Energy harvesting from water impact using piezoelectric energy harvester.

Energy, as an indispensable part of human life, has been a hot topic of research among scholars. The water kinetic energy generated by ocean currents, as a kind of clean energy, has high utilization rate, high power generation potential, and a broad prospect of powering microelectronic devices. As a result, the water kinetic piezoelectric energy harvester (WKPEH) has made significant progress in powering ocean sensors by harvesting ocean currents. This paper provides a comprehensive review of technologies that have been used in recent years to harvest energy from marine fluids using WKPEH. Detailed study of the energy harvesting mechanism of WKPEH. WKPEH can use the flutter-induced vibrations, vortex-induced vibrations, and wake oscillation principles to harvest water kinetic energy. The structural characteristics and output performance of each mechanism are also discussed and compared, and finally, a prospect on WKPEH is given.

High fatigue resistance in a titanium alloy via near-void-free 3D printing.

The advantage of 3D printing-that is, additive manufacturing (AM) of structural materials-has been severely compromised by their disappointing fatigue properties1,2. Commonly, poor fatigue properties appear to result from the presence of microvoids induced by current printing process procedures3,4. Accordingly, the question that we pose is whether the elimination of such microvoids can provide a feasible solution for marked enhancement of the fatigue resistance of void-free AM (Net-AM) alloys. Here we successfully rebuild an approximate void-free AM microstructure in Ti-6Al-4V titanium alloy by development of a Net-AM processing technique through an understanding of the asynchronism of phase transformation and grain growth. We identify the fatigue resistance of such AM microstructures and show that they lead to a high fatigue limit of around 1 GPa, exceeding the fatigue resistance of all AM and forged titanium alloys as well as that of other metallic materials. We confirm the high fatigue resistance of Net-AM microstructures and the potential advantages of AM processing in the production of structural components with maximum fatigue strength, which is beneficial for further application of AM technologies in engineering fields.

Treatment of Ejaculatory Duct Obstruction by Seminal Vesiculoscopy Assisted Flow Modification.

Transurethral resection of ejaculatory duct (TURED) is a primary surgical approach to treat ejaculatory duct obstruction (EDO) caused by the ejaculatory duct cyst. Intraoperative excision of the verumontanum is usually required to expose the ejaculatory ducts. However, preserving the verumontanum structure allows for a better simulation of normal physiological anatomy. Maintaining the verumontanum may increase the risk of postoperative distal ejaculatory duct scarring, leading to recurrent obstruction or reduced semen volume. Therefore, we attempted a novel technique that preserves the verumontanum, which is relatively easier and safer compared to TURED. The following were the procedural steps: 1. A 6F seminal vesiculoscope was introduced through the external urethral orifice to the vicinity of the verumontanum, locating the opening of the affected-side ejaculatory duct and introducing a guidewire into the cyst. This successful step preserved the verumontanum, maximizing the retention of the anti-reflux mechanism in the distal ejaculatory duct. 2. The holmium laser enlarged the affected-side ejaculatory duct opening to 5 mm, decreasing the likelihood of postoperative closure of the ejaculatory duct opening and simplifying the procedure. 3. A window was created within the cyst to access the contralateral seminal vesicle, and then a holmium laser was used to burn and dilate the opening to 5 mm, redirecting the contralateral ejaculatory duct into the cystic cavity. This modification preserved the opening of the healthy-side ejaculatory duct and provided a new outflow passage for semen, reducing the risk of decreased semen volume postoperatively. The patients experienced no complications postoperatively, had shorter hospital stays, and showed improvement in semen volume. Hence, this surgical approach is simple yet effective.

[Three surgical strategies for the treatment of intercourse-related hematuria in males: A summary of clinical experience].

