Association of the CUN-BAE body adiposity estimator and other obesity indicators with cardiometabolic multimorbidity: a cross-sectional study.

Cardiometabolic multimorbidity (CM), defined as the coexistence of two or three cardiometabolic disorders, is one of the most common and deleterious multimorbidities. This study aimed to investigate the association of Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with the prevalence of CM. The data were obtained from the 2021 health checkup database for residents of the Electronic Health Management Center in Xinzheng, Henan Province, China. 81,532 participants aged ≥ 60 years were included in this study. Logistic regression models were used to estimate the odd ratios (ORs) and 95% confidence intervals (CIs) for CUN-BAE, BMI, WC, and WHtR in CM. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory ability of different anthropometric indicators for CM. The multivariable-adjusted ORs (95% CIs) (per 1 SD increase) of CM were 1.799 (1.710-1.893) for CUN-BAE, 1.329 (1.295-1.364) for BMI, 1.343 (1.308-1.378) for WC, and 1.314 (1.280-1.349) for WHtR, respectively. Compared with BMI, WC and WHtR, CUN-BAE had the highest AUC in both males and females (AUC: 0.642; 95% CI 0.630-0.653 for males, AUC: 0.614; 95% CI 0.630-0.653 for females). CUN-BAE may be a better measure of the adverse effect of adiposity on the prevalence of CM than BMI, WC, and WHtR.

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.

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.

Epicardial left atrial appendage clipping versus direct oral anticoagulant to reduce stroke risk in non-paroxysmal atrial fibrillation (LAA-CLIP): rationale, design and study protocol for a multicentre randomised controlled trial.

INTRODUCTION: The prevalence of atrial fibrillation (AF) is increasing globally, and stroke prevention is the key to reduce the morbidity and mortality related to AF. Currently, direct oral anticoagulants (DOACs) are the primary options for stroke prevention, while it increases risk of bleeding. Left atrial appendage (LAA) is suspected as a vital source of cerebral emboli and may lead to ischaemic stroke, and thoracoscopic LAA clipping procedure provides an alternative option for stroke prevention in high-risk patients. However, high-quality evidence comparing LAA clipping to DOACs in terms of stroke prevention is lacking. This trial is designed to assess whether the efficacy of thoracoscopic LAA clipping is superior to DOACs for stroke prevention in AF patients at high risk of thrombosis (CHA2DS2-VASc≥2 in men and ≥3 in women)[CHA2DS2-VASc stands for "congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female)"]. METHODS AND ANALYSIS: This is a prospective, multicentre, open-labelled, randomised controlled study. This trial will randomly assign 290 patients with non-paroxysmal AF to thoracoscopic LAA clipping group or DOAC therapy group in a 1:1 randomisation. The primary endpoint is defined as a composite endpoint event consisting of stroke, systemic embolism, all-cause mortality, major bleeding events and clinically relevant non-major bleeding events at 24 months after randomisation. The secondary endpoints consist of the components of the primary composite endpoint, surgery-related adverse events and minor bleeding events. ETHICS AND DISSEMINATION: The central ethics committee at Fuwai Hospital approved the trial entitled "Epicardial left atrial appendage clipping versus direct oral anticoagulant to reduce stroke risk in non-paroxysmal atrial fibrillation (LAA-CLIP trial)". The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT06021808.

Methylation changes of liver DNA during the formation of gallstones.

Aim: To explore the overall methylation changes in liver tissues during the formation of gallstones, as well as the key pathways and genes involved in the process. Methods: Reduced-representation bisulfite sequencing and RNA sequencing were conducted on the liver tissues of mice with gallstones and control normal mice. Results: A total of 8705 differentially methylated regions in CpG and 1410 differentially expressed genes were identified. The joint analysis indicated that aberrant DNA methylation may be associated with dysregulated gene expression in key pathways such as cholesterol metabolism and bile secretion. Conclusion: We propose for the first time that methylation changes in some key pathway genes in liver tissue may be involved in the formation of gallstones.

Acute effects of different Tai Chi practice protocols on cardiac autonomic modulation.

