Does invasive submerged macrophyte diversity affect dissimilatory nitrate reduction processes in sediments with varying microplastics?

Nitrogen removal is essential for restoring eutrophic lakes. Microorganisms and aquatic plants in lakes are both crucial for removing excess nitrogen. However, microplastic (MP) pollution and the invasion of exotic aquatic plants have become increasingly serious in lake ecosystems due to human activity and plant-dominant traits. This field mesocosm study explored how the diversity of invasive submerged macrophytes affects denitrification (DNF), anammox (ANA), and dissimilatory nitrate reduction to ammonium (DNRA) in lake sediments with varying MPs. Results showed that invasive macrophytes suppressed DNF rates, but DNRA and ANA were less sensitive than DNF to the diversity of invasive species. Sediment MPs increased the biomass of invasive species more than native species, but did not affect microbial processes. The effects of MPs on nitrate dissimilatory reduction were process-specific. MPs increased DNF rates and the competitive advantage of DNF over DNRA by changing the sediment environment. The decoupling of DNF and ANA was also observed, with increased DNF rates and decreased ANA rates. The study findings suggested new insights into how the invasion of exotic submerged macrophytes affects the sediment nitrogen cycle complex environments.

Red light mitigates Cd toxicity in Egeria densa by restricting Cd accumulation and modulating antioxidant defense system.

Controlling light qualities have been acknowledged as an effective method to enhance the efficiency of phytoremediation, as light has a significant impact on plant growth. This study examined the effects of light qualities on cadmium (Cd) tolerance in aquatic plant Egeria densa using a combination of biochemical and transcriptomic approaches. The study revealed that E. densa exhibits higher resistance to Cd toxicity under red light (R) compared to blue light (B), as evidenced by a significant decrease in photosynthetic inhibition and damage to organelle ultrastructure. After Cd exposure, there was a significantly reduced Cd accumulation and enhanced levels of both glutathione reductase (GR) activity and glutathione (GSH), along with an increase in jasmonic acid (JA) in R-grown E. densa compared to B. Transcriptional analysis revealed that R caused an up-regulation of Cd transporter genes such as ABCG (G-type ATP-binding cassette transporter), ABCC (C-type ATP-binding cassette transporter), and CAX2 (Cation/H+ exchanger 2), while down-regulated the expression of HIPP26 (Heavy metal-associated isoprenylated plant protein 26), resulting in reduced Cd uptake and enhanced Cd exportation and sequestration into vacuoles. Moreover, the expression of genes involved in phytochromes and JA synthesis was up-regulated in Cd treated E. densa under R. In summary, the results suggest that R could limit Cd accumulation and improve antioxidant defense to mitigate Cd toxicity in E. densa, which might be attributed to the enhanced JA and phytochromes. This study provides a foundation for using light control methods with aquatic macrophytes to remediate heavy metal contamination in aquatic systems.

Using rice straw-augmented ecological floating beds to enhance nitrogen removal in carbon-limited wastewater.

Agricultural biomass used as solid carbon substrates in ecological floating beds (EFBs) has been proven to be applicable in nitrogen removal for carbon-limited wastewater treatment. However, the subtle interactions among plants, rhizosphere microorganisms, and supplementary carbon sources have not been thoroughly studied. This study combined rice straw mats with different aquatic macrophytes in EFBs to investigate denitrification efficiency in carbon-limited eutrophic waters. Results showed that rice straw significantly enhanced the nitrogen removal efficiency of EFBs, while enriching nitrogen-fixing and denitrifying bacteria (such as Rhizobium, Rubrivivax, and Rhodobacter, etc.). Additionally, during the denitrification process in EFBs, rice straw can release humic acid-like fraction as electron donors to support the metabolic activities of microorganisms, while aquatic macrophytes provide a more diverse range of dissolved organic matters, facilitating a sustainable denitrification process. These findings help to understand the synergistic effect of denitrification processes within wetland ecosystems using agricultural biomass.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

Safety and Efficacy Analysis of Radical Surgery for 403 Patients with Colon Cancer over 80 Years Old.

