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N-doped TiO2/carbon composites (N-TiPC) have shown excellent photodegradation performances to the organic contaminants but are limited by the multistage preparation (i.e., preparation of porous carbon, preparation of N-doped TiO2, and loading of N-doped TiO2 on porous carbon). Here, we develop a handy way by combining the Pickering emulsion-gel template route and chelation reaction of polysaccharides. The N-TiPC is obtained by calcinating pectin/Dl-serine hydrazide hydrochloride (SHH)-Ti4+ chelate and is further described by modern characterization techniques. The results show that the N atom is successfully doped into the TiO2 lattice, and the bandgap value of N-TiPC is reduced to 2.3 eV. Moreover, the particle size of N-TiPC remains about 10 nm. The configurations of the composites are simulated using DFT calculation. The photocatalytic experiments show that N-TiPC has a high removal efficiency for methylene blue (MB) and oxytetracycline hydrochloride (OTC-HCL). The removal ratios of MB (20 mg/L, 50 mL) and OTC-HCL (30 mg/L, 50 mL) are 99.41 % and 78.29 %, respectively. The cyclic experiments show that the photocatalyst has good stability. Overall, this study provides a handy way to form N-TiPC with enhanced photodegradation performances. It can also be promoted to other macromolecules such as cellulose and its derivatives, sodium alginate, chitosan, lignin, etc.
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BACKGROUND: Elagolix, an approved non-peptide GnRH antagonist, shows promise in relieving endometriosis-related pain, but its short- and mid-term efficacy and potential side effects are still under investigation. OBJECTIVE: The aim is to provide data for therapeutic applications by methodically evaluating elagolix's safety and effectiveness in treating endometriosis-related pain. METHODS: Databases such as PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and others were thoroughly searched. The search time was from the establishment date to September 2023. The study included randomized controlled trials (RCTs) that compared the efficacy of elagolix versus placebo in treating endometriosis-associated pain. After data extraction and literature scanning, quality assessment was carried out using Quality evaluation was carried out using the bias risk assessment tool suggested by the Cochrane Reviewers' Handbook 5.1.0 after literature screening and data extraction. Stata 15.0 was used to do the meta-analysis. RESULTS: In total, five RCTs involving 2056 patients were included in the analysis. The meta-analysis demonstrated a significant superiority of elagolix over placebo in the management of endometriosis-related pain, specifically in endometriosis pain [WMD=-0.77, 95% CI (-1.00, -0.53), P<0.001], as well as in non-menstrual pelvic pain, daily assessment of dysmenorrhea (DYS), and dyspareunia (DYSP), all of which are associated with endometriosis. Regarding safety, no discernible variation was observed in the incidence of serious adverse responses between the elagolix and placebo groups [RR=0.90, 95% CI (0.58, 1.40), P=0.643]. Conversely, the elagolix group exhibited a significantly higher incidence rate of general adverse responses [RR = 1.34, 95% CI (1.18, 1.52), P<0.001] compared to the control group. CONCLUSIONS: The efficacy of elagolix in reducing pain in premenopausal women with endometriosis has been demonstrated over the short- to mid-term. However, careful monitoring for potential adverse effects is essential throughout the treatment duration.
