Population exposure to emerging perfluoroalkyl acids (PFAAs) via drinking water resources: Application of multivariate statistics and risk assessment models.

This study assessed the occurrence, origins, and potential risks of emerging perfluoroalkyl acids (PFAAs) for the first time in drinking water resources of Khyber Pakhtunkhwa, Pakistan. In total, 13 perfluoroalkyl carboxylic acids (PFCAs) with carbon (C) chains C4-C18 and 4 perfluoroalkyl sulfonates (PFSAs) with C chains C4-C10 were tested in both surface and ground drinking water samples using a high-performance liquid chromatography system (HPLC) equipped with an Agilent 6460 Triple Quadrupole liquid chromatography-mass spectrometry (LC-MS) system. The concentrations of ∑PFCAs, ∑PFSAs, and ∑PFAAs in drinking water ranged from 1.46 to 72.85, 0.30-8.03, and 1.76-80.88 ng/L, respectively. Perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), and perfluoropentanoic acid (PFPeA) were the dominant analytes in surface water followed by ground water, while the concentration of perfluorobutane sulfonate (PFBS), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) were greater than long-chain PFOA and PFOS. The correlation statistics, which showed a strong correlation (p < 0.05) between the PFAA analytes, potentially indicated the fate of PFAAs in the area's drinking water sources, whereas the hierarchical cluster analysis (HCA) and principal component analysis (PCA) statistics identified industrial, domestic, agricultural, and commercial applications as potential point and non-point sources of PFAA contamination in the area. From risk perspectives, the overall PFAA toxicity in water resources was within the ecological health risk thresholds, where for the human population the hazard quotient (HQ) values of individual PFAAs were < 1, indicating no risk from the drinking water sources; however, the hazard index (HI) from the ∑PFAAs should not be underestimated, as it may significantly result in potential chronic toxicity to exposed adults, followed by children.

Contributing Factors Affecting the Length of Hospital Stay among Febrile Patients with Omicron Reported in Suzhou.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had global attention with regard to the urgent challenging threat to global public health. Currently, the novel Omicron variant is showing rapid transmission across the world, which appears to be more contagious than the previous variants of COVID-19. Early recognition of disease is critical for patients' prognosis. Fever is the most common symptom. We evaluated the clinical characteristics of febrile patients with COVID-19 reported in Suzhou and explored the predictors for a longer duration of hospitalization in febrile patients. METHODS: This retrospective study was carried out in 146 Omicron variant infected patients confirmed by nucleic acid tests in the Affiliated Infectious Hospital of Soochow University between February 13, 2022 and March 2, 2022. Data of febrile and afebrile laboratory-confirmed patients on hospital admission in Suzhou were collected and compared. According to the median length of stay (LOS), febrile cases were divided into short and long LOS groups. Then the predictive factors for a prolonged duration of hospitalization were analyzed using logistic regression methods. Receiver Operating Characteristic (ROC) Curve analysis was used to analyze the effectiveness of the risk factors for prolonged duration of hospitalization in febrile COVID-19 patients. RESULTS: Of the 146 discharged patients in our study, 112 patients (76.7%) caught a fever. Compared to afebrile Omicron patients, febrile patients showed a significantly longer duration of hospitalization (15.00 (5.80) vs. 13.00 (6.00), p = 0.002). Taking the median LOS (15 days) as the dividing point, 64 febrile cases were assigned to the short LOS group and the rest to the long LOS group. The long LOS group had a longer virus shedding duration than the short LOS group (18.42 ± 2.86 vs. 11.94 ± 2.50 days, p < 0.001). Compared to short LOS febrile patients, long LOS patients were older (44.88 ± 21.36 vs. 30.89 ± 17.95 years, p < 0.001) and showed a higher proportion of greater than 60 years old (33.3% vs. 9.4%, p = 0.002; Supplemental Table S2). Febrile patients with long LOS also showed a higher proportion of hypertension (25% vs. 6.3%, p = 0.005) and higher levels of cTnI (5.00 (3.00) vs. 4.00 (2.00) µg/L, p = 0.025). The multivariate analysis indicated that virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was the independent risk factor associated with long-term hospital stay in febrile patients with Omicron. Furthermore, ROC Curve analysis revealed that the area under the curve (AUC) for virus shedding duration to diagnose prolonged duration of hospitalization in febrile COVID-19 patients was 0.951 (95% CI 0.913 - 0.989). The cutoff point was set at 14.5 days. CONCLUSIONS: More than half of the non-severe patients exposed to the new Omicron variant had symptoms of fever. In total, 42.86% of the febrile patients were discharged within 15 days since hospital admission. Febrile Omicron cases took a longer duration of hospitalization compared to afebrile patients, and virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was probably a predictive factor for long-term hospital stays.

