Cisplatin induces acute kidney injury by downregulating miR-30e-5p that targets Galnt3 to activate the AMPK signaling pathway.

Cisplatin nephrotoxicity is an etiological factor for acute kidney injury (AKI). MicroRNA (miRNA) expression is dysregulated in cisplatin-induced AKI (cAKI) although the underlying mechanisms are unclear. A cAKI model was established by intraperitoneally injecting cisplatin, and key miRNAs were screened using high-throughput miRNA sequencing. The functions of key miRNAs were determined using the cell viability, live/dead, reactive oxygen species (ROS), and 5-ethynyl-2'-deoxyuridine (EdU) proliferation assays. Additionally, the macrophage membrane was wrapped around a metal-organic framework (MOF) loaded with miRNA agomir to develop a novel composite material, macrophage/MOF/miRNA agomir nanoparticles (MMA NPs). High-throughput miRNA sequencing revealed that miR-30e-5p is a key miRNA that is downregulated in cAKI. The results of in vitro experiments demonstrated that miR-30e-5p overexpression partially suppressed the cisplatin-induced or lipopolysaccharide (LPS)-induced downregulation of cell viability, proliferation, upregulation of ROS production, and cell death. Meanwhile, the results of in vivo and in vitro experiments demonstrated that MMA NPs alleviated cAKI by exerting anti-inflammatory effects. Mechanistically, cisplatin downregulates the expression of miR-30e-5p, and the downregulated miR-30e-5p can target Galnt3 to activate the adenosine 5'-monophosphate activated protein kinase (AMPK) signaling pathway, which promotes the progression of AKI. Our study found that miR-30e-5p is a key downregulated miRNA in cAKI. The downregulated miR-30e-5p promotes AKI progression by targeting Galnt3 to activate the AMPK signaling pathway. The newly developed MMA NPs were found to have protective effects on cAKI, suggesting a potential novel strategy for preventing cAKI.

Carbon ion radiotherapy with pencil beam scanning for hepatocellular carcinoma: Long-term outcomes from a phase I trial.

This study evaluates the feasibility of the pencil beam scanning technique of carbon ion radiotherapy (CIRT) in the setting of hepatocellular carcinoma (HCC) and establishes the maximum tolerated dose (MTD) calculated by the Local Effect Model version I (LEM-I) with a dose escalation plan. The escalated relative biological effectiveness-weighted dose levels included 55, 60, 65, and 70 Gy in 10 fractions. Active motion management techniques were employed, and several measures were applied to mitigate the interplay effect induced by a moving target. CIRT was planned with the LEM-I-based treatment planning system and delivered by raster scanning. Offline PET/CT imaging was used to verify the beam range. Offline adaptive replanning was performed whenever required. Twenty-three patients with a median tumor size of 4.3 cm (range, 1.7-8.5 cm) were enrolled in the present study. The median follow-up time was 56.1 months (range, 5.7-74.4 months). No dose limiting toxicity was observed until 70 Gy, and MTD had not been reached. No patients experienced radiation-induced liver disease within 6 months after the completion of CIRT. The overall survival rates at 1, 3, and 5 years were 91.3%, 81.9%, and 67.1% after CIRT, respectively. The local progression-free survival and progression-free survival rates at 1, 3 and 5 years were 100%, 94.4%, and 94.4% and 73.6%, 59.2%, and 37.0%, respectively. The raster scanning technique could be used to treat HCC. However, caution should be exercised to mitigate the interplay effect. CIRT up to 70 Gy in 10 fractions over 2 weeks was safe and effective for HCC.

Fibrinogen Is Associated with Prognosis of Critically Ill Patients with Sepsis: A Study Based on Cox Regression and Propensity Score Matching.

