Electrolyte disorders induced by six multikinase inhibitors therapy for renal cell carcinoma: a large-scale pharmacovigilance analysis

Abstract To provide evidence for optimization of multi-kinase inhibitors (MKIs) use in the clinic, we use the public database to describe and evaluate electrolyte disorders (EDs) related to various MKIs treated for renal cell carcinoma. We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS) in an observational and retrospective manner. Selecting electrolyte disorders' adverse events to multikinase inhibitors (axitinib, cabozantinib, lenvatinib, pazopanib, sunitinib, and sorafenib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of electrolyte disorders induced by MKIs (which were treated for renal cell carcinoma) between January 2004 and December 2022. As of December 2022, 2772 MKIs (which were treated for renal cell carcinoma) ICSRs were related to electrolyte disorders AEs. In general, there were more AEs cases in males, except lenvatinib and 71.8% of the cases were submitted from North America. ICSRs in this study, the age group most frequently affected by electrolyte disorders AEs was individuals aged 45–64 years for axitinib, cabozantinib, pazopanib, and sunitinib, whereas electrolyte disorders AEs were more common in older patients (65–74 years) for sorafenib and lenvatinib. For all EDs documented in ICSRs (excluding missing data), the most common adverse outcome was hospitalization(1429/2674, 53.4%), and the most serious outcome was death/life-threat(281/2674, 10.5%). The prevalence of mortality was highest for sunitinib-related EDs (145/616, 23.5%), excluding missing data (n = 68), followed by cabozantinib-related EDs (20/237, 8.4%), excluding missing data (n = 1). The distribution of time-to-onset of Each drug-related ICSRs was not all the same, and the difference was statistically significant (P = 0.001). With the criteria of ROR, the six MKIs were all significantly associated with electrolyte disorders AEs, the strongest association was the association between cabozantinib and hypermagnesaemia. MKIs have been reported to have significant electrolyte disorders AEs. Patients and physicians need to recognize and monitor these potentially fatal adverse events

Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer’s disease

Abstract Background Chronic noise exposure is associated with neuroinflammation and gut microbiota dysregulation and increases the risk of Alzheimer’s disease (AD). Environmental hazards are also thought to be associated with genetic susceptibility factors that increase AD pathogenesis. However, there is limited experimental evidence regarding the link between chronic noise stress and microbiome-gut-brain axis alterations, which may be closely related to AD development. Methods The aim of the present study was to systematically investigate the effects of chronic noise exposure on the microbiome-gut-brain axis in the senescence-accelerated mouse prone 8 (SAMP8) strain. We established SAMP8 mouse models to examine the consequences of noise exposure on the microbiome-gut-brain axis. Hippocampal amyloid-β (Aβ) assessment and the Morris water maze were used to evaluate AD-like changes, 16S ribosomal RNA sequencing analyses were used for intestinal flora measurements, and assessment of endothelial tight junctions and serum neurotransmitter and inflammatory mediator levels, as well as fecal microbiota transplant, was conducted to explore the underlying pathological mechanisms. Results Chronic noise exposure led to cognitive impairment and Aβ accumulation in young SAMP8 mice, similar to that observed in aging SAMP8 mice. Noise exposure was also associated with decreased gut microbiota diversity and compositional alterations. Axis-series studies showed that endothelial tight junction proteins were decreased in both the intestine and brain, whereas serum neurotransmitter and inflammatory mediator levels were elevated in young SAMP8 mice exposed to chronic noise, similar to the observations made in the aging group. The importance of intestinal bacteria in noise exposure-induced epithelial integrity impairment and Aβ accumulation was further confirmed through microbiota transplantation experiments. Moreover, the effects of chronic noise were generally intensity-dependent. Conclusion Chronic noise exposure altered the gut microbiota, accelerated age-related neurochemical and inflammatory dysregulation, and facilitated AD-like changes in the brain of SAMP8 mice

Effects of chronic noise on the corticotropin-releasing factor system in the rat hippocampus: relevance to Alzheimer’s disease-like tau hyperphosphorylation