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BACKGROUND: Remnant cholesterol (RC) reportedly contributes to the development of diabetes mellitus. However, evidence on the relationship between maternal RC and the risk of developing gestational diabetes mellitus (GDM) during pregnancy is limited. This study aimed to assess the relationship between maternal RC and GDM risk during early pregnancy, and explore the potential pathways involved in the relationship between RC levels and GDM risk. METHODS: From 2018 to 2021, a prospective birth cohort study was designed and carried out in China. The associations of maternal RC and other lipid parameters with GDM risk were estimated using logistic regression models and restricted cubic splines. Subgroup analyses were performed stratified by prepregnancy body mass index (pre-BMI), maternal age and gravidity. Mediation analyses were conducted to explore the mediating effect of some related factors on the relationship between RC levels and the risk of GDM. RESULTS: A total of 33,018 pregnant women were included. The median RC level was 0.47 ± 0.20 mmol/L. The prevalence of GDM was 15.19%. As RC quartiles increased, the incidence of GDM increased substantially, reaching 19.24% for the highest quartile of RC (P < 0.001). Maternal RC in the first trimester was positively correlated with GDM risk (OR: 2.254, 95% CI: 1.943-2.615). Compared to the lowest RC quartile, higher RC quartiles were correlated with an increased risk of GDM, and the ORs (95% CIs) for Q3 and Q4 were 1.208 (1.101-1.325) and 1.489 (1.364-1.626), respectively. Moreover, a linear dose-response relationship was found for this association (P for all < 0.001, P for nonlinearity > 0.05) and was consistent across subgroups with different pre-BMIs, maternal ages and gravidities (all P values for interactions > 0.05). Furthermore, the correlation between RC level and GDM risk was partially mediated by pre-BMI (9.20%) and blood glucose level (-11.1%). CONCLUSIONS: Higher maternal RC levels in the early stage of pregnancy was positively associated with an increased risk of developing GDM. This association was partially mediated by pre- BMI and blood glucose levels.
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Indice de masse corporelle , Cholestérol , Diabète gestationnel , Humains , Diabète gestationnel/sang , Diabète gestationnel/épidémiologie , Grossesse , Femelle , Adulte , Études prospectives , Cholestérol/sang , Facteurs de risque , Chine/épidémiologie , Premier trimestre de grossesse/sang , Modèles logistiquesRÉSUMÉ
Anisopteromalus calandrae (Howard) shows great promise as an ectoparasitoid for controlling various coleopteran pests in warehouses. However, for a large-scale release, it is crucial to establish an ample supply of A. calandrae while carefully maintaining their quality and effectiveness. Appropriate cold storage techniques are the key to achieving these goals. Previous studies on cold storage have focused on specific developmental stages and explored cold storage conditions that can be applied only to those stages. Herein, we examined the development, survival and reproductive capacity of A. calandrae at different temperatures (13, 16, and 19 °C) and storage durations (30, 60, and 90 d) and evaluated the fitness of the offspring. A. calandrae completed its egg-to-larva development and pupated at 16 °C, but its development was arrested at an early pupal stage. Even after 90 d of cold storage at 16 °C, the survival rate of A. calandrae remained high at 77%, with no significant impact on reproductive capacity. Furthermore, cold storage showed no negative effect on the F1 generation. In contrast, eggs stored at 13 °C failed to hatch, whereas those stored at 19 °C developed. Adults emerged after > 60 d. This indicates that storage at 19 °C is only suitable for short durations. Our findings highlight the developmental pattern of A. calandrae at 16 °C, indicating that the parasitic wasp can be stored for a long time at this temperature across all stages of development before pupation, substantially facilitating its mass reproduction and industrial production.
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Ferroptosis is a newly defined mode of cellular demise. The increasing investigation supports that ferroptosis is a crucial factor in the complex mechanisms of myocardial ischemia-reperfusion (I/R) injury. Hence, targeting ferroptosis is a novel strategy for treating myocardial injury. Although evidence suggests that trimetazidine (TMZ) is potentially efficacious against myocardial injury, the exact mechanism of this efficacy is yet to be fully elucidated. This study aimed to determine whether TMZ can act as a ferroptosis resistor and affect I/R-mediated myocardial injury. To this end, researchers have constructed in vitro and in vivo models of I/R using H9C2 cardiomyocytes, primary cardiomyocytes, and SD rats. Here, I/R mediated the onset of ferroptosis in vitro and in vivo, as reflected by excessive iron aggregation, GSH depletion, and the increase in lipid peroxidation. TMZ largely reversed this alteration and attenuated cardiomyocyte injury. Mechanistically, we found that TMZ upregulated the expression of Sirt3. Therefore, we used si-Sirt3 and 3-TYP to interfere with Sirt3 action in vitro and in vivo, respectively. Both si-Sirt3 and 3-TYP partly mitigated the inhibitory effect of TMZ on I/R-mediated ferroptosis and upregulated the expression of Nrf2 and its downstream target, GPX4-SLC7A11. These results indicate that TMZ attenuates I/R-mediated ferroptosis by activating the Sirt3-Nrf2/GPX4/SLC7A11 signaling pathway. Our study offers insights into the mechanism underlying the cardioprotective benefits of TMZ and establishes a groundwork for expanding its potential applications.
