Colorectal cancer subtyping and immune landscape analysis based on natural killer cell-related genes.

BACKGROUND AND STUDY AIMS: The prognosis of colorectal cancer (CRC) is related to natural killer (NK) cells, but the molecular subtype features of CRC based on NK cells are still unknown. This study aimed to identify NK cell-related molecular subtypes of CRC and analyze the survival status and immune landscape of patients with different subtypes. PATIENTS/MATERIAL AND METHODS: mRNA expression data, single nucleotide variant (SNV) data, and clinical information of CRC patients were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were obtained through differential analysis, and the intersection was taken with NK cell-associated genes to obtain 103 NK cell-associated CRC DEGs (NCDEGs). Based on NCDEGs, CRC samples were divided into three clusters through unsupervised clustering analysis. Survival analysis, immune analysis, Gene Set Enrichment Analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Finally, NCDEG-related small-molecule drugs were screened using the CMap database. RESULTS: Survival analysis revealed that cluster2 had a lower survival rate than cluster1 and cluster3 (p < 0.05). Immune infiltration analysis found that the immune infiltration levels and immune checkpoint expression levels of cluster1_3 were substantially higher than those of cluster2, and the tumor purity was the opposite (p < 0.05). GSEA presented that cluster1_3 was significantly enriched in the chemokine signaling pathway, ECM receptor interaction, and antigen processing and presentation pathways (p < 0.05). The TMB of cluster1_3 was significantly higher than that of cluster2 (p < 0.05). Genes with the highest mutation rate in CRC were APC, TP53, TTN, and KRAS. Drug prediction results showed that small-molecule drugs that reverse the upregulation of NCDEGs, deoxycholic acid, dipivefrine, phenformin, and other drugs may improve the prognosis of CRC. CONCLUSION: NK cell-associated CRC subtypes can be used to evaluate the tumor characteristics of CRC patients and provide an important reference for CRC patients.

A novel TGFbeta/TGILR axis mediates crosstalk between cancer-associated fibroblasts and tumor cells to drive gastric cancer progression.

Transforming growth factor beta (TGFß) signaling plays a critical role in tumorigenesis and metastasis. However, little is known about the biological function of TGFbeta-induced lncRNA in cancer. In this study, we discovered a novel TGFbeta-induced lncRNA, termed TGILR, whose function in cancer remains unknown to date. TGILR expression was directly activated by the canonical TGFbeta/SMAD3 signaling axis, and this activation is highly conserved in cancer. Clinical analysis showed that TGILR overexpression showed a significant correlation with lymph node metastasis and poor survival and was an independent prognostic factor in gastric cancer (GC). Depletion of TGILR caused an obvious inhibitory effect on GC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. More importantly, we demonstrated that TGFbeta signaling in GC was overactivated due to cancer-associated fibroblast (CAF) infiltration. Mechanistically, increased level of CAF-secreted TGFbeta activates TGFbeta signaling, leading to TGILR overexpression in GC cells. Meanwhile, TGILR overexpression inhibited the microRNA biogenesis of miR-1306 and miR-33a by interacting with TARBP2 and reducing its protein stability, thereby promoting GC progression via TCF4-mediated EMT signaling. In conclusion, CAF infiltration drives GC metastasis and EMT signaling through activating TGFbeta/TGILR axis. Targeted blocking of CAF-derived TGFbeta should be a promising anticancer strategy in GC.

PRDX1 Interfering Peptide Disrupts Amino Acids 70-90 of PRDX1 to Inhibit the TLR4/NF-κB Signaling Pathway and Attenuate Neuroinflammation and Ischemic Brain Injury.

Ischemic stroke ranks among the leading causes of death and disability in humans and is accompanied by motor and cognitive impairment. However, the precise mechanisms underlying injury after stroke and effective treatment strategies require further investigation. Peroxiredoxin-1 (PRDX1) triggers an extensive inflammatory cascade that plays a pivotal role in the pathology of ischemic stroke, resulting in severe brain damage from activated microglia. In the present study, we used molecular dynamics simulation and nuclear magnetic resonance to detect the interaction between PRDX1 and a specific interfering peptide. We used behavioral, morphological, and molecular experimental methods to demonstrate the effect of PRDX1-peptide on cerebral ischemia-reperfusion (I/R) in mice and to investigate the related mechanism. We found that PRDX1-peptide bound specifically to PRDX1 and improved motor and cognitive functions in I/R mice. In addition, pretreatment with PRDX1-peptide reduced the infarct area and decreased the number of apoptotic cells in the penumbra. Furthermore, PRDX1-peptide inhibited microglial activation and downregulated proinflammatory cytokines including IL-1ß, IL-6, and TNF-α through inhibition of the TLR4/NF-κB signaling pathway, thereby attenuating ischemic brain injury. Our findings clarify the precise mechanism underlying PRDX1-induced inflammation after ischemic stroke and suggest that the PRDX1-peptide can significantly alleviate the postischemic inflammatory response by interfering with PRDX1 amino acids 70-90 and thereby inhibiting the TLR4/NF-κB signaling pathway. Our study provides a theoretical basis for a new therapeutic strategy to treat ischemic stroke.