Propelling gold nanozymes: catalytic activity and biosensing applications.

Recently, gold nanomaterials have been rapidly developed owing to their high stability, good biocompatibility, and multifunctionality. The unique catalytic activity of gold nanomaterials has driven the emergence of the concept for a "gold nanozyme." Understanding the characteristics of gold nanozymes is crucial for improving their catalytic performance as well as expanding their applications. In this review, we provide an overview of the intrinsic enzyme-like activities of gold nanozymes, including peroxidase-, catalase-, superoxide dismutase-, and glucose oxidase-like activities, and the catalytic mechanisms involved. In addition, strategies for modulating the catalytic activity of gold nanozymes and their applications in biosensing were discussed in detail. Moreover, we highlight the current challenges of gold nanozymes and look forward to attracting more attention for propelling the developments in this field.

Effect of polyethoxylated flavonoids (PMFs)-loaded citral and chitosan composite coatings on citrus preservation: From the perspective of fruit resistance.

Previous studies have shown that polymethoxylated flavonoids-loaded citral emulsion (PCT) can inhibit the growth and reproduction of Penicillium in citrus; however, PCT is difficult to apply to fruit preservation due to its high fluidity and volatility. Therefore, in this study, we combined PCT with chitosan (CS) to investigate the effect of a composite coating on citrus preservation. The results showed that compared to the control group, the CS-PCT group could effectively reduce the decay rate and maintain moisture availability, color difference, and hardness. Moreover, the contents of nonenzymatic antioxidants and volatile substances with antimicrobial activity were better preserved. In addition, the activities of related antioxidant enzymes were greater in the treatment group, and the expression of the corresponding enzyme-encoding genes was upregulated. Consequently, CS-PCT treatment could effectively maintain fruit quality and improve the resistance of citrus fruits during storage; moreover, it can be considered a nontoxic and efficient citrus preservative.

Polypropylene mesh coated with hyaluronic acid/polyvinyl alcohol composite hydrogel for preventing bowel adhesion.

Polypropylene (PP) mesh is the most widely used prosthetic material in hernia repair. However, the efficacy of implanted PP mesh is often compromised by adhesion between viscera and PP mesh. Thus, there is a recognized need for developing an anti-adhesive PP mesh. Here, a composite hydrogel coated PP mesh with the prevention of adhesion after hernia repair was designed. The composite hydrogel coating was prepared from polyvinyl alcohol (PVA) and hyaluronic acid (HA) by using the freezing-thawing (FT) method. To overcome the shortcoming of the long time of the traditional freezing-thawing method, a small molecule 3,4-dihydroxyphenylacetic acid (DHPA) was introduced to promote the formation of composite hydrogel. The as-prepared composite hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro studies illustrated that the resulting meshes showed excellent coating stability, hemocompatibility, and non-cytotoxicity. In vivo experiments using a rat abdominal wall defect model demonstrated that the composite hydrogel coated PP mesh could prevent the formation of adhesion, alleviate the inflammatory response, and reduce the deposition of collagen around the damaged tissue. These disclosed results manifested that the PP mesh coated with HA/PVA composite hydrogel might be a promising application in preventing adhesion for hernia repair.

New lignans from Phyllanthodendron dunnianum.