Tai Chi serves as an effective exercise modality for enhancing autonomic regulation. However, a majority of existing studies have employed the single routine (SR) protocol as the basis for health interventions. The extent to which the gong routine application (GRA) protocol achieves similar levels of exercise load stimulation as traditional single practice routines remains uncertain. Therefore, this study the distinct characteristics of autonomic load stimulation in these different protocols, thus providing a biological foundation to support the development of Tai Chi health promotion intervention programs. we recruited a cohort of forty-five university students to participate in the 15 min GRA protocol and SR protocol. We collected heart rate and heart rate variability indicators during periods of rest, GRA protocol, and SR protocol utilizing the Polar Scale. Additionally, we assessed the mental state of the participants using the BFS State of Mind Scale. In summary, the autonomic load is lower in the GRA protocol compared to the SR protocol, with lower sympathetic activity but higher parasympathetic activity in the former. Results are specific to college students, additional research is necessary to extend support for frail older adults. It is advised to incorporate GRA protocol alongside SR protocol in Tai Chi instruction. This approach is likely to enhance Tai Chi skills and yield greater health benefits.

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.

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.

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.

Green Printing for Scalable Organic Photovoltaic Modules by Controlling the Gradient Marangoni Flow.

Despite the rapid development in the performances of organic solar cells (OSCs), high-performance OSC modules based on green printing are still limited. The severe Coffee-ring effect (CRE) is considered to be the primary reason for the nonuniform distribution of active layer films. To solve this key printing problem, the cosolvent strategy is presented to deposit the active layer films. The guest solvent Mesitylene with a higher boiling point and a lower surface tension is incorporated into the host solvent o-XY to optimize the rheological properties, such as surface tension and viscosity of the active layer solutions. And the synergistic effect of inward Marangoni flow generation and solution thickening caused by the cosolvent strategy can effectively restrain CRE, resulting in highly homogeneous large-area active layer films. In addition, the optimized crystallization and phase separation of active layer films effectively accelerate the charge transport and exciton dissociation of devices. Consequently, based on PM6:BTP-eC9 system, the device prepared with the co-solvent strategy shows the a power conversion efficiency of 17.80%. Moreover, as the effective area scales to 1 and 16.94 cm2 , the recorded performances are altered to 16.71% and 14.58%. This study provides a universal pathway for the development of green-printed high-efficiency organic photovoltaics.

Novel sizing role of 3D transesophageal echocardiography in a novel left atrial appendage clip device for patients undergoing video-assisted atrial fibrillation ablation: a cohort study.

Background: Three-dimensional (3D) transesophageal echocardiography (TEE) has been successfully used in the sizing of left atrial appendage (LAA) occlusion devices, but its use has not yet been studied in LAA clip devices. We sought to develop and validate the novel use of 3D-TEE sizing in a novel LAA clip device for atrial fibrillation (AF) patients undergoing video-assisted thoracic surgery (VATS) ablation. Methods: Consecutive patients with isolated AF undergoing LAA clipping or excision during VATS ablation were included in the study between June 2021 and September 2022 at Fuwai Hospital. The patients underwent 3D-TEE examinations preoperatively and postoperatively. The VATS length, LAA clip effective length, and LAA excision margin length were recorded. A correlation analysis, intraclass correlation coefficient (ICC) analysis, and Bland-Altman plot analysis were conducted to examine the TEE parameters, VATS length, LAA clip effective length, and LAA excision margin length. Results: In total, 26 AF patients undergoing LAA clipping and 15 undergoing LAA excision were included in the study. In the LAA clipping group, in which the Atriclip size served as the control, the 3D-TEE with volumetric measurement (the perimeter-derived maximum orifice diameter) (R=0.938; ICC =0.934; Bland-Altman plot variability, 3.85%) showed the best sizing efficacy for the LAA clip device among the 3D-TEE with multiplanar reformatting sizing (the perimeter-derived maximum orifice diameter) (R=0.808; ICC =0.772; Bland-Altman plot variability, 3.85%), VATS sizing (R=0.851; ICC =0.756; Bland-Altman plot variability, 11.54%), and VATS plus 0.5-cm sizing (R=0.851; ICC =0.775; Bland-Altman plot variability, 11.54%) measurements (all P<0.001). In addition, for the distribution of matched sizing in the LAA clip group, 3D-TEE with volumetric measurement sizing (20/26) had a higher proportion than 3D-TEE with multiplanar reformatting sizing (11/26, P=0.011), VATS sizing (9/26, P=0.002), and VATS plus 0.5-cm sizing (14/26, P=0.08). Using the LAA excision margin length as the control, the mean difference in the LAA diameter was 1.17 cm [95% confidence interval (CI): 0.71-1.62 cm , P<0.001] in the maximum orifice diameter of two-dimensional-TEE, 0.15 cm (95% CI: -0.32 to 0.61 cm , P=0.523) in the perimeter-derived 3D multiplanar reformatting (the maximum orifice diameter), and 0.03 cm (95% CI: -0.47 to 0.53, P=0.901) in the perimeter-derived 3D volumetric (3DV) measurement (the maximum orifice diameter), and the related Pearson correlation coefficients for these modalities were 0.760 (P=0.001), 0.843 (P<0.001), and 0.963 (P<0.001), respectively. Conclusions: Our study showed that 3D-TEE might be employed in the sizing of a novel LAA clip device using the VATS approach in patients with AF. The 3DV measurement (the perimeter-derived maximum orifice diameter) was superior to the VATS measurement. These findings might also apply to LAA VATS excision patients with AF.