Cobalt telluride regulated by nickel for efficient electrooxidation of 5-hydroxymethylfurfural.

Replacing the anodic oxygen evolution reaction (OER) in water splitting with 5-hydroxymethylfurfural oxidation reaction (HMFOR) can not only reduce the energy required for hydrogen production but also yield the valuable chemical 2,5-furandicarboxylic acid (FDCA). Co-based catalysts are known to be efficient for HMFOR, with high-valent Co being recognized as the main active component. However, efficiently promoting the oxidation of Co2+ to produce high-valent reactive species remains a challenge. In this study, Ni-doped CoTe (CoNiTe) nanorods were prepared as efficient catalysts for HMFOR, achieving a high HMFOR current density of 65.3 mA cm-2 at 1.50 V. Even after undergoing five successive electrolysis processes, the Faradaic efficiency (FE) remained at approximately 90.7 %, showing robust electrochemical durability. Mechanistic studies indicated that Ni doping changes the electronic configuration of Co, enhancing its charge transfer rate and facilitating the oxidation of Co2+ to high-valent CoO2 species. This work reveals the effect of Ni doping on the reconfiguration of the active phase during HMFOR.

Distribution, mobilization, risk assessment and source identification of heavy metals and nutrients in surface sediments of three urban-rural rivers after long-term water pollution treatment.

Sediments are critical pollution carriers in urban-rural rivers, which can threaten the water quality of the river and downstream lakes for a long time. However, it is still not clear whether conventional water pollution treatments could abate sediment pollution or not. In this study, heavy metals (HMs) and nutrient salts in the surface sediments and overlying water were investigated after decades' water pollution treatment in three urban-rural rivers. HM speciation was determined by the sequential extraction; diffusion fluxes were estimated using Fick's first law; HM ecological risk and nutrient pollution were evaluated; and pollution sources were identified by statistical analysis and GIS. The results showed that the HMs and nutrients were extremely serious in the urban regions. The accumulation level of Pb, Cu and Cd in the sediments of the three rivers were all much higher than the soil background value, and the labile fractions accounted for high proportions (57 % for Pb, 55 % for Cu and 43 % for Cd), which could be easily eluate from the sediments and caused hazards to the aquatic environment. The sediment diffusion fluxes of HMs and ammonia nitrogen were mostly positive, which indicated these sites currently released these pollutants from sediment to overlying water. Cd, Pb, Cu and Cr may mainly originate from industrial discharge and domestic sewage, while Cr was also greatly affected by crustal weathering; nutrient pollution may originate from agricultural activities and domestic sewage. Our study demonstrated that after decades' conventional water treatment in these rivers, the sediment pollution was still in a serious level with high ecological risk, and Cd was the dominant pollutant. At present, the external point source pollution has been effectively controlled, thus, the in-depth understanding of the sediment pollution characteristics after long-term water treatment could provide a scientific basis for the accurate elimination of river pollution.

Nanoparticles for inducing Gaucher disease-like damage in cancer cells.

Nutrient avidity is one of the most distinctive features of tumours. However, nutrient deprivation has yielded limited clinical benefits. In Gaucher disease, an inherited metabolic disorder, cells produce cholesteryl-glucoside which accumulates in lysosomes and causes cell damage. Here we develop a nanoparticle (AbCholB) to emulate natural-lipoprotein-carried cholesterol and initiate Gaucher disease-like damage in cancer cells. AbCholB is composed of a phenylboronic-acid-modified cholesterol (CholB) and albumin. Cancer cells uptake the nanoparticles into lysosomes, where CholB reacts with glucose and generates a cholesteryl-glucoside-like structure that resists degradation and aggregates into microscale crystals, causing Gaucher disease-like damage in a glucose-dependent manner. In addition, the nutrient-sensing function of mTOR is suppressed. It is observed that normal cells escape severe damage due to their inferior ability to compete for nutrients compared with cancer cells. This work provides a bioinspired strategy to selectively impede the metabolic action of cancer cells by taking advantage of their nutrient avidity.

