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Recently, advanced oxidation processes (AOPs) based upon peracetic acid (PAA) with high efficiency for degrading aqueous organic contaminants have attracted extensive attention. Herein, a novel metal-free N-doped carbonaceous catalyst, namely, carbonized polyaniline (CPANI), was applied to activate PAA to degrade phenolic and pharmaceutical pollutants. The results showed that the CPANI/PAA system could effectively degrade 10 µM phenol in 60 min with low concentrations of PAA (0.1 mM) and catalyst (25 mg L-1). This system also performed well within a wide pH range of 5-9 and displayed high tolerance to Cl-, HCO3- and humic acid. The nonradical pathway [singlet oxygen (1O2)] was found to be the dominant pathway for degrading organic contaminants in the CPNAI/PAA system. Systematic characterization revealed that the graphitic N, pyridinic N, carbonyl groups (CO) and defects played the role of active sites on CPANI during the activation of PAA. The catalytic capacity of spent CPANI could be conveniently recovered by thermal treatment. The findings will be helpful for the application of metal-free carbonaceous catalyst/PAA processes in decontaminating water.
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Peróxido de Hidrogênio , Poluentes Químicos da Água , Ácido Peracético , Metais , Oxirredução , Fenóis , ÁguaRESUMO
Inspired by the principles of the biological nervous system, neuromorphic engineering has brought a promising alternative approach to intelligence computing with high energy efficiency and low consumption. As pivotal components of neuromorphic system, artificial spiking neurons are powerful information processing units and can achieve highly complex nonlinear computations. By leveraging the switching dynamic characteristics of memristive device, memristive neurons show rich spiking behaviors with simple circuit. This report reviews the memristive neurons and their applications in neuromorphic sensing and computing systems. The switching mechanisms that endow memristive devices with rich dynamics and nonlinearity are highlighted, and subsequently various nonlinear spiking neuron behaviors emulated in these memristive devices are reviewed. Then, recent development is introduced on neuromorphic system with memristive neurons for sensing and computing. Finally, we discuss challenges and outlooks of the memristive neurons toward high-performance neuromorphic hardware systems and provide an insightful perspective for the development of interactive neuromorphic electronic systems.
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A Gram-stain-negative, strictly aerobic, non-flagellated, oxidase- and catalase-positive, rod-shaped marine bacterium, designated strain DM8T, was isolated from the intestine of Trichiurus japonicus in Weihai, China. The strain optimally grew at 25-35â, with 1.0-4.0% (w/v) NaCl and at pH 7.0-8.0. Its colonies were circular, slightly yellow, non-transparent, smooth, and approximately 0.8-1.5 mm in diameter, after being cultured for 48 h on marine agar 2216. Based on the result of phylogenetic analysis of 16S rRNA gene sequence, strain DM8T had close relationship with Oceanisphaera profunda SM1222T (96.9%) and the type strain DSM 15406 T of the type species Oceanisphaera litoralis (94.7%), respectively. Genome sequencing revealed a genome size of 3,109,059 bp and a G + C content of 46.9 mol%. It had Q-8 as the sole respiratory quinone and possessed C16:0, summed features 3 (C16:1ω7c/C16:1ω6c) and summed features 8 (C18:1ω7c/C18:1ω6c) as major fatty acids. The major polar lipid profile was composed of phosphatidylglycerol and phosphatidylethanolamine. Based on the phenotypic, chemotaxonomic characterizations, phylogenetic properties and genome analysis, strain DM8T should represent a novel species of the genus Oceanisphaera, for which the name Oceanisphaera pacifica sp. nov. is proposed. The type strain is DM8T (= KCTC 82764 T = MCCC 1K06133T).
