Online-to-offline combined with problem-based learning is an effective teaching modality in the standardized residency training of nephrology.

BACKGROUND: The online-to-offline (O2O) teaching method is recognized as a new educational model that integrates network learning into offline classroom education, while problem-based learning (PBL) is a teaching modality that guides students to apply acquired theoretical knowledge to solve practical problems. However, implementing O2O combined with PBL has not been extensively explored in nephrology residency training. This study aims to explore the efficacy of O2O combined with PBL in the standardized residency training of nephrology by comparing it with the traditional lecture-based teaching (LBT). METHODS: Sixty residency trainees who participated in the standardized training of internal medicine in the nephrology department of the Second Affiliated Hospital of Zhejiang University School of Medicine were equally allocated into O2O combined with PBL (O2O/PBL) or the LBT group demographically matched. Examinations of theory, practice skills, clinical thinking and teaching satisfaction surveys were utilized to assess the teaching effects of the two groups. RESULTS: Participants from the O2O/PBL group outperformed those from the LBT group in the examination of theory (81.233 ± 9.156 vs. 75.800 ± 7.009, mean ± SEM), practice skills (104.433 ± 3.569 vs.100.316 ± 4.628, mean ± SEM) and clinical thinking (88.933 ± 4.473 vs. 86.667 ± 3.844, mean ± SEM). There was no significant difference in the teaching satisfaction between the two groups. CONCLUSION: The current study shows the positive impact of O2O combined with PBL approach on standardized residency training in nephrology without reducing teaching satisfaction.

A combination of case-based learning with flipped classroom improved performance of medical students in nephrology bedside teaching.

BACKGROUND: Bedside teaching remains a challenging endeavor for clinical doctors and medical students, as the students often encounter difficulties in applying their knowledge to clinical situations. This study aims to evaluate the efficacy of combining case-based learning (CBL) with a flipped classroom (FC) approach in nephrology bedside teaching. METHODS: A total of 92 medical students were enrolled in this study, including clerks and interns. The students were assigned into two groups. The CBL/FC group students received the combined teaching approach of CBL and FC (CBL/FC). Students who received the traditional lecture-based teaching (LBT) approach were treated as the control group. General knowledge tests, clinical case scenarios, and questionnaires were used to evaluate the teaching efficacy. RESULTS: Ninety-two students were included in this study. Overall, 46 students were assigned to the CBL/FC group, while the other 46 students were assigned to the LBT group. The students in both groups showed comparable performance in the knowledge test. However, in clinical case scenarios, students in the CBL/FC group demonstrated superior performance compared to those in the LBT group. Additionally, the analysis of questionnaires revealed that the CBL/FC group students expressed more positive attitudes toward their proficiency in medical history taking, physical examination, medical record documentation, clinical reasoning, and consideration for patients' welfare. Moreover, the students from the CBL/FC group regarded the CBL/FC teaching approach as an effective and satisfying method without increasing the learning burden. CONCLUSION: This study reveals that the CBL/FC combined teaching approach shows promise in nephrology education and provides an effective and alternative format for medical teaching.

The Degree of Anxiety and Depression in Patients With Cardiovascular Diseases as Assessed Using a Mobile App: Cross-Sectional Study.