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Parthenocarpy is an important way for seedless fruit production in citrus. However, the molecular mechanism(s) of parthenocarpy in pomelo is still unknown. Our initial study found significantly different parthenocarpic abilities in Guanximiyou (G) and Shatianyou (S) pomelo following emasculation, and an endogenous hormone content assay revealed that indole-3-acetic acid (IAA), gibberellic acid (GA3) and zeatin (ZT) jointly promoted fruit expansion and cell division in parthenocarpic pomelo (G pomelo). To unravel the underlying molecular mechanism(s), we conducted the first transcriptome analysis on the two pomelo accessions at these two critical stages: the fruit initiation stage and the rapid expansion stage, in order to identify genes associated with parthenocarpy. This analysis yielded approximately 7.86 Gb of high-quality reads, and the subsequent de novo assembly resulted in the identification of 5,792 DEGs (Differentially Expressed Genes). Among these, a range of transcription factor families such as CgERF, CgC2H2, CgbHLH, CgNAC and CgMYB, along with genes like CgLAX2, CgGH3.6 and CgGH3, emerged as potential candidates contributing to pomelo parthenocarpy, as confirmed by qRT-PCR analysis. The present study provides comprehensive transcriptomic profiles of both parthenocarpic and non-parthenocarpic pomelos, reveals several metabolic pathways linked to parthenocarpy, and highlights the significant role of plant hormones in its regulation. These findings deepen our understanding of the molecular mechanisms underlying parthenocarpy in pomelo.
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ConspectusThe market demand for lithium-ion batteries (LIBs) has been proliferating in wide applications, from portable electronics and electric vehicles to renewable energy storage, due to their advantages of high energy density and reliable life cycles. Currently, further development of LIBs is hindered by the limited specific/volumetric capacity and high cost of conventional intercalation-type cathode materials. In this context, sulfur (S) has gained intensive attention as a conversion-type cathode because of its abundance, low cost, and high theoretical capacity (1675 mAh g-1). However, the insulating nature of S causes severe issues of sluggish redox kinetics, low S utilization, and unsatisfactory practical capacity. So far, extensive efforts have been devoted to boosting Li-S redox kinetics and enhancing cycling stability by inhibiting the shuttle effect, including developing functional electrolyte additives, introducing redox catalysts, and tailoring the S cathode structure. Partially substituting S atoms in S8 rings with high-electrical-conductivity elements (e.g., selenium, 1 × 10-3 S m-1) at the molecular level proves to be an effective strategy for tackling the above-mentioned challenges in Li-S batteries. It is noteworthy that tellurium (Te), with remarkable electrical conductivity (2 × 102 S m-1) and high density (6.24 g cm-3), is a promising battery electrode material that can realize fast electron transport and deliver volumetric capacity comparable to that of S or Se. Additionally, Te-S molecular regulation is one facile strategy to reshape Li-S chemistry, accelerate redox kinetics, and manipulate the lithiation/delithiation behaviors. Te is an effective eutectic accelerator that prevents polysulfide dissolution in Li-S batteries under the dissolution-deposition mechanism. Meanwhile, the Li-Te electrochemistry can contribute to reversible capacity in Li-TexSy batteries through Te-Li2Te conversion and enhance the materials utilization of TexSy.This Account highlights state-of-the-art advancements in applying Te or TexSy as high-capacity cathodes for rechargeable batteries. First, battery configuration and reaction pathways in Li-Te batteries are discussed, followed by the introduction of cathode design strategies to improve cathode structure stability. The limitations of this Te-only cathode are outlined in terms of the abundance, cost, and energy density. Second, the role of Te in Li-S chemistry is clarified by the analysis of the crystal structure, electrochemical behaviors, solid electrolyte interphase composition, and energy profiles. Third, recent progresses on quasi-solid-state Li-Te batteries have been introduced, focusing on flexible gel polymer electrolytes with adjustable ionic conductivity. Afterward, advancements in interface engineering by the atomic layer deposition technique in metal-Te batteries are highlighted. Additionally, mechanistic analysis in emerging zinc-TexSy batteries with outstanding areal capacity is demonstrated. Finally, we provide insightful perspectives on the future directions of material design in Te-based energy storage technologies. This Account is expected to deepen the fundamental understanding of metal-Te/TexSy chemistry and offer inspiration for the further development of Te-based high-energy-density rechargeable batteries.