Effects of sulfamonomethoxine and trimethoprim co-exposures at different environmentally relevant concentrations on microalgal growth and nutrient assimilation.

In aquaculture around the world, sulfamonomethoxine (SMM), a long-acting antibiotic that harms microalgae, is widely employed in combination with trimethoprim (TMP), a synergist. However, their combined toxicity to microalgae under long-term exposures at environmentally relevant concentrations remains poorly understood. Therefore, we studied the effects of SMM single-exposures and co-exposures (SMM:TMP=5:1) at concentrations of 5 µg/L and 500 µg/L on Chlorella pyrenoidosa within one aquacultural drainage cycle (15 days). Photosynthetic activity and N assimilating enzyme activities were employed to evaluate microalgal nutrient assimilation. Oxidative stress and flow cytometry analysis for microalgal proliferation and death jointly revealed mechanisms of inhibition and subsequent self-adaptation. Results showed that exposures at 5 µg/L significantly inhibited microalgal nutrient assimilation and induced oxidative stress on day 7, with a recovery to levels comparable to the control by day 15. This self-adaptation and over 95 % removal of antibiotics jointly contributed to promoting microalgal growth and proliferation while reducing membrane-damaged cells. Under 500 µg/L SMM single-exposure, microalgae self-adapted to interferences on nutrient assimilation, maintaining unaffected growth and proliferation. However, over 60 % of SMM remained, leading to sustained oxidative stress and apoptosis. Remarkably, under 500 µg/L SMM-TMP co-exposure, the synergistic toxicity of SMM and TMP significantly impaired microalgal nutrient assimilation, reducing the degradation efficiency of SMM to about 20 %. Consequently, microalgal growth and proliferation were markedly inhibited, with rates of 9.15 % and 17.7 %, respectively, and a 1.36-fold increase in the proportion of cells with damaged membranes was observed. Sustained and severe oxidative stress was identified as the primary cause of these adverse effects. These findings shed light on the potential impacts of antibiotic mixtures at environmental concentrations on microalgae, facilitating responsible evaluation of the ecological risks of antibiotics in aquaculture ponds.

Dietary flavonoids modulate the gut microbiota: A new perspective on improving autism spectrum disorder through the gut-brain axis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unknown etiology. It is associated with various factors and causes great inconvenience to the patient's life. The gut-brain axis (GBA), which serves as a bidirectional information channel for exchanging information between the gut microbiota and the brain, is vital in studying many neurodegenerative diseases. Dietary flavonoids provide anti-inflammatory and antioxidant benefits, as well as regulating the structure and function of the gut microbiota. The occurrence and development of ASD are associated with dysbiosis of the gut microbiota. Modulation of gut microbiota can effectively improve the severity of ASD. This paper reviews the links between gut microbiota, flavonoids, and ASD, focusing on the mechanism of dietary flavonoids in regulating ASD through the GBA.

Cloning and Function Analysis of the CsTAU1 in Response to Salt-Alkali Stress.

To investigate the role of candidate genes for salt-alkali tolerance in cucumber (Cucumis sativus L.), this study screened CsTAU1 in the glutathione pathway from previous transcriptome data for cloning and functional analysis. Clone cucumber CsTAU1 contains one 675 bp open reading frame, containing one GST-N-Tau domain and one GST-C-Tau domain, and is expressed in cytoplasm. After successfully constructing overexpression vectors of CsTAU1 (+) and CsTAU1 (-), they were transferred into cucumber varieties 'D1909' (high salt alkali resistance) and 'D1604' (low salt alkali resistance) for salt-alkali resistance identification. It was found that under salt-alkali stress, CsTAU1 (+)-overexpressing plants showed strong resistance to salt-alkali stress, while CsTAU1 (-)-overexpressing plants showed the opposite situation. qRT-PCR analysis was performed on other glutathione pathway-related genes in CsTAU1-overexpressing plants. The expression patterns of LOC101219529 and LOC105434443 were the same as CsTAU1, and the introduction of CsTAU1 (+) increased the chlorophyll, α-Naphthylamine oxidation, glutathione S-transferase (GST), and catalase (CAT) content of cucumber. The research results provide a theoretical basis for cultivating salt-alkali-tolerant cucumber varieties.