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Perciformes , Água do Mar , Animais , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/química , Intestinos , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Água do Mar/microbiologia , Análise de Sequência de DNA , Ubiquinona/químicaRESUMO
Members of the genus Marinomonas are known for their environmental adaptation and metabolically versatility, with abundant proteins associated with antifreeze, osmotic pressure resistance, carbohydrase and multiple secondary metabolites. Comparative genomic analysis focusing on secondary metabolites and orthologue proteins was conducted with 30 reference genome sequences in the genus Marinomonas. In this study, a Gram-stain-negative, rod-shaped, non-flagellated and strictly aerobic bacterium, designated as strain E8T, was isolated from the red algae (Gelidium amansii) in the coastal of Weihai, China. Optimal growth of the strain E8T was observed at temperatures 25-30 °C, pH 6.5-8.0 and 1-3% (w/v) NaCl. The DNA G + C content was 42.8 mol%. The predominant isoprenoid quinone was Q-8 and the major fatty acids were C16:0, summed feature 3 and summed feature 8. The major polar lipids were phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). Based on data obtained from this polyphasic taxonomic study, strain E8T should be considered as a novel species of the genus Marinomonas, for which the name Marinomonas algarum is proposed. The type strain is E8T (= KCTC 92201T = MCCC 1K07070T).
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Marinomonas , Rodófitas , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/química , Genômica , Marinomonas/genética , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Rodófitas/genética , Rodófitas/microbiologia , Análise de Sequência de DNA , Ubiquinona/químicaRESUMO
We found that Gm15290 was one of the most upregulated lncRNAs in the adipose of ob/ob mice through lncRNA microarray analysis. Then, manipulations of overexpression and silencing in mouse primary adipocytes showed that Gm15290 positively regulated adipogenesis, manifested by increasing lipid deposition and upregulating adipogenic genes including PPARγ, C/EBPα, and aP2. However, overexpression of mutant Gm15290 (at the binding site of miR-27c) did not have an promoting effect on adipogenesis. Additionally, Gm15290 was found to potentially interact with miR-27b that had been identified as a PPARγ targeting miRNA, and we verified their interaction by luciferase activity and RNA pull down assays. Furthermore, inhibition of Gm15290, by injection of the Gm15290 siRNA, decreased the body weight gain and mass of adipose tissues, including iWAT and eWAT, in mice fed with HFD. In conclusion, Gm15290 sponges miR-27b to increase fat deposition and body weight in HFD-fed mice.
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MicroRNAs/genética , PPAR gama/metabolismo , RNA Longo não Codificante/genética , Aumento de Peso/genética , Adipócitos/citologia , Adipócitos/fisiologia , Adipogenia/genética , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/fisiologia , Animais , Diferenciação Celular/genética , Regulação da Expressão Gênica , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , PPAR gama/genética , RNA Interferente Pequeno/farmacologia , Aumento de Peso/fisiologiaRESUMO
To avoid recurrent variceal bleeding, transjugular intrahepatic portosystemic shunt (TIPS) in conjunction with variceal embolization is considered to be an effective strategy. However, due to changes in conditions and variations in the patient's state, individuals undergoing TIPS may face challenges and limitations during procedures. The transjugular technique and combined transsplenic portal venous recanalization (PVR) with TIPS were not effective in this case due to a blocked portal vein and a previous splenectomy. With an abdominal incision, we successfully punctured the mesenteric venous system and navigated the occluded segment of the portal vein through the mesenteric approach. TIPS was then performed under balloon guidance. This study aims to explore the management of risks and complications during surgical operations and propose multiple preoperative surgical techniques to improve the success rate of the procedure.
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Most of the existing low-light image enhancement methods suffer from the problems of detail loss, color distortion and excessive noise. To address the above-mentioned issues, this paper proposes a neural network-based low-light image enhancement network. The network is divided into three parts: decomposition network, reflection component denoising network, and illumination component enhancement network. In the decomposition network, the input image is decomposed into a reflection image and an illumination image. In the reflection component denoising network, the Unet3+ network improved by fusion CA attention is adopted to denoise the reflection image. In the illumination component enhancement network, the adaptive mapping curve is adopted to enhance the illumination image iteratively. Finally, the processed illumination and reflection images are fused based on Retinex theory to obtain the final enhanced image. The experimental results show that the proposed network achieves excellent visual effects in subjective evaluation. Additionally, it shows a significant improvement in objective evaluation metrics, including PSNR, SSIM, NIQE, and so on, when compared to the results in several public datasets.