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Line edge roughness (LER) has been an important issue in the nanofabrication research, especially in integrated circuits. Despite numerous research studies has made efforts on achieving smaller LER value, a strategy to achieve sub-nanometer level LER still remain challenging due to inability to deposit energy with a profile of sub-nanometer LER. In this work, we use scanning helium ion beam to expose hydrogen silsesquioxane (HSQ) resist on SiNx membrane and present the 0.16 nm spatial imaging resolution based on this suspended thin membrane geometric construction, which is characterized by scanning transmission electron microscope (STEM). The suspended membrane serves as an energy filter of helium ion beam and due to the elimination of backscattering induced secondary electrons, we can systematically study the factors that influences the LER of the fabricated nanostructures. Furthermore, we explore the parameters including step size, designed exposure linewidth (DEL), delivered dosage and resist thickness and choosing the high contrast developer, the process window allows to fabricate lines with 0.2nm LER is determined. AFM measurement and simulation work further reveal that at specific beam step size and DEL, the nanostructures with minimum LER can only be fabricated at specific resist thickness and dosage. .
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Swine enteric coronaviruses (SeCoVs) pose a significant threat to the global pig industry, but no effective drugs are available for treatment. Previous research has demonstrated that thapsigargin (TG), an ER stress inducer, has broad-spectrum antiviral effects on human coronaviruses. In this study, we investigated the impact of TG on transmissible gastroenteritis virus (TGEV) infection using cell lines, porcine intestinal organoid models, and piglets. The results showed that TG effectively inhibited TGEV replication both in vitro and ex vivo. Furthermore, animal experiments demonstrated that oral administration of TG inhibited TGEV infection in neonatal piglets and relieved TGEV-associated tissue injury. Transcriptome analyses revealed that TG improved the expression of the ER-associated protein degradation (ERAD) component and influenced the biological processes related to secretion, nutrient responses, and epithelial cell differentiation in the intestinal epithelium. Collectively, these results suggest that TG is a potential novel oral antiviral drug for the clinical treatment of TGEV infection, even for infections caused by other SeCoVs.
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Antiviraux , Gastroentérite transmissible du porc , Thapsigargine , Virus de la gastroentérite transmissible , Animaux , Virus de la gastroentérite transmissible/effets des médicaments et des substances chimiques , Virus de la gastroentérite transmissible/physiologie , Suidae , Gastroentérite transmissible du porc/traitement médicamenteux , Gastroentérite transmissible du porc/virologie , Antiviraux/pharmacologie , Thapsigargine/pharmacologie , Lignée cellulaire , Réplication virale/effets des médicaments et des substances chimiquesRÉSUMÉ
Cancer is generally defined as a disease of aging. With aging, the composition, diversity and functional characteristics of the gut microbiota occur changes, with a decline of beneficial commensal microbes triggered by intrinsic and extrinsic factors (e.g., diet, drugs and chronic health conditions). Nowadays, dysbiosis of the gut microbiota is recognized as a hallmark of cancer. At the same time, aging is accompanied by changes in innate and adaptive immunity, known as immunosenescence, as well as chronic low-grade inflammation, known as inflammaging. The elevated cancer incidence and mortality in the elderly are linked with aging-associated alterations in the gut microbiota that elicit systemic metabolic alterations, leading to immune dysregulation with potentially tumorigenic effects. The gut microbiota and immunosenescence might both affect the response to treatment in cancer patients. In-depth understanding of age-associated alterations in the gut microbiota and immunity will shed light on the risk of cancer development and progression in the elderly. Here, we describe the aging-associated changes of the gut microbiota in cancer, and review the evolving understanding of the gut microbiota-targeted intervention strategies. Furthermore, we summarize the knowledge on the cellular and molecular mechanisms of immunosenescence and its impact on cancer. Finally, we discuss the latest knowledge about the relationships between gut microbiota and immunosenescence, with implications for cancer therapy. Intervention strategies targeting the gut microbiota may attenuate inflammaging and rejuvenate immune function to provide antitumor benefits in elderly patients.