BACKGROUND: Depression and anxiety are common comorbidities in cardiovascular clinic outpatients. Timely identification and intervention of these mental and psychological disorders can contribute to correct diagnosis, better prognosis, less medical expenses, and improved quality of life. The convenience of online doctor-patient communication platforms has increasingly attracted patients to online consultations. However, online health care and offline health care are very different. Research on how to identify psychological disorders in patients who engage in an online cardiology consultation is lacking. OBJECTIVE: This study aimed to explore the feasibility of using a self-rating scale to assess mental illness among patients who consult with a cardiologist online and to compare the differences in anxiety and depression between online and offline patients. METHODS: From June 2022 to July 2022, we conducted follow-up visits with 10,173 patients on the Haodf platform. We conducted detailed consultations with 286 patients who visited the same cardiologist in the outpatient department. We used the self-rated Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) scales to assess anxiety and depression, respectively. We analyzed the influencing factors related to the degree of coordination of online patients. We also compared the prevalence of anxiety or depression between online and offline patients and analyzed the factors related to anxiety or depression. RESULTS: Of the 10,173 online consultation patients, only 186 (1.8%) responded effectively. The response rate of the offline consultation patients was 96.5% (276/286). Frequent online communication and watching live video broadcasts were significantly related to effective responses from online patients (P<.001). The prevalence of anxiety (70/160, 43.7% vs 69/266, 25.8%; P<.001) or depression (78/160, 48.7% vs 74/266, 27.7%; P<.001) in online consultation patients was significantly higher than that in offline patients. In bivariate analyses, the factors related to anxiety included female sex, unemployment, no confirmed cardiovascular disease, and the online consultation mode, while smokers and those who underwent COVID-19 quarantine were less likely to present with anxiety. The factors related to depression included female sex, divorced or separated individuals, and the online consultation mode. COVID-19 quarantine was related with a lower likelihood of depression. BMI was negatively correlated with depression. In multiple ordered logistic regression analysis, women were more likely than men to present with anxiety (odds ratio [OR] 2.181, 95% CI 1.365-3.486; P=.001). Women (OR 1.664, 95% CI 1.082-2.559; P=.02) and online patients (OR 2.631, 95% CI 1.305-5.304; P=.007) were more likely to have depression. CONCLUSIONS: Online patients had more anxiety or depression than offline patients. Anxiety was more prevalent in women, the unemployed, and those without confirmed cardiovascular disease. Women and divorced or separated individuals were more prone to depression. Increasing the frequency of doctor-patient communication and participating in video interactions can help improve patient cooperation.

Retinoic acid attenuates contrast-induced acute kidney injury in a miniature pig model.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) has been the third leading cause of hospital-acquired AKI. Retinoic acid (RA), the main derivative of vitamin A, has preventative and therapeutic effects in ischemia-reperfusion-AKI and UUO models, but little is known about its effects on CI-AKI. This study aimed to explore the effects of RA on CI-AKI as well as the underlying mechanisms. METHODS: We established a new miniature pig model of CI-AKI by catheterizing the external jugular vein and injecting a single dose of iohexol after dehydration. Bun, Scr, serum and urinary RBP and ß-MG levels were measured. Renal histological, TEM examination, LDH assays, TUNEL assays, GFP-LC3 plasmid transfection and western blotting were performed. RESULTS: The levels of Bun, Scr, serum and urinary RBP and ß-MG were increased after CI-AKI and decreased by RA pretreatment. The renal histology showed foamy degeneration and dilated tubules after CI-AKI, and the tissue damage was alleviated significantly by RA pretreatment. RA mitigated renal fibrosis after CI-AKI. In vitro, RA protected proximal TECs against iohexol-induced injury. RA inhibited TECs apoptosis and activated autophagy in vivo and in vitro. CONCLUSIONS: RA alleviates CI-AKI and mitigates renal fibrosis after CI-AKI. Autophagy activation and apoptosis inhibition are involved in the protective effect of RA on CI-AKI. RA may be a new agent for the prevention and therapeutic treatment of CI-AKI in the future.

Organic charge transfer complexes on graphene with ultrahigh near infrared photogain.

Photodetectors have widespread applications in fields including telecommunications, thermal imaging and bio-medical imaging. The photogating effect, arising from charge trapping at defects and/or interfaces, can have extremely high photoelectric gain which can be a benefit to high-sensitivity room temperature photodetection. Here, we introduce thin layered organic charge transfer complexes (CPXs) integrated on graphene transistors for the development of hybrid phototransistors with ultra-high photoresponsivity of ∼106 A W-1 in the near infrared (NIR) region at room temperature. Our study has demonstrated a graphene-organic CPX with a broadband photoresponse ranging from the visible to the NIR region. The high photoelectric gain was from the photogating effect at the graphene/CPX interface. In addition, the photoresponse properties of the graphene-organic CPX can be regulated by electrical gating of graphene.

Cisplatin nephrotoxicity as a model of chronic kidney disease.