OBJECTIVE: To summarize the clinical experience in the treatment of sexual intercourse-related hematuria in males using biopsy forceps, electrocoagulation and holmium laser cauterization. METHODS: From July 2018 to April 2022, we treated 11 male patients with intercourse-related hematuria using biopsy forceps, electrocoagulation and holmium laser cauterization. The patients ranged in age from 29 to 47 years, with clinical manifestations of gross hematuria, blood dripping from the urethral orifice or blood clots in the urine after sexual intercourse or erection, 3 with hemospermia, but none with pain. All the patients received urological imaging examination to exclude lesions in the upper urinary tract and bladder preoperatively. During the operation, varicose vessels were found around the posterior urethral verumontanum under the cystourethroscope in all the cases, 5 with active bleeding in the posterior varicose vessel. The 3 cases with hemospermia first underwent trans-prostatic utricle seminal vesiculoscopy. According to the range and number of varicose vessels, 5 of the patients were treated by electrocoagulation with the resectoscope, 2 by holmium laser cauterization and the other 4 with biopsy forceps to destroy the vascular tissue. After the operation, urinary catheters were retained for 3－7 days, abstinence lasted 30 days, and the patients were followed up for 6 months. RESULTS: The operations were successfully completed in all the cases, 10 with good prognosis and none with recurrence. Occasional postoperative hematuria and blood clots in the urine were observed in 1 of the patients treated by electrocoagulation under the resectoscope, with dysuria at 3 months after operation, who underwent repeated electrocoagulation and experienced no more recurrence thereafter. Different degrees of postoperative urethral irritation and gross hematuria were found in all the cases, which spontaneously disappeared within 1－4 weeks, with no such complications as ED, ejaculation pain, ejaculation difficulty and ejaculation weakness. CONCLUSION: In the absence of other genitourinary diseases, painless hematuria, blood clots in the urine or even dysuria in males after sexual intercourse can be considered as the results of possible varicose veins around the posterior urethral verumontanum, which can be treated satisfactorily by destroying the vascular tissue with biopsy forceps, electrocoagulation with the resectoscope or holmium laser cauterization according to the location, number and degree of varicose veins.

The Frequency-Variable Rotor-Blade-Based Two-Degree-of-Freedom Actuation Principle for Linear and Rotary Motion.

Piezoelectric accurate actuation plays an important role in industrial applications. The intrinsic frequency of previous actuators is invariable. However, variable frequency can approach the range near the low-intrinsic-frequency and realize a high actuation capability. The frequency-variable linear and rotary motion (FVLRM) principle is proposed for rotor-blade-based two-degree-of-freedom driving. Inertial force is generated by frequency-variable piezoelectric oscillators (FVPO), the base frequency and vibration modes of which are adjustable by the changeable mass and position of the mass block. The variable-frequency principle of FVPO and the FVLRM are recognized and verified by the simulations and experiments, respectively. The experiments show that the FVLRM prototype moves the fastest when the mass block is placed at the farthest position and the prototype is at the second-order intrinsic frequencies of 42 Hz and 43 Hz, achieving a linear motion of 3.52 mm/s and a rotary motion of 286.9 mrad/s. The actuator adopts a lower operating frequency of less than 60 Hz and has the function of adjusting the natural frequency. It can achieve linear and rotational motion with a larger working stroke with 140 mm linear movement and 360° rotation.

Performance analysis of a novel flat lay-type synthetic jet pump with Y-shaped jet chamber.

Recently, synthetic jet pumps have been expected to be used in electronic heat dissipation devices due to the vortex suction phenomenon for transporting fluids. Aiming to improve the delivery ability of the jet pump to output fluid continuously, a novel flat lay-type synthetic jet pump (FLTSJP) with a Y-shaped jet chamber is proposed in this paper. Based on the synthetic jet effect, the pump chamber continuously outputs fluid in one cycle. The output performance of FLTSJP is theoretically analyzed to be affected by the outlet cone angle. The one-cycle flow mechanism of the fluid in the Y-shaped jet chamber is simulated. FLTSJP is manufactured, and a test system is built. Experiments show that the Y-shaped jet chamber effectively improves the output performance. The optimum flow rate and outlet pressure were both reached at 160 V and 40 Hz, which were 20.63 ml/min and 333.43 Pa, respectively. This FLTSJP effectively improves the output performance of synthetic jet pumps and provides a new research concept of water-cooled devices for electronic heat dissipation.

Policy analysis in the field of rare diseases in China: a combined study of content analysis and Bibliometrics analysis.

Introduction: The Chinese government has made significant strides in addressing the needs of individuals affected by rare diseases in recent years. This paper aims to provide a comprehensive analysis of national rare disease policies in China from 2009 to 2022, using a mixed-methods approach. Methods: A two-dimensional analytical framework, which includes policy tools and policy themes, is introduced to analyze the rare disease policies comprehensively. Drawing on the policy tools theory proposed by Rothwell and Zegveld, this paper evaluates the tools used in rare disease policies. Co-word analyses and network analyses are employed to identify key themes in rare disease policies and collaboration among government departments. Results: The rare disease policy landscape in China is undergoing rapid growth, with an increasing number of government departments involved in policy formulation. However, further collaboration between departments is needed to strengthen these policies. Environment-based and supply-based tools are preferred in rare disease policies. The policy themes can be grouped into four categories: (1) Registration, Approval and Supply of Rare Disease Drugs, (2) Construction of Diagnosis and Treatment System for Rare Diseases, (3) Development and Genericization of Rare Disease Drugs, and (4) Social Security for Patients with Rare Diseases. Discussion: The study provides valuable insights into the current state of rare disease policies in China and offers suggestions for policy improvement. The results show that the Chinese government has made efforts to address the needs of individuals affected by rare diseases, but there is still room for improvement. The collaboration between government departments needs to be strengthened to achieve better rare disease policies. The findings of this study have implications for other countries with similar healthcare systems and can contribute to a better understanding of the impact of rare disease policies on public health.

