STK33 Phosphorylates Fibrous Sheath Protein AKAP3/4 to Regulate Sperm Flagella Assembly in Spermiogenesis.

Spermatogenesis defects are important for male infertility; however, the etiology and pathogenesis are still unknown. Herein, we identified two loss-of-function mutations of STK33 in seven individuals with non-obstructive azoospermia. Further functional studies of these frameshift and nonsense mutations revealed that Stk33-/KI male mice were sterile, and Stk33-/KI sperm were abnormal with defects in the mitochondrial sheath, fibrous sheath, outer dense fiber, and axoneme. Stk33KI/KI male mice were subfertile and had oligoasthenozoospermia. Differential phosphoproteomic analysis and in vitro kinase assay identified novel phosphorylation substrates of STK33, fibrous sheath components A-kinase anchoring protein 3 and A-kinase anchoring protein 4, whose expression levels decreased in testis after deletion of Stk33. STK33 regulated the phosphorylation of A-kinase anchoring protein 3/4, affected the assembly of fibrous sheath in the sperm, and played an essential role in spermiogenesis and male infertility.

Nonlocal Metasurface with Chiral Exceptional Points in the Telecom-Band.

The exceptional point (EP) is the critical phase transition point in parity-time (PT) symmetry systems, offering many unique physical phenomena, such as a chiral response. Achieving chiral EP in practical applications has been challenging due to the delicate balance required between gain and loss and complicated fabrication, limiting both working band and device miniaturization. Here, we proposed a nonlocal metasurface featuring orthogonal gold nanorods, where loss modulation is achieved through rod size and lattice pitch. By tuning the coupling strength, we experimentally observed the PT symmetry phase transition and chiral EP in the telecom-band. The experimental and simulated circular conversion dichroism at EP reach 0.79 and 0.99, respectively. We also demonstrated an abrupt phase flip of a specific component near EP theoretically. This work provides a feasible scheme for exploring EP in polarized space within the telecom-band, which may find applications in polarization control, wavelength division multiplexing, ultrasensitive sensing, imaging, etc.

Unconventional Superconducting Diode Effects via Antisymmetry and Antisymmetry Breaking.

Symmetry breaking plays a pivotal role in unlocking intriguing properties and functionalities in material systems. For example, the breaking of spatial and temporal symmetries leads to a fascinating phenomenon: the superconducting diode effect. However, generating and precisely controlling the superconducting diode effect pose significant challenges. Here, we take a novel route with the deliberate manipulation of magnetic charge potentials to realize unconventional superconducting flux-quantum diode effects. We achieve this through suitably tailored nanoengineered arrays of nanobar magnets on top of a superconducting thin film. We demonstrate the vital roles of inversion antisymmetry and its breaking in evoking unconventional superconducting effects, namely a magnetically symmetric diode effect and an odd-parity magnetotransport effect. These effects are nonvolatilely controllable through in situ magnetization switching of the nanobar magnets. Our findings promote the use of antisymmetry (breaking) for initiating unconventional superconducting properties, paving the way for exciting prospects and innovative functionalities in superconducting electronics.

Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): a single-arm, multicentre, phase 2 trial.

