-doped ceria (SmxCe1-xO2-δ, x = 0-1) are investigated to explore the doping effect of Sm3+ on the ceria-based nanoctrystals. The SmxCe1-xO2-δ films composed of nanoctrystals are elaborately prepared via electrodeposition under mild conditions to prevent phase separation. A combination of studies, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman, photoluminescence (PL), and methanol electro-oxidation (MEO) reaction, reveals that variation trends for the VO concentration and catalytic property of SmxCe1-xO2-δ are unsynchronized. The lattice structures of SmxCe1-xO2-δ nanoctrystals undergo a smooth and steady transition from F-type (fluorite CeO2) to C-type (cubic Sm2O3) with the increase of Sm3+ contents. The structural transition occurs in the Sm3+ concentration range of 64-84%, within which the VO concentration reaches the maximum as well. However, the optimal MEO performance is obtained at a relatively lower doping concentration of 24%. Above this concentration, significant dopant-vacancy associates are observed by XRD, Raman, and PL characterizations. It is inferred that, for these ceria-based nanocrystals, the dopant-vacancy association induced by high doping would impede the growth of catalytic performance despite all the benefits of VO.

The Effectiveness of Medial Femoral Epicondyle Up-Sliding Osteotomy to Correct Severe Valgus Deformity in Primary Total Knee Arthroplasty.

BACKGROUND: While many surgical techniques can achieve neutral limb alignment and soft tissue balance in severe valgus deformity during total knee arthroplasty (TKA), few published reports concern medial femoral epicondyle up-sliding osteotomy. METHODS: A prospective investigation was conducted of patients with severe valgus deformities who underwent medial femoral epicondyle up-sliding osteotomy. Clinical measurements, radiological evaluation, and complication data were recorded. RESULTS: Using posterior-stabilized prostheses, 26 patients underwent 28 TKAs performed by the same surgeon using medial femoral epicondyle up-sliding osteotomy to balance the soft tissue. On average, the follow-up was 54 ± 18 months, and the patient age was 63 ± 11 years. All knees were type II according to Krackow's classification. Varus-valgus knee motion was prohibited with the protection of long-leg knee brace for 3 months. At the last follow-up, the Knee Society function score, Hospital for Special Surgery knee-rating scale, and range of motion were 94 ± 6, 91 ± 4, and 116° ± 8°, respectively. All knees were stable laterally, whereas 2 knees had mild medial laxity and the others were stable. The hip-knee-ankle angle, femorotibial angle, condylar-hip angle, plateau-ankle angle, and valgus angle were 179.9° ± 3.4°, 172.9° ± 3.6°, 89.8° ± 2.5°, 90.2° ± 1.1°, and 7.3° ± 3.5°, respectively. CONCLUSION: Medial femoral epicondyle up-sliding osteotomy during TKA in patients with severe valgus deformities facilitates the restoration of lower limb alignment, soft tissue balance, and knee stability.

[Design, synthesis and antiproliferative activity in cancer cells of novel dihydropyrazolyl and pyrazolyl artemisinin-phenyl ethers].

To explore potent anticancer agent based on artemisinin scaffold, a series of 10-O-phenyl ethers derivatives containing dihydropyrazolyl or pyrazolyl moiety have been designed and synthesized. Their structures were determined by LC-MS and ¹H-NMR date. Inhibitory effects of the target compounds in human breast cancer MCF-7, MCF/Adr, MDA-MB-231 cells and prostate cell line PC-3 were determined by MTT assay. Those derivatives displayed good antiproliferative activity against the tested cancer cells. Particularly, target compounds exhibited significant cytotoxicity against drug-resistance cells MCF/Adr, which was worthy for further investigation.

[Research on Relationship of HIF-1 Signaling Pathway and Postmenstrual Osteoporosis].