Simultaneous profiling of dust aerosol mass concentration and optical properties with polarized high-spectral-resolution lidar.

Dust particles originating from arid desert regions can be transported over long distances, presenting severe risks to climate, environment, social economics, and human health at the source and downwind regions. However, there has been a dearth of continuous diurnal observations of vertically resolved mass concentration and optical properties of dust aerosols, which hinders our understanding of aerosol mixing, stratification, aerosol-cloud interactions, and their impacts on the environment. To fill the gap of the insufficient observations, to the best of our knowledge, this work presents the first high-spectral-resolution lidar (HSRL) observation providing days of continuous profiles of the mass concentration, along with particle linear depolarization ratio (PLDR), backscattering coefficient, extinction coefficient and lidar ratio (LR), simultaneously. We present the results of two strong dust events observed by HSRL over Beijing in 2021. The maximum particle mass concentrations reached (1.52 ± 3.5) x103 µg/m3 and (19.48 ± 0.36) x103 µg/m3 for the two dust events, respectively. The retrieved particle mass concentrations and aerosol optical depth (AOD) agree well with the observation from the surface PM10 concentrations and sun photometer with correlation coefficients of 0.90 and 0.95, respectively. The intensive properties of PLDR and LR of the dust aerosols are 0.31 ± 0.02 and 39 ± 7 sr at 532 nm, respectively, which are generally close to those obtained from observations in the downwind areas. Moreover, inspired by the observations from HSRL, a universal analytical relationship is discovered to evaluate the proportion of dust aerosol backscattering, extinction, AOD, and mass concentration using PLDR. The universal analytical relationship reveals that PLDR can directly quantify dust aerosol contribution, which is expected to further expand the application of polarization technology in dust detection. These valuable observations and findings further our understanding of the contribution of dust aerosol to the environment and help supplement dust aerosol databases.

Effect of thyroid dysfunction on N-terminal pro-B-type natriuretic peptide levels: A systematic review and meta-analysis.

Purpose: Thyroid hormones (THs) significantly affect the cardiovascular system. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful biomarker for diagnosing, evaluating, and predicting outcomes in heart failure (HF). This comprehensive review and meta-analysis aimed to investigate the effects of thyroid dysfunction (hypothyroidism and hyperthyroidism) on NT-proBNP levels. Methods: Two investigators independently searched PubMed, Embase, Cochrane Library, and Web of Science databases for studies published from inception to July 31, 2022, without any restrictions on language. Results: 21 studies were included. In participants without HF, NT-proBNP levels may be elevated in those with overt hyperthyroidism (standardized mean difference [SMD] 2.38, 95% confidence interval [CI]:1.0-3.76). Notably, among patients with preexisting HF, significantly higher NT-proBNP levels were found in patients with overt hyperthyroidism, overt hypothyroidism, or subclinical hypothyroidism than in euthyroid subjects (SMD [95%CI] = 0.31[0.01, 0.62], 0.32[0.08, 0.56], and 0.33[0.21, 0.46], respectively). Seven trials compared NT-proBNP levels in patients with thyroid dysfunction before and after therapy, and significant drops in NT-proBNP levels were observed in patients with hyperthyroidism (SMD [95%CI] = -1.53[-2.50, -0.55]) upon achieving a euthyroid state. In contrast, increased NT-proBNP levels were observed in hypothyroid patients after treatment (SMD [95%CI] = 1.07[0.28, 1.85]). Conclusion: Thyroid dysfunction can significantly affect NT-proBNP levels, which may change upon achieving a euthyroid state. Notably, the effect of thyroid dysfunction on cardiac function may depend on the underlying cardiac status. Thus, timely recognition and effective treatment of cardiac symptoms in patients with thyroid dysfunction are mandatory because the prognosis of HF may be improved with appropriate treatment of thyroid dysfunction. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022353700.

