The p. S178L mutation in Tbc1d24 disrupts endosome-mediated synaptic vesicle trafficking of cochlear hair cells and leads to hearing impairment in mice.

The ribbon synapses of cochlear inner hair cells (IHCs) employ efficient vesicle resupply to enable fast and sustained release rates. However, the molecular mechanisms of these physiological activities remain unelucidated. Previous studies showed that the RAB-specific GTPase-activating protein TBC1D24 controls the endosomal trafficking of the synaptic vesicles (SVs) in Drosophila and mammalian neurons, and mutations in TBC1D24 may lead to non-syndromic hearing loss or hearing loss associated with the DOORS syndrome in humans. In this study, we generated a knock-in mouse model for the p. S178L mutation in TBC1D24, which leads to autosomal dominant non-syndromic hearing loss (DFNA65). The p.S178L mutant mice show mild hearing loss and progressively declined wave I amplitude of the auditory brainstem responses. Despite the normal gross and cellular morphology of the cochlea, transmission electron microscopy reveals accumulation of endosome-like vacuoles and a lower-than-normal number of SVs directly associated with the ribbons in the IHCs. Consistently, patch clamp of the IHCs shows reduced exocytosis under prolonged stimulus. ARF6, a TBC1D24-interacting protein also involved in endosomal membrane trafficking, was underexpressed in the cochleae of the mutant mouse and has weakened in vitro interaction with the p.S178L mutant TBC1D24. Our results suggest an important role of TBC1D24 in maintaining endosomal-mediated vesicle recycling and sustained exocytosis of hair cell ribbon synapses.

Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of SIRT3.

Hesperetin (HST) is a flavonoid compound naturally occurring in citrus fruits and is widespread in various traditional medicinal herbs such as grapefruit peel, orange peel, and tangerine peel. These plant materials are commonly used in traditional Chinese medicine to prepare herbal remedies. The study aimed to investigate the potential molecular mechanisms through which HST reduces ferroptosis in human umbilical vein endothelial cells (HUVECs) and promotes angiogenesis and wound healing. We employed network pharmacology to predict the downstream targets affected by HST. The expression of markers related to ferroptosis was assessed through Western blot (WB) and polymerase chain reaction. Intracellular levels of ferroptosis-related metabolism were examined using glutathione/oxidized glutathione (GSH/GSSG) and malondialdehyde (MDA) assay kits. Mitochondrial status and iron levels within the cells were investigated through staining with Mitosox, FerroOrange, and JC1 staining. Potential downstream direct targets of HST were identified using molecular docking. Additionally, wound healing and neovascularization within the wound site were analyzed using various methods including HE staining, Masson's staining, immunohistochemistry, and Doppler hemodynamics assessment. HST effectively inhibits the elevated levels of intracellular ferroptosis stimulated by ERASTIN. Furthermore, we observed that HST achieves this inhibition of ferroptosis by activating SIRT3. In a diabetic rat wound model, HST significantly promotes wound healing, reducing levels of tissue ferroptosis, consistent with our in vitro findings. This study demonstrates that HST can inhibit the progression of ferroptosis and protect the physiological function of HUVECs by activating SIRT3. HST holds promise as a natural compound for promoting diabetic wound healing.

A Reliability Analysis of a MEMS Flow Sensor with an Accelerated Degradation Test.

With the wide application of flow sensors, their reliability under extreme conditions has become a concern in recent years. The reliability of a Micro Electro Mechanical Systems (MEMS) flow sensor under temperature (Ts) is researched in this paper. This flow sensor consists of two parts, a sensor chip and a signal-processing system (SPS). Firstly, the step-stress accelerated degradation test (SSADT) is implemented. The sensor chip and the flow sensor system are tested. The results show that the biggest drift is 3.15% for sensor chips under 150 °C testing conditions, while 32.91% is recorded for the flowmeters. So, the attenuation of the SPS is significant to the degeneration of this flowmeter. The minimum drift of the SPS accounts for 82.01% of this flowmeter. Secondly, using the Coffin-Manson model, the relationship between the cycle index and Ts is established. The lifetime with a different Ts is estimated using the Arrhenius model. In addition, Weibull distribution (WD) is applied to evaluate the lifetime distribution. Finally, the reliability function of the WD is demonstrated, and the survival rate within one year is 87.69% under 85 °C conditions. With the application of accelerated degradation testing (ADT), the acquired results are innovative and original. This research illustrates the reliability research, which provides a relational database for the application of this flow sensor.