Abstract Background Chronic noise exposure has been associated with tau hyperphosphorylation and Alzheimer’s disease (AD)-like pathological changes, but the underlying mechanism is unknown. In this study, we explored the effects of long-term noise exposure on the corticotropin-releasing factor (CRF) system in the hippocampus and its role in noise-induced tau phosphorylation. Methods Sixty-four rats were randomly divided into the noise-exposed group and the control group, and rats in the exposure group were exposed to 95 dB SPL white noise for 30 consecutive days. The levels of CRF, CRFR1, CRFR2, and total tau and phosphorylated tau (p-tau) at Ser396 (S396) and Thr205 (T205) in the hippocampus were measured at different time points after the final noise exposure. The co-localized distribution of CRF and p-tau (T205) in the hippocampus was evaluated using double-labeling immunofluorescence. Results Long-term exposure to noise for 30 consecutive days significantly increased the expression of CRF and CRFR1 and their mRNAs levels in the hippocampus, which persisted for 7 days after final exposure. In contrast, CRFR2 was raised for 3–7 days following the last exposure. These alterations were also concomitant with the phosphorylation of tau at S396 and T205. Furthermore, there was co-localization of p-tau and CRF in hippocampal neurons. Conclusion Chronic noise leads to long-lasting increases in the hippocampal CRF system and the hyperphosphorylation of tau in the hippocampus. Our results also provide evidence for the involvement of the CRF system in noise-induced AD-like neurodegeneration

Mimicking neuroplasticity in a hybrid biopolymer transistor by dual modes modulation

Neuromorphic computing systems that are capable of parallel information storage and processing with high area and energy efficiencies, offer important opportunities for future storage systems and in‐memory computing. Here, it is shown that a carbon dots/silk protein (CDs/silk) blend can be used as a light‐tunable charge trapping medium to fabricate an electro‐photoactive transistor synapse. The synaptic device can be optically operated in volatile or nonvolatile modes, ensuring concomitant short‐term and long‐term neuroplasticity. The synaptic‐like behaviors are attributed to the photogating effect induced by trapped photogenerated electrons in the hybrid CDs/silk film which is confirmed with atomic force microscopy based electrical techniques. In addition, system‐level pattern recognition capability of the synaptic device is evaluated by a single‐layer perceptron model. The remote optical operation of neuromorphic architecture provides promising building blocks to complete bioinspired photonic computing paradigms

Additional file 2: of Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer’s disease

Figure S2. Protein array format. Representative images of the control (A), low intensity noise exposure (LN) (B), high intensity noise exposure (HN) (C), and aging (D) group cytokine arrays in the Cy3 channel. A key to the location of the spotted primary antibodies is shown in Table 2. (TIF 3812 kb

Mimicking Neuroplasticity in a Hybrid Biopolymer Transistor by Dual Modes Modulation

Neuromorphic computing systems that are capable of parallel information storage and processing with high area and energy efficiencies, offer important opportunities for future storage systems and in‐memory computing. Here, it is shown that a carbon dots/silk protein (CDs/silk) blend can be used as a light‐tunable charge trapping medium to fabricate an electro‐photoactive transistor synapse. The synaptic device can be optically operated in volatile or nonvolatile modes, ensuring concomitant short‐term and long‐term neuroplasticity. The synaptic‐like behaviors are attributed to the photogating effect induced by trapped photogenerated electrons in the hybrid CDs/silk film which is confirmed with atomic force microscopy based electrical techniques. In addition, system‐level pattern recognition capability of the synaptic device is evaluated by a single‐layer perceptron model. The remote optical operation of neuromorphic architecture provides promising building blocks to complete bioinspired photonic computing paradigms

Additional file 3: of Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer’s disease

Figure S3. Chronic noise exposure results in abnormal serum corticosterone levels in SAMP8 mice. Enzyme-linked immunosorbent assay analysis of corticosterone concentrations for each group (n = 8). Data are shown as the mean ± standard deviation. HN, high intensity noise exposure; LN, low intensity noise exposure. (TIF 130 kb

Additional file 1: of Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer’s disease

Figure S1. Dominant bacteria taxa at the phylum (A) and genus (B) level from all samples. Only phyla with ≥ 0.1% abundance and genera with ≥ 0.1% abundance detected in ≥ 5 samples are shown. (TIF 334 kb

Near-infrared-irradiation-mediated synaptic behavior from tunable charge-trapping dynamics

Parallel information storage coupled with storage density is a major focus for non‐volatile memory devices to achieve neuromorphic computing that can work at low power. In this regard, a photoactive charge‐trapping medium consisting of inorganic heteronanosheets for the fabrication of a synaptic transistor is demonstrated. This synaptic device senses and responds to near‐infrared (NIR) light signals and mimics the memorization and dynamic forgetting process due to the reversible nature of photogenerated charge interaction. Device‐level synaptic evolutions from short‐term plasticity to long‐term plasticity, paired pulse facilitation, and paired pulse depression are realized with light modulation on the weight update terminal. To understand the underlying mechanism of the synaptic behavior under NIR signals, systematic analysis is carried out using in situ atomic force microscopy based electrical techniques. With its photoactive architecture, this information processing analogue is validated for visual object recognition, which paves the way for implementing NIR‐controlled neuromorphic computing