BACKGROUND: The KEYNOTE-057 trial evaluated activity and safety of pembrolizumab in patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer who were ineligible for or declined radical cystectomy. In cohort A (patients with carcinoma in situ, with or without papillary tumours) of the KEYNOTE-057 study, pembrolizumab monotherapy led to a complete response rate of 41% at 3 months, and 46% of responders maintained a response lasting at least 12 months. Here, we evaluate pembrolizumab monotherapy in cohort B of patients with papillary tumours without carcinoma in situ. METHODS: KEYNOTE-057 is a single-arm, phase 2 study in 54 sites (hospitals and cancer centres) in 14 countries. Cohort B eligible patients were aged 18 years and older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had BCG-unresponsive high-risk non-muscle-invasive bladder cancer with papillary tumours (high-grade Ta or any-grade T1) without carcinoma in situ. Transurethral resection of bladder tumour within 12 weeks of first pembrolizumab dose was required. Patients received pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles. Primary endpoint was 12-month disease-free survival of high-risk non-muscle-invasive bladder cancer or progressive disease as assessed by cystoscopy, cytology, and central pathology and radiology review. Activity was assessed in all patients who received at least one dose of the study drug and had a baseline evaluation. Safety was assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov number, NCT02625961, and is ongoing. FINDINGS: Between April 12, 2016, and June 17, 2021, 132 patients (104 [79%] men and 28 [21%] women) who had received a median of ten (IQR 9-15) previous BCG instillations were enrolled into cohort B of the study. Patients received a median of 10 cycles (IQR 6-27) of pembrolizumab. At data cutoff date, Oct 20, 2022, median follow-up was 45·4 months (IQR 36·4-59·3) and five (4%) of 132 patients remained on treatment. The 12-month disease-free survival was 43·5% (95% CI 34·9-51·9). Treatment-related adverse events occurred in 97 (73%) of 132 patients; 19 (14%) had a grade 3 or 4 treatment-related adverse event; the most common grade 3 or 4 treatment-related adverse events were colitis (in three [2%] patients) and diarrhoea (in two [2%]). 17 (13%) of 132 patients experienced serious treatment-related adverse events, of which colitis (three patients [2%]) was most common. No treatment-related deaths occurred. INTERPRETATION: Pembrolizumab monotherapy showed antitumour activity and manageable toxicity in patients with BCG-unresponsive high-risk Ta or T1 bladder cancer without carcinoma in situ and could potentially be a suitable treatment option for patients who decline or are ineligible for radical cystectomy. Findings will need to be confirmed in a randomised controlled trial. FUNDING: Merck Sharp & Dohme.

Identification, validation and candidate gene analysis of major QTL for Supernumerary spikelets in wheat.

BACKGROUND: The number of spikelets per spike is a key trait that affects the yield of bread wheat (Triticum aestivum L.). Identification of the QTL for spikelets per spike and its genetic effects that could be used in molecular assistant breeding in the future. RESULTS: In this study, four recombinant inbred line (RIL) populations were generated and used, having YuPi branching wheat (YP), with Supernumerary Spikelets (SS) phenotype, as a common parent. QTL (QSS.sicau-2 A and QSS.sicau-2D) related to SS trait were mapped on chromosomes 2 A and 2D through bulked segregant exome sequencing (BSE-Seq). Fourteen molecular markers were further developed within the localization interval, and QSS.sicau-2 A was narrowed to 3.0 cM covering 7.6 Mb physical region of the reference genome, explaining 13.7 - 15.9% the phenotypic variance. Similarly, the QSS.sicau-2D was narrowed to 1.8 cM covering 2.4 Mb physical region of the reference genome, and it explained 27.4 - 32.9% the phenotypic variance. These two QTL were validated in three different genetic backgrounds using the linked markers. QSS.sicau-2 A was identified as WFZP-A, and QSS.sicau-2D was identified a novel locus, different to the previously identified WFZP-D. Based on the gene expression patterns, gene annotation and sequence analysis, TraesCS2D03G0260700 was predicted to be a potential candidate gene for QSS.sicau-2D. CONCLUSION: Two significant QTL for SS, namely QSS.sicau-2 A and QSS.sicau-2D were identified in multiple environments were identified and their effect in diverse genetic populations was assessed. QSS.sicau-2D is a novel QTL associated with the SS trait, with TraesCS2D03G0260700 predicted as its candidate gene.

Association of carotid duplex ultrasonography screening with stroke and mortality among patients undergoing coronary artery bypass grafting.