Aim: To investigate the safety and efficacy of radical surgery in colon cancer patients over 80 years old. Methods: Data from colon cancer patients aged ≥80 years who underwent radical surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences and affiliated Heji Hospital of Changzhi Medical College from January 2011 to December 2022 were retrospectively analysed. Data on clinical characteristics, pathological features, perioperative data, and long-term prognosis were collected. Severe complications were classified as grade III-V. Logistic regression models were used to identify the risk factors for severe postoperative complications, and a Cox regression model was used to determine prognostic variables. Results: A total of 403 eligible patients were included in the study. A total of 118 (29.3%) patients developed postoperative complications, of which 51 (12.7%) experienced grade 3-5 severe complications. Two (0.5%) patients died of pulmonary embolism and myocardial infarction during the perioperative period. The multivariate logistic regression analysis showed that preoperative albumin levels <35 g/L and right colon cancer were independent risk factors for grade 3-5 postoperative complications. In terms of prognosis, multivariate analysis revealed that overall survival was significantly affected by TNM stage III and grade 3-4 postoperative complications. In addition, TNM stage III and perineural invasion were the independent prognostic factors for disease-free survival. Conclusion: Radical surgery can be performed safely in elderly colon cancer patients aged over 80 years, with an acceptable morbidity and mortality. Patients with preoperative albumin levels <35 g/L or tumors in the right colon should be alerted to the development of severe postoperative complications. In addition, the occurrence of severe complications can significantly affect the prognosis of elderly colon cancer patients.

MTCH2 stimulates cellular proliferation and cycles via PI3K/Akt pathway in breast cancer.

The MTCH2 protein is located on the mitochondrial outer membrane and regulates mitochondria-related cell death. This study set out to investigate the role of MTCH2 in the underlying pathophysiological mechanisms of breast cancer (BC). MTCH2 expression levels in BC were analyzed using bioinformatics prior to verification by cell lines in vitro. Experiments of over-expression and siRNA-mediated knockdown of MTCH2 were conducted to assess its biological functions, including its effects on cellular proliferation and cycle progression. Xenografts were utilised for in vivo study and signaling pathway alterations were examined to identify the mechanisms driven by MTCH2 in BC proliferation and cell-cycle regulation. MTCH2 was up-regulated in BC and correlated with patients' overall survival. Over-expression of MTCH2 promoted cellular proliferation and cycle progression, while silencing MTCH2 had the opposite effect. Xenograft experiments were utilised to confirm the in vitro cellular findings and it was identified that the PI3K/Akt signaling pathway was activated by MTCH2 over-expression and suppressed by its silencing. Moreover, the activation of IGF-1R rescued cellular growth and cycle arrest induced by MTCH2-silencing. Overall, this study reveals that expression of MTCH2 in BC is upregulated and potentiates cellular proliferation and cycle progression via the PI3K/Akt pathway.

Value of ultra-high b-value diffusion-weighted imaging for the evaluation of renal ischemia-reperfusion injury.

To explore the feasibility of ultra-high b-value diffusion-weighted imaging (ubDWI) in assessment of renal IRI. Thirty-five rabbits were randomized into a control group (n = 7) and a renal IRI group (n = 28). The rabbits in the renal IRI group underwent left renal artery clamping for 60 min. Rabbits underwent axial ubDWI before and at 1, 12, 24, and 48 h after IRI. Apparent diffusion coefficient (ADCst) were calculated from ubDWI with two b-values (b = 0, 1000 s/mm2). Triexponential fits were applied to calculate the pure diffusion coefficients (D), perfusion-related diffusion coefficient (D⁎), and ultra-high ADC (ADCuh). The interobserver reproducibility were evaluated. The repeated measurement analysis of variance and Spearman correlation analysis was used for statistical analysis. The ADCst, D, and ADCuh values showed good reproducibility. The ADCst, D, and D⁎ values of renal Cortex (CO) and outer medulla (OM) significantly decreased after IRI (all P < 0.05). The ADCuh values significantly increased from pre-IRI to 1 h after IRI (P < 0.05) and significantly declined at 24 h and 48 h after IRI (all P < 0.05). ADCuh was strongly positively correlated with AQP-1 in the renal CO and OM (ρ = 0.643, P < 0.001; ρ = 0.662, P < 0.001, respectively). ubDWI can be used to non-invasively evaluate early renal IRI, ADCuh may be adopted to reflect AQP-1 expression.