OBJECTIVE: Exploring the role of hypoxia-induceibal factor-1 (HIF-1) signaling pathway in postmenstrual osteoporosis (PMOP) and how to play a role in PMOP. METHODS: Sixty C57BL/6J female mouse were randomly divided into 4 groups: sham-operation group (A group),ovariectomized PMOP group (B group),HIF-1 alpha inhibitor 2-methoxy estradiol (2ME2) treatment group(D group) and solvent control group(C group),15 mice in each group. There months after modeling,the metabolism product of mouse bone tissue including serum propeptide of typeⅠ procollagen (PINP),C-terminal telopeptide-Ⅰ (CTX-1) and serum estrogen were quantified by enzyme-linked immunosorbent assay (ELISA). Changes of bone structure were observed on HE stained tissue sections. Regulation products of HIF-1 signaling pathway including HIF-1α,HIF-1ß,specific prolyl hydroxylases (PHD),Hipple-Lindau tumor suppressor protein (VHL),and factor inhibiting HIF (FIH) were measured by immuno-histochenmistry staining. Osteoclasts derived from OVX-mice were treated with inhibitors of extracellular regulated protein kinases (ERK),protein kinase B (Akt) and nuclear factor kappa B (NF-κB) signaling pathways. HIF-1α expression were detected by Western blot to obtain a rudimentary knowledge of possible mechanism of up-regulation of HIF-1α in osteoclasts of postmenospausal osteoporosis. RESULTS: Metabolism product of mouse bone tissue of B group were higher than A group ( P<0.001). The positive expression of HIF-1-alpha protein was found in osteoclasts,and the expression of HIF-1-alpha protein in bone marrow region was higher than that in A group ( P<0.001), while the change od HIF-1ß,PHD,VHL,and FIH were not obviously. After the HIF-1α inhibitor treatment,markers of bone resorption of bone metabolism in ovariectomized mice reduced and the osteoporosis get greatly relieved ( P<0.001). HIF-1α expression was down-regulated in osteoclasts of OVX-mice after treated with inhibitors of ERK,Akt and NF-κB signaling pathways ( P<0.05). CONCLUSION: HIF-1 signaling pathway get involved in the pathological evolution of osteoporosis after menopause,and inhibition of HIF-1 can significantly improve the severity of osteoporosis after menopause. ERK,Akt and NF-κB signaling pathways may involve in the up-regulation of HIF-1 signaling pathway in osteoclasts of PMOP.

Activin A/Smads signaling pathway negatively regulates Oxygen Glucose Deprivation-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells.

Activin A (Act A), a member of the transforming growth factor-beta (TGF-ß), reduces neuronal apoptosis during cerebral ischemia through Act A/Smads signaling pathway. However, little is known about the effect of Act A/Smads pathway on autophagy in neurons. Here, we found that oxygen-glucose deprivation (OGD)-induced autophagy was suppressed by exogenous Act A in a concentration-dependent manner and enhanced by Act A/Smads pathway inhibitor (ActRIIA-Ab) in neuronal PC12 cells. These results indicate that Act A/Smads pathway negatively regulates autophagy in OGD-treated PC12 cells. In addition, we found that c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways are involved in the OGD-induced autophagy. The activation of JNK and p38 MAPK pathways in OGD-treated PC12 cells was suppressed by exogenous Act A and enhanced by ActRIIA-Ab. Together, our results suggest that Act A/Smads signaling pathway negatively regulates OGD-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells.

[Design, synthesis and antiproliferative activities of artemisinin derivatives substituted by N-heterocycles].

Increasing attention has been focused on the antitumor activity of artemisinin derivatives in recent years, for artemisinin had been reported to have cytotoxic effects against HL-60, P388 and MCF-7 tumor cells. We report here the synthesis and evaluation for antitumor activity of a series of artemisinin-ether derivatives bearing tetrahydropyrrole, morpholine, piperidine, substituted piperidines and azoles with various linkers. Sixteen 10-O-substituted dihydroartemisinin derivatives were designed and synthesized, all of which have never been reported in literatures and whose antiproliferative effects on human breast cancer MCF-7, MCF-7/Adr and HL-60 cells were determined by MTT assay or direct cell counting. Each of these artemisinin derivatives possessed better effects than dihydroartemisinin evidently against HL-60 and MCF-7 cells growth, while less potent than doxorubicin. All target compounds exhibited significantly improved potency compared to DHA and doxorubicin on the doxorubicin-resistant MCF-7/Adr cells, so did they in their sensitive counterparts MCF-7 cells. Among them, compounds GF02, GH04 and ZH04 showed strong activity against these three cell lines growth. Further research is undergoing.

A stable and flexible Au@Ag NPs/PVA SERS platform for thiram residue detection on rough surface.

Flexible and transparent surface-enhanced Raman scattering (SERS) substrates have gained great attention in analysis field as they offer a fast, non-destructive, and highly sensitive platform for in-situ detection. In this work, we present a facile one-pot strategy for synthesizing gold-cored silver shell nanoparticles (Au@Ag NPs) in the polyvinyl alcohol (PVA) colloid. With no other reducing agents, PVA can serve as both reducing and stabilizing agents for forming Au@Ag NPs. Besides, PVA acts as a scaffold to maintain SERS "hot-spots" by preventing nanoparticle aggregation. By using this flexible Au@Ag NPs/PVA colloid, the analytes can be extracted from rough surfaces for SERS measurements with excellent sensitivity, repeatability and stability. The SERS activity of the Au@Ag NPs/PVA remained at 89.8% even after 120 days of storage at room temperature in sealed air atmosphere. The selective detection of thiram residues on the surface of fruits and vegetables was successfully achieved. The limits of detection for thiram residues on apple and tomato surfaces were measured to be 0.58 and 0.56 ng cm-2, respectively, with recovery rate ranging from 91% to 107%. This work demonstrates the immense application potential of SERS colloid platform in the fields of food safety and environmental analysis.