OBJECTIVE: Selection criteria for carotid duplex ultrasonography screening (DUS) before coronary artery bypass grafting (CABG) is primarily based on limited observational analysis, and the risks associated with carotid artery stenosis (CAS) detected by this approach to preoperative DUS are uncertain. This study aimed to determine the association of carotid DUS with stroke and mortality among patients undergoing CABG. METHODS: Adult patients with coronary artery disease who underwent isolated CABG or CABG with concomitant valvular or congenital procedure were identified. CHA2DS2-VASc score was assessed before CABG, and patients were recorded as high risk if they had a score of 3 or higher. The primary outcomes were stroke and all-cause mortality. Secondary outcomes included ischemic stroke, non-ischemic stroke, transient ischemic attack, and cardiovascular mortality. RESULTS: Among 8958 patients who underwent CABG, 70.9% (n = 6347) received carotid DUS preoperatively (low-risk, 57.3%; high-risk, 42.7%). In the low-risk cohort, there was no significant difference in the risk of stroke (20.7 per 1000 patient-years for CAS vs 13.1 per 1000 patient-years for no CAS; adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 0.78-1.68) or mortality (20.5 per 1000 patient-years for CAS vs 16.8 per 1000 patient-years for no CAS; aHR, 1.33; 95% CI, 0.97-1.83) at 15 years. In the high-risk cohort, CAS was associated with significantly higher risks of stroke at 30 days (433.2 vs 279.5 per 1000 patient-years; aHR, 1.92; 95% CI, 1.00-3.70) and mortality at 15 years (38.4 vs 32.7 per 1000 patient-years; aHR, 1.25; 95% CI, 1.01-1.57) compared with no CAS. CONCLUSIONS: CAS did not impact the incidence of stroke or mortality in the low-risk cohort who underwent CABG. However, in the high-risk cohort, CAS was associated with a significant increase in the risks of 30-day stroke and 15-year mortality, indicating selective carotid DUS is necessarily recommended for these patients.

Construction and Preparation of the Novel ADN/CL-20 Cocrystal via Directional Hydrogen Bonding Design for Turning Hygroscopicity.

Ammonium dinitramide (ADN), as a novel and environmentally friendly oxidizer, has strong hygroscopicity when exposed to high-humidity air, which seriously hinders its application in solid propellants. Modification of oxidizers by cocrystallization is an effective strategy to improve the hygroscopicity of energetic components. In this paper, the theoretical simulation of ADN/CL-20 cocrystals was developed via a directional hydrogen bonding design to establish a cocrystal with improved hygroscopicity. Intermolecular interaction analyses reveal that hydrogen bonds and van der Waals interactions synergistically lead to the formation of cocrystals. The ADN/CL-20 cocrystal was prepared experimentally by the spray drying self-assembly technique, and the corresponding thermal analysis and sensitivity properties were conducted to illustrate the thermal stability and high safety. Furthermore, the critical relative humidity (CRH) measurement was carried out to evaluate the hygroscopicity of the cocrystal, exhibiting a certain degree of antihygroscopic effect with a CRH of 65%. The hydrogen bonds formed between ADN and CL-20 saturate the ammonium ions of ADN, further preventing ADN from absorbing water molecules in the air. The ADN/CL-20 cocrystal has high specific impulse characteristics (Isp: 272.6 s). Accordingly, this work clearly demonstrates that the ADN/CL-20 cocrystal is expected to be used in a solid propellant to make up for the deficiency of the ADN oxidizer.

Construction of High Energy Nanoscale Lead Azide Composite with Improved Flame Sensibility from Intercalated Hydroxide.

It is of great significance to develop efficient methods for preparing high-content modified nanoscale lead azide (LA) composites used in microinitiating devices. In this work, a structurally controllable salicylate-intercalated lead hydroxide with a nanoscale mesoporous structure is designed. Using it as a precursor, carbon-based lead azide (LA/C) and salicylate-based lead azide (LA/SA) are fabricated by the gas-solid azidation of the framework (GAF) method within 3 h, greatly reducing the preparation time of nano-LA composites. The characterizations of the composites demonstrate that the Pb in the precursors is transformed into nanoscale LA attached to the salicylate radical or its carbonized skeleton. Due to the unique embedded nanostructures and excellent electrical and thermal conductivity of salicylate-derived carbon materials, LA/C exhibits excellent electrostatic safety (E50 = 0.25 J) and flame sensitivity (H50 = 28 cm). The adjustable organic-inorganic ratio of intercalated hydroxides allows the LA content in LA/C to reach as high as 92.5%, enabling 6.50 mg of LA/C to successfully detonate secondary explosive CL-20 in a microinitiating device, demonstrating an amazing detonation ability superior to other reported LA complexes. The research provides a new perspective for the development of nanoscale LA composites with high LA content and appropriate sensitivity.