Heterotopic Ossification in Burn Patients.

ABSTRACT: Heterotopic ossification (HO) is a known complication of burns. The incidence of this complication is low. The etiology is unclear, but experiment conducted about HO can be significant. Currently, there are still no targeted, effective preventive and therapeutic measures against it. In this study, the relevant literature is summarized to demonstrate the potential pathogenic mechanisms, diagnosis, prophylaxis, and treatment measures of HO in burn patients. Early diagnosis and treatment can be effective in improving the prognosis of patients.

High-power high-brightness 980 nm lasers with >50% wall-plug efficiency based on asymmetric super large optical cavity.

High-power high-brightness super large optical cavity laser diodes with an optimized epitaxial structure are investigated at the wavelength of 980 nm range. The thicknesses of P- and N-waveguides are prudently chosen based on a systematic consideration about mode characteristics and vertical far-field divergences. Broad area laser diodes show a high internal quantum efficiency of 98% and a low internal optical loss of 0.58 cm-1. The ridge-waveguide laser with 7 µm ridge and 3 mm cavity yields 1.9 W single spatial mode output with far-field divergence angles of 6.8° in lateral and 11.5° in vertical at full width at half maximum under 2 A CW operating current. The corresponding M2 values are 1.77 and 1.47 for lateral and vertical, respectively, and the corresponding brightness is 76.8 MW‧cm-2‧sr-1. The far-field divergence angles with 95% power content are in the range of 24.7° to 26.1° across the whole measured range.

Development of a Compact NDIR CO2 Gas Sensor for a Portable Gas Analyzer.

A carbon dioxide (CO2) gas sensor based on non-dispersive infrared (NDIR) technology has been developed and is suitable for use in portable devices for high-precision CO2 detection. The NDIR gas sensor comprises a MEMS infrared emitter, a MEMS thermopile detector with an integrated optical filter, and a compact gas cell with high optical coupling efficiency. A dual-ellipsoid mirror optical system was designed, and based on optical simulation analysis, the structure of the dual-ellipsoid reflective gas chamber was designed and optimized, achieving a coupling efficiency of up to 54%. Optical and thermal simulations were conducted to design the sensor structure, considering thermal management and light analysis. By optimizing the gas cell structure and conditioning circuit, we effectively reduced the sensor's baseline noise, enhancing the overall reliability and stability of the system. The sensor's dimensions were 20 mm × 10 mm × 4 mm (L × W × H), only 15% of the size of traditional NDIR gas sensors with equivalent detection resolution. The developed sensor offers high sensitivity and low noise, with a sensitivity of 15 µV/ppm, a detection limit of 90 ppm, and a resolution of 30 ppm. The total power consumption of the whole sensor system is 6.5 mW, with a maximum power consumption of only 90 mW.

Lipid accumulation product, poverty income ratio, and bone mineral density in U.S. adults: a mediation analysis based on NHANES (2009-2020).

Objective: This study aims to investigate the relationship between the lipid accumulation product (LAP) index and total femur bone mineral density (BMD), while also examining the mediating role of the poverty-income ratio (PIR). Methods: Using the most recent data from the National Health and Nutrition Examination Survey (NHANES) spanning 2009 to 2020, multivariate logistic regression models were employed in this study to investigate the relationship between the LAP index and total femur BMD. Saturation effects and potential non-linear associations were examined using a smooth curve-fitting approach to determine saturation levels. Interaction tests and subgroup analyses were also performed. Additionally, a mediation analysis was conducted to explore the mediating role of PIR. Results: Three thousand two hundred and twenty three participants aged 20 years or older were recruited for this study. Multivariate regression analysis demonstrated a greater total femur BMD in individuals with a high LAP index. Additionally, analysis of the saturation effect and smooth curve fitting identified a clear saturation effect between the LAP index and total femur BMD. A saturation value of 16.05 was determined when investigating the relationship between the LAP index and total femur BMD. Subgroup analysis revealed no significant interaction effects after adjusting for covariates. Moreover, mediation analysis indicated that the LAP index had a substantial direct effect on total femur BMD (p < 0.0001), with PIR partially mediating this relationship (1.115%, p = 0.0280). Conclusion: The results of this investigation demonstrated a saturation effect between the LAP index and total femur BMD, which may have been mediated by PIR.