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Iluminação , Redes Neurais de Computação , Iluminação/métodos , Humanos , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , LuzRESUMO
Parabens (PBs) and triclosan (TCS) are commonly found in pharmaceuticals and personal care products (PPCPs). As a result, they have been extensively found in the environment, particularly in aquaculture operations. Red swamp crayfish (Procambarus clarkii) consumption has significantly risen in China. Nevertheless, the levels of PBs and TCS in this species and the associated risk to human dietary intake remain undisclosed. This study assessed the amounts of five PBs, i.e., methyl-paraben (MeP), ethyl-paraben (EtP), propyl-paraben (PrP), butyl-paraben (BuP) and benzyl-paraben (BzP), as well as TCS in crayfish taken from five provinces of the middle-lower Yangtze River. MeP, PrP and TCS showed the highest detection rates (hepatopancreas: 46-86 %; muscle: 63-77 %) since they are commonly used in PPCPs. Significantly higher levels of ∑5PBs (median: 3.69 ng/g) and TCS (median: 7.27 ng/g) were significantly found in the hepatopancreas compared to the muscle (median: 0.39 ng/g for ∑5PBs and 0.16 ng/g for TCS) (p < 0.05), indicating bioaccumulation of these chemicals in the hepatopancreas. The estimated daily intake values of ∑5PBs and TCS calculated from the median concentrations of crayfish were 6.44-7.94 ng/kg bw/day and 11.4-14.0 ng/kg bw/day, respectively. Although no health risk was predicted from consuming crayfish (HQ <1), consumption of the hepatopancreas is not recommended.
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Astacoidea , Exposição Dietética , Parabenos , Triclosan , Poluentes Químicos da Água , Animais , Triclosan/análise , China , Poluentes Químicos da Água/análise , Parabenos/análise , Exposição Dietética/estatística & dados numéricos , Exposição Dietética/análise , Humanos , Medição de Risco , Distribuição Tecidual , Monitoramento Ambiental , Contaminação de Alimentos/análiseRESUMO
Constructing crossmodal in-sensor processing system based on high-performance flexible devices is of great significance for the development of wearable human-machine interfaces. A bio-inspired crossmodal in-sensor computing system can perform real-time energy-efficient processing of multimodal signals, alleviating data conversion and transmission between different modules in conventional chips. Here, we report a bio-inspired crossmodal spiking sensory neuron (CSSN) based on a flexible VO2 memristor, and demonstrate a crossmodal in-sensor encoding and computing system for wearable human-machine interfaces. We demonstrate excellent performance in the VO2 memristor including endurance (>1012), uniformity (0.72% for cycle-to-cycle variations and 3.73% for device-to-device variations), speed (<30 ns), and flexibility (bendable to a curvature radius of 1 mm). A flexible hardware processing system is implemented based on the CSSN, which can directly perceive and encode pressure and temperature bimodal information into spikes, and then enables the real-time haptic-feedback for human-machine interaction. We successfully construct a crossmodal in-sensor spiking reservoir computing system via the CSSNs, which can achieve dynamic objects identification with a high accuracy of 98.1% and real-time signal feedback. This work provides a feasible approach for constructing flexible bio-inspired crossmodal in-sensor computing systems for wearable human-machine interfaces.
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Células Receptoras Sensoriais , Dispositivos Eletrônicos Vestíveis , Humanos , Células Receptoras Sensoriais/fisiologia , Sistemas Homem-Máquina , Potenciais de Ação/fisiologia , Desenho de EquipamentoRESUMO
A sustainable pathway for the synthesis of tetracyclic purinium salts via ruthenium-catalyzed electro-oxidative annulation of C6-arylpurine nucleosides with alkynes without a stoichiometric metal oxidant has been developed. The protocol described herein exhibits high regioselectivity, broad scope, and wide functional group tolerance, allowing efficient coupling of various biologically important molecules including acyclic, ribosyl, arabinosyl, and deoxyribosyl purine nucleoside derivatives. A novel purinoisoquinolinium-coordinated ruthenium(0) sandwich intermediate has been isolated, crystallographically characterized, and electrochemically analyzed, offering direct mechanistic insight.