Comparison of the efficacy between the dual therapy of tegoprazan and the quadruple therapy of tegoprazan: A randomized, controlled, multicenter study.

INTRODUCTION: Tegoprazan (TPZ), a potassium-competitive acid blocker, exerts a strong acid-suppression effect and a rapid onset of action. However, research on TPZ-amoxicillin (TA) dual treatment is limited. Here, we compared the safety and efficacy of TPZ-amoxicillin dual treatment and TPZ, bismuth potassium citrate, amoxicillin, and clarithromycin (TBAC) quadruple therapy in patients newly diagnosed with H. pylori infection over a 14-day treatment period. METHODS: A total of 236 patients newly diagnosed with H. pylori were enrolled in this multi-center, prospective, open-label, and randomized controlled study. Patients randomly received either TA dual or TBAC quadruple therapy. The incidence of adverse reactions and treatment compliance were recorded and then analyzed. RESULTS: The intention-to-treat analysis revealed that H. pylori-eradication rates were 83.9% (95% confidence interval [CI] 78.2%-91.3%) and 81.4% (95% CI 74.2%-88.5%) for the TA and TBAC groups, respectively, with no statistically significant difference between them (P = 0.606). The per-protocol analysis revealed that the H. pylori-eradication rates were 88.3% and 84.8% for the TA and TBAC groups, respectively (P = 0.447). The incidence of adverse reactions was significantly lower in the TA group than in the TBAC group (4.2% vs. 15.3%, P = 0.004). Moreover, the TA group demonstrated substantially higher treatment compliance than the TBAC group (94.1% vs. 89.0%, P = 0.020). CONCLUSION: The TA dual therapy successfully eradicated H. pylori with a high eradication rate and a low incidence of adverse reactions. Therefore, this treatment is recommended as an alternative course for patients newly diagnosed with H. pylori infection.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

A cubic DNA nanocage probe for in situ analysis of miRNA-10b in tumor-derived extracellular vesicles.

A cubic DNA nanocage probe is able to enter EVs derived from MDA-MB-231 cells and react with miRNA-10b. The probe-loaded EVs were employed to monitor the process of entry of miRNA-10b into MCF-10A cells, allowing visualization of EV-mediated intercellular communication of miRNA-10b between the cancer cells.

Single-atom platinum with asymmetric coordination environment on fully conjugated covalent organic framework for efficient electrocatalysis.

Two-dimensional (2D) covalent organic frameworks (COFs) and their derivatives have been widely applied as electrocatalysts owing to their unique nanoscale pore configurations, stable periodic structures, abundant coordination sites and high surface area. This work aims to construct a non-thermodynamically stable Pt-N2 coordination active site by electrochemically modifying platinum (Pt) single atoms into a fully conjugated 2D COF as conductive agent-free and pyrolysis-free electrocatalyst for the hydrogen evolution reaction (HER). In addition to maximizing atomic utilization, single-atom catalysts with definite structures can be used to investigate catalytic mechanisms and structure-activity relationships. In this work, in-situ characterizations and theoretical calculations reveal that a nitrogen-rich graphene analogue COF not only exhibits a favorable metal-support effect for Pt, adjusting the binding energy between Pt sites to H* intermediates by forming unique Pt-N2 instead of the typical Pt-N4 coordination environment, but also enhances electron transport ability and structural stability, showing both conductivity and stability in acidic environments.

Multiparametric MRI-based intratumoral and peritumoral radiomics for predicting the pathological differentiation of hepatocellular carcinoma.