A new lignan phyllanins A (1) and a lignan phyllanins B (2) for which the absolute configuration was determined for the first time, along with four known lignans (3-6) were isolated from the branch and leaf extracts of Phyllanthodendron dunnianum. Their planar structures were mainly determined by a combination of 1D and 2D NMR, HRESIMS spectral analyses, and the absolute configurations of the compounds 1 and 2 were established by DFT GIAO 13C NMR and electronic circular dichroism (ECD) calculations. In addition, all these six lignans were firstly tested for the antibacterial activities against MRSA, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli. Among these compounds, 2 and 5 showed potential antibacterial activities against MRSA and S. aureus with MIC values of 4 and 8 µg/mL, respectively.

Relationship Between Air Pollutants and the Incidence of Epistaxis in Yangzhou.

Objectives: This project aims to explore the relationship between the air quality index (AQI), the concentration of 6 air pollutants, and the incidence of epistaxis in Yangzhou. Also, to provide reference information for the prevention and treatment of epistaxis. Methods: Data of patients with epistaxis admitted to the Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2017 to December 2021 were collected. In addition, the local AQI and the concentrations of 6 air pollutants, namely particulate matter (PM2.5, PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3), were analyzed at the time of onset. Furthermore, the correlation with the incidence of epistaxis has been analyzed. Results: From 2017 to 2021, there were 24,721 patients with epistaxis aged from 0 to 17 years old while male patients were more than females. The incidence was higher in April, May, and June. There was a statistically significant difference in the number of daily epistaxis in different months and under AQI conditions (P < .05). Spearman's correlation analysis showed that there was a positive correlation between the number of daily epistaxis and the concentrations of AQI, CO, NO2, O3, PM2.5, PM10, and SO2 in Yangzhou, in which O3, PM10, and SO2 were highly correlated with the average number of daily epistaxis, and there was no obvious time lag effect of air pollutants on epistaxis. Conclusion: Epistaxis in the Yangzhou area is more common in males, mostly occurs in 0 to 17 years old, with seasonal. There was also a positive correlation between the incidence of epistaxis and air pollutants in Yangzhou. Therefore, by reducing the AQI index in daily life, and reducing the concentration of environmental pollutants in the air, the occurrence of epistaxis could be prevented and reduced to a certain extent.

The expression characteristic and prognostic role of Siglec-15 in lung adenocarcinoma.

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has been identified as an immune suppressor and a promising candidate for immunotherapy of cancer management. However, the association between Siglec-15 expression and clinicopathological features of lung adenocarcinoma (LUAD), especially the prognostic role, is not fully elucidated. In this present study, a serial of bioinformatics analyses in both tissue and cell levels were conducted to provide an overview of Siglec-15 expression. Real-time quantitative PCR (qPCR) test, western blotting assay, and immunohistochemistry (IHC) analyses were conducted to evaluate the expression of Siglec-15 in LUAD. Survival analysis and Kaplan-Meier curve were employed to describe the prognostic parameters of LUAD. The results of bioinformatics analyses demonstrated the up-regulation of Siglec-15 expression in LUAD. The data of qPCR, western blotting, and IHC analyses further proved that the expression of Siglec-15 in LUAD tissues was significantly increased than that in noncancerous tissues. Moreover, the expression level of Siglec-15 protein in LUAD was substantially associated with TNM stage. LUAD cases with up-regulated Siglec-15 expression, positive N status, and advance TNM stage suffered a critical unfavorable prognosis. In conclusion, Siglec-15 could be identified as a novel prognostic biomarker in LUAD and targeting Siglec-15 may provide a promising strategy for LUAD immunotherapy.

lncRNAs regulate cell stemness in physiology and pathology during differentiation and development.

Long non-coding RNA (lncRNA) are an important class of ubiquitous genes involved in diverse biological functions. lncRNAs, defined as noncoding RNAs with a length exceeding 200 nucleotides, are abundantly expressed throughout cells; however, their precise functions remain largely elusive. From embryonic stem cell proliferation and differentiation to cancer cell proliferation and invasion, lncRNAs play multifaceted regulatory roles across various cellular stages. Moreover, lncRNAs participate in the regulation of differentiation and regeneration during cellular development processes while also playing a pivotal role in maintaining and regulating cell stemness. In this article, we comprehensively review the current knowledge regarding lncRNAs in this field, discussing their biological functions and mechanisms underlying stemness regulation along with the factors implicated in these processes. We emphasize the growing evidence supporting the significance of lncRNAs in governing cell stemness while indicating that disruptions or mutations within them may serve as fundamental causes for certain developmental disorders.