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RATIONALE AND OBJECTIVES: We aimed at developing and validating a nomogram and machine learning (ML) models based on radiomics score (Radscore), morphology, and PHASES to predict intracranial aneurysm (IA) rupture. MATERIALS AND METHODS: We collected 440 patients with IAs in our hospital from 2015 to 2023, totaling 475 IAs (214 ruptured and 261 unruptured). A 7:3 random split was utilized to allocate participants into training and testing sets. To optimize the selection of radiomics features extracted from digital subtraction angiography, we employed t-tests and LASSO regression. Subsequently, we built single-factor and multifactor logistic regression (LR) models, alongside a nomogram. Furthermore, we employed four ML algorithms. After a comprehensive evaluation, including area under the curve (AUC), calibration curves, decision curve analysis (DCA), and other metrics, the best model was determined. RESULTS: The AUCs for LR models P (PHASES), M (Morphology), and R (Radscore) in the testing set were 0.859, 0.755, and 0.803, respectively, while those for multifactor models R+M (Radscore and Morphology), R+P (Radscore and PHASES), and R+M+P (Radscore, Morphology, and PHASES) were 0.818, 0.899, and 0.887, respectively. The AUCs of random forest, extreme gradient boosting, gradient boosting machine, and light gradient boosting machine were 0.880, 0.888, 0.891, and 0.892 in testing set, respectively. In the training set, the LR model showed significant differences in AUCs compared with the four ML models (all p < 0.05). However, in the testing set, no statistically significant differences were found between them (all p > 0.05). Both ML models and the nomogram exhibit excellent performance in DCA and calibration curves. CONCLUSION: Nomogram and ML models based on Radscore, morphology, and PHASES show high precision in predicting aneurysm rupture.
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Techniques cosmétiques , Rajeunissement , Vieillissement de la peau , Ultrasonothérapie , Humains , Vieillissement de la peau/effets des radiations , Ultrasonothérapie/méthodes , Ultrasonothérapie/effets indésirables , Techniques cosmétiques/effets indésirables , Résultat thérapeutique , Peau/effets des radiationsRÉSUMÉ
Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ -10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3's role in EM pathogenesis.
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, Mutation , Danio zébré , Humains , Animaux , Danio zébré/génétique , Mâle , Femelle , Fibroblastes/métabolisme , Exome/génétique , Étude d'association pangénomique , Adulte , Myopie/génétique , Myopie/métabolisme , Myopie/anatomopathologie , Sclère/métabolisme , Sclère/anatomopathologie , Matrice extracellulaire/métabolisme , Matrice extracellulaire/génétique , Prédisposition génétique à une maladie , Analyse sur cellule unique , Études cas-témoins , Enfant , Jeune adulteRÉSUMÉ
Graphite carbon nitride (g-C3N4) is a two-dimensional conjugated polymer with a unique energy band structure similar to graphene. Due to its outstanding analytical advantages, such as relatively small band gap (2.7 eV), low-cost synthesis, high thermal stability, excellent photocatalytic ability, and good biocompatibility, g-C3N4 has attracted the interest of researchers and industry, especially in the medical field. This paper summarizes the latest research on g-C3N4-based composites in various biomedical applications, including therapy, diagnostic imaging, biosensors, antibacterial, and wearable devices. In addition, the application prospects and possible challenges of g-C3N4 in nanomedicine are also discussed in detail. This review is expected to inspire emerging biomedical applications based on g-C3N4.