Ethyl cellulose/gelatin-carboxymethyl chitosan bilayer films doped with Euryale ferox seed shell polyphenol for cooked meat preservation.

This study evaluated the effects of an edible bilayer containing polyphenols from the Euryale ferox seed shell on ready-to-eat cooked beef products, including the physical, mechanical, antioxidant, and antibacterial capabilities. Here, the bilayer films were prepared by layer-by-layer solution pouring using hydrophobic ethyl cellulose (EC) as the outer layer, and hydrophilic gelatin/carboxymethyl chitosan (GC) as the inner layer. By adjusting the proportion of gelatin to carboxymethyl chitosan, the optical, mechanical, and barrier characteristics of bilayer films were markedly enhanced. Extracted polyphenol (EP) from shell of the Euryale ferox seed performed potent antibacterial property against Listeria monocytogenes (L. monocytogenes). The addition of EP to the inner layer of the optimized bilayer film further improved the mechanical and barrier properties of films, and as expected, the film exhibited antioxidant and antibacterial abilities. Additionally, cooked beef and cooked chicken preservation tests indicated that the active bilayer film showed good inhibition of L. monocytogenes and delayed lipid oxidation in ready-to-eat meat products, and significantly delayed the pH, moisture loss, color and texture changes. This study developed multifunctional bilayer active edible films, which has a great potential in the preservation ready-to-eat cooked meat products.

Exploring functional metabolites and proteomics biomarkers in late-preterm and natural-born pigs.

Introduction: Pigs are often used to study the intestinal development of newborns, particularly as preterm pig models that mimic the intestinal growth of human preterm infants. Neonatology's study of delivery mode's impact on neonatal development is crucial. Methods: We established 14 newborn pigs delivered via cesarean sections (C-section, at 113 days of gestational age, CS group) and 8 naturally born pigs were used as controls (at 114 days of gestational age, NF group). The impact of two alternative delivery procedures (C-section and natural birth) on the levels of short-chain fatty acids (SCFAs) and organic acids in the hepatic and intestines of newborn pigs were compared using metabolomics. The underlying molecular pathways are examined at the "protein-metabolite" level by integrating proteomic data. Results: The findings demonstrated that the mode of delivery changed the metabolism of SCFAs in newborn pigs, perhaps by affecting the physiology levels of cyclic intermediates such as lactate and malate in the pyruvate metabolic pathway. Additionally, by participating in the fatty acid metabolism pathway, two distinct proteins (FASN and HSD17B4) may impact the physiological concentration of these tiny metabolites. Discussion: In conclusion, this study provided reliable animal model data for understanding the physiological SCFA metabolic information and its affecting mechanism of large-gestational age preterm infants.

Modulation of Performance, Plasma Constituents, Small Intestinal Morphology, and Cecum Microbiota in Growing Geese by Dietary Citric Acid Supplementation.

To investigate the efficiency and optimum inclusion level of CA in growing geese diets on performance, plasma constituents, and intestinal health, 240 healthy female geese at the age of 28d were randomly allotted six treatment diets incorporated with 0, 0.8, 1.6, 2.4, 3.2, and 4% CA. Each treatment group consisted of five replicates and eight birds per replicate. The findings demonstrated that 3.2% CA supplementation resulted in improved growth performance (ADG, ADFI, and FBW) (p = 0.001), and geese who received CA also showed lower body fat contents (p < 0.05) than the control group. Moreover, geese from the 2.4% and 3.2% CA group had the highest plasma glutathione peroxidase and insulin-like growth factor 1 levels compared to the other groups (p < 0.05). A microbial diversity analysis of the cecum conducted by 16S rDNA sequencing revealed that 3.2% CA supplementation showed a significantly higher abundance of beneficial bacteria (Muribaculaceae, CHKCI001, Erysipelotricha-ceae_UCG_003, and UCG_009) (p < 0.05) and a lower abundance of harmful bacteria (Atopobiaceae, Streptococcus, Acinetobacter, Pseudomonas, and Alistipes) (p < 0.10). Collectively, our results revealed that dietary supplementation with 3.2% CA had several benefits on the performance and physiological health of growing geese by promoting nutrients metabolism, improving antioxidant capacity, and modulating cecum microbiota.

Metagenomic profiling uncovers microbiota and antibiotic resistance patterns across human, chicken, pig fecal, and soil environments.