PURPOSE: To explore the predictive potential of intratumoral and multiregion peritumoral radiomics features extracted from multiparametric MRI for predicting pathological differentiation in hepatocellular carcinoma (HCC) patients. METHODS: A total of 265 patients with 277 HCCs (training cohort n = 193, validation cohort n = 84) who underwent preoperative MRI were retrospectively analyzed. The risk factors identified through stepwise regression analysis were utilized to construct a clinical model. Radiomics models based on MRI (arterial phase, portal venous phase, delayed phase) across various regions (entire tumor, Peri_5mm, Peri_10mm, Peri_20mm) were developed using the LASSO approach. The features obtained from the intratumoral region and the optimal peritumoral region were combined to design the IntraPeri fusion model. Model performance was assessed using the area under the curve (AUC). RESULTS: Larger size, non-smooth margins, and mosaic architecture were risk factors for poorly differentiated HCC (pHCC). The clinical model achieved AUCs of 0.77 and 0.73 in the training and validation cohorts, respectively, while the intratumoral model achieved corresponding AUC values of 0.92 and 0.82. The Peri_10mm model demonstrated superior performance to the Peri_5mm and Peri_20mm models, with AUC values of 0.87 vs. 0.84 vs. 0.73 in the training cohort and 0.80 vs. 0.77 vs. 0.68 in the validation cohort, respectively. The IntraPeri model exhibited remarkable AUC values of 0.95 and 0.86 in predicting pHCC in the training and validation cohorts, respectively. CONCLUSIONS: Our study highlights the potential of a multiparametric MRI-based radiomic model that integrates intratumoral and peritumoral features as a tool for predicting HCC differentiation. CRITICAL RELEVANCE STATEMENT: Both clinical and multiparametric MRI-based radiomic models, particularly the intratumoral radiomic model, are non-invasive tools for predicting HCC differentiation. Importantly, the IntraPeri fusion model exhibited remarkable predictiveness for individualized HCC differentiation. KEY POINTS: • Both the intratumoral radiomics model and clinical features were useful for predicting HCC differentiation. • The Peri_10mm radiomics model demonstrated better diagnostic ability than other peritumoral region-based models. • The IntraPeri radiomics fusion model outperformed the other models for predicting HCC differentiation.

Research on adults with subthreshold depression after aerobic exercise: a resting-state fMRI study based on regional homogeneity (ReHo).

Objective: Subthreshold depression (StD)/subsyndromal depression refers to a threatening precursor to depression. Aerobic exercise is a promising self-supportive adjunctive intervention and an effective measure for StD. Our study utilizes regional homogeneity (ReHo) to investigate the impact of aerobic exercise on resting-state brain function. Methods: A total of 78 subjects, aged between 18 and 48 years, (StD group, n = 44; healthy control (HC) group, n = 34) engaged in moderate-intensity aerobic exercise 3-4 times per week for 8 weeks. Resting-state brain function and structural images were acquired before and after the exercise intervention. The ReHo method was employed to analyze abnormal changes in regional brain function, and a correlation analysis was performed using the Patient Health Questionnaire-9 (PHQ-9) and Self-Rating Anxiety Scale (SAS) scores. Results: The principal observation reveals synchronous abnormalities in the right anterior cingulate gyrus of the brain in StD subjects compared to HCs at baseline, with these differences dissipating after the implementation of aerobic exercise. After completing the aerobic exercise program, the StD group exhibited a difference in the right middle cingulate gyrus, while the left supplementary motor area (SMA) was altered in the HC group. Conclusion: Disparities in neural synchronization are evident between HCs and StD subjects, and the implementation of aerobic exercise intervention can effectively mitigate these distinctions, leading to a significant reduction in depressive symptoms among StD subjects. The primary mechanism of StD symptoms may involve the inhibition of the anterior cingulate gyrus, while the effects of aerobic exercise may be related to the modulation of neural synchronization of emotional reflexes. The discovery of these fMRI evidence findings may offer novel strategies for early detection and intervention in cases of StD.

Uranium Biogeochemistry in the Rhizosphere of a Contaminated Wetland.

The objective of this study was to determine if U sediment concentrations in a U-contaminated wetland located within the Savannah River Site, South Carolina, were greater in the rhizosphere than in the nonrhizosphere. U concentrations were as much as 1100% greater in the rhizosphere than in the nonrhizosphere fractions; however and importantly, not all paired samples followed this trend. Iron (but not C, N, or S) concentrations were significantly enriched in the rhizosphere. XAS analyses showed that in both sediment fractions, U existed as UO22+ coordinated with iron(III)-oxides and organic matter. A key difference between the two sediment fractions was that a larger proportion of U was adsorbed to Fe(III)-oxides, not organic matter, in the rhizosphere, where significantly greater total Fe concentrations and greater proportions of ferrihydrite and goethite existed. Based on 16S rRNA analyses, most bacterial sequences in both paired samples were heterotrophs, and population differences were consistent with the generally more oxidizing conditions in the rhizosphere. Finally, U was very strongly bound to the whole (unfractionated) sediments, with an average desorption Kd value (Usediment/Uaqueous) of 3972 ± 1370 (mg-U/kg)/(mg-U/L). Together, these results indicate that the rhizosphere can greatly enrich U especially in wetland areas, where roots promote the formation of reactive Fe(III)-oxides.