Introduction: Sepsis is a common syndrome in critically ill patients. Fibrinogen was reported to be associated with the prognosis of sepsis patients. Materials and Methods: Data was acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression was utilized to estimate the relationship between fibrinogen and inhospital mortality. The cumulative incidence of mortality by fibrinogen level was estimated through the Kaplan-Meier curve. Restricted cubic spline (RCS) was used to assess nonlinear relationship. Subgroup analysis was also conducted to evaluate the robustness of the association between fibrinogen and inhospital mortality. Propensity score matching (PSM) was applied to adjust for confounding factors. Results: A total of 3365 patients, including 2031 survivors and 1334 nonsurvivors, were enrolled in our study. The survivors had a significantly elevated levels of fibrinogen compared with the deceased. The elevated level of fibrinogen was significantly associated with a decrease in mortality in multivariate Cox regression before and after PSM (HR 0.66, P < 0.001 and HR 0.73, P < 0.001, respectively). RCS showed a nearly linear relationship. Subgroup analysis demonstrated the robustness of the association in most subpopulations. However, the association between decreased levels of fibrinogen and increased inhospital mortality was denied after PSM. Conclusion: The elevated level of fibrinogen hints at better overall survival in critically ill patients with sepsis. Decreased levels of fibrinogen may be of little value in identifying patients with a high risk of death.

Bariatric surgery reduces sleep apnea in obese patients with obstructive sleep apnea by increasing pharyngeal cross-sectional area during the early postoperative period.

OBJECTIVE: Bariatric surgery (BS) is considered one of the most effective treatments for obese individuals with Obstructive Sleep Apnea (OSA). However, otolaryngologists have raised concerns about the structural alterations caused by BS on the upper respiratory tract, especially, on the pharyngeal cavity. METHODS: In this study, we recruited 42 individuals who underwent BS at our hospital. They were divided into two groups based on apnea-hypopnea index (AHI): mild group (5 ≤ AHI < 15) and moderate-severe group (AHI ≥ 15). The participants were followed up for 12 months and several indicators, including body mass index (BMI), polysomnography (PSG), and acoustic pharyngometry (APh), were assessed repeatedly before surgery and at 3, 6, and 12 months (m) after surgery. RESULTS: Participants exhibited significant decreases in BMI (F = 128.1, P = 0.001) and total weight loss (F = 176.7, P < 0.001) after BS. The AHI value among obese patients with mild OSA decreased significantly within three months after surgery (0 day vs. 3 months, P < 0.01), and decreased significantly more than 12 months with moderate-to-severe patients (0 day vs. 3 months, 3 months vs. 6 months, 6 months vs. 12 months, P < 0.01). The therapeutic effect of OSA of the mild group was significantly better compared with that of the moderate-severe group at 6 months (mean rank = 28.13 vs. 14.21, P < 0.001) and 12 m (mean rank = 26.75 vs. 15.52, P = 0.001). The APh results revealed that the pharyngeal volume of the two groups increased significantly between 0 day and 6 months after surgery (P < 0.01). The oropharyngeal junction (OPJ) area and the glottal area were increased significantly between 0 day and 6 m after surgery (P < 0.01). CONCLUSION: BS can relieve apnea and OSA symptoms among obese patients with OSA, especially in the early postoperative period. Moreover, OSA severity was closely associated with OPJ and glottal areas, rather than pharyngeal cavity volume.

Underwater Source Counting with Local-Confidence-Level-Enhanced Density Clustering.

Source counting is the key procedure of autonomous detection for underwater unmanned platforms. A source counting method with local-confidence-level-enhanced density clustering using a single acoustic vector sensor (AVS) is proposed in this paper. The short-time Fourier transforms (STFT) of the sound pressure and vibration velocity measured by the AVS are first calculated, and a data set is established with the direction of arrivals (DOAs) estimated from all of the time-frequency points. Then, the density clustering algorithm is used to classify the DOAs in the data set, with which the number of the clusters and the cluster centers are obtained as the source number and the DOA estimations, respectively. In particular, the local confidence level is adopted to weigh the density of each DOA data point to highlight samples with the dominant sources and downplay those without, so that the differences in densities for the cluster centers and sidelobes are increased. Therefore, the performance of the density clustering algorithm is improved, leading to an improved source counting accuracy. Experimental results reveal that the enhanced source counting method achieves a better source counting performance than that of basic density clustering.

Decision Method of Optimal Needle Insertion Angle for Dorsal Hand Intravenous Robot.