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Techniques de biocapteur , Graphite , Composés de l'azote , Graphite/composition chimique , Humains , Composés de l'azote/composition chimique , Matériaux biocompatibles/composition chimique , Animaux , Nitriles/composition chimique , Antibactériens/composition chimique , Antibactériens/pharmacologie , Dispositifs électroniques portables , Nanomédecine/méthodesRÉSUMÉ
Microbes in the sediments across a series of seamounts along the island arc of the Yap and Mariana trenches were investigated by metagenome. In this study, we reconstructed 107 metagenome-assembled genomes (MAGs), including 100 bacteria and 7 archaea. All the MAGs exhibited >75% completeness and <10% contamination, with 26 MAGs being classified as 'nearly complete' (completeness >90%), while 50 falling within 80-90% range and 31 between 75-80% complete. Phylogenomic analysis revealed that 86% (n = 92) of these MAGs represented new taxa at different taxonomical levels. The species composition of these MAGs was most consistent with the previous reports, with the most abundant phyla being Proteobacteria (n = 39), Methylomirabilota (n = 27), and Nitrospirota (n = 7). These draft genomes provided novel data on species diversity and function in the seamount microbial community, which will provide reference data for extensive comparative genomic studies across crucial phylogenetic groups worldwide.
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Archéobactéries , Bactéries , Sédiments géologiques , Métagénome , Phylogenèse , Sédiments géologiques/microbiologie , Bactéries/génétique , Bactéries/classification , Archéobactéries/génétique , Génome microbien , Génome d'archéobactérie , Génome bactérienRÉSUMÉ
Chronic stress-induced epinephrine (EPI) accelerates breast cancer progression and metastasis, but the molecular mechanisms remain unclear. Herein, we found a strong positive correlation between circulating EPI levels and the tumoral expression of ubiquitin-specific peptidase 22 (USP22) in patients with breast cancer. USP22 facilitated EPI-induced breast cancer progression and metastasis by enhancing adipose triglyceride lipase (ATGL)-mediated lipolysis. Targeted USP22 deletion decreased ATGL expression and lipolysis, subsequently inhibiting EPI-mediated breast cancer lung metastasis. USP22 acts as a bona fide deubiquitinase for the Atgl gene transcription factor FOXO1, and EPI architects a lipolysis signaling pathway to stabilize USP22 through AKT-mediated phosphorylation. Notably, USP22 phosphorylation levels are positively associated with EPI and with downstream pathways involving both FOXO1 and ATGL in breast cancers. Pharmacological USP22 inhibition synergized with ß-blockers in treating preclinical xenograft breast cancer models. This study reveals a molecular pathway behind EPI's tumor-promoting effects and provides a strong rationale for combining USP22 inhibition with ß-blockers to treat aggressive breast cancer.