The relationship between perceived social support and rumination among parents of children with autism: moderating effect of the degree of intervention received by children.

Objective: As the number of children diagnosed with autism rises year by year, the issue of nurturing this particular group becomes increasingly salient. Parents of autistic children, as the nearest and most reliable caregivers for their children, shoulder immense psychological strain and accountability. They are compelled to confront an array of daily life challenges presented by their children, as well as endure multiple pressures such as societal scrutiny and financial burdens. Consequently, the mental health status of the parents is of utmost significance. Methods: In this study, questionnaire survey combined with literature analysis were applied. The rumination thinking scale and the social support scale were used to investigate the relationship between social support perceived by parents of autistic children and rumination. Meanwhile, the moderating effects of intervention on children with autism were also explored. It hopes that our research would provide a basis for alleviating psychological stress and improving the mental health levels of the parents. A total of 303 parents of children with autism were collected (including 160 females and 143 males). Corresponding data analyses were conducted using SPSS 26.0. Results: Parents of autistic children generally exhibited high levels of rumination, with significant gender differences. At the same time, the perceived social support by the parents significantly influenced their level of rumination. It showed that the higher the social support received by parents, the lower the level of rumination. More importantly, the extent of intervention received by the children had a regulating effect on rumination of their parents. Conclusion: The personalized psychological support programs should be developed based on the actual situation of parents, to better manage the challenges presented by raising a child with autism. Our findings would provide important theoretical underpinnings and practical guidance for psychological intervention efforts aimed at families of autistic children. Moreover, these findings offer novel insights for future research, with the potential to advance the field of mental health studies concerning parents of children with autism.

Aromatic 1,4,2,3-Diazadiborole Featuring an Unsymmetrical B=B Entity: A Versatile Synthon for Unusual Boron Heterocycles.

The replacement of a CC unit with an isoelectronic BN unit in aromatic systems can give rise to molecules and materials with fascinating properties. We report here the synthesis, characterization, and reactivity of a 1,4,2,3-diazadiborole species, 2, featuring an unprecedented 6π-aromatic BN-heterocyclic moiety that is isoelectronic to cyclopentadienide (Cp-). Bearing an unsymmetrical B=B entity, 2 exhibits reactivity toward oxidants, protic reagents, electrophiles, and unsaturated substrates. This reactivity facilitates the synthesis of a variety of novel mono- and bicyclic organoboron derivatives through mechanisms including ring retention, cleavage/recombination, annulation, and expansion. These findings reveal innovative synthetic routes to BN-embedded aromatic compounds via desymmetrization, affording unique building blocks for synthetic chemistry.

Optical enhancement mode 2 improves the detection rate of gastric neoplastic lesion in high-risk populations: A multicenter randomized controlled clinical study.

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

Transcriptome analysis reveals the molecular mechanisms underlying the enhancement of salt-tolerance in Melia azedarach under salinity stress.

Melia azedarach demonstrates strong salt tolerance and thrives in harsh saline soil conditions, but the underlying mechanisms are poorly understood. In this study, we analyzed gene expression under low, medium, and high salinity conditions to gain a deeper understanding of adaptation mechanisms of M. azedarach under salt stress. The GO (gene ontology) analysis unveiled a prominent trend: as salt stress intensified, a greater number of differentially expressed genes (DEGs) became enriched in categories related to metabolic processes, catalytic activities, and membrane components. Through the analysis of the category GO:0009651 (response to salt stress), we identified four key candidate genes (CBL7, SAPK10, EDL3, and AKT1) that play a pivotal role in salt stress responses. Furthermore, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis revealed that DEGs were significantly enriched in the plant hormone signaling pathways and starch and sucrose metabolism under both medium and high salt exposure in comparison to low salt conditions. Notably, genes involved in JAZ and MYC2 in the jasmonic acid (JA) metabolic pathway were markedly upregulated in response to high salt stress. This study offers valuable insights into the molecular mechanisms underlying M. azedarach salt tolerance and identifies potential candidate genes for enhancing salt tolerance in M. azedarach.