In the context of COVID-19, the research on various aspects of the venipuncture robot field has become increasingly hot, but there has been little research on robotic needle insertion angles, primarily performed at a rough angle. This will increase the rate of puncture failure. Furthermore, there is sometimes significant pain due to the patients' differences. This paper investigates the optimal needle entry angle decision for a dorsal hand intravenous injection robot. The dorsal plane of the hand was obtained by a linear structured light scan, which was used as a basis for calculating the needle entry angle. Simulation experiments were also designed to determine the optimal needle entry angle. Firstly, the linear structured optical system was calibrated and optimized, and the error function was constructed and solved iteratively by the optimization method to eliminate measurement error. Besides, the dorsal hand was scanned to obtain the spatial point clouds of the needle entry area, and the least squares method was used to fit it to obtain the dorsal hand plane. Then, the needle entry angle was calculated based on the needle entry area plane. Finally, the changes in the penetration force under different needle entry angles were analyzed to determine the optimal needle insertion angle. According to the experimental results, the average error of the optimized structured light plane position was about 0.1 mm, which meets the needs of the project, and a large angle should be properly selected for needle insertion during the intravenous injection.

Acoustic Vector Sensor Multi-Source Detection Based on Multimodal Fusion.

The direction of arrival (DOA) and number of sound sources is usually estimated by short-time Fourier transform and the conjugate cross-spectrum. However, the ability of a single AVS to distinguish between multiple sources will decrease as the number of sources increases. To solve this problem, this paper presents a multimodal fusion method based on a single acoustic vector sensor (AVS). First, the output of the AVS is decomposed into multiple modes by intrinsic time-scale decomposition (ITD). The number of sources in each mode decreases after decomposition. Then, the DOAs and source number in each mode are estimated by density peak clustering (DPC). Finally, the density-based spatial clustering of applications with the noise (DBSCAN) algorithm is employed to obtain the final source counting results from the DOAs of all modes. Experiments showed that the multimodal fusion method could significantly improve the ability of a single AVS to distinguish multiple sources when compared to methods without multimodal fusion.

Evaluating the Performance of Different Large Language Models on Health Consultation and Patient Education in Urolithiasis.

OBJECTIVES: To evaluate the effectiveness of four large language models (LLMs) (Claude, Bard, ChatGPT4, and New Bing) that have large user bases and significant social attention, in the context of medical consultation and patient education in urolithiasis. MATERIALS AND METHODS: In this study, we developed a questionnaire consisting of 21 questions and 2 clinical scenarios related to urolithiasis. Subsequently, clinical consultations were simulated for each of the four models to assess their responses to the questions. Urolithiasis experts then evaluated the model responses in terms of accuracy, comprehensiveness, ease of understanding, human care, and clinical case analysis ability based on a predesigned 5-point Likert scale. Visualization and statistical analyses were then employed to compare the four models and evaluate their performance. RESULTS: All models yielded satisfying performance, except for Bard, who failed to provide a valid response to Question 13. Claude consistently scored the highest in all dimensions compared with the other three models. ChatGPT4 ranked second in accuracy, with a relatively stable output across multiple tests, but shortcomings were observed in empathy and human caring. Bard exhibited the lowest accuracy and overall performance. Claude and ChatGPT4 both had a high capacity to analyze clinical cases of urolithiasis. Overall, Claude emerged as the best performer in urolithiasis consultations and education. CONCLUSION: Claude demonstrated superior performance compared with the other three in urolithiasis consultation and education. This study highlights the remarkable potential of LLMs in medical health consultations and patient education, although professional review, further evaluation, and modifications are still required.

ADAR1p110 promotes Enterovirus D68 replication through its deaminase domain and inhibition of PKR pathway.