Reciprocal REGγ-Nrf2 Regulation Promotes Long Period ROS Scavenging in Oxidative Stress-Induced Cell Aging.

Increased accumulation of reactive oxygen species (ROS) and decline of adaptive response of antioxidants to oxidative stimuli has been implicated in the aging process. Nuclear factor erythroid 2-related factor 2 (Nrf2) activation is a core event in attenuating oxidative stress-associated aging. The activity is modulated by a more complex regulatory network. In this study, we demonstrate the proteasome activator REGγ function as a new regulator of Nrf2 activity upon oxidative stress in cell aging model induced by hydrogen peroxide (H2O2). REGγ deficiency promotes cell senescence in primary MEF cells after H2O2 treatment. Accordingly, ROS scavenging is accelerated in WT cells but blunted in REGγ lacking cells during 12-hour recovery from a 1-hour H2O2 treatment, indicating long-lasting antioxidant buffering capacity of REGγ. Mechanistically, through GSK-3ß inhibition, REGγ enhances the nuclear distribution and transcriptional activity of Nrf2, which is surveyed by induction of phase II enzymes including Ho1 and Nqo1. Meanwhile, Nrf2 mediates the transcriptional activation of REGγ upon H2O2 stimulation. More interestingly, short-term exposure to H2O2 leads to transiently upregulation and gradually descent of REGγ transcription, however sustained higher REGγ protein level even in the absence of H2O2 for 24 hours. Thus, our results establish a positive feedback loop between REGγ and Nrf2 and a new layer of adaptive response after oxidative stimulation that is the REGγ-GSK-3ß-Nrf2 pathway.

[Clinical management of skin necrosis after penis lengthening surgery: Report of 12 cases].

OBJECTIVE: To analyze the causes of skin necrosis after penis lengthening surgery and corresponding treatment measures, and observe the clinical effect of free skin graft repair in the treatment of penile skin defects. METHODS: We retrospectively analyzed the clinical data on 12 cases of extensive penile skin necrosis and defect after penis lengthening surgery performed in our department from January 2017 to January 2022. The patients underwent free skin graft repair with medium- or full-thickness skin grafts from the thigh after wound preparation. RESULTS: The skin grafts survived well in all the 12 patients and the incisions healed in the first stage without any complications. At 6 months after surgery, skin sensation was mostly recovered in the area of penis skin grafting, no obvious skin ulceration or edema was observed, and the appearance of the penis was satisfactory. The IIEF-5 scores, Erectile Hardness Scale (EHS) scores, and the results of penile hardness tests of the patients all indicated normal erectile function. CONCLUSION: Free skin graft repair with autologous medium- or full-thickness skin grafts is a safe and effective surgical option for extensive penile skin necrosis after penis lengthening surgery.

Aging-associated REGγ proteasome decline predisposes to tauopathy.

The REGγ-20S proteasome is an ubiquitin- and ATP-independent degradation system, targeting selective substrates, possibly helping to regulate aging. The studies we report here demonstrate that aging-associated REGγ decline predisposes to decreasing tau turnover, as in a tauopathy. The REGγ proteasome promotes degradation of human and mouse tau, notably phosphorylated tau and toxic tau oligomers that shuttle between the cytoplasm and nuclei. REGγ-mediated proteasomal degradation of tau was validated in 3- to 12-month-old REGγ KO mice, REGγ KO;PS19 mice, and PS19 mice with forebrain conditional neuron-specific overexpression of REGγ (REGγ OE) and behavioral abnormalities. Coupled with tau accumulation, we found with REGγ-deficiency, neuron loss, dendrite reduction, tau filament accumulation, and microglial activation are much more prominent in the REGγ KO;PS19 than the PS19 model. Moreover, we observed that the degenerative neuronal lesions and aberrant behaviors were alleviated in REGγ OE;PS19 mice. Memory and other behavior analysis substantiate the role of REGγ in prevention of tauopathy-like symptoms. In addition, we investigated the potential mechanism underlying aging-related REGγ decline. This study provides valuable insights into the novel regulatory mechanisms and potential therapeutic targets for tau-related neurodegenerative diseases.

The speckle-type POZ protein (SPOP) inhibits breast cancer malignancy by destabilizing TWIST1.