Phytic Acid-Promoted Deposition of Gold Nanoparticles with Grafted Cationic Polymer Brushes for the Construction of Synergistic Contact-Killing and Photothermal Bactericidal Coatings.

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.

An ALP-responsive, anionic iridium complex for specific recognition of osteosarcoma cells.

Poor cellular permeability greatly hampers the utilization of anionic Ir(III) complexes, though efficiently emissive and remarkably stable, in cell-based diagnosis. To overcome this barrier, we present the development of an alkaline phosphatase (ALP)-responsive, anionic, and aggregation-induced emission (AIE)-active Ir(III) complex (Ir1) for specific recognition of osteosarcoma cells. Containing phosphate moieties, Ir1 exhibits a net -1 charge, enabling charge repulsion from the cell membrane and resulting in low cellular uptake and good biocompatibility in normal osteoblast cells. Upon ALP-mediated hydrolysis of phosphate groups, the resulting dephosphorylated product, Ir2, demonstrates a positive charge and increased lipophilicity, promoting cellular uptake and activating its AIE properties for specific recognition of osteosarcoma cells that express elevated levels of ALP. This study elucidates the role of ALP as an ideal trigger for enhancing the cellular permeability of phosphate ester-containing Ir(III) complexes, thus expanding the potential of anionic Ir(III) complexes for biomedical applications.

Polyoxometalate-based plasmonic electron sponge membrane for nanofluidic osmotic energy conversion.

Nanofluidic membranes have demonstrated great potential in harvesting osmotic energy. However, the output power densities are usually hampered by insufficient membrane permselectivity. Herein, we design a polyoxometalates (POMs)-based nanofluidic plasmonic electron sponge membrane (PESM) for highly efficient osmotic energy conversion. Under light irradiation, hot electrons are generated on Au NPs surface and then transferred and stored in POMs electron sponges, while hot holes are consumed by water. The stored hot electrons in POMs increase the charge density and hydrophilicity of PESM, resulting in significantly improved permselectivity for high-performance osmotic energy conversion. In addition, the unique ionic current rectification (ICR) property of the prepared nanofluidic PESM inhibits ion concentration polarization effectively, which could further improve its permselectivity. Under light with 500-fold NaCl gradient, the maximum output power density of the prepared PESM reaches 70.4 W m-2, which is further enhanced even to 102.1 W m-2 by changing the ligand to P5W30. This work highlights the crucial roles of plasmonic electron sponge for tailoring the surface charge, modulating ion transport dynamics, and improving the performance of nanofluidic osmotic energy conversion.

SlCarE054 in Spodoptera litura (Lepidoptera: Noctuidae) showed direct metabolic activity to ß-cypermethrin with stereoselectivity.

Carboxylesterases (CarEs) is an important detoxification enzyme system in phase Ⅰ participating in insecticides resistance. In our previous study, SlCarE054, a CarEs gene from lepidoptera class, was screened out to be upregulated in a pyrethroids and organophosphates resistant population. Its overexpression was verified in two field-collected populations of Spodoptera litura (Lepidoptera: Noctuidae) resistant to pyrethroids and organophosphates by qRT-PCR. Spatiotemporal expression results showed that SlCarE054 was highly expressed in the pupae stage and the digestive tissue midgut. To further explore its role in pyrethroids and organophosphates resistance, its metabolism activity to insecticides was determined by UPLC. Its recombinant protein showed significant metabolism activity to cyhalothrin and fenvalerate, but not to phoxim or chlorpyrifos. The metabolic activity of SlCarE054 to ß-cypermethrin showed stereoselectivity, with higher metabolic activity to θ-cypermethrin than the enantiomer α-cypermethrin. The metabolite of ß-cypermethrin was identified as 3-phenoxybenzaldehyde. Further modelling and docking analysis indicated that ß-cypermethrin, cyhalothrin and fenvalerate could bind with the catalytic triad of the 3D structure of SlCarE054. The interaction of ß-cypermethrin with SlCarE054 also showed the lowest binding energy. Our work provides evidence that SlCarE054 play roles in ß-cypermethrin resistance in S. litura.