Design and Simulation of an Ultra-Low-Power Hydrogen Sulfide Gas Sensor with a Cantilever Structure.

Metal oxide gas sensors usually require a few tens of milliwatts of power consumption to operate at high temperature, which limits their application in mobile and portable devices. Here, we proposed a cantilever structure to build an ultra-low power gas sensor for hydrogen sulfide gas detection. By employing a nano-film size effect to reduce the thermal conductivity of the material, and self-heated corrugation configuration, the power consumption of the gas sensor is significantly reduced. Through numerical analysis and finite element simulation, two different gas sensors were designed and the power consumption and stress distribution were analyzed and optimized. Under the operating temperature of 200 °C, only 0.27 mW power is consumed, the stress value is less than 250 MPa and the displacement is a few hundred of nanometers. The results serve as a guide and reference for ultra-low power MEMS device designs.

Design and Performance Evaluation of a Deep Ultraviolet LED-Based Ozone Sensor for Semiconductor Industry Applications.

Ozone (O3) is a critical gas in various industrial applications, particularly in semiconductor manufacturing, where it is used for wafer cleaning and oxidation processes. Accurate and reliable detection of ozone concentration is essential for process control, ensuring product quality, and safeguarding workplace safety. By studying the UV absorption characteristics of O3 and combining the specific operational needs of semiconductor process gas analysis, a pressure-insensitive ozone gas sensor has been developed. In its optical structure, a straight-through design without corners was adopted, achieving a coupling efficiency of 52% in the gas chamber. This device can operate reliably in a temperature range from 0 °C to 50 °C, with only ±0.3% full-scale error across the entire temperature range. The sensor consists of a deep ultraviolet light-emitting diode in a narrow spectrum centered at 254 nm, a photodetector, and a gas chamber, with dimensions of 85 mm × 25 mm × 35 mm. The performance of the sensor has been meticulously evaluated through simulation and experimental analysis. The sensor's gas detection accuracy is 750 ppb, with a rapid response time (t90) of 7 s, and a limit of detection of 2.26 ppm. It has the potential to be applied in various fields for ozone monitoring, including the semiconductor industry, water treatment facilities, and environmental research.

Mitochondrial transfer in tunneling nanotubes-a new target for cancer therapy.

A century ago, the Warburg effect was first proposed, revealing that cancer cells predominantly rely on glycolysis during the process of tumorigenesis, even in the presence of abundant oxygen, shifting the main pathway of energy metabolism from the tricarboxylic acid cycle to aerobic glycolysis. Recent studies have unveiled the dynamic transfer of mitochondria within the tumor microenvironment, not only between tumor cells but also between tumor cells and stromal cells, immune cells, and others. In this review, we explore the pathways and mechanisms of mitochondrial transfer within the tumor microenvironment, as well as how these transfer activities promote tumor aggressiveness, chemotherapy resistance, and immune evasion. Further, we discuss the research progress and potential clinical significance targeting these phenomena. We also highlight the therapeutic potential of targeting intercellular mitochondrial transfer as a future anti-cancer strategy and enhancing cell-mediated immunotherapy.

Novel insights into the role of ubiquitination in osteoarthritis.

