Intrathecal or intraventricular antimicrobial therapy for post-neurosurgical Gram-negative bacillary meningitis or ventriculitis: a systematic review and meta-analysis.

PURPOSE: Extensively-drug-resistant Gram-negative bacteria (XDR GNB)-related post-neurosurgical infection is closely related to mortality, which represents a major challenge for neurosurgeons. There is an urgent need to review and evaluate methods to reduce mortality. METHODS: Both international and Chinese databases were searched independently from their inception to 15 June 2023. A meta-analysis was conducted using RevMan 5.4 to compare the efficacy and safety of intravenous (IV) treatment in combination with intrathecal or intraventricular (ITH/IVT) treatment with IV treatment alone for post-neurosurgical meningitis or ventriculitis due to GNB. Mortality, microbiological clearance and adverse events were considered as primary outcomes. RESULTS: In total, 18 eligible studies involving 602 patients were included in the meta-analysis. The IV + ITH/IVT group was associated with significantly lower mortality (especially in the XDR GNB subgroup) and acceptable safety. In terms of microbiological clearance, a significant decrease was shown in the XDR GNB subgroup. Significant benefits were shown in laboratory parameters and clinical symptoms after patients were treated with ITH/IVT. CONCLUSION: Additional ITH/IVT treatment may promote XDR GNB clearance and reduce mortality. In addition, ITH/IVT administration can improve clinical symptoms and cerebrospinal fluid indicators of patients with post-neurosurgical infections. Significantly, ITH/IVT treatment does not increase the incidence of adverse events at the recommended dose.

Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study.

BACKGROUND: This study aimed to explore the changes of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) expression on antigen-presenting cells (APCs) and evaluate their association with organ failure and mortality during early sepsis. METHODS: In total, 40 healthy controls and 198 patients with sepsis were included in this study. Peripheral blood was collected within the first 24 h after the diagnosis of sepsis. The expression of PD-L1 and PD-1 was determined on APCs, such as B cells, monocytes, and dendritic cells (DCs), by flow cytometry. Cytokines in plasma, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, and IL-17A were determined by Luminex assay. RESULTS: PD-1 expression decreased significantly on B cells, monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) as the severity of sepsis increased. PD-1 expression was also markedly decreased in non-survivors compared with survivors. In contrast, PD-L1 expression was markedly higher on mDCs, pDCs, and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors. The PD-L1 expression on APCs (monocytes and DCs) was weakly related to organ dysfunction and inflammation. The area under the receiver operating characteristic curve (AUC) of the PD-1 percentage of monocytes (monocyte PD-1%)+APACHE II model (0.823) and monocyte PD-1%+SOFA model (0.816) had higher prognostic value than other parameters alone. Monocyte PD-1% was an independent risk factor for 28-day mortality. CONCLUSION: The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs. PD-L1 in monocytes and DCs was weakly correlated with inflammation and organ dysfunction during early sepsis. The combination of SOFA or APACHE II scores with monocyte PD-1% could improve the prediction ability for mortality.

Novel pyrimidin-4-one derivatives as potential T3SS inhibitors against Xanthomonas campestris pv. campestris.

BACKGROUND: Cruciferous black rot is caused by Xanthomonas campestris pv. campestris (Xcc) infection and is a widespread disease worldwide. Excessive and repeated use of bactericide is an important cause of the development of bacterial resistance. It is imperative to take new approaches to screening compounds that target virulence factors rather than kill bacterial pathogens. The type III secretion system (T3SS) invades a variety of cells by transporting virulence effector factors into the cytoplasm and is an attractive antitoxic target. Toward the search of new T3SS inhibitors, an alternative series of novel pyrimidin-4-one derivatives were designed and synthesized and assessed for their effect in blocking the virulence. RESULTS: All of the target compounds were characterized by proton (1 H) nuclear magnetic resonance (NMR), carbon-13 (13 C) NMR, fluorine-19 (19 F) NMR and high-resolution mass spectrometry (HRMS). All compounds were evaluated using high-throughput screening systems against Xcc. The results of the biological activity test revealed that the compound SPF-9 could highly inhibit the activity of xopN gene promoter and the hypersensitivity (HR) of tobacco without affecting bacterial growth. Moreover, messenger RNA (mRNA) level measurements showed that compound SPF-9 inhibited the expression of some representative genes (hrp/hrc genes). Compound SPF-9 weakened the pathogenicity of Xcc to Raphanus sativus L. CONCLUSION: Compound SPF-9 has good potential for further development as a novel T3SS inhibitor against Xcc. © 2023 Society of Chemical Industry.

Prenylated xanthones with α-glucosidase and α-amylase inhibitory effects from the pericarp of Garcinia mangostana.

Two new prenylated xanthones, mangoxanthones A-B (1-2), together with four known compounds 3-6, were isolated from the ethanol extract of the pericarp of Garcinia mangostana. The structures of these compounds have been elucidated based on spectroscopic analysis. The analysis results of chiral HPLC revealed compounds 1 and 2 were scalemic mixtures respectively. All isolated compounds were biologically evaluated for their α-glucosidase and α-amylase inhibitory effects using in-vitro assays. Compound 1 showed moderate inhibitory activities against α-glucosidase and α-amylase with IC50 of 29.06 ± 1.86 and 22.74 ± 2.07 µM, respectively. Molecular docking predicted the binding sites of compound 1 to α-glucosidase and α-amylase. A preliminary structure-activity relationship was discussed.