BACKGROUND: Severe respiratory and neurological diseases caused by human enterovirus D68 (EV-D68) pose a serious threat to public health, and there are currently no effective drugs and vaccines. Adenosine deaminase acting on RNA1 (ADAR1) has diverse biological functions in various viral infections, but its role in EV-D68 infections remains undetermined. METHODS: Rhabdomyosarcoma (RD) and human embryonic kidney 293 T (293 T) cells, and HeLa cells were used to evaluate the expression level of ADAR1 upon EV-D68 (Fermon strain) and human parainfluenza virus type 3 (HPIV3; NIH47885) infection, respectively. Knockdown through silencing RNA (siRNA) and overexpression of either ADAR1p110 or ADAR1p150 in cells were used to determine the function of the two proteins after viral infection. ADAR1p110 double-stranded RNA binding domains (dsRBDs) deletion mutation was generated using a seamless clone kit. The expression of ADAR1, EV-D68 VP1, and HPIV3 hemagglutinin-neuraminidase (HN) proteins was identified using western blotting. The median tissue culture infectious dose (TCID50) was applied to detect viral titers. The transcription level of EV-D68 mRNA was analyzed using reverse transcription-quantitative PCR (RT-qPCR) and the viral 5'-untranslated region (5'-UTR)-mediated translation was analyzed using a dual luciferase reporter system. CONCLUSION: We found that the transcription and expression of ADAR1 was inhibited upon EV-D68 infection. RNA interference of endogenous ADAR1 decreased VP1 protein expression and viral titers, while overexpression of ADAR1p110, but not ADAR1p150, facilitated viral replication. Immunofluorescence assays showed that ADAR1p110 migrated from the nucleus to the cytoplasm after EV-D68 infection. Further, ADAR1p110 lost its pro-viral ability after mutations of the active sites in the deaminase domain, and 5'-UTR sequencing of the viral genome revealed that ADAR1p110 likely plays a role in EV-D68 RNA editing. In addition, after ADAR1 knockdown, the levels of both phosphorylated double-stranded RNA dependent protein kinase (p-PKR) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) increased. Attenuated translation activity of the viral genome 5'-UTR was also observed in the dual-luciferase reporter assay. Lastly, the deletion of ADAR1p110 dsRBDs increased the level of p-PKR, which correlated with a decreased VP1 expression, indicating that the promotion of EV-D68 replication by ADAR1p110 is also related to the inhibition of PKR activation by its dsRBDs. Our study illustrates that ADAR1p110 is a novel pro-viral factor of EV-D68 replication and provides a theoretical basis for EV-D68 antiviral research.

Establishing the Interface Layer on the Pentaerythritol Tetranitrate Surface via In Situ Reaction.

Pentaerythritol tetranitrate (PETN) was coated by tannic acid (TA), polydopamine (PDA), and melamine-formaldehyde (MF) resins via in situ reaction to prepare PETN@TA, PETN@PDA, and PETN@MF microcapsules for reducing sensitivity and enhancing thermal stability of PETN. The coating effects of TA, PDA, and MF shells on PETN surfaces are characterized by scanning electron microscopy and atomic force microscopy. The structures of PETN@TA, PETN@PDA, and PETN@MF microcapsules are characterized by X-ray photoelectron spectroscopy, X-ray diffraction, and Fourier-transform infrared spectra. The performances of PETN@TA, PETN@PDA, and PETN@MF microcapsules are characterized by differential scanning calorimetry, accelerating rate calorimetry, explosion point, vacuum deflation volume, and mechanical sensitivity. The study results show that TA, PDA, and MF shells can coat the PETN surface well. Compared with pure PETN, the explosion point has an increase while the vacuum deflation volume and mechanical sensitivity have a decrease for PETN@TA, PETN@PDA, and PETN@MF microcapsules, illustrating that the safeties of PETN@TA, PETN@PDA, and PETN@MF microcapsules are enhanced. In addition, the initial decomposition temperature (T0) and peak decomposition temperature (Tp) of PETN@TA, PETN@PDA, and PETN@MF microcapsules have a slight increase, demonstrating that the thermal stabilities of PETN@TA, PETN@PDA, and PETN@MF microcapsules are better than that of pure PETN. The obtained method can provide some guidance for the desensitizing of other energetic materials with high sensitivities.

Fibrinogen and antithrombin III are associated with in-hospital mortality among critically ill patients with acute kidney injury.