Comparing simultaneous hybrid ablation with stand-alone thoracoscopic surgical ablation for the treatment of non-paroxysmal atrial fibrillation: a prospective randomized controlled trial.

AIMS: Advanced atrial fibrillation (AF) is currently a dilemma for electrophysiologists when choosing a minimally invasive treatment strategy. Previous studies have demonstrated the outcome of either catheter ablation or thoracoscopic surgical ablation (SA) is unsatisfactory in these patients. Whether hybrid ablation (HA) could improve outcomes in these patients is unknown. The purpose of this study was to evaluate the clinical efficacy of HA for the treatment of advanced AF. METHODS AND RESULTS: A randomized controlled trial was designed to enrol patients with persistent AF (PerAF) and enlarged left atrium or long-standing persistent AF (LSPAF) who were randomized to HA or thoracoscopic SA at a 1:1 ratio. The primary endpoint was freedom from any recurrence of AF off antiarrhythmic drugs (AADs) 12 months after operation. The primary endpoint was monitored by 7-day electrocardiogram monitoring devices. One hundred patients were enrolled. The mean age was 58.5 ± 7.6 years, and the mean left atrial diameter (LAD) was 50.1 ± 6.1 mm. At 12 months, freedom from AF off AADs was recorded in 71.4% (35/49) of patients in HA group and 45.8% (22/48) in SA group [odds ratio 2.955, 95% confidence interval (1.275-6.848), P = 0.014]. HA significantly reduced patients' AF burden (30.2% in SA group and 14.8% in HA group, P = 0.048) and the LAD (mean differences: -5.53 ± 4.97 mm in HA group and -3.27 ± 5.20 mm in SA group, P = 0.037) at 12 months after operation. CONCLUSION: In patients with PerAF and enlarged left atrium or LSPAF, HA achieved better freedom from AF after 1 year of follow-up compared with thoracoscopic SA.

Construction of amine-rich coating utilizing amine curing reaction of triglycidyl isocyanate with triethylenetetramine on the surface of poly(styrene-divinylbenzene) microspheres for preparation of anion exchange stationary phase.

Epoxy resins, as important thermosetting polymers, exhibit excellent adhesion to various substrates. In view of this, reticulate coating of triglycidyl isocyanate with triethylenetetramine was introduced onto the surface of poly(styrene-divinylbenzene) utilizing amine curing reaction to obtain poly(styrene-divinylbenzene)@triglycidyl isocyanate-triethylenetetramine composite microspheres. The amino groups and epoxy groups of triglycidyl isocyanate-triethylenetetramine endowed poly(styrene-divinylbenzene) with good reactivity, which could be quaternized under mild conditions to obtain an anion exchange chromatographic stationary phase. The quaternized poly(styrene-divinylbenzene)@triglycidyl isocyanate-triethylenetetramine was characterized by scanning electron microscope, Fourier-transform infrared spectroscopy, N2 adsorption-desorption experiment, et al. The chromatographic performance of the customized column was evaluated by separating seven conventional anions, organic weak acids, and carbohydrates. Poly(styrene-divinylbenzene)@triglycidyl isocyanate-triethylenetetramine possesses the uniform size of poly(styrene-divinylbenzene) microspheres and good reactivity of triglycidyl isocyanate-triethylenetetramine, which offers a flexible strategy for the preparation of anion exchange stationary phase. The column exhibits excellent chemical and mechanical stability and chromatographic performance. Finally, the column was successfully applied for the determination of nitrite in pickles.