Ubiquitination (Ub) and deubiquitination are crucial post-translational modifications (PTMs) that precisely regulate protein degradation. Under the catalysis of a cascade of E1-E2-E3 ubiquitin enzymes, ubiquitination extensively regulates protein degradation exerting direct impact on various cellular processes, while deubiquitination opposes the effect of ubiquitination and prevents proteins from degradation. Notably, such dynamic modifications have been widely investigated to be implicated in cell cycle, transcriptional regulation, apoptosis and so on. Therefore, dysregulation of ubiquitination and deubiquitination could lead to certain diseases through abnormal protein accumulation and clearance. Increasing researches have revealed that the dysregulation of catalytic regulators of ubiquitination and deubiquitination triggers imbalance of cartilage homeostasis that promotes osteoarthritis (OA) progression. Hence, it is now believed that targeting on Ub enzymes and deubiquitinating enzymes (DUBs) would provide potential therapeutic pathways. In the following sections, we will summarize the biological role of Ub enzymes and DUBs in the development and progression of OA by focusing on the updating researches, with the aim of deepening our understanding of the underlying molecular mechanism of OA pathogenesis concerning ubiquitination and deubiquitination, so as to explore novel potential therapeutic targets of OA treatment.

Orientin promotes diabetic wounds healing by suppressing ferroptosis via activation of the Nrf2/GPX4 pathway.

Diabetic patients often experience delayed wound healing due to impaired functioning of human umbilical vein endothelial cells (HUVECs) under high glucose (HG) conditions. This is because HG conditions trigger uncontrolled lipid peroxidation, leading to iron-dependent ferroptosis, which is caused by glucolipotoxicity. However, natural flavonoid compound Orientin (Ori) possesses anti-inflammatory bioactive properties and is a promising treatment for a range of diseases. The current study aimed to investigate the function and mechanism of Ori in HG-mediated ferroptosis. A diabetic wound model was established in mice by intraperitoneal injection of streptozotocin (STZ), and HUVECs were cultured under HG to create an in vitro diabetic environment. The results demonstrated that Ori inhibited HG-mediated ferroptosis, reducing levels of malondialdehyde (MDA), lipid peroxidation, and mitochondrial reactive oxygen species (mtROS), while increasing decreased levels of malondialdehyde, lipid peroxidation, and mitochondrial reactive oxygen species, as well as increased levels of glutathione (GSH). Ori treatment also improved the wound expression of glutathione peroxidase 4 (GPX4) and angiogenesis markers, reversing the delayed wound healing caused by diabetes mellitus (DM). Additional investigations into the mechanism revealed that Ori may stimulate the nuclear factor-erythroid 2-related factor 2 (Nrf2)/GPX4 signaling pathway. Silencing Nrf2 in HG-cultured HUVECs negated the beneficial impact mediated by Ori. By stimulating the Nrf2/GPX4 signaling pathway, Ori may expedite diabetic wound healing by decreasing ferroptosis.

Circ_0006174 Accelerates Colorectal Cancer Progression Through Regulating miR-138-5p/MACC1 Axis.

BACKGROUND: Circular RNAs (circRNAs) were reported to be involved in the progression of a variety of cancers, including colorectal cancer (CRC). However, the precise functions and mechanism of circRNAs in CRC have not been elucidated. This study aimed to investigate the effect and mechanism underlying circ_0006174 in CRC. METHODS: The expression of circ_0006174, microRNA (miR-138-5p) and metastasis associated in colon cancer 1 (MACC1) mRNA was detected by quantitative real-time polymerase chain reaction (RT-qPCR) assay. Western blot was employed to measure MACC1 protein expression. The effects of circ_0006174 knockdown, MACC1 overexpression or miR-138-5p inhibition on cell proliferation, migration, invasion, and apoptosis were assessed by cell counting kit 8 (CCK-8) assay, clone formation assay, transwell assay and flow cytometry assay, respectively. The interaction between miR-138-5p and circ_0006174 or MACC1 was confirmed by RNA pull down assay or dual-luciferase reporter assay. Xenograft tumor model in nude mice was used to verify the function of circ_0006174 in vivo. RESULTS: Circ_0006174 and MACC1 expression was highly expressed, while miR-138-5p expression was downregulated in CRC cells and tissues. Meanwhile, circ_0006174 functioned as a sponge of miR-138-5p to upregulate MACC1 expression. Furthermore, circ_0006174 knock down-mediated suppression on cell proliferation, migration and invasion, and promotion on cell apoptosis could be alleviated by MACC1 overexpression or miR-138-5p inhibition in CRC cells. Besides, circ_0006174 knockdown also inhibited CRC procession in vivo. CONCLUSION: Circ_0006174 advanced CRC progression via sponging miR-138-5p to upregulate MACC1 expression, which may provide a promising molecular target for CRC treatment.