Microplastics enhance the invasion of exotic submerged macrophytes by mediating plant functional traits, sediment properties, and microbial communities.

Plant invasions and microplastics (MPs) have significantly altered the structure and function of aquatic habitats worldwide, resulting in severe damage to aquatic ecosystem health. However, the effects of MPs on plant invasion and the underlying mechanisms remain largely unknown. In this study, we conducted mesocosm experiments over a 90-day period to assess the effects of polystyrene microplastics on the invasion of exotic submerged macrophytes, sediment physicochemical properties, and sediment bacterial communities. Our results showed that PS-MPs significantly promoted the performance of functional traits and the invasive ability of exotic submerged macrophytes, while native plants remained unaffected. Moreover, PS-MPs addition significantly decreased sediment pH while increasing sediment carbon and nitrogen content. Additionally, MPs increased the diversity of sediment bacterial community but inhibited its structural stability, thereby impacting sediment bacterial multifunctionality to varying degrees. Importantly, we identified sediment properties, bacterial composition, and bacterial multifunctionality as key mediators that greatly enhance the invasion of exotic submerged macrophytes. These findings provide compelling evidence that the increase in MPs may exacerbate the invasion risk of exotic submerged macrophytes through multiple pathways. Overall, this study enhances our understanding of the ecological impacts of MPs on aquatic plant invasion and the health of aquatic ecosystems.

Microbiota associated with urban forests.

Urban forests are essential for maintaining urban ecological stability. As decomposers, soil microorganisms play an indispensable role in the stability of urban forest ecosystems, promoting the material cycle of the ecosystems. This study used high-throughput sequencing technology to explore the bacteria in six forest stands, including Phyllostachys edulis (ZL), Metasequoia glyptostroboides (SSL), Cornus officinalis (SZY), mixed broad-leaved shrub forest (ZKG), mixed pine and cypress forest (SBL), and mixed broad-leaved tree forest (ZKQ). Meanwhile, the differences in fungal communities were investigated. The results show that ZL has the highest alpha diversity of bacterial communities, while its fungal community is the lowest; Proteobacteria is the most abundant bacterial phylum in the six forest stands; ZKQ has the highest fungal diversity. In addition, soil microbial communities are affected by environmental factors. Soil pH, organic matter (SOM), and available phosphorus (AP) significantly influence the compositions of urban forest soil microbial communities. This study revealed the differences in bulk soil (BS) microbial community structures among six forest stands and the relationship between environmental factors and soil microbial communities, which has important guiding significance for creating healthy and stable urban forests with profound ecological benefits.

Multi-omics profiling reveal responses of three major Dendrobium species from different growth years to medicinal components.

Dendrobium is a perennial herb found in Asia that is known for its medicinal and ornamental properties. Studies have shown that the stem is the primary medicinal component of Dendrobium spp. To investigate the effect of the species and age of Dendrobium (in years) on the content of its medicinal components, we collected the stems of 1-to-4-year-old D. officinale, D. moniliforme, and D. huoshanense, sequenced the transcriptome, metabolome, and microbiome, and analyzed the data in a comprehensive multi-omics study. We identified 10,426 differentially expressed genes (DEGs) with 644 differentially accumulated metabolites (DAMs) from 12 comparative groups and mapped the flavonoid pathway based on DEGs and DAMs. Transcriptomic and metabolomic data indicated a general trend of the accumulation of flavonoids exhibiting pharmacological effects in the three Dendrobium species. In addition, joint metabolome and microbiome analyses showed that actinobacteria was closely associated with flavonoid synthesis with increasing age. Our findings provide novel insights into the interactions of flavonoids of Dendrobium with the transcriptome and microbiome.

Upregulation of outer membrane porin gene ompC contributed to enhancement of azithromycin susceptibility in multidrug-resistant Escherichia coli.