Epithelial-mesenchymal transition (EMT) inducing transcription factor TWIST1 plays a vital role in cancer metastasis. How the tumor-suppressive E3 ligase, speckle-type POZ protein (SPOP), regulates TWIST1 in breast cancer remains unknown. In this study, we report that SPOP physically interacts with, ubiquitinates, and destabilizes TWIST1. SPOP promotes K63-and K48-linked ubiquitination of TWIST1, predominantly at K73, thereby suppressing cancer cell migration and invasion. Silencing SPOP significantly enhances EMT, which accelerates breast cancer cell migration and invasiveness in vitro and lung metastasis in vivo. Clinically, SPOP is negatively correlated with the levels of TWIST1 in highly invasive breast carcinomas. Reduced SPOP expression, along with elevated TWIST1 levels, is associated with poor prognosis in advanced breast cancer patients, particularly those with metastatic triple-negative breast cancer (TNBC). Taken together, we have disclosed a new mechanism linking SPOP to TWIST1 degradation. Thus SPOP may serve as a prognostic marker and a potential therapeutic target for advanced TNBC patients.

Running vs. resistance exercise to counteract deconditioning induced by 90-day head-down bedrest.

Spaceflight is associated with enhanced inactivity, resulting in muscular and cardiovascular deconditioning. Although physical exercise is commonly used as a countermeasure, separate applications of running and resistive exercise modalities have never been directly compared during long-term bedrest. This study aimed to compare the effectiveness of two exercise countermeasure programs, running and resistance training, applied separately, for counteracting cardiovascular deconditioning induced by 90-day head-down bedrest (HDBR). Maximal oxygen uptake ( V ˙ O2max), orthostatic tolerance, continuous ECG and blood pressure (BP), body composition, and leg circumferences were measured in the control group (CON: n = 8), running exercise group (RUN: n = 7), and resistive exercise group (RES: n = 7). After HDBR, the decrease in V ˙ O2max was prevented by RUN countermeasure and limited by RES countermeasure (-26% in CON p < 0.05, -15% in RES p < 0.05, and -4% in RUN ns). Subjects demonstrated surprisingly modest orthostatic tolerance decrease for different groups, including controls. Lean mass loss was limited by RES and RUN protocols (-10% in CON vs. -5% to 6% in RES and RUN). Both countermeasures prevented the loss in thigh circumference (-7% in CON p < 0.05, -2% in RES ns, and -0.6% in RUN ns) and limited loss in calf circumference (-10% in CON vs. -7% in RES vs. -5% in RUN). Day-night variations in systolic BP were preserved during HDBR. Decrease in V ˙ O2max positively correlated with decrease in thigh (r = 0.54 and p = 0.009) and calf (r = 0.52 and p = 0.012) circumferences. During this 90-day strict HDBR, running exercise successfully preserved V ˙ O2max, and resistance exercise limited its decline. Both countermeasures limited loss in global lean mass and leg circumferences. The V ˙ O2max reduction seems to be conditioned more by muscular than by cardiovascular parameters.

Prevalence of Treponema Pallidum Antibody among Volunteer Blood Donors in China.

Background: Infection with syphilis is still a major public health problem. The precise data for syphilis seroprevalence in the populations will help to develop a strategy for prevention and treatment of it. However, the data for syphilis prevalence in continuous years among volunteer blood donors in China is rare. Methods: A retrospective study for Treponema pallidum (TP) antibody in blood donors was conducted from January 2010 to December 2019 at the Blood Center of Zhejiang Province, China. TP antibody was detected with two different reagents using enzyme-linked immunosorbent assay and the only sample which was reactive in the two reagents was defined as seropositive. Results: A total of 992,646 volunteer blood donors were analyzed and the positive rate of TP antibody in the blood donors was 0.43%. From 2010 to 2019, the positive rates of TP antibody were 0.53%, 0.51%, 0.51%, 0.43%, 0.36%, 0.18%, 0.11%, 0.12%, 0.11%, and 0.10%, respectively. The positive rates of TP antibody were significantly different among blood donor age group (p < 0.001), with the highest positive rate in 45-54-years-old group (0.93%). The positive rates of TP antibody in male and female blood donors were 0.44% and 0.41%, respectively. The positive rate was 0.57% among the first-time blood donors, which was significantly higher than that of the repeat blood donors (0.17%). The positive rate of TP antibody in blood donors decreased gradually with the increase of educational level. Conclusion: The syphilis seroprevalence is low in the blood donors of the Hangzhou area, and the positive rate of blood donors is associated with age, educational level, and times of blood donation. Increasing the number of repeat blood donations is helpful to improve blood safety.

Tug1 Acts on ERK12 Signaling Pathway to Aggravate Neuronal Damage after Acute Ischemic Stroke.