Cisplatin (CP)-induced nephrotoxicity is widely accepted as a model for acute kidney injury (AKI). Although cisplatin-induced chronic kidney disease (CKD) in rodent has been reported, the role of phosphate in the cisplatin-induced CKD progression is not described. In this study, we gave a single peritoneal injection of CP followed by high (2%) phosphate diet for 20 weeks. High dose CP (20 mg/Kg) led to high mortality; whereas a lower dose (10 mg/Kg) resulted in a full spectrum of AKI with tubular necrosis, azotemia, and 0% mortality 7 days after CP injection. After consuming a high phosphate diet, mice developed CKD characterized by low creatinine clearance, interstitial fibrosis, hyperphosphatemia, high plasma PTH and FGF23, low plasma 1,25(OH)2 Vitamin D3 and αKlotho, and classic uremic cardiovasculopathy. The CP model was robust in demonstrating the effect of aging, sexual dimorphism, and dietary phosphate on AKI and also AKI-to-CKD progression. Finally, we used the CP-high phosphate model to examine previously validated methods of genetically manipulated high αKlotho and therapy using exogenous soluble αKlotho protein supplementation. In this CP CKD model, αKlotho mitigated CKD progression, improved mineral homeostasis, and ameliorated cardiovascular disease. Taken together, CP and high phosphate nephrotoxicity is a reproducible and technically very simple model for the study of AKI, AKI-to-CKD progression, extrarenal complications of CKD, and for evaluation of therapeutic efficacy.

Molecular mechanism of the increased tissue uptake of trivalent inorganic arsenic in mice with type 1 diabetes mellitus.

Arsenic is associated with several adverse health outcomes, and people with diabetes may be more susceptible to arsenic. In this study, we found that arsenic levels in some tissues such as liver, kidney, and heart but not lung of type 1 diabetes mellitus (T1DM) mice were higher than in those of normal mice after a single oral dose of arsenic trioxide for 2 h. However, little is known about the molecular mechanism of the increased tissue uptake of trivalent inorganic arsenic in mice with T1DM. This study aimed to investigate the expression of the mammalian arsenic transporters aquaglyceroporins (AQPs) and glucose transporter 1 (GLUT1) in T1DM mice and compare them with those in normal mice. Results showed that the levels of AQP9 and GLUT1 mRNA and protein were higher in T1DM mouse liver than in the normal one. The levels of AQP7 mRNA and protein were higher in T1DM mouse kidney. In the heart, we observed that the levels of AQP7 and GLUT1 mRNA and protein were higher in T1DM mice, but the levels of AQP9 mRNA and protein in the lung had no significant difference between both mice. These results suggested that T1DM may increase the expression of transporters of trivalent inorganic arsenic and thus increase the arsenic uptake in specific tissues.

Development and initial validation of the Engagement in Athletic Training Scale.

The current study presents the development process and initial validation of the Engagement in Athletic Training Scale (EATS), which was designed to evaluate athletes' engagement in athletic training. In study 1, item generation and initial content validity of the EATS were achieved. In study 2, the factor structure of the EATS was examined using exploratory factor analysis (EFA) and exploratory structural equation modeling (ESEM). Internal consistency reliabilities of the subscales were examined (N = 460). In study 3, factor structure, discriminant validity, internal consistency reliability, and nomological validity of the EATS were further examined in an independent sample (N = 513). Meanwhile, measurement invariance of the EATS across samples (study 2 and study 3) and genders was evaluated. Overall, results from the 3 rigorous studies provided initial psychometric evidence for the 19-item EATS and suggested that the EATS could be used as a valid and reliable measure to evaluate athletes' engagement in athletic training.

Development of a non-intercepting weak beam current measurement electronics for Heavy Ion Accelerator Facility in Lanzhou.

Non-destructive measurements of low-intensity charged particle beams are particularly challenging for beam diagnostics. At the Heavy Ion Accelerator Facility in Lanzhou (HIRFL), beams with weak currents below 1 µA are often provided for experiments. The detection of such low beam current is below the threshold of typical standard beam current transformers. Therefore, a low-intensity monitoring system is developed by using a sensitive capacitive pick-up (PU) and low-noise electronics. This device measures beam currents by digitally analyzing the amplitude of the PU signals using a homodyne detection scheme. During lab tests, the amplitude nonlinearity is <0.5% in the operational range of 1 nA-45 µA and the amplitude resolution is 0.94 nA. At present, four measurement systems for low beam currents are installed at HIRFL for the monitoring of standard operating conditions with low beam currents below 1 µA. After an absolute calibration with a Faraday cup, it can be used for accurate beam intensity measurement with a current resolution of about 1 nA.

Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway.

Dihydroartemisinin (DHA) has been found to inhibit the expression of von Willebrand factor (VWF), a marker of endothelial cell injury, but its mechanism in cerebral ischemia/reperfusion (I/R) injury remains obscure. In this study, I/R model was constructed through middle cerebral artery occlusion (MCAO) in rats, followed by DHA administration. The effect of DHA on rat cerebral I/R injury was investigated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin staining, TUNEL staining, and Western blot. Brain microvascular endothelial cells (BMVECs) isolated from newborn rats were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), and then treated with DHA. The results showed that MCAO treatment induced infarction, nerve cell apoptosis, and brain tissue impairment in rats, which was mitigated by DHA. OGD/R inhibited viability and accelerated apoptosis of BMVECs, which was alleviated by DHA. I/R procedures or OGD/R up-regulated expressions of VWF, ATG7, Beclin1, and LC3-II/LC3-I ratio, while down-regulating Occludin, Claudin-5, ZO-1, P62, SIRT1, and FOXO1 expressions in vivo and in vitro; however, these effects of I/R procedures or OGD/R were offset by DHA. VWF overexpression reversed the above effects of DHA on OGD/R-induced BMVECs. In summary, DHA ameliorates cerebral I/R injury in rats by reducing VWF level and activating autophagy-mediated SIRT1/FOXO1 signaling pathway.

Design of a 0.15-2 GHz high-resolution vector-sum broadband phase shifter with controlled programmable attenuators for stochastic cooling system.

In this paper, a new 0.15-2 GHz broadband phase shifter with 9-bit phase resolution is presented. This broadband digital adjustable phase shifter is implemented by utilizing the signal vector summation technology. The phase shifter consists of one 90° hybrid coupler, two digital attenuators, two 180° hybrid couplers, two microwave switches, and one combiner. By adjusting the attenuation value of the two digital attenuators, the device creates a minimum 0.7° stepped phase shift. In addition, by switching the two microwave switches, a 360° range of phase shift is achieved while almost keeping the amplitude of the phase shifter constant. The measurement results show that the proposed phase shifter achieves a phase resolution of 0.7° while exhibiting an average insertion loss of 9 ± 2 dB and phase unbalance within ±10°. The calculated RMS phase error of the broadband phase shifter is below 5° from 0.15 to 2 GHz.

Stochastic cooling notch filter developments for the high-precision spectrometer ring in the high intensity heavy-ion accelerator facility project.

Stochastic cooling of the high-precision spectrometer ring (SRing) at the High Intensity Heavy-Ion Accelerator Facility (HIAF) project in China, which is used mainly for experiments with radioactive fragment beams, is applied to speed up the cooling process of a stored ion beam. In this article, a new coaxial-type notch filter with an amplitude equalizer in the long branch and an optical-type notch filter with phase-stabilized optical fiber are discussed and evaluated for the SRing stochastic cooling system. Both prototypes of coaxial and optical notch filters are fabricated and tested. The minimum notch depth of coaxial and optical notch filters reaches to 26 and 40 dB, respectively. The performance of both coaxial notch filter and optical fiber notch filter is presented in this work. These developments will be used not only for the longitudinal stochastic cooling system but also have potential for the beam feedback system.

Measurement and optimization of the beam coupling impedance of a novel 3D-printed titanium alloy cage inside the thin-wall vacuum chamber.