Irradiance uniformity reshaping method for solar simulators based on computer-generated spatial filter films.

Irradiance uniformity is critical to the accuracy of photovoltaic device test results. Therefore, to post-correct the irradiance uniformity inherent in artificial lighting systems, a spatial irradiance filter scheme for film patterns is proposed based on the physical phenomenon of a positively related relationship between inkjet concentration and the transparency of the flexible film. The scheme first establishes the characteristic equation between the irradiance absorption and pattern grayscale values and then generates the spatial filtering pattern by utilizing the light intensity distribution to be calibrated, matrix operations, and bilinear interpolation. To evaluate its performance, an STM32 microprocessor-based irradiance distribution measurement system was developed and used to test and verify single lamp, planar array, and curved surface array light sources. The results reveal that the corrected irradiance uniformity improves by 15.5%, 24.01 %, and 13.11%, all of which achieve the Class A irradiance uniformity of the IEC 60904-9 standard.

Temporal Convolutional Neural Network-Based Prediction of Vascular Health in Elderly Women Using Photoplethysmography-Derived Pulse Wave during Exercise.

(1) Background: The objective of this study was to predict the vascular health status of elderly women during exercise using pulse wave data and Temporal Convolutional Neural Networks (TCN); (2) Methods: A total of 492 healthy elderly women aged 60-75 years were recruited for the study. The study utilized a cross-sectional design. Vascular endothelial function was assessed non-invasively using Flow-Mediated Dilation (FMD). Pulse wave characteristics were quantified using photoplethysmography (PPG) sensors, and motion-induced noise in the PPG signals was mitigated through the application of a recursive least squares (RLS) adaptive filtering algorithm. A fixed-load cycling exercise protocol was employed. A TCN was constructed to classify flow-mediated dilation (FMD) into "optimal", "impaired", and "at risk" levels; (3) Results: TCN achieved an average accuracy of 79.3%, 84.8%, and 83.2% in predicting FMD at the "optimal", "impaired", and "at risk" levels, respectively. The results of the analysis of variance (ANOVA) comparison demonstrated that the accuracy of the TCN in predicting FMD at the impaired and at-risk levels was significantly higher than that of Long Short-Term Memory (LSTM) networks and Random Forest algorithms; (4) Conclusions: The use of pulse wave data during exercise combined with the TCN for predicting the vascular health status of elderly women demonstrated high accuracy, particularly in predicting impaired and at-risk FMD levels. This indicates that the integration of exercise pulse wave data with TCN can serve as an effective tool for the assessment and monitoring of the vascular health of elderly women.

Multilayer Perceptron-Based Wearable Exercise-Related Heart Rate Variability Predicts Anxiety and Depression in College Students.

(1) Background: This study aims to investigate the correlation between heart rate variability (HRV) during exercise and recovery periods and the levels of anxiety and depression among college students. Additionally, the study assesses the accuracy of a multilayer perceptron-based HRV analysis in predicting these emotional states. (2) Methods: A total of 845 healthy college students, aged between 18 and 22, participated in the study. Participants completed self-assessment scales for anxiety and depression (SAS and PHQ-9). HRV data were collected during exercise and for a 5-min period post-exercise. The multilayer perceptron neural network model, which included several branches with identical configurations, was employed for data processing. (3) Results: Through a 5-fold cross-validation approach, the average accuracy of HRV in predicting anxiety levels was 89.3% for no anxiety, 83.6% for mild anxiety, and 74.9% for moderate to severe anxiety. For depression levels, the average accuracy was 90.1% for no depression, 84.2% for mild depression, and 82.1% for moderate to severe depression. The predictive R-squared values for anxiety and depression scores were 0.62 and 0.41, respectively. (4) Conclusions: The study demonstrated that HRV during exercise and recovery in college students can effectively predict levels of anxiety and depression. However, the accuracy of score prediction requires further improvement. HRV related to exercise can serve as a non-invasive biomarker for assessing psychological health.