Approximately 85% of stroke patients suffer from ischemic stroke, which has a high incidence and difficult prognosis. It has become one of the leading causes of death in middle-aged and elderly people and seriously threatens human health. This study mainly considers the role of lncRNA tug 1 on the ERK 12 signaling pathway to enhance neuronal damage after acute ischemic stroke. In the experiment, the middle cerebral artery occlusion (MCAO) model was constructed using the thread embolization method. The real-time quantitative RT-CR method was used to detect the relative transcriptional activity of TG1, GAS5 and SM22a genes in tissues. The relative expression level of SM22a protein in tissues was detected by the immune-histochemical method. Twenty-four hours after cerebral infarction, the nerve function, cerebral infarction area and ERK1/2 protein expression level of cerebral cortex on the side of cerebral infarction were detected in each group. The experimental results showed that the successful animal behavior scores of the MCAO model in the normal saline control group and Pepstatin A interference group were 1 point 25, 2 points 17 and 3 points 18. The results show that lncRNA tug1 can enhance the neuronal damage of the ERK12 signaling pathway after acute ischemic stroke. lncRNATUGl plays an important role after OGD/RX and can accelerate cell apoptosis. If the expression of lncRNATUGl is inhibited, the number of apoptosis is significantly reduced.

Cancer metabolism control by natural products: Pyruvate kinase M2 targeting therapeutics.

Glycolysis is the primary source of energy for cancer growth and metastasis. The shift in metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis is called the Warburg effect. Cancer progression due to aerobic glycolysis is often associated with the activation of oncogenes or the loss of tumor suppressors. Therefore, inhibition of glycolysis is one of the effective strategies in cancer control. Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme overexpressed in breast, prostate, lung, colorectal, and liver cancers. Here, we discuss published studies regarding PKM2 inhibitors from natural products that are promising drug candidates for cancer therapy. We have highlighted the potential of natural PKM2 inhibitors for various cancer types. Moreover, we encourage researchers to evaluate the combinational effects between natural and synthetic PKM2 inhibitors. Also, further high-quality studies are needed to firmly establish the clinical efficacy of natural products.

The proteasome activator REGγ promotes diabetic endothelial impairment by inhibiting HMGA2-GLUT1 pathway.

Diabetic vascular endothelial impairment is one of the main causes of death in patients with diabetes lacking adequately defined mechanisms or effective treatments. REGγ, the 11S proteasome activator known to promote the degradation of cellular proteins in a ubiquitin- and ATP-independent manner, emerges as a new regulator in the cardiovascular system. Here, we found that REGγ was upregulated in streptozocin (STZ)-induced diabetic mouse aortic endothelium in vivo and high glucose (HG)-treated vascular endothelial cells (ECs) in vitro. REGγ deficiency ameliorated endothelial impairment in STZ-induced diabetic mice by protecting against a decline in cellular glucose uptake and associated vascular ECs dysfunction by suppressing high mobility group AT-hook 2 (HMGA2) decay. Mechanically, REGγ interacted with and degraded the transcription factor HMGA2 directly, leading to decreased HMGA2 transcriptional activity, subsequently lowered expression of glucose transporter type 1 (GLUT1), and reduced cellular glucose uptake, vascular endothelial dysfunction, and impaired diabetic endothelium. Ablation of endogenous GLUT1 or HMGA2 or overexpressing exogenous HMGA2 in vascular ECs significantly blocked or reestablished the REGγ-dependent action on cellular glucose uptake and vascular endothelial functions of HG stimulation in vitro. Furthermore, exogenously introducing HMGA2 improved diabetic mice endothelial impairment features caused by REGγ in vivo, thereby substantiating a REGγ-HMGA2-GLUT1 pathway in diabetic endothelial impairment. Our findings indicate that modulating REGγ-proteasome activity may be a potential therapeutic approach for diabetic disorders with endothelial impairment.

Formation of the Looming-evoked Innate Defensive Response during Postnatal Development in Mice.

Environmental threats often trigger innate defensive responses in mammals. However, the gradual development of functional properties of these responses during the postnatal development stage remains unclear. Here, we report that looming stimulation in mice evoked flight behavior commencing at P14-16 and had fully developed by P20-24. The visual-evoked innate defensive response was not significantly altered by sensory deprivation at an early postnatal stage. Furthermore, the percentages of wide-field and horizontal cells in the superior colliculus were notably elevated at P20-24. Our findings define a developmental time window for the formation of the visual innate defense response during the early postnatal period and provide important insight into the underlying mechanism.