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Tumeurs du sein , Épinéphrine , Lipolyse , Ubiquitin thiolesterase , Tumeurs du sein/métabolisme , Tumeurs du sein/anatomopathologie , Tumeurs du sein/génétique , Tumeurs du sein/traitement médicamenteux , Lipolyse/effets des médicaments et des substances chimiques , Femelle , Ubiquitin thiolesterase/métabolisme , Ubiquitin thiolesterase/génétique , Épinéphrine/métabolisme , Humains , Animaux , Souris , Lignée cellulaire tumorale , Protéine O1 à motif en tête de fourche/métabolisme , Protéine O1 à motif en tête de fourche/génétique , Triacylglycerol lipase/métabolisme , Triacylglycerol lipase/génétique , Transduction du signal/effets des médicaments et des substances chimiques , Métastase tumorale , Phosphorylation , Tumeurs du poumon/métabolisme , Tumeurs du poumon/secondaire , Tumeurs du poumon/anatomopathologie , Tumeurs du poumon/génétique , Tumeurs du poumon/traitement médicamenteux , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , AcyltransferasesRÉSUMÉ
BACKGROUND: Antimicrobial resistance poses a major threat to public health. There are few comprehensive nationwide studies that quantify long-term trends in infection incidence and antimicrobial resistance for multiple pathogens. We aimed to analyse trends in inpatient infection incidence and antimicrobial resistance for nine pathogens over the past 15 years across the USA. METHODS: In this US nationwide retrospective cohort study, we analysed clinical microbiology data from electronic health records from all patients admitted to all 138 Veterans Affairs (VA) Medical Centers with acute care wards across the USA from Feb 1, 2007, to March 31, 2022. We quantified inpatient antibiotic use as days of therapy (DOT) per 1000 patient-days and antimicrobial resistance by resistance proportion (proportion of incident isolates identified as resistant) and phenotypic incidence (incidence of infections per 1000 admissions classified as resistant, susceptible, or missing). To analyse trends before the COVID-19 pandemic and during the COVID-19 pandemic, we used generalised estimating equation models and reported average annual percentage changes (AAPC). FINDINGS: We collected 991 527 30-day incident isolates from 507 760 patients in 138 VA Medical Centers and 50 states in the USA. Between Feb 1, 2007, and Dec 31, 2019, infection incidence and antimicrobial resistance declined for many pathogens and pathogen-drug combinations. The proportion of methicillin resistance in Staphylococcus aureus decreased from 57·7% (11 876 of 20 584 incident isolates) to 44·6% (5916 of 13 257) over these 13 years (AAPC -1·8%; 95% CI -2·4 to -1·2; p<0·0001), and vancomycin-resistant Enterococcus faecium infections decreased from 77·8% (2555 of 3285) to 65·1% (893 of 1371; AAPC -1·2%; 95% CI -2·5 to 0·0; p=0·052). Fluoroquinolone resistance declined in both proportion and incidence for most pathogens. These trends correlated with substantial reductions in fluoroquinolone use, from 125 DOT per 1000 patient-days to 20 DOT per 1000 patient-days. Third generation cephalosporin resistance increased steeply in Escherichia coli infections from 6·7% (942 of 14 042) in 2007 to 15·3% (2153 of 14 053) in 2019 (AAPC 8·5%; 95% CI 6·2 to 10·7; p<0·0001). Carbapenem resistance proportion increased in Enterobacter cloacae infections from 1·1% (30 of 2852) in 2007 to 7·3% (212 of 2919) in 2019 (AAPC 19·8%; 95% CI 13·7 to 26·2; p<0·0001), but remained low for Klebsiella pneumoniae and E coli. During the COVID-19 pandemic between Jan 1, 2020, and March 31, 2022, several pathogen-drug combinations increased in both incidence and resistance for hospital-associated infections. For some pathogen-drug combinations, trends in incidence of resistant and susceptible infections were divergent, whereas for other combinations, these trends were in the same direction. INTERPRETATION: Significant reductions in methicillin resistance in S aureus, vancomycin-resistant E faecium, and fluoroquinolone resistance across multiple pathogens suggest that control efforts have had an effect on resistance. The rise in extended-spectrum ß-lactamases-producing Enterobacterales and recent surge in hospital-associated infections emphasise the need for ongoing surveillance and interventions. Our study highlights how coupling the analysis of phenotypic incidence with resistance proportion can enhance interpretation of antimicrobial resistance data. FUNDING: US Centers for Disease Control and Prevention.
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Traditional clustering methods rely on pairwise affinity to divide samples into different subgroups. However, high-dimensional small-sample (HDLSS) data are affected by the concentration effects, rendering traditional pairwise metrics unable to accurately describe relationships between samples, leading to suboptimal clustering results. This article advances the proposition of employing high-order affinities to characterize multiple sample relationships as a strategic means to circumnavigate the concentration effects. We establish a nexus between different order affinities by constructing specialized decomposable high-order affinities, thereby formulating a uniform mathematical framework. Building upon this insight, a novel clustering method named uniform tensor clustering (UTC) is proposed, which learns a consensus low-dimensional embedding for clustering by the synergistic exploitation of multiple-order affinities. Extensive experiments on synthetic and real-world datasets demonstrate two findings: 1) high-order affinities are better suited for characterizing sample relationships in complex data and 2) reasonable use of different order affinities can enhance clustering effectiveness, especially in handling high-dimensional data.