Effect of neutrophil CD64 for diagnosing sepsis in emergency department.

BACKGROUND: The aim of this study is to investigate the diagnostic and prognostic value of neutrophil CD64 (nCD64) as a novel biomarker in sepsis patients. METHODS: One hundred fifty-one adult patients diagnosed with sepsis and 20 age-matched healthy controls were enrolled in the study. Patients with sepsis were further subdivided into a sepsis group and a septic shock group. nCD64 expression, serum procalcitonin (PCT) level, C-reactive protein (CRP) level, and white blood cell (WBC) count were obtained for each patient, and Sequential Organ Failure Assessment (SOFA) scores were calculated. RESULTS: nCD64 expression was higher in the sepsis group with confirmed infection than in the control group. The receiver operating characteristic (ROC) curve of nCD64 was higher than those of SOFA score, PCT, CRP and WBC for diagnosing infection. The area under the curve (AUC) of nCD64 combined with SOFA score was the highest for all parameters. The AUC of nCD64 for predicting 28-day mortality in sepsis was significantly higher than those of PCT, CRP, and WBC, but slightly lower than that of SOFA score. The AUC of nCD64 or PCT combined with SOFA score was significantly higher than that of any single parameter for predicting 28-day mortality. CONCLUSION: nCD64 expression and SOFA score are valuable parameters for early diagnosis of infection and prognostic evaluation of sepsis patients.

Changes in the Intestinal Microbiota of Gibel Carp (Carassius gibelio) Associated with Cyprinid herpesvirus 2 (CyHV-2) Infection.

Gut microbiota are integral to the host, and have received increased attention in recent years. However, information regarding the intestinal microbiota of many aquaculture animals is insufficient; elucidating the dynamics of the intestinal microbiota can be beneficial for nutrition, immunity, and disease control. In this study, we used 16S rRNA sequencing to observe changes in the intestinal microbiota of gibel carp (Carassius auratus gibelio) associated with cyprinid herpesvirus 2 (CyHV-2) infection. Our results indicate that the diversity of the intestinal microbiota was strongly reduced, and the composition was dramatically altered following CyHV-2 infection. The most dominant species in healthy fish were Cetobacterium, Rhodobacter, and Crenothrix; meanwhile, Cetobacterium, Plesiomonas, Bacteroides, and Flavobacterium were the most abundant species in sick fish. Plesiomonas was highly abundant in infected samples, and could be used as a microbial biomarker for CyHV-2 infection. Chemical properties of the aquaculture water were significantly correlated with the microbial community structure; however, it is difficult to determine whether these changes are a cause or consequence of infection. However, it may be possible to use probiotics or prebiotics to restore the richness of the host intestinal microbiota in infected animals to maintain host health.

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Methane (CH4) is the second abundant greenhouse gas. Aerobic methane oxidations of topsoil in forest are identified as an important sink of atmosphere methane, playing critical roles in carbon cycle and global warming alleviation. Comparing the community structure and diversity of methane oxidizing bacteria (MOBs) in different vegetation ecosystems could provide new insights into the relationships between vegetation types and community of MOBs. In this study, we collected 92 soil samples from four types of vegetation along the elevation gradient of Gongga Mountain, and further assessed the community structure, diversity and potential drivers of MOBs across the four vegetation types using Miseq sequencing and bioinformatics methods. The result indicated that MOBs community compositions in evergreen and deciduous broad-leaved forest (EDBF) and coniferous and broad-leaved mixed forest (CBMF) was more similar, whereas in dark coniferous forest (DCF) and shrub meadow area (SMA) soils, MOB composition was more similar. In the four types of vegetation, α-diversities of MOBs in EDBF and CBMF were significantly higher than that in the other three vegetation types (P＜0.001), whereas ß-diversities in soils of DCF and SMA were significantly higher than those in EDBF and CBMF (P＜0.001). Spearman analysis indicated that the relative abundance of different MOBs in four types of vegetation showed different responses to environmental change. Factors including soil total nitrogen, conductivity and soil temperature appeared to govern the variation of α-diversity across the four vegetation types. Partial Mantel test and redundancy ana-lysis (RDA) suggested that environmental parameters likely contributed more to diversity variations in soils from EDBF and CBMF, whereas diversity variations in soils from DCF and SAM might be driven by other potential environmental factors or mechanism. Precipitation appeared to drive the ß-diversity variation between vegetation of EDBF and CBMF and vegetation of DCF and SAM. Our study suggested that the community structure and diversity variation of MOBs in different vegetation types might be governed by both soil properties and climate change.

Novel synthesis of a versatile magnetic adsorbent derived from corncob for dye removal.

Corncob, an agricultural waste, was successfully converted into a novel magnetic adsorbent by a low-temperature hydrothermal method (453K), including carbonization under saline conditions and magnetization using iron (III) salt. The resultant magnetic carbonaceous adsorbent (MCA) exhibited a porous structure with a higher specific surface area and more oxygen-containing functional groups than its carbonaceous precursor (CP), which can be attributed to the catalytic effect of Fe (III). The adsorption behaviors of both MCA and CP could be described well by Langmuir isotherm and pseudo-second-order model. The adsorption capacity for Methylene blue (MB) revealed by adsorption isotherms were 163.93mg/g on MCA and 103.09mg/g on CP, respectively. Moreover, MCA was demonstrated as a versatile adsorbent for removal of both anionic and cationic dyes, and it showed good reusability in regeneration studies. This work provides an alternative approach for effective conversion of biomass waste and application of them in pollutant removal.