Shifting the Oxygen-Evolution Reaction Pathway via Cation Engineering to Activate Lattice Oxygen in Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) as promising electrocatalysts have been widely studied, but their performance is limited by conductivity and coordinating saturation. This study proposes a cationic (V) modification strategy and evaluates its effect on the electrocatalytic performance of CoFe-MOF nanosheet arrays. The optimal V-CoFe-MOF/NF electrocatalyst exhibits excellent oxygen-evolution reaction (OER)/hydrogen-evolution reaction (HER) performance (231 mV at 100 mA cm-2/86 mV at 10 mA cm-2) in alkaline conditions, with its OER durability exceeding 400 h without evident degradation. Furthermore, as a bifunctional electrocatalyst for water splitting, a small cell voltage is achieved (1.60 V at 10 mA cm-2). The practicability of the catalyst is further evaluated by membrane electrode assembly (MEA), showing outstanding activity (1.53 V at 10 mA cm-2) and long-term stability (at 300 mA cm-2). Moreover, our results reveal the apparent reconstruction properties of V-CoFe-MOF/NF in alkaline electrolytes, where the partially dissolved V promotes the formation of more active ß-MOOH. The mechanism study shows the OER mechanism shifts to a lattice oxygen oxidation mechanism (LOM) after V doping, which directly avoids complex multistep adsorption mechanism and reduces reaction energy. This study provides a cation mediated strategy for designing efficient electrocatalysts.

Long Non-Coding RNA FLG-AS1 Inhibits Cervical Cancer Progression through Negatively Modulating miR-147b.

OBJECTIVE: The study investigated the association between FLG-AS1 and cervical cancer prognosis and the interaction mechanism between FLG-AS1 and miR-147b in order to identify potential therapeutic targets for cervical cancer. METHODS: In this study, tissue samples and clinicopathological characteristics were obtained from 125 cervical cancer patients. FLG-AS1 expression levels in the samples were detected by polymerase chain reaction assay. CCK-8 and Transwell assays were used to evaluate FLG-AS1's impact on cervical cancer cell proliferation and metastasis. The mechanism of action of FLG-AS1 and miR-147b was probed by a dual luciferase reporter gene assay. The prognostic nature of FLG-AS1 in cervical cancer was explored by a series of statistical approaches. RESULTS: In cervical cancer cells and tissues, FLG-AS1 expression is markedly downregulated. FLG-AS1 inhibits the activities of cervical cancer cells by negatively regulating miR-147b expression. Patients with cervical cancer have a poor prognosis when FLG-AS1 expression is low. CONCLUSION: FLG-AS1 may be considered as a novel cervical cancer prognostic biomarker candidate, which affects cancer cell progression by negatively regulating miR-147b.

Influence of Pteris vittata-maize intercropping on plant agronomic parameters and soil arsenic remediation.

To achieve "production while remediation" in arsenic (As) -contaminated farmlands, a field experiment was conducted to investigate the effects of five Pteris vittata L. (PV) - maize intercropping modes on the growth, nutrient, and As accumulation characteristics of PV and maize. The intercropping increased the As content of PV by 2.9%-132.0% and decreased the As content in maize shoots by 15.5%-37.0%. Total As accumulation in above-ground plant parts reached 202.03-941.97 g hm-2. Intercropping also improved nitrogen and phosphorus content in maize kernels by 27.6%-124.7% and 15.9%-31.5%, respectively. Additionally, intercropping increased maize kernel 100-grain weight by 10.0%-16.6% and resulted in a 1.1%-24.1% increase in maize yield compared to sole cultivation. The intercropping transformed soil As from iron-bound to calcium-bound and aluminum-bound forms. Analysis of soil microbial diversity showed that the intercropping decreases the abundance of Chloroflexi and increases the abundance of Proteobacteria. Among the five modes, the intercropping mode with 4 rows of maize and 4 rows of PV showed the highest remediation efficiency and mechanized operation. These findings contribute to a theoretical framework and technical support for the simultaneous soil pollution remediation and productive farming practices.

Brain fingerprinting and cognitive behavior predicting using functional connectome of high inter-subject variability.