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BACKGROUND: Existing guidelines recommend a triple immunosuppressive regimen with calcineurin inhibitors, antimetabolites, and corticosteroids for postoperative immunosuppression in renal transplant patients. However, few studies have compared cyclosporine and tacrolimus for long-term outcomes. In this study, the meta-analysis was used to compare long-term outcomes in renal transplant patients to evaluate the use of cyclosporine vs. tacrolimus. The pros and cons of suppression programs have been analyzed. METHODS: Cyclosporine, tacrolimus, and kidney transplantation, were used as search terms to retrieve relevant publications in PubMed, Embase, and The Cochrane library. Two independent researchers screened and evaluated the relevant results of each search using the RevMan5.4 program to make relevant charts for the meta-analysis. Odds ratios (OR) and 95% confidence intervals (CI) were used to report dichotomous variables, while mean differences (MD) and 95% confidence intervals (CI) were used to report continuous variables. The study took tacrolimus- and cyclosporine-based maintenance immunosuppression as experimental and control groups, respectively. The graft and patient survival outcomes were followed for 5 or more years. RESULTS: Overall, thirteen studies were included in the meta-analysis, including nine randomized controlled trials and four non-randomized controlled trials. Compared with the cyclosporine group, the incidence of rejection, drug conversion, and dyslipidemia were significantly lower in the tacrolimus group. Furthermore, there was higher glomerular filtration rates and graft survival rates in the tacrolimus group than in the cyclosporine group. In contrast, there were no significant differences between the two groups in terms of patient survival, incidence of infection, hypertension and new tumors. However, the use of tacrolimus was associated with a high risk of a new onset of diabetes. CONCLUSION: The meta-analysis showed that, compared with cyclosporine, tacrolimus increases the risk of a new-onset diabetes. However, tacrolimus had higher graft survival rate and better creatinine clearance than cyclosporine.
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Diabetes Mellitus , Transplante de Rim , Humanos , Inibidores de Calcineurina/uso terapêutico , Tacrolimo/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Ciclosporina/uso terapêutico , Prognóstico , Diabetes Mellitus/tratamento farmacológicoRESUMO
Purpose: The association between minimally invasive surgery (MIS) for hematoma evacuation and late seizures after intracerebral hemorrhage (ICH) remains uncertain. We aimed to investigate whether MIS increases the risk of late seizures after ICH and identify the risk factors for late seizures in this patient subgroup. Methods: We retrospectively included consecutive inpatients diagnosed with ICH at two tertiary hospitals in China. The subjects were divided into the MIS group (ICH patients who received MIS including hematoma aspiration and thrombolysis) and conservative treatment group (ICH patients who received conservative medication). Propensity score matching was performed to balance possible risk factors for late seizures between the MIS and conservative treatment groups. Before and after matching, between-group comparisons of the incidence of late seizures were performed between the MIS and conservative treatment groups. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for late seizures in MIS-treated patients. Results: A total of 241 and 1,689 patients were eligible for the MIS and conservative treatment groups, respectively. After matching, 161 ICH patients from the MIS group were successfully matched with 161 ICH patients from the conservative treatment group (1:1). Significant differences (p < 0.001) were found between the MIS group (31/241, 12.9%) and conservative treatment group (69/1689, 4.1%) in the incidence of late seizures before matching. However, after matching, no significant differences (p = 0.854) were found between the MIS group (17/161, 10.6%) and conservative treatment group (16/161, 9.9%). Multivariate logistic regression analysis revealed that cortical involvement (OR = 2.547; 95% CI = 1.137-5.705; p value = 0.023) and higher National Institutes of Health Stroke Scale (NIHSS) scores (OR = 1.050; 95% CI = 1.008-1.094; p value = 0.019) were independent risk factors for late seizures. Conclusion: Our study revealed that receiving MIS did not increase the incidence of late seizures after ICH. Additionally, cortical involvement and NIHSS scores were independent risk factors for late seizures in MIS-treated patients.