Dipole magnet vacuum chambers are among the most critical and costly components of rapid-cycling accelerator facilities. Alternative approaches to traditional ceramic chambers have been explored for the implementation of fast-ramping dipole-magnet vacuum chambers, including thin-wall metallic beam pipe chambers strengthened with transverse ribs and ceramic rings inside thin-walled chambers. Here, we report a novel 3D-printed titanium alloy cage inside the thin-wall vacuum chamber, which is designed for high-intensity heavy ion accelerator facility (HIAF) to reduce manufacturing difficulty and cost, shorten the production cycle, and improve the quality. Comprehensive studies were undertaken to characterize the impedance of the 3D-printed titanium alloy cage inside the thin-wall vacuum chamber. The beam-coupling impedance and eddy currents of the new thin-wall vacuum chamber were studied mostly numerically. Strategies for further reducing the beam-coupling impedance were explored. In addition, impedance bench measurements using the "half wavelength" resonant method were conducted to identify the longitudinal and transverse impedances of the 3D-printed titanium alloy cage inside the thin-wall vacuum chamber prototype experimentally. The simulated and measured results for the impedance were consistent. Furthermore, a campaign for resonance-check measurements on the 3D-printed titanium alloy ring loaded inside a thin-wall vacuum chamber prototype was launched. This novel thin-wall vacuum chamber structure is now entering the fabrication stage and will soon be ready for installation in the Booster Ring (BRing).

Exploring the nonlinear piezoresistive effect of 4H-SiC and developing MEMS pressure sensors for extreme environments.

Microelectromechanical system (MEMS) pressure sensors based on silicon are widely used and offer the benefits of miniaturization and high precision. However, they cannot easily withstand high temperatures exceeding 150 °C because of intrinsic material limits. Herein, we proposed and executed a systematic and full-process study of SiC-based MEMS pressure sensors that operate stably from -50 to 300 °C. First, to explore the nonlinear piezoresistive effect, the temperature coefficient of resistance (TCR) values of 4H-SiC piezoresistors were obtained from -50 to 500 °C. A conductivity variation model based on scattering theory was established to reveal the nonlinear variation mechanism. Then, a piezoresistive pressure sensor based on 4H-SiC was designed and fabricated. The sensor shows good output sensitivity (3.38 mV/V/MPa), accuracy (0.56% FS) and low temperature coefficient of sensitivity (TCS) (-0.067% FS/°C) in the range of -50 to 300 °C. In addition, the survivability of the sensor chip in extreme environments was demonstrated by its anti-corrosion capability in H2SO4 and NaOH solutions and its radiation tolerance under 5 W X-rays. Accordingly, the sensor developed in this work has high potential to measure pressure in high-temperature and extreme environments such as are faced in geothermal energy extraction, deep well drilling, aeroengines and gas turbines.

Caveolin-1, E-cadherin and ß-catenin in Gastric Carcinoma, Precancerous Tissues and Chronic Non-atrophic Gastritis.

OBJECTIVE: To investigate the expressions of caveolin-1, E-cadherin and ß-catenin in gastric carcinoma, precancerous gastric and chronic non-atrophic gastritis tissues, and evaluate the correlation of these expressions with the development of gastric cancer. METHODS: The expressions of caveolin-1, E-cadherin and ß-catenin were detected by biotin-streptavidin- peroxidase (SP) immunohistochemistry on 58 gastric cancer tissues, 40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues. The correlation between the expressions of caveolin-1, E-cadherin and ß-catenin, and the clinicopathologic parameters of gastric cancer was analyzed retrospectively. RESULTS: The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues (P<0.01). An abnormal rate of ß-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues (P<0.01). Moreover, low expressions of caveolin-1, E-cadherin and ß-catenin correlated with tumor size, depth of invasion, lymph node metastasis and TNM stage (P<0.05). The positive rates of caveolin-1 and E-cadherin expressions decreased (P<0.01), while an abnormal rate of ß-catenin expression increased inversely, with the degree of atypical hyperplasia (P<0.01). Caveolin-1 expression correlated positively with E-cadherin (r=0.41, P<0.05). Caveolin-1 (r=-0.36, P<0.05) and E-cadherin (r=-0.45, P<0.05) expressions negatively correlated with abnormal ß-catenin expression. CONCLUSION: These results suggested that dysregulated expressions of caveolin-1, E-cadherin and ß-catenin correlated with the development of gastric cancer and its biological behavior.

Exosome from indoleamine 2,3-dioxygenase-overexpressing bone marrow mesenchymal stem cells accelerates repair process of ischemia/reperfusion-induced acute kidney injury by regulating macrophages polarization.