The functional connectivity (FC) graph of the brain has been widely recognized as a ``fingerprint'' that can be used to identify individuals from a group of subjects. Research has indicated that individual identification accuracy can be improved by eliminating the impact of shared information among individuals. However, current research extracts not only shared information of inter-subject but also individual-specific information from FC graphs, resulting in incomplete separation of shared information and fingerprint information among individuals, leading to lower individual identification accuracy across all functional magnetic resonance imaging (fMRI) states session pairs and poor cognitive behavior prediction performance. In this paper, we propose a method to enhance inter-subject variability combining conditional variational autoencoder (CVAE) network and sparse dictionary learning (SDL) module. By embedding fMRI state information in the encoding and decoding processes, the CVAE network can better capture and represent the common features among individuals and enhance inter-subject variability by residual. Our experimental results on Human Connectome Project (HCP) data show that the refined connectomes obtained by using CVAE with SDL can accurately distinguish an individual from the remaining participants. The success accuracies reached 99.7 % and 99.6 % in the session pair rest1-rest2 and reverse rest2-rest1, respectively. In the identification experiment involving task-task combinations carried out on the same day, the identification accuracies ranged from 94.2 % to 98.8 %. Furthermore, we showed the Frontoparietal and Default networks make the most significant contributions to individual identification and the edges that significantly contribute to individual identification are found within and between the Frontoparietal and Default networks. Additionally, high-level cognitive behaviors can also be better predicted with the obtained refined connectomes, suggesting that higher fingerprinting can be useful for resulting in higher behavioral associations. In summary, our proposed framework provides a promising approach to use functional connectivity networks for studying cognition and behavior, promoting a deeper understanding of brain functions.

Role of small nucleolar RNAs in alternative splicing of the doublesex gene in the silkworm, Bombyx mori.

More and more evidence shows that small noncoding RNAs (ncRNAs) play diverse roles in development, stress response and other cellular processes, but functional study of intermediate-size ncRNAs is still rare. Here, the expression profile of 16 intermediate-size ncRNAs in ovary and testis of silkworm Bombyx mori were analyzed. Twelve ncRNAs, including 5 small nucleolar RNAs (snoRNAs) and 7 unclassified ncRNAs, accumulated more in the testis than in the ovary of silkworm, especially Bm-163, Bm-51 and Bm-68. Four ncRNAs (including three orphan snoRNAs and one unclassified ncRNA) had higher expression level in the ovary than in the testis, especially Bm-86. Overexpression of the testis-enriched snoRNA Bm-68 in the female led to the accumulation of male-specific isoform of doublesex (BmdsxM) and increased the expression ratio of BmdsxM: BmdsxF. While overexpression of ovary-enriched snoRNA Bm-86 in the male decreased the expression ratio of BmdsxM: BmdsxF, indicating the roles of the two snoRNAs played in the alternative splicing of Bmdsx of silkworm, which will provide new clues for the functional study of snoRNAs in insects.

Effect of atmospheric pressure plasma jet on the structure and physicochemical properties of wheat starch.

The effect of atmospheric pressure plasma jet (APPJ) with different discharge power (0, 400, 600, and 800 W) on the structure and physicochemical properties of wheat starch were evaluated in this study. After APPJ treatments, significant declines in peak viscosity, breakdown viscosity, and final viscosity of wheat starch pasting parameters were observed with increase of plasma treatment power. Being treated with discharge power of 800 W, the PV and BD value of wheat starch paste significantly dropped to 2,578 and 331 cP, respectively. Apparently, APPJ could raise the solubility of wheat starch, while reduce the swelling capacity, and also lower the G' and G″ value of wheat starch gel. Roughness and apparent scratch was observed on the surface of the treated wheat starch granules. Although APPJ treatment did not alter wheat starch's crystallization type, it abated the relative crystallinity. APPJ treatment might be useful in producing modified wheat starch with lower viscosity and higher solubility.

Peritoneal B1 and B2 cells respond differently to LPS and IL-21 stimulation.