IRF7 Exacerbates Candida albicans Infection by Compromising CD209-Mediated Phagocytosis and Autophagy-Mediated Killing in Macrophages.

IFN regulatory factor 7 (IRF7) exerts anti-infective effects by promoting the production of IFNs in various bacterial and viral infections, but its role in highly morbid and fatal Candida albicans infections is unknown. We unexpectedly found that Irf7 gene expression levels were significantly upregulated in tissues or cells after C. albicans infection in humans and mice and that IRF7 actually exacerbates C. albicans infection in mice independent of its classical function in inducing IFNs production. Compared to controls, Irf7-/- mice showed stronger phagocytosis of fungus, upregulation of C-type lectin receptor CD209 expression, and enhanced P53-AMPK-mTOR-mediated autophagic signaling in macrophages after C. albicans infection. The administration of the CD209-neutralizing Ab significantly hindered the phagocytosis of Irf7-/- mouse macrophages, whereas the inhibition of p53 or autophagy impaired the killing function of these macrophages. Thus, IRF7 exacerbates C. albicans infection by compromising the phagocytosis and killing capacity of macrophages via regulating CD209 expression and p53-AMPK-mTOR-mediated autophagy, respectively. This finding reveals a novel function of IRF7 independent of its canonical IFNs production and its unexpected role in enhancing fungal infections, thus providing more specific and effective targets for antifungal therapy.

An Amino Acids and Dipeptide Injection Inhibits the TNF-α/HMGB1 Inflammatory Signaling Pathway to Reduce Pyroptosis and M1 Microglial Polarization in POCD Mice: the Gut to the Brain.

Peripheral surgery-induced neural inflammation is a key pathogenic mechanism of postoperative cognitive dysfunction (POCD). However, the mechanism underlying neuroinflammation and associated neural injury remains elusive. Surgery itself can lead to gut damage, and the occurrence of POCD is accompanied by high levels of TNF-α in the serum and blood‒brain barrier (BBB) damage. Reductions in stress, inflammation and protein loss have been emphasized as strategies for enhanced recovery after surgery (ERAS). We designed an amino acids and dipeptide (AAD) formula for injection that could provide intestinal protection during surgery. Through the intraoperative infusion of AAD based on the ERAS concept, we aimed to explore the effect of AAD injection on POCD and its underlying mechanism from the gut to the brain. Here, we observed that AAD injection ameliorated neural injury in POCD, in addition to restoring the function of the intestinal barrier and BBB. We also found that TNF-α levels decreased in the ileum, blood and hippocampus. Intestinal barrier protectors and TNF-α inhibitors also alleviated neural damage. AAD injection treatment decreased HMGB1 production, pyroptosis, and M1 microglial polarization and increased M2 polarization. In vitro, AAD injection protected the impaired gut barrier and decreased TNF-α production, alleviating damage to the BBB by stimulating cytokine transport in the body. HMGB1 and Caspase-1 inhibitors decreased pyroptosis and M1 microglial polarization and increased M2 polarization to protect TNF-α-stimulated microglia in vitro. Collectively, these findings suggest that the gut barrier-TNF-α-BBB-HMGB1-Caspase-1 inflammasome-pyroptosis-M1 microglia pathway is a novel mechanism of POCD related to the gut-brain axis and that intraoperative AAD infusion is a potential treatment for POCD.

Clinical and Molecular Characteristics of Patients with Bloodstream Infections Caused by KPC and NDM Co-Producing Carbapenem-Resistant Klebsiella pneumoniae.

Purpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-ß-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains. Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently. Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%). Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next "superbug" highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.