BACKGROUND: Ischemia-reperfusion injury (IRI)-induced acute kidney injury (AKI) can repair itself completely. However, most moderate and severe patients undergoing IRI-AKI progress to chronic kidney disease due to incomplete repair. The present study is aimed to investigate the role of bone marrow mesenchymal stem cell-derived exosomes (MSC-Exo) with indoleamine 2,3-dioxygenase (IDO) overexpression on incomplete repair in mice after IRI. METHODS: IRI mice was established by clamping the unilateral renal pedicles and challenged with MSC-Exo. Blood biochemical indexes and inflammation factors contents were measured by ELISA assay. Histopathological examinations were monitored by HE, Masson, Immunohistochemical and TUNEL staining. Immunofluorescence, flow cytometry and immunoblotting were used to detect the polarization of macrophages, respectively. RESULTS: As compared to sham operation mice, IRI mice showed high contents of serum BUN and Scr, and more severe damaged kidney tissues on days 1 and 3, which all gradually declined over time, showing the lowest level on day 7 after injury. Once treated with MSCs-Exo that could directly transfer to kidney tubular cells, the restoration of kidney functions significantly accelerated by contrast to IRI mice, and the promotive effects were more obvious in IDO-overexpressed MSCs-Exo (MSCs-Exo-IDO)-treated IRI mice. Furthermore, MSCs-Exo-IDO administration also accelerated renal tubular cells proliferation, restrained tubular cells apoptosis, fibrosis and inflammation factor secretions during self-repair process compared to IRI mice, whose effects were higher than MSCs-Exo-NC-challenged IRI mice and IDO overexpressing plasmid-injected IRI mice. Mechanistically, MSCs-Exo-NC and MSCs-Exo-IDO exposure promoted the polarization from M1 macrophage to M2 macrophage, leading to more anti-inflammatory factors production, and subsequently altered the inflammatory microenvironment of renal tubular cells, which facilitated the self-repair process in mice after IRI. CONCLUSION: MSCs-derived exosome accelerated renal self-repair in IRI mice by activating M2 macrophages polarization, which effects were amplified by IDO overexpression in MSCs. Potentially, genetically modified MSCs-Exo is an effective approach to improve renal self-repair in IRI-AKI mice.

A new digital beam position and phase measurement implementation based on a field programmable gate array for the high intensity heavy-ion accelerator iLinac.

A new digital beam position and phase measurement (BPM) system was designed for the ion-Linac accelerator at the high intensity heavy ion accelerator facility. The fundamental and second harmonic signals are retrieved from the BPM electrodes to simultaneously calculate their respective beam positions and phases. All data acquisition and digital signal processing algorithm routines are performed in a field programmable gate array (FPGA). The position and phase information are obtained by using the in-phase and quadrature demodulation method. A practical and straightforward method is used to generate the second harmonic reference signal for processing the second harmonic beam signal. The reconfigurable filters are integrated into the FPGA to allow the measurement of short beam pulse length. The laboratory test results show that the achieved phase resolution is better than 0.2° and 0.03° when the input signal is -60 and -45 dBm, respectively. A position resolution better than 30 µm was achieved for an input power level of approximately -60 dBm, and it can reach 7 µm with the input power higher than -45 dBm. The entire execution time of the algorithm is accomplished within 3.4 µs, which provides a sufficient reaction time for the fast beam interlock signal to the machine protection system. The performance of this newly designed prototype BPM electronics was evaluated with the online proton beam.

Development of a diagonal-cut type beam position monitor for the booster ring in the High Intensity Heavy-Ion Accelerator Facility project.

A diagonal-cut type beam position monitor (BPM) has been developed for the High Intensity Heavy-Ion Accelerator Facility (HIAF) project at the Institute of Modern Physics. Compared with other types of BPMs, the diagonal-cut type BPM has almost perfect position linearity, i.e., no non-linear correction required, which is advantageous for beams that are transversally large and have a complex charge distribution. The key parameters for the diagonal-cut type BPM have been simulated and optimized in detail and systematically herein. It was found that the crosstalk is improved by ∼10 dB at 160 MHz by insertion of a separate ring between two horizontal or vertical electrodes of the BPM made of stainless steel with vacuum as a dielectric. Furthermore, the longitudinal and transverse numerical simulation to evaluate the beam impedance on the diagonal-cut type BPM has been performed. The results for the crosstalk, position sensitivity, and electrode capacitance to ground obtained from simulations and laboratory measurements agree well. The vacuum of the BPM prototype after baking out at 250 °C for 72 h is better than 1.0 × 10-11 mbar. The simulated and on-line measured BPM output signal magnitude results are consistent with each other. This diagonal-cut type BPM structure will be considered for application to the HIAF project as a priority.

Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy.

Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal injury. However, the effect and mechanism of RA on CIAKI are still unclear. The aim of this study is to investigate whether RA can alleviate CIAKI through activation of autophagy. In this study, we evaluated the effect of RA, RA's effect on autophagy and apoptosis after cisplatin-induced injury on renal tubular epithelial cells (RTECs) by LDH assay, immunoblotting and TUNEL staining. Then we established Atg5flox/flox:Cagg-Cre mice in which Cagg-Cre is tamoxifen inducible, and Atg5 is conditional deleted after tamoxifen injection. The effect of RA and RA's effect on autophagy on CIAKI model were evaluated by biochemical assessment, hematoxylin and eosin (HE) staining, and immunoblotting in the control and autophagy deficient mice. In vitro, RA protected RTECs against cisplatin-induced injury, activated autophagy, and inhibited cisplatin-induced apoptosis. In vivo, RA attenuated cisplatin-induced tubular damage, shown by improved renal function, decreased renal cast formation, decreased NGAL expression, and activated autophagy in the control mice. Furthermore, the nephrotoxicity of cisplatin was aggravated, and the protective effect of RA was attenuated in autophagy deficient mice, indicating that RA works in an autophagy-dependent manner on CIAKI. RA activates autophagy and alleviates CIAKI in vivo and in vitro.Thus RA may be a renoprotective adjuvant for cisplatin-based chemotherapy.

Trib1 Contributes to Recovery From Ischemia/Reperfusion-Induced Acute Kidney Injury by Regulating the Polarization of Renal Macrophages.

Increasing evidence suggests that macrophage polarization is involved in the recovery from ischemia-reperfusion (I/R)-induced acute kidney injury (AKI), implying that the regulation of macrophage polarization homeostasis might mediate AKI recovery. Trib1 is a key regulator of macrophage differentiation, but its role in AKI remains unclear. Here, we aimed to investigate the role of Trib1 and its link with the macrophage phenotype in the process of adaptive recovery from I/R-induced renal injury. Lentiviral vector-mediated RNA interference (RNAi) was used to knock down Trib1 expression in vitro and in vivo, and a mouse model of moderate AKI was established by the induction of I/R injury. Renal function measurements and inflammatory factors were determined by the corresponding kits. Histomorphology was assessed by hematoxylin-eosin, Masson and PAS staining. Western blot and flow cytometry were employed for the analysis of signal transduction, cell apoptosis and macrophage phenotypes. Trib1 knockdown inhibited cell viability of tubular epithelial cells (TECs) by inhibiting proliferation and enhancing apoptosis in vitro. I/R-induced AKI significantly impaired renal function in mice via increasing the levels of BUN, Scr, NGAL and renal tubular damage, leading to renal fibrosis from days 1 to 3. Through the adaptive self-repair mechanism, renal dysfunction recovered over time and returned to almost normal levels on day 28 after I/R intervention. However, Trib1 depletion worsened renal damage on day 3 and blunted the adaptive repair process of the renal tissue. Mechanistically, Trib1 inhibition suppressed renal tubular cell proliferation under adaptive self-repair conditions by affecting the expression of the proliferation-related proteins cyclin D1, cyclin B, p21, and p27, the apoptosis-related proteins Bcl-2 and Bax, and the fibrosis-related proteins collagen I and III. Furthermore, the M1/M2 macrophage ratio increased in the first 3 days and decreased from day 7 to day 28, consistent with changes in the expression of inflammatory factors, including TNFα, IL-6, IL-12, IL-10, and IL-13. Trib1 inhibition blocked macrophage polarization during adaptive recovery from I/R-induced moderate AKI. Our results show that Trib1 plays a role in kidney recovery and regeneration via the regulation of renal tubular cell proliferation by affecting macrophage polarization. Thus, Trib1 might be a viable therapeutic target to improve renal adaptive repair following I/R injury.