OBJECTIVES: Coagulation factors participates in the inflammatory cascade, known to play a crucial role in the development of acute kidney injury (AKI). Thus, it's likely that some factors may be associated with AKI. Among them, low levels of fibrinogen and antithrombin III (ATIII) activity have been proved to increase mortality in patients with sepsis. Moreover, they are also reported to be associated with higher incidence of AKI. However, the association between coagulation parameters, especially fibrinogen and ATIII, and prognosis of AKI has not been examined. METHODS: Data were acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression model was used to estimate the relationship between coagulation parameters and in-hospital mortality in critically ill patients with AKI. Subgroup analysis was also conducted to assess the robustness of the association. Restricted cubic spline (RCS) curve was utilized to examine the nonlinear relationships between fibrinogen or ATIII and in-hospital mortality. Kaplan-Meier method was used to estimate cumulative incidence of mortality by fibrinogen or ATIII levels. Receiver-operating characteristic (ROC) curve was plotted and area under curve was calculated to evaluate predictive ability of fibrinogen or ATIII. RESULTS: A total of 5914 eligible patients were enrolled in fibrinogen cohort study and 115 patients were eligible for ATIII cohort study. The baseline of low fibrinogen (<150 mg/dL) or ATIII (<80%) activity was associated with significantly higher in-hospital mortality (fibrinogen HR [95% CIs] 2.01 [1.79, 2.27]; ATIII 3.73 [1.11, 12.54]). The HR [95% CIs] of low fibrinogen remained significant 1.29 (1.13, 1.48) in multivariate analysis. The RCS curve showed nearly linear relationship. Subgroup analysis also proved the robustness of the association between fibrinogen and in-hospital mortality. Kaplan-Meier survival curve and ROC demonstrated the predictive capability of fibrinogen and ATIII. CONCLUSION: Low fibrinogen is an independent predictor of in-hospital mortality in critically ill patients with AKI. Low ATIII activity is also likely to impact the risk of in-hospital death.

Butterfly: µW Level ULP Sensor Nodes with High Task Throughput.

The rapid development of Internet of Things (IoT) applications calls for light-weight IoT sensor nodes with both low-power consumption and excellent task execution efficiency. However, in the existing system framework, designers must make trade-offs between these two. In this paper, we propose an "edge-to-end integration" design paradigm, Butterfly, which assists sensor nodes to perform sensing tasks more efficiently with lower power consumption through their (high-performance) network infrastructures (i.e., a gateway). On the one hand, to optimize the power consumption, Butterfly offloads the energy-intensive computational tasks from the nodes to the gateway with only microwatt-level power budget, thereby eliminating the power-consuming Microcontroller (MCU) from the node. On the other hand, we address three issues facing the optimization of task execution efficiency. To start with, we buffer the frequently used instructions and data to minimize the volume of data transmitted on the downlink. Furthermore, based on our investigation on typical sensing data structures, we present a novel last-bit transmission and packaging mechanism to reduce the data amount on the uplink. Finally, we design a task prediction mechanism on the gateway to support efficient scheduling of concurrent tasks on multiple MCU-free Butterfly nodes. The experiment results show that Butterfly can speed up the task rate by 4.91 times and reduce the power consumption of each node by 94.3%, compared to the benchmarks. In addition, Butterfly nodes have natural security advantages (e.g., anti-capture) as they offload the control function with all application information up to the gateway.

Folic acid: a potential inhibitor against SARS-CoV-2 nucleocapsid protein.

CONTEXT: Coronavirus disease 2019 is a global pandemic. Studies suggest that folic acid has antiviral effects. Molecular docking shown that folic acid can act on SARS-CoV-2 Nucleocapsid Phosphoprotein (SARS-CoV-2 N). OBJECTIVE: To identify novel molecular therapeutic targets for SARS-CoV-2. MATERIALS AND METHODS: Traditional Chinese medicine targets and virus-related genes were identified with network pharmacology and big data analysis. Folic acid was singled out by molecular docking, and its potential target SARS-CoV-2 N was identified. Inhibition of SARS-CoV-2 N of folic acid was verified at the cellular level. RESULTS: In total, 8355 drug targets were potentially involved in the inhibition of SARS-CoV-2. 113 hub genes were screened by further association analysis between targets and virus-related genes. The hub genes related compounds were analysed and folic acid was screened as a potential new drug. Moreover, molecular docking showed folic acid could target on SARS-CoV-2 N which inhibits host RNA interference (RNAi). Therefore, this study was based on RNAi to verify whether folic acid antagonises SARS-CoV-2 N. Cell-based experiments shown that RNAi decreased mCherry expression by 81.7% (p < 0.001). This effect was decreased by 8.0% in the presence of SARS-CoV-2 N, indicating that SARS-CoV-2 N inhibits RNAi. With increasing of folic acid concentration, mCherry expression decreased, indicating that folic acid antagonises the regulatory effect of SARS-CoV-2 N on host RNAi. DISCUSSION AND CONCLUSIONS: Folic acid may be an antagonist of SARS-CoV-2 N, but its effect on viruses unclear. In future, the mechanisms of action of folic acid against SARS-CoV-2 N should be studied.

The interaction of folate-modified Bletilla striata polysaccharide-based micelle with bovine serum albumin.