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Hepatocellular carcinoma (HCC) is a most common primary liver cancer among the most deadly malignancies. Selectively killing the cancer cells within the liver urgently requires the novel treatment strategies. The combination of sonodynamic therapy (SDT) and chemotherapy based on the nanotechnology have achieved some achievements in the HCC treatments. However, off-targeting drug delivery to healthy cells and the hypoxic microenvironment in the solid tumors frustrate the efforts to the combined strategy. The hypoxic microenvironment restrains the generation of ROS, leading to the decreased effects of SDT. To improve the clinical outcomes of chemo/SDT strategy, we created a novel oxygen self-enriched active targeted nanovesicle (ICG-DOX NPs/PFH@SP94-Lip). SP94 peptide could enhance the selectivity of the nanovesicles to liver tumor cells rather than normal liver cells. Besides, an oxygen carrier, perfluorohexanes (PFH), was co-loaded into liposomes to increase the oxygen level in tumor tissue, thus improving the effects of SDT. The in vivo studies showed that the ICG-DOX NPs/PFH@SP94-Lip combined with the external US stimulation significantly inhibited effects on tumor growth. Therefore, this novel oxygen self-enriched chemo/SDT nanocomposites represents a proof-of-concept liver tumor treatment strategy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Terapia por Ultrassom , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Lipossomos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Oxigênio , Peptídeos/uso terapêutico , Espécies Reativas de Oxigênio , Microambiente TumoralRESUMO
Soilless culture experiments with tobacco were conducted to explore how the signal molecule H2S (0.3, 0.6, 0.9, and 1.2 µM) alleviated the toxicity of Cd2+ (50 mg/L). The results suggested that photosynthesis was enhanced as H2S improved the tobacco ΦPSII, ETR, Photo, Cond, and Tr, and that by increasing the NPQ, it consumed considerable amount of energy to enhance plant resistances during Cd2+ exposure. Furthermore, H2S increased the gene transcription of NtSOD3, NtPOD1, and CAT1, to enhance antioxidant enzyme activity, which reduces the generation of the reactive oxygen protective membrane integrity. Additionally, H2S increased the gene expression of the tobacco PC genes, Pr2 and Pr8 promoted the formation of the Cd2+ complexes and transportation to the vacuole, resulting in improved Cd-ATPase gene expression, away from organelles, to alleviate the Cd2+ poison. Furthermore, H2S regulated the relative absorption of K+ and Ca2+, which antagonized the Cd2+, and reduced its transportation to the aboveground plant material. Finally, the expression level of CaM increased with the application of H2S, and was highly correlated with the fitted results of a variety of resistance indicators, thereby indicating that H2S regulatory resistance mechanisms might be associated with Ca2+ signal transduction.
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Sulfeto de Hidrogênio , Antioxidantes , Cádmio/toxicidade , Sulfeto de Hidrogênio/toxicidade , Transdução de Sinais , NicotianaRESUMO
Previous studies reported that Stat5 promotes adipogenesis and white adipocyte differentiation. However, the role of Stat5 in brown adipocyte development is poorly understood. We found Stat5a was higher expressed in brown adipocytes than in white adipocytes, and its level was increased during the process of brown adipocyte differentiation. In addition, Stat5a expression was affected by cold stress and high-fat diet-feeding, suggesting a potential role in thermogenesis. Knockdown of Stat5a induced downregulation of brown fat specific genes (UCP1, PGC-1α, Acox-1 and Cidea), while overexpression of Stat5a did the opposite effect. What is more, bioinformatics analysis, ChIP assay and Luciferase activity assay all verified that Stat5a directly bind and transactivate Kdm6a promoter (Lysine-specific demethylase 6A). Further, we found that Stat5a overexpression promoted the expression of Kdm6a and inhibited the trimethylation of H3K27. While inhibiting of Kdm6a reversed the promoting effect of Stat5a overexpression on the expression of brown fat specific genes. Therefore, we conclude that Stat5a participated in brown adipocyte differentiation and thermogenic program through binding and transactivating the Kdm6a promoter.Abbreviations: Stat5: Signal transducers and activators of transcription 5; BAT: brown adipose tissue; WAT; white adipose tissue; eWAT: epididymal white adipose tissue; sWAT: subcutaneous white adipose tissue; SVFs: stromal vascular fractions; UCP1: Uncoupling protein 1; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; Acox-1: Peroxisomal acyl-coenzyme A oxidase 1; Cidea: Cell death activator CIDE-A; ChIP: Chromatin Immunoprecipitation; HFD: High fat diet; FBS: Fetal bovine serum; siStat5a: Stat5a siRNA; siKdm6: Kdm6a siRNA; pcDNA-Stat5a: over expression of Stat5a pcDNA3.1 vector; IgG: mouse immunoglobulin G; Kdm6a: Lysine-specific demethylase 6A; H3K27me3: trimethylated H3K27.