Peritoneal B cells can be divided into B1 cells (CD11b+CD19+) and B2 cells (CD11b-CD19+) based on CD11b expression. B1 cells play a crucial role in the innate immune response by producing natural antibodies and cytokines. B2 cells share similar traits with B1 cells, influenced by the peritoneal environment. However, the response of both B1 and B2 cells to the same stimuli in the peritoneum remains uncertain. We isolated peritoneal B1 and B2 cells from mice and assessed differences in Interleukin-10(IL-10) secretion, apoptosis, and surface molecule expression following exposure to LPS and Interleukin-21(IL-21). Our findings indicate that B1 cells are potent IL-10 producers, possessing surface molecules with an IgMhiCD43+CD21low profile, and exhibit a propensity for apoptosis in vitro. Conversely, B2 cells exhibit lower IL-10 production and surface markers characterized as IgMlowCD43-CD21hi, indicative of some resistance to apoptosis. LPS stimulates MAPK phosphorylation in B1 and B2 cells, causing IL-10 production. Furthermore, LPS inhibits peritoneal B2 cell apoptosis by enhancing Bcl-xL expression. Conversely, IL-21 has no impact on IL-10 production in these cells. Nevertheless, impeding STAT3 phosphorylation permits IL-21 to increase IL-10 production in peritoneal B cells. Moreover, IL-21 significantly raises apoptosis levels in these cells, a process independent of STAT3 phosphorylation and possibly linked to reduced Bcl-xL expression. This study elucidates the distinct functional and response profiles of B1 and B2 cells in the peritoneum to stimuli like LPS and IL-21, highlighting their differential roles in immunological responses and B cell diversity.

Prognostic and Predictive Significance of Ki67 in Primary Non-metastatic or Recurrent Acral Melanoma: Evidence from a Multicenter Retrospective Study.

BACKGROUND: The purpose of this work was to investigate the prognostic significance of Ki67 in acral melanoma (AM). PATIENTS AND METHODS: Ki67 values in primary lesions (pKi67) of 481 patients with primary non-metastatic AM (primary cohort) from three tertiary hospitals and in recurrent lesions (rKi67) of 97 patients (recurrent cohort) were recorded. The associations of p/rKi67 with clinicopathological features and prognosis were analyzed. RESULTS: In the primary cohort, high pKi67 group tended to have more ulceration, pT4, lymph node metastasis (LNM), nodal macrometastases, and recurrence (all P < 0.05). Logistic regression analysis revealed that pKi67 was significantly associated with pT4 and LNM (P = 0.004 and 0.027, respectively). Furthermore, both 5-year overall survival (OS) and recurrence-free survival (RFS) rates in high pKi67 group were significantly worse than those in moderate and low pKi67 groups (OS 47.8% versus 55.7 versus 76.8%, P = 0.002; RFS: 27.1 versus 42.8 versus 61.8%, P < 0.001). Similarly, in the recurrent cohort, the 5-year survival after recurrence (SAR) rates in high rKi67 group was significantly worse than those in moderate and low rKi67 groups (31.7 versus 47.4 versus 75%; P = 0.026). Stratified analysis also indicated a significant survival difference among pKi67 groups within various subgroups. Most importantly, multivariate Cox analysis demonstrated that pKi67 could be independently associated with OS and RFS, as well as rKi67 for SAR (all P < 0.05). CONCLUSIONS: A high Ki67 value was significantly associated with adverse pathological and prognostic features in both primary and recurrent AM cohorts. Ki67 should be routinely evaluated to guide risk stratification and prognostic prediction.

A pharmacovigilance study of adverse events associated with polymyxins based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.

BACKGROUND: Polymyxins have been regarded as last-line treatment for multidrug-resistant gram-negative bacterial infections. Nonetheless, concerns regarding toxicity persist. This study aimed to explore and compare potential adverse events (AEs) between colistin and polymyxin B (PMB). METHODS: Outpatient antibiotic use associated with acute upper respiratory infections in China: a nationwide cross-sectional study Polymyxins-related AEs were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System between 2004 and 2022. Potential signals were estimated by the reporting odds ratio (ROR), and subgroup analyses were preformed to adjust for potential factors in AEs with significant disproportionality. RESULTS: Analysis of 3,915 records involving 718 patients revealed a higher disproportionality of renal and urinary disorders (ROR 1.62, 95% CI 1.01-2.59) and acute kidney injury (ROR 1.75, 95% CI 1.07-2.87) with colistin treatment. Conversely, colistin exhibited a lower risk for neurotoxicity (ROR 0.47, 95% CI 0.30-0.73). Seven cases of skin hyperpigmentation were reported with PMB, whereas none were reported with colistin. Over 80% of cases involving polymyxin-related AEs occurred during the first two weeks of therapies, with a median onset time of 4.5 days. CONCLUSIONS: Outpatient antibiotic use associated with acute upper respiratory infections in China: a nationwide cross-sectional study Patients received colistin displayed a higher potential risk of nephrotoxicity but a lower risk of neurotoxicity. Clinicians should be vigilant in monitoring the AEs of hyperpigmentation disorders induced by PMB.