Tai Chi Movement Recognition and Precise Intervention for the Elderly Based on Inertial Measurement Units and Temporal Convolutional Neural Networks.

(1) Background: The objective of this study was to recognize tai chi movements using inertial measurement units (IMUs) and temporal convolutional neural networks (TCNs) and to provide precise interventions for elderly people. (2) Methods: This study consisted of two parts: firstly, 70 skilled tai chi practitioners were used for movement recognition; secondly, 60 elderly males were used for an intervention study. IMU data were collected from skilled tai chi practitioners performing Bafa Wubu, and TCN models were constructed and trained to classify these movements. Elderly participants were divided into a precision intervention group and a standard intervention group, with the former receiving weekly real-time IMU feedback. Outcomes measured included balance, grip strength, quality of life, and depression. (3) Results: The TCN model demonstrated high accuracy in identifying tai chi movements, with percentages ranging from 82.6% to 94.4%. After eight weeks of intervention, both groups showed significant improvements in grip strength, quality of life, and depression. However, only the precision intervention group showed a significant increase in balance and higher post-intervention scores compared to the standard intervention group. (4) Conclusions: This study successfully employed IMU and TCN to identify Tai Chi movements and provide targeted feedback to older participants. Real-time IMU feedback can enhance health outcome indicators in elderly males.

Research on UAV Flight Parameter Identification Method Based on Launch Force and Airspeed.

Flight parameters are crucial criteria for UAV control, playing a significant role in ensuring the safe and efficient completion of missions. Launch force and airspeed information are key parameters in the early and middle stages of flight, serving as important data for monitoring the UAV's flight status. In response to challenges such as weak launch force, low identification rates, small airspeed, and low recognition accuracy in UAVs, a method for identifying UAV flight parameters based on launch force and airspeed is proposed. From the aspect of launch force identification, a recognition method based on a low-g value accelerometer information source is proposed, utilizing a 'multi-level time window + threshold' approach. For airspeed identification, an optimization method for airspeed measurement under the Kalman filter architecture is introduced. A device for airspeed measurement based on pressure sensors is designed, and the recommended installation position is determined through simulation. Furthermore, the feasibility and robustness of the proposed launch force identification and airspeed measurement optimization methods are validated through simulation. Finally, the effectiveness of the design is verified through centrifuge and wind tunnel experiments. This research provides technical support for the identification of the launch force and airspeed measurement in UAVs.

Designing of Airspeed Measurement Method for UAVs Based on MEMS Pressure Sensors.

Airspeed measurement is crucial for UAV control. To achieve accurate airspeed measurements for UAVs, this paper calculates airspeed data by measuring changes in air pressure and temperature. Based on this, a data processing method based on mechanical filtering and the improved AR-SHAKF algorithm is proposed to indirectly measure airspeed with high precision. In particular, a mathematical model for an airspeed measurement system was established, and an installation method for the pressure sensor was designed to measure the total pressure, static pressure, and temperature. Secondly, the measurement principle of the sensor was analyzed, and a metal tube was installed to act as a mechanical filter, particularly in cases where the aircraft has a significant impact on the gas flow field. Furthermore, a time series model was used to establish the sensor state equation and the initial noise values. It also enhanced the Sage-Husa adaptive filter to analyze the unavoidable error impact of initial noise values. By constraining the range of measurement noise, it achieved adaptive noise estimation. To validate the superiority of the proposed method, a low-complexity airspeed measurement device based on MEMS pressure sensors was designed. The results demonstrate that the airspeed measurement device and the designed velocity measurement method can effectively calculate airspeed with high measurement accuracy and strong interference resistance.

Impact of a Precision Intervention for Vascular Health in Middle-Aged and Older Postmenopausal Women Using Polar Heart Rate Sensors: A 24-Week RCT Study Based on the New Compilation of Tai Chi (Bafa Wubu).