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Adipócitos Marrons/citologia , Diferenciação Celular/genética , Histona Desmetilases/metabolismo , Regiões Promotoras Genéticas/genética , Fator de Transcrição STAT5/metabolismo , Termogênese/genética , Ativação Transcricional , Adipócitos Marrons/metabolismo , Adipócitos Brancos/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Células Cultivadas , Dieta Hiperlipídica , Técnicas de Silenciamento de Genes , Histona Desmetilases/genética , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica/genética , Fator de Transcrição STAT5/genética , Transdução de Sinais/genética , Gordura Subcutânea/metabolismo , TransfecçãoRESUMO
We have developed a unique approach for the thermally promoted cycloaddition of cyclohexadienone-tethered allenes to form a versatile cyclobutane-fused oxygen-containing tricyclic framework in an environmentally friendly and atomic economic fashion with high regioselectivity. The reaction encompasses a broad substrate scope and functional group tolerance of cyclohexadienone moieties. Moreover, the cycloaddition was also applicable to the late-stage functionalization of pharmaceutically relevant compounds.
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Human epidermal growth factor receptor-2 positive breast cancer (HER2+ BC) is characterized by a high rate of metastasis and drug resistance. The advent of targeted therapy drugs greatly improves the prognosis of HER2+ BC patients. However, drug resistance or severe side effects have limited the application of targeted therapy drugs. To achieve more effective treatment, considerable research has concentrated on strategies to overcome drug resistance. Abemaciclib (CDK4/6 inhibitor), a new antibody-drug conjugate (ADC), src homology 2 (SH2) containing tyrosine phosphatase-1 (SHP-1) and fatty acid synthase (FASN) have been demonstrated to improve drug resistance. In addition, using an effective vector to accurately deliver drugs to tumors has shown good application prospects. Many studies have also found that natural anti-cancer substances produced effective results during in vitro and in vivo anti-HER2+ BC research. This review aimed to summarize the current status of potential clinical drugs that may benefit HER2+ BC patients in the future.
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BACKGROUNDS: Neratinib is a potent EGFR/HER2 kinase inhibitor. Gastrointestinal complications (i.e. diarrhea, vomiting and nausea) are the most common adverse events. In this study, we aimed to investigate (1) the overall incidence and relative risk (RR) of diarrhea, vomiting and nausea and (2) whether combination neratinib therapy increased the incidence of gastrointestinal complications versus neratinib alone. METHODS: Relevant studies were identified from the PubMed database, from abstracts presented at the American Society of Clinical Oncology annual conference and from the Web of Science database. Incidences, RRs, and 95% confidence intervals (CIs) were calculated. RESULTS: The incidences of all-grade diarrhea, vomiting and nausea in the neratinib groups were 89% (95% CI = 77-95%), 31% (95% CI = 25-37%) and 44% (95% CI = 33-55%), respectively. The neratinib arms significantly increased the risk of diarrhea and vomiting in comparison with the control groups (diarrhea: all-grade, RR = 2.06, 95% CI = 1.38-3.08, P = 0.0004; grade 3/4, RR = 8.77, 95% CI = 2.91-26.40, P = 0.0001; vomiting: all-grade, RR = 2.02, 95% CI = 1.10-3.71, P = 0.02; grade 3/4, RR = 7.10, 95% CI = 3.33-15.15, P < 0.00001). CONCLUSIONS: Our meta-analysis demonstrates that the neratinib arms are associated with a significantly increased risk of diarrhea and vomiting.