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.

An RCT META analysis based on the effect of tai chi exercise therapy on the outcome of elderly patients with moderate-to-severe sleep disorders-A systematic review study.

Background: According to statistics, about one-fifth of the world's elderly people suffer from sleep disorders, and the problem of sleep disorders in the elderly is extremely serious, and this problem is one of the important causes of chronic diseases such as hypertension, hyperlipidemia, diabetes mellitus, and coronary heart disease in the elderly. The positive effect of Tai Chi exercise therapy on sleep problems has been confirmed, but at present, the effect of the specific duration of Tai Chi exercise on the improvement of elderly people with moderate to severe sleep disorders varies. Objective: META analysis was used to investigate and find that long-term Tai Chi exercise therapy has the best effect on improving sleep in elderly patients with moderate to severe sleep disorders. Methods: META analysis was performed using Revman 5.3 after searching Web of science, Pubmed, Scopus, The Cochroae Library, OVID, CBM, CNKI, VIP, and other databases, and then filtering and extracting. Results: A total of seven papers were included. Meta-analysis showed that tai chi exercise was more effective in improving sleep problems in elderly patients with sleep disorders compared to the control group, and the difference was significant. This was demonstrated by a decrease in the global Pittsburgh Sleep Quality Index (PSQI) score [SMD = -0.66, 95 % CI (-0.91, -0.41), P < 0.00001], as well as its subdomains of subjective sleep quality [SMD = -0.79, 95 % CI (-1.06, -0.52), P < 0.00001], sleep latency [SMD = -0.80, 95 % CI (-1.21, -0.40), P < 0.00001], sleep duration [SMD = -0.38, 95 % CI (-0.72, -0.04), P = 0.03], habitual sleep efficiency [SMD = -0.58, 95 % CI (-0.84, -0.31), P < 0.0001], sleep disturbance [SMD = -0.51, 95 % CI (-0.78, -0.25), P = 0.00001] and daytime dysfunction [SMD = -0.33, 95 % CI (-0.59, -0.07), P = 0.01]. Improvement was also observed in the Epworth Sleepiness Scale (ESS) and Insomnia Severity Index Scale (ISI). The results showed that the optimal duration and frequency of Tai Chi exercise therapy for improving moderately severe elderly patients with sleep disorders was long-term. Conclusion: This study systematically assessed the efficacy of Tai Chi exercise therapy for elderly patients with moderate-to-severe sleep disorders. Through a meta-analysis of relevant randomized controlled trials (RCTs), it aims to determine the effectiveness of Tai Chi exercise in improving sleep quality in elderly patients with moderate-to-severe sleep disorders, as well as to compare its effects with those of traditional treatments; to analyze the safety of Tai Chi exercise for this patient population and assess its feasibility as a non-pharmacological therapy; and to fill the research gaps and provide more comprehensive and systematic evidence support. This study provides a practical approach to reducing the risk of medication side effects in older adults with sleep disorders and offers a potentially effective non-pharmacological treatment option, especially for those who are unable or unwilling to use medication. Tai chi exercise may not only improve sleep, but also improve coordination, muscle strength, balance, and reduce stress and anxiety in older adults. It also helps older adults socialize and enhances their social connections and emotional support. This study suggests that community centers or activity centers for the elderly can organize tai chi classes to promote the participation of older adults, and can be used as a scientific exercise rehabilitation tool in clinical treatment, incorporating tai chi practice into daily life, such as tai chi practice at a fixed time every day or every week, which not only helps to improve the sleep disorders of older adults, but also improves their overall quality of life.

Content-Aware Rectified Activation for Zero-Shot Fine-Grained Image Retrieval.