We fabricated an amphiphilic folate-modified Bletilla striata polysaccharide (FA-BSP-SA) copolymer that exhibited good biocompatibility and superior antitumor effects. This study investigated the affinity between FA-BSP-SA and bovine serum albumin (BSA) via multispetroscopic approaches. Changes in the morphology and particle size showed that FA-BSP-SA formed a blurry "protein corona". Stern-Volmer equation demonstrated that FA-BSP-SA micelles decreased the fluorescence of BSA via static quenching. The measurement results of thermodynamic parameters (entropy change, enthalpy change, and Gibbs free energy) suggested that the binding between FA-BSP-SA and BSA was spontaneous in which Van der Waals forces and hydrogen bonding played major roles. The results from synchronous fluorescence, circular dichroism, and UV spectra also revealed that BSA conformation was slightly altered by decreasing α-helical contents. In addition, the antitumor effects in vitro of Dox@FA-BSP-SA micelles and the cellular uptake behavior of micelles in 4T1 cells were decreased after incubating with BSA.

Using an Internet of Behaviours to Study How Air Pollution Can Affect People's Activities of Daily Living: A Case Study of Beijing, China.

This study aims to quantitatively model rather than to presuppose whether or not air pollution in Beijing (China) affects people's activities of daily living (ADLs) based on an Internet of Behaviours (IoB), in which IoT sensor data can signal environmental events that can change human behaviour on mass. Peoples' density distribution computed by call detail records (CDRs) and air quality data are used to build a fixed effect model (FEM) to analyse the influence of air pollution on four types of ADLs. The following four effects are discovered: Air pollution negatively impacts people going sightseeing in the afternoon; has a positive impact on people staying-in, in the morning and the middle of the day. Air pollution lowers people's desire to go to restaurants for lunch, but far less so in the evening. As air quality worsens, people tend to decrease their walking and cycling and tend to travel more by bus or subway. We also find a monotonically decreasing nonlinear relationship between air quality index and the average CDR-based distance for each person of two citizen groups that go walking or cycling. Our key and novel contributions are that we first define IoB as a ubiquitous concept. Based on this, we propose a methodology to better understand the link between bad air pollution events and citizens' activities of daily life. We applied this methodology in the first comprehensive study that provides quantitative evidence of the actual effect, not the presumed effect, that air pollution can significantly affect a wide range of citizens' activities of daily living.

[Nur77 inhibits the proliferation of prostate cancer cells].

OBJECTIVE: To study the effects of Nur77 on prostate cancer (PCa) cell growth and its potential value in the treatment of PCa. METHODS: We detected the expression of the NUR77 protein in human PCa tissues and cells by Western blot and determined the effects of Nur77 on the proliferation and apoptosis of the PCa cells by flow cytometry. RESULTS: Nur77 and AR were expressed in the human PCa tissue and cells, and overexpressed NUR77 inhibited the proliferation and cell cycle progression of the PCa LNCaP cells. The small-molecule receptor agonists cytosporone B and DIMC of Nur7 significantly suppressed the growth and induced the apoptosis of the PCa LNCaP cells. CONCLUSIONS: Nur77 inhibits the proliferation and induces the apoptosis of PCa cells, and is expected to be a potential molecular target for the treatment of PCa.

IL-17C has a pathogenic role in kidney ischemia/reperfusion injury.

Cytokines are necessary to trigger the inflammatory response in kidney ischemia/reperfusion injury. Interleukin-17C (IL-17C), a unique member of the IL-17 family, is a cytokine produced by epithelial cells implicated in host defense and autoimmune diseases. However, little is known about the role of IL-17C in acute kidney injury. We investigated this and found that IL-17C was significantly increased in kidney biopsies of patients and mice with acute kidney injury. Exposure to hypoxia induced upregulation of IL-17C in kidney tubular epithelial cells. To further investigate the role of IL-17C, kidney ischemia/reperfusion injury was induced in mice. Inhibition of IL-17C action with a neutralizing antibody or IL-17 receptor E (IL-17RE) knockout attenuated tubular injury, kidney oxidative stress, and kidney inflammation. Mechanistically, both IL-17C neutralization and IL-17RE knockout attenuated TH17 activation and IL-17A expression in kidneys of mice with acute kidney injury. TNF-α and IL-1ß, downstream cytokines of IL-17C, were also reduced in IL-17C antibody pretreated and IL-17RE knockout mice. Additionally, IL-17C knockdown with siRNA decreased hypoxia-induced inflammation in kidney tubular cells and silencing IL-17RE abrogated the effects of IL-17C in kidney tubular cells. Thus, IL-17C may participate in the inflammatory response of acute kidney injury and inhibition of IL-17C or blockade of IL-17 RE may be a novel therapeutic strategy for the treatment of acute kidney injury.