(1) Background: This study utilized a 24-week intervention incorporating heart rate sensors for real-time monitoring of intervention training, aiming to comprehensively assess the effects of Tai Chi on vascular endothelial function, atherosclerosis progression, and lipid metabolism. The insights gained may inform personalized non-pharmacological interventions to enhance the management of cardiovascular health in this population to provide sustainable benefits and improve quality of life. (2) Methods: Forty postmenopausal middle-aged and elderly women were randomly assigned to an exercise or control group. The exercise group underwent a 24-week Tai Chi (BaFa WuBu) training intervention with real-time heart rate monitoring using Polar sensors. Pre- and post-intervention assessments included body composition, blood pressure, vascularity, and blood parameters measured with the Inbody 720, Vascular Endothelial Function Detector, and Arteriosclerosis. Data were analyzed using SPSS 26.0 and mixed-design ANOVA to assess the effects of time, group, and their interactions on study outcomes. (3) Results: After training through 24 weeks of Tai Chi (BaFa WuBu) intervention, compared with the control group, systolic blood pressure in the exercise group was significantly lower (p < 0.05), and the difference between left and right arm pulse pressure, left and right ankle mean arterial pressure, left and right side baPWV, left and right side ABI, TC, TG, LDL, and blood pressure viscosity were all very significantly lower (p < 0.01), and the diastolic blood pressure was significantly higher (p < 0.05). Compared with baseline values in the exercise group, systolic blood pressure, right and left arm pulse pressure difference, right and left ankle mean arterial pressure, right and left side baPWV, right and left side ABI, TC, TG, LDL, and blood pressure viscosity decreased very significantly (p < 0.01) and diastolic blood pressure and FMD increased very significantly (p < 0.01) in the exercise group after the intervention. (4) Conclusions: In our study, a 24-week Tai Chi (BaFa WuBu) program significantly improved vascular health in middle-aged and older postmenopausal women. This simplified Tai Chi form is gentle and effective, ideal for older adults. Regular practice led to reduced vascular obstruction, improved lipid metabolism, and enhanced vascular endothelial function, crucial for preventing vascular diseases. The real-time heart rate sensors used were pivotal, enabling precise monitoring and adjustment of exercise intensity, thereby enhancing the study's scientific rigor and supporting Tai Chi (BaFa WuBu) as a beneficial therapeutic exercise.

The Simultaneous Detection of Dopamine and Uric Acid In Vivo Based on a 3D Reduced Graphene Oxide-MXene Composite Electrode.

Dopamine (DA) and uric acid (UA) are essential for many physiological processes in the human body. Abnormal levels of DA and UA can lead to multiple diseases, such as Parkinson's disease and gout. In this work, a three-dimensional reduced graphene oxide-MXene (3D rGO-Ti3C2) composite electrode was prepared using a simple one-step hydrothermal reduction process, which could separate the oxidation potentials of DA and UA, enabling the simultaneous detection of DA and UA. The 3D rGO-Ti3C2 electrode exhibited excellent electrocatalytic activity towards both DA and UA. In 0.01 M PBS solution, the linear range of DA was 0.5-500 µM with a sensitivity of 0.74 µA·µM-1·cm-2 and a detection limit of 0.056 µM (S/N = 3), while the linear range of UA was 0.5-60 µM and 80-450 µM, with sensitivity of 2.96 and 0.81 µA·µM-1·cm-2, respectively, and a detection limit of 0.086 µM (S/N = 3). In 10% fetal bovine serum (FBS) solution, the linear range of DA was 0.5-500 µM with a sensitivity of 0.41 µA·µM-1·cm-2 and a detection limit of 0.091 µM (S/N = 3). The linear range of UA was 2-500 µM with a sensitivity of 0.11 µA·µM-1·cm-2 and a detection limit of 0.6 µM (S/N = 3). The modified electrode exhibited advantages such as high sensitivity, a strong anti-interference capability, and good repeatability. Furthermore, the modified electrode was successfully used for DA measurement in vivo. This could present a simple reliable route for neurotransmitter detection in neuroscience.