The outer membrane (OM) in gram-negative bacteria contains proteins that regulate the passive or active uptake of small molecules for growth and cell function, as well as mediate the emergence of antibiotic resistance. This study aims to explore the potential mechanisms for restoring bacteria to azithromycin susceptibility based on transcriptome analysis of bacterial membrane-related genes. Transcriptome sequencing was performed by treating multidrug-resistant Escherichia coli T28R with azithromycin or in combination with colistin and confirmed by reverse transcription-quantitative PCR (RT-qPCR). Azithromycin enzyme-linked immunosorbent assay (ELISA) test, ompC gene overexpression, and molecular docking were utilized to conduct the confirmatory research of the potential mechanisms. We found that colistin combined with azithromycin led to 48 differentially expressed genes, compared to azithromycin alone, such as downregulation of tolA, eptB, lpxP, and opgE and upregulation of ompC gene. Interestingly, the addition of colistin to azithromycin differentially downregulated the mph(A) gene mediating azithromycin resistance, facilitating the intracellular accumulation of azithromycin. Also, overexpression of the ompC elevated azithromycin susceptibility, and colistin contributed to further suppression of the Mph(A) activity in the presence of azithromycin. These findings suggested that colistin firstly enhanced the permeability of bacterial OM, causing intracellular drug accumulation, and then had a repressive effect on the Mph(A) activity along with azithromycin. Our study provides a novel perspective that the improvement of azithromycin susceptibility is related not only to the downregulation of the mph(A) gene and conformational remodeling of the Mph(A) protein but also the upregulation of the membrane porin gene ompC.IMPORTANCEUsually, active efflux via efflux pumps is an important mechanism of antimicrobial resistance, such as the AcrAB-TolC complex and MdtEF. Also, bacterial porins exhibited a substantial fraction of the total number of outer membrane proteins in Enterobacteriaceae, which are involved in mediating the development of the resistance. We found that the upregulation or overexpression of the ompC gene contributed to the enhancement of resistant bacteria to azithromycin susceptibility, probably due to the augment of drug uptakes caused and the opportunity of Mph(A) function suppressed by azithromycin with colistin. Under the combination of colistin and azithromycin treatment, OmpC exhibited an increased selectivity for cationic molecules and played a key role in the restoral of the antibiotic susceptibility. Investigations on the regulation of porin expression that mediated drug resistance would be important in clinical isolates treated with antibiotics.

Prognostic nomogram model for selecting between transarterial chemoembolization plus lenvatinib, with and without PD-1 inhibitor in unresectable hepatocellular carcinoma.

OBJECTIVES: To establish and verify a prognostic nomogram model for selecting in unresectable hepatocellular carcinoma (uHCC) treated by transarterial chemoembolization plus lenvatinib (TACE-L) with or without PD-1 inhibitor. METHODS: Data of 241 uHCC patients who underwent TACE-L (n = 128) and TACE-L plus PD-1 inhibitor (TACE-L-P, n = 113) were retrospectively reviewed. The differences in tumour responses, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between two groups were compared, and a prognostic nomogram model was established based on independent clinical-radiologic factors and confirmed by Cox regression analysis for predicting PFS and OS. The treatment selection for uHCC patients was stratified by the nomogram score. RESULTS: Compared to TACE-L, TACE-L-P presented prolonged PFS (14.0 vs. 9.0 months, P < .001), longer OS (24.0 vs. 15.0 months, P < .001), and a better overall objective response rate (54.0% vs. 32.8%, P = .001). There was no significant difference between the rate of AEs in the TACE-L-P and the TACE-L (56.64% vs. 46.09%, P = .102) and the rate of grade ≥ 3 AEs (11.50% vs. 9.38%, P = .588), respectively. The nomogram model presented good discrimination, with a C-index of 0.790 for predicting PFS and 0.749 for predicting OS. Patients who underwent TACE-L and obtained a nomogram score >9 demonstrated improved 2-year PFS when transferred to TACE-L-P, and those with a nomogram ≤25 had better 2-year OS when transferred to TACE-L-P. CONCLUSIONS: TACE-L-P showed significant improvements in efficiency and safety for uHCC patients compared with TACE-L. The nomogram was useful for stratifying treatment decisions and selecting a suitable population for uHCC patients. ADVANCES IN KNOWLEDGE: Prognostic nomogram model is of great value in predicting individualized survival benefits for uHCC patients after TACE-L or/and TACE-L-P. And the nomogram was helpful for selection between TACE-L-P and TACE-L among uHCC patients.