Fine-grained image retrieval mainly focuses on learning salient features from the seen subcategories as discriminative embedding while neglecting the problems behind zero-shot settings. We argue that retrieving fine-grained objects from unseen subcategories may rely on more diverse clues, which are easily restrained by the salient features learnt from seen subcategories. To address this issue, we propose a novel Content-aware Rectified Activation model, which enables this model to suppress the activation on salient regions while preserving their discrimination, and spread activation to adjacent non-salient regions, thus mining more diverse discriminative features for retrieving unseen subcategories. Specifically, we construct a content-aware rectified prototype (CARP) by perceiving semantics of salient regions. CARP acts as a channel-wise non-destructive activation upper bound and can be selectively used to suppress salient regions for obtaining the rectified features. Moreover, two regularizations are proposed: 1) a semantic coherency constraint that imposes a restriction on semantic coherency of CARP and salient regions, aiming at propagating the discriminative ability of salient regions to CARP, 2) a feature-navigated constraint to further guide the model to adaptively balance the discrimination power of rectified features and the suppression power of salient features. Experimental results on fine-grained and product retrieval benchmarks demonstrate that our method consistently outperforms the state-of-the-art methods.

Streptococcus suis subtilisin-like serine proteases SspA-1 and SspA-2 interplay with complement C3a and C5a to facilitate bacterial immune evasion and infection.

Streptococcus suis (S. suis), a significant zoonotic bacterial pathogen impacting swine and human, is associated with severe systemic diseases such as streptococcal toxic shock-like syndrome, meningitis, septicaemia, and abrupt fatality. The multifaceted roles of complement components C5a and C3a extend to orchestrating inflammatory cells recruitment, oxidative burst induction, and cytokines release. Despite the pivotal role of subtilisin-like serine proteases in S. suis pathogenicity, their involvement in immune evasion remains underexplored. In the present study, we identify two cell wall-anchored subtilisin-like serine proteases in S. suis, SspA-1 and SspA-2, as binding partners for C3a and C5a. Through Co-Immunoprecipitation, Enzyme-Linked Immunosorbent and Far-Western Blotting Assays, we validate their interactions with the aforementioned components. However, SspA-1 and SspA-2 have no cleavage activity against complement C3a and C5a performed by Cleavage assay. Chemotaxis assays reveal that recombinant SspA-1 and SspA-2 effectively attenuate monocyte chemotaxis towards C3a and C5a. Notably, the ΔsspA-1, ΔsspA-1, and ΔsspA-1/2 mutant strains exhibit compromised survival in blood, and resistance of opsonophagocytosis, alongside impaired survival in blood and in vivo colonization compared to the parental strain SC-19. Critical insights from the murine and Galleria mellonella larva infection models further underscore the significance of sspA-1 in altering mortality rates. Collectively, our findings indicate that SspA-1 and SspA-2 are novel binding proteins for C3a and C5a, thereby shedding light on their pivotal roles in S. suis immune evasion and the pathogenesis.

Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice.

Excessive consumption of fluoride can cause skeletal fluorosis. Mitophagy has been identified as a novel target for bone disorders. Meanwhile, calcium supplementation has shown great potential for mitigating fluoride-related bone damage. Hence, this study aimed to elucidate the association between mitophagy and skeletal fluorosis and the precise mechanisms through which calcium alleviates these injuries. A 100 mg/L sodium fluoride (NaF) exposure model in Parkin knockout (Parkin-/-) mice and a 100 mg/L NaF exposure mouse model with 1% calcium carbonate (CaCO3) intervention were established in the current study. Fluoride exposure caused the impairment of mitochondria and activation of PTEN-induced putative kinase1 (PINK1)/E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy and mitochondrial apoptosis in the bones, which were restored after blocking Parkin. Additionally, the intervention model showed fluoride-exposed mice exhibited abnormal bone trabecula and mechanical properties. Still, these bone injuries could be effectively attenuated by adding 1% calcium to their diet, which reversed fluoride-activated mitophagy and apoptosis. To summarize, fluoride can activate bone mitophagy through the PINK1/Parkin pathway and mitochondrial apoptosis. Parkin-/- and 1% calcium provide protection against fluoride-induced bone damage. Notably, this study provides theoretical bases for the prevention and therapy of animal and human health and safety caused by environmental fluoride contamination.

Prediction of jaywalker-vehicle conflicts based on encoder-decoder framework utilizing multi-source data.

Jaywalker-vehicle (J-V) conflicts at mid-blocks without crossing facilities in China are frequent and hazardous. Due to the unexpected and sudden nature of jaywalking activity, it is crucial to develop predictive models for J-V conflicts to offer pre-conflict warnings for road users. This study introduces a novel encoder-decoder framework that utilizes multi-source data to predict J-V conflict severity. We define three encoders to represent three types of input data, (1) J-V interaction encoder (