Customized Heteronuclear Dual Single-Atom and Cluster Assemblies via D-band Orchestration for Oxygen Reduction Reaction.

The advanced oxygen reduction reaction (ORR) catalysts, integrating with well-dispersed single atom (SA) and atomic cluster (AC) sites, showcase potential in bolstering catalytic activity. However, the precise structural modulation and in-depth investigation of their catalytic mechanisms pose ongoing challenges. Herein, a proactive cluster lockdown strategy is introduced, relying on the confinement of trinuclear clusters with metal atom exchange in the covalent organic polymers, enabling the targeted synthesis of a series of multicomponent ensembles featuring FeCo (Fe or Co) dual-single-atom (DSA) and atomic cluster (AC) configurations (FeCo-DSA/AC) via thermal pyrolysis. The designed FeCo-DSA/AC surpasses Fe- and Co-derived counterparts by 18 mV and 49 mV in ORR half-wave potential, whilst exhibiting exemplary performance in Zn-air batteries. Comprehensive analysis and theoretical simulation elucidate the enhanced activity stems from adeptly orchestrating dz2-dxz and O 2p orbital hybridization proximate to the Fermi level, fine-tuning the antibonding states to expedite OH* desorption and OOH* formation, thereby augmenting catalytic activity. This work elucidates the synergistic potentiation of active sites in hybrid electrocatalysts, pioneering innovative targeted design strategies for single-atom-cluster electrocatalysts.

Lipotoxicity-polarised macrophage-derived exosomes regulate mitochondrial fitness through Miro1-mediated mitophagy inhibition and contribute to type 2 diabetes development in mice.

AIMS/HYPOTHESIS: Insulin resistance is a major pathophysiological defect in type 2 diabetes and obesity. Numerous experimental and clinical studies have provided evidence that sustained lipotoxicity-induced mitophagy deficiency can exacerbate insulin resistance, leading to a vicious cycle between mitophagy dysfunction and insulin resistance, and thereby the onset of type 2 diabetes. Emerging evidence suggests that exosomes (Exos) from M2 macrophages play an essential role in modulating metabolic homeostasis. However, how macrophages are affected by lipotoxicity and the role of lipotoxicity in promoting macrophage activation to the M1 state have not been determined. The objective of this study was to determine whether M1 macrophage-derived Exos polarised by lipopolysaccharide (LPS) + palmitic acid (PA)-induced lipotoxicity contribute to metabolic homeostasis and impact the development of insulin resistance in type 2 diabetes. METHODS: Lipotoxicity-polarised macrophage-derived M1 Exos were isolated from bone marrow (C57BL/6J mouse)-derived macrophages treated with LPS+PA. Exos were characterised by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Flow cytometry, H&E staining, quantitative real-time PCR, immunofluorescence, glucose uptake and output assays, confocal microscopy imaging, western blotting, GTTs and ITTs were conducted to investigate tissue inflammation, mitochondrial function and insulin resistance in vitro and in vivo. The roles of miR-27-3p and its target gene Miro1 (also known as Rhot1, encoding mitochondrial rho GTPase 1) and relevant pathways were predicted and assessed in vitro and in vivo using specific miRNA mimic, miRNA inhibitor, miRNA antagomir and siRNA. RESULTS: miR-27-3p was highly expressed in M1 Exos and functioned as a Miro1-inactivating miRNA through the miR-27-3p-Miro1 axis, leading to mitochondria fission rather than fusion as well as mitophagy impairment, resulting in NOD-like receptor 3 inflammatory activation and development of insulin resistance both in vivo and in vitro. Inactivation of miR-27-3p induced by M1 Exos prevented type 2 diabetes development in high-fat-diet-fed mice. CONCLUSIONS/INTERPRETATION: These findings suggest that the miR-27-3p-Miro1 axis, as a novel regulatory mechanism for mitophagy, could be considered as a new therapeutic target for lipotoxicity-related type 2 diabetes disease development.