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The current study aimed to explore the combined and individual effects of vitamin D (VitD) status in three trimesters during pregnancy and cord blood (CB) on child growth trajectories from birth to 4 years of age. Pregnant women (n = 1100) were recruited between 2013 and 2016 in the Shanghai Birth Cohort (SBC) Study. A total of 959 mother-child dyads were included. VitD status was measured by LC-MS/MS at three trimesters (T1, T2, T3) and CB. Children's weight, length/height, and head circumference were assessed at birth, 42 days, 6, 12, 24 months, and 4 years of age, and standardized into z-scores [weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HCZ) and weight-for-length z-score (WLZ)]. Using the group-based trajectory model (GBTM), the trajectories of the four growth parameters were categorized into discrete groups. The generalized estimating equation (GEE) was employed to analyze the mixed effect of 25(OH)D throughout pregnancy on growth trajectories. The association between 25(OH)D status and each growth trajectory group was examined by multivariable logistic regression. Each 10 ng/mL increase in 25(OH) throughout three trimesters was not associated with four anthropometric parameters. Each 10 ng/mL increase in VitD in T3 was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.75; 95% CI: 0.62, 0.91; p < 0.01). Each 10 ng/mL increase in VitD in CB was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.57; 95% CI: 0.43, 0.76; p < 0.01). No significant association was found between maternal or CB VitD and LAZ or HCZ. Three trimesters' VitD throughout pregnancy had no persistent effect on the offspring's growth trajectory. However, higher VitD status in the third trimester and CB related to a lower risk of high-increasing WAZ from birth to 4 years of age. Elevated VitD levels in late pregnancy and cord blood may protect against continuous early-life weight growth at high levels.
Sujet(s)
Développement de l'enfant , Sang foetal , Vitamine D , Humains , Femelle , Sang foetal/composition chimique , Vitamine D/sang , Grossesse , Enfant d'âge préscolaire , Nourrisson , Nouveau-né , Adulte , Chine , Carence en vitamine D/sang , Carence en vitamine D/épidémiologie , Études longitudinales , Mâle , État nutritionnel , Phénomènes physiologiques nutritionnels maternels , Cohorte de naissanceRÉSUMÉ
Introduction: 68Ga labeled DOTA-Ibandronate (68Ga-DOTA-IBA) positron emission tomography/computed tomography (PET/CT), is a novel bone-targeting imaging tracer and promising diagnostic method for bone metastases detection. Therefore, this study aimed to compare 68Ga-DOTA-IBA PET/CT to the 99mTc-MDP whole-body bone scan (WBBS) for detecting bone metastases in breast cancer (BC). Materials and methods: In this prospective study, 45 women with BC underwent imaging via 68Ga-DOTA-IBA PET/CT and 99mTc-MDP WBBS. Clinical and demographic information as well as BC imaging features were recorded. The two methods were compared in terms of their detection rate for bone metastases and the number of lesions. Results: The 45 women were aged 53.5 ± 11.0 years. The bone metastases detection rate with 68Ga-DOTA-IBA PET/CT was 100% (45/45) and with 99mTc-MDP WBBS was 95.6% (43/45). A total of 546 bone metastases lesions were detected. The lesion detection rate using 68Ga-DOTA-IBA PET/CT was 100% (546/546) and using 99mTc-MDP WBBS was 67.8% (370/546). More lesions were found at each site via 68Ga-DOTA-IBA than via 99mTc-MDP WBBS. Conclusions: 68Ga-DOTA-IBA PET/CT is a more sensitive method than 99mTc-MDP WBBS for assessing bone metastases in BC and may therefore represent a useful imaging technique for bone metastases, while offering a visual basis for 177Lu-DOTA-IBA diagnosis and therapy response assessments for BC. Further validation using a broader study cohort is warranted to confirm these findings. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=170163, identifier ChiCTR2200064487.