Effects of aerobic exercise and resistance exercise on physical indexes and cardiovascular risk factors in obese and overweight school-age children: A systematic review and meta-analysis.

BACKGROUND: Obesity is a serious social and public health problem in the world, especially in children and adolescents. For school-age children with obesity, this stage is in the transition from childhood to adolescence, and both physical, psychological, and external environments will be full of challenges. Studies have showed that school-age children are the largest proportion of people who continue to be obese in adulthood. Physical exercise is considered as an effective way to control weight. Therefore, we focus on this point to study which factors will be improved to reduce childhood obesity. OBJECTIVE: To assess the effects of aerobic and resistance exercise on physical indexes, such as body mass index (BMI) and body fat percentage, and cardiovascular risk factors such as VO2peak, triglycerides (TG) and low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), insulin and insulin resistance in school-age children who are overweight or obese. METHOD: PubMed, SPORTDiscus, Medline, Cochrane-Library, Scopus, Ovid and Web of Science were searched to locate studies published between 2000 and 2021 in obese and overweight school-age children between 6-12 years old. The articles are all randomized controlled trials (RCTs) and in English. Data were synthesized using a random-effect or a fixed-effect model to analyze the effects of aerobic and resistance exercise on six elements in in school-age children with overweight or obese. The primary outcome measures were set for BMI. RESULTS: A total of 13 RCTs (504 participants) were identified. Analysis of the between-group showed that aerobic and resistance exercise were effective in improving BMI (MD = -0.66; p < 0.00001), body fat percentage (MD = -1.29; p = 0.02), TG (std.MD = -1.14; p = 0.005), LDL (std.MD = -1.38; p = 0.003), TC (std.MD = -0.77; p = 0.002), VO2peak (std.MD = 1.25; p = 0.001). However, aerobic and resistance exercise were not significant in improving HDL (std.MD = 0.13; p = 0.27). CONCLUSIONS: Aerobic exercise and resistance exercise are associated with improvement in BMI, body fat percentage, VO2peak, TG, LDL, TC, while not in HDL in school-age children with obesity or overweight. Insulin and insulin resistance were not able to be analyzed in our review. However, there are only two articles related to resistance exercise in children with obesity and overweight at school age, which is far less than the number of 12 articles about aerobic exercise, so we cannot compare the effects of the two types of exercises.

Bispectrum and Histogram Features for the Identification of Atrial Fibrillation Based on Electrocardiogram.

Atrial Fibrillation (AF) is probably the most common serious abnormal heart rhythm. It affects about 2% to 3% of the population in Europe and North America. In this study, we proposed an effective Atrial Fibrillation (AF) identification system based on RR interval (RRI) analysis. Two preprocessing methods were employed to remove the motion artifacts and ectopic beats. Three categories of RRI features, including base, bispectrum, and histogram features, were proposed to enhance the performance of the identifier. The roles of different feature categories were evaluated. The combination of the three categories of features were demonstrated to compensate with one another to construct an effective feature set for AF identification. When compared to other representative AF identifiers in the literature, the proposed method outperforms them with superior recognition rates by using much larger number of testing data.

Interference of Visual Conditions and Stance Postures on Center of Pressure Sway in Patients with Schizophrenia with History of Fall.

This study examines the interaction effects among incidences of falls, visual conditions, and stance postures on the magnitude of center of pressure sway (MCOPS) in patients with schizophrenia. The coordinates of COP in ten postural control demands were measured in subjects with at least one or without any falls in the previous year. MCOPS was calculated by the default program in Balance 3.78 software. Cognitive functions were also measured. The findings include: (1) the MCOPS increased as the postural control demands increase in subjects who have fallen; (2) MCOPS in subjects without falls was the largest for the lowest postural control demands; (3) MCOPS increased when the eyes were closed in subjects without a history of falls but decreased in subjects with a history of falls; (4) cognition function in subjects who have fallen was inferior to that in those without falls. The interference visual condition and stance postures on MCOPS tended to be different in schizophrenia with or without incidences of falls indicating the possible association between psychomotor dysfunction and falls in the subjects.