Mitochondria transfer via tunneling nanotubes is an important mechanism by which CD133+ scattered tubular cells eliminate hypoxic tubular cell injury.

Renal CD133 + scattered tubular cells (STCs) have been regarded as progenitor-like cells in the kidney and participated in ischemic renal injury repair. However, the mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the protective effect of CD133 + STCs depends on the transfer of mitochondria to injured tubular cells in vitro. In this study, renal ischemic reperfusion injury (IRI) rat model was established with one side kidney ischemic for 45 min and animals were sacrificed at 48 h after operation. Tubular cells were isolated and cultured in vitro, and then CD133 + STCs were selected from the cultured cells. Then, CD133 + STCs were co-cultured with CD133-tubular cells (TECs) to detect the tunneling nanotubes like structures, and the transfer of mitochondria from CD133 + STCs to injured tubular cells were detected by fluorescent imaging and flow cytometry. Further, cellular protective effects of CD133 + STCs were tested when cultured with TECs under hypoxic conditions. In results, renal CD133 + STCs were scattered throughout the normal kidney and increased upon ischemic injury. Nanotube formations were commonly found between CD133 + STCs and TECs, and the transfer of mitochondria was detected from CD133 + STCs to TECs. Further, CD133 + STCs exist significant anti-apoptosis and pro-proliferation effects for TECs under hypoxic culture conditions. Thus, this study was first described that renal CD133 + STCs could transfer mitochondria to injured TECs in vitro for its protective effects, which revealed an important novel mechanism for renal repair after ischemic injury.

Intramuscular injection of tetracycline decreased gut microbial diversity in mouse.

Antibiotics contribute a lot to human beings and can kill bacteria effectively. However, more and more studies show that antibiotics can disturb the intestinal microbial community. It has been widely reported that oral antibiotics can reduce the diversity of intestinal microflora, but the effect of intramuscular injection on intestinal microflora is less studied. In this study, we sequenced the intestinal microflora of mice treated with tetracycline by 16SrRNA method, and found that intramuscular injection of tetracycline (TET) can also reduce the intestinal microbial richness of mice. In addition, the results showed that within a certain range (3 mg), with the increase of TET injection concentration, the wind of intestinal microflora in mice decreased significantly. When the injection concentration reached saturation, although the amount of TET injection was increased, the degree of intestinal flora affected was not increased. The results showed that the degree of diversity decrease was in direct proportion to the amount of tetracycline injection in the saturated concentration, but not positively related to the high amount of TET injection after exceeding the saturated concentration.

[The transcription factor NF-kB1 regulates miR-195 expression in prostate cancer].

OBJECTIVE: To investigate the regulatory effect of the transcription factor NF-kB1 on the expression of miR-195 in prostate cancer (PCa). METHODS: We analyzed the possibility of NF-kB1 binding to the miR-195 promoter and the expression of NF-kB1 in PCa using the JASPAR and Oncomine databases, respectively, and determined the expressions of NF-kB1 and miR-195 in PCa cells by real-time quantitative PCR after inhibiting the former by interfering RNA targeting NF-kB1. We detected the activity of the luciferase reporter gene after constructing its gene plasmid in the miR-195 promoter region and having it co-transfected with the NF-kB1 plasmid. Then we analyzed the correlation between the expressions of miR-195 and NF-kB1 in the prostate tissue. RESULTS: NF-kB1 was overexpressed in PCa. After inhibition of the expression of NF-kB1, that of miR-195 was increased in PC-3 and DU-145 cell lines, with a negative correlation between the NF-kB1 and miR-195 expressions in the PCa tissue. The results of luciferase reporter gene assay showed direct binding of NF-kB1 to the miR-195 promoter zone. CONCLUSIONS: NF-kB1 regulates the expression of miR-195 in prostate cancer.