The ongoing and progressive evolution of antibiotic resistance presents escalating challenges for the clinical management and prevention of bacterial infections. Understanding the makeup of resistance genomes and accurately quantifying the current abundance of antibiotic resistance genes (ARGs) are crucial for assessing the threat of antimicrobial resistance (AMR) to public health. This comprehensive study investigated the distribution and diversity of bacterial community composition, ARGs, and virulence factors (VFs) across human, chicken, pig fecal, and soil microbiomes in various provinces of China. As a result, multidrug resistance was identified across all samples. Core ARGs primarily related to multidrug, MLS (Macrolides-Lincosamide-Streptogramins), and tetracycline resistance were characterized. A significant correlation between ARGs and bacterial taxa was observed, especially in soil samples. Probiotic strains such as Lactobacillus harbored ARGs, potentially contributing to the dissemination of antibiotic resistance. We screened subsets of ARGs from samples from different sources as indicators to assess the level of ARGs contamination in samples, with high accuracy. These results underline the complex relationship between microbial communities, resistance mechanisms, and environmental factors, emphasizing the importance of continued research and monitoring to better understand these dynamics.

The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19.

BACKGROUND: COVID-19 clinical course is highly variable and secondary infections contribute to COVID-19 complexity. Early detection of secondary infections is clinically relevant for patient outcome. Procalcitonin (PCT) and C-reactive protein (CRP) are the most used biomarkers of infections. Pentraxin 3 (PTX3) is an acute phase protein with promising performance as early biomarker in infections. In patients with COVID-19, PTX3 plasma concentrations at hospital admission are independent predictor of poor outcome. In this study, we assessed whether PTX3 contributes to early identification of co-infections during the course of COVID-19. METHODS: We analyzed PTX3 levels in patients affected by COVID-19 with (n = 101) or without (n = 179) community or hospital-acquired fungal or bacterial secondary infections (CAIs or HAIs). FINDINGS: PTX3 plasma concentrations at diagnosis of CAI or HAI were significantly higher than those in patients without secondary infections. Compared to PCT and CRP, the increase of PTX3 plasma levels was associated with the highest hazard ratio for CAIs and HAIs (aHR 11.68 and 24.90). In multivariable Cox regression analysis, PTX3 was also the most significant predictor of 28-days mortality or intensive care unit admission of patients with potential co-infections, faring more pronounced than CRP and PCT. INTERPRETATION: PTX3 is a promising predictive biomarker for early identification and risk stratification of patients with COVID-19 and co-infections. FUNDING: Dolce & Gabbana fashion house donation; Ministero della Salute for COVID-19; EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT) and MUR PNRR Italian network of excellence for advanced diagnosis (Project no. PNC-E3-2022-23683266 PNC-HLS-DA); EU MSCA (project CORVOS 860044).

Development and validation of a deep-learning model for the detection of non-displaced femoral neck fractures with anteroposterior and lateral hip radiographs.

Background: Hip fractures, including femoral neck fractures, are a significant cause of morbidity and mortality in the elderly population and are typically diagnosed using plain radiography. However, diagnosing non-displaced femoral neck fractures can be challenging due to their subtle appearance on hip radiographs. Previous deep-learning models have shown low accuracy in identifying these fractures on anteroposterior (AP) radiographs; however, no studies have used lateral radiographs. This study aimed to evaluate the potential of using deep-learning with both AP and lateral hip radiographs to automatically identify non-displaced femoral neck fractures. Methods: We conducted a retrospective analysis of patients with femoral neck fractures at The First Affiliated Hospital of Xiamen University. All the hip radiographs were reviewed, and cases of non-displaced femoral neck fractures were included in the study. Additionally, 439 participants with normal hip radiographs were also included in the study. A vision transformer (Vit) model was developed using 1,536 AP and lateral hip radiograph. The model's performance was compared to the performance of two groups of human observers: an expert group comprising orthopedic surgeons and radiologists, and a non-expert group, including emergency physicians and general practice doctors. We also carried out the external validation using two additional data sets to assess the generalizability of the model. Results: The Vit model showed exceptional performance in detecting non-displaced femoral neck fractures on paired AP and lateral hip radiographs, achieving a binary accuracy of 95.8% [95% confidence interval (CI): 94.9%, 96.8%] and an area under the curve (AUC) of 0.988. Compared to the human observers, the model had a higher accuracy of 96.7% (95% CI: 93.9%, 99.5%) on the paired AP and lateral hip radiographs, while the accuracy of the expert group was 90.5% (95% CI: 85.7%, 95.2%). Further, the model maintained good performance during the external validation, with an AUC of 0.959 on the paired AP and lateral views. Conclusions: Our Vit model showed expert-level performance in identifying non-displaced femoral neck fractures on paired AP and lateral hip radiographs. This model has the potential to enhance diagnosis accuracy and improve patient outcomes by reducing the need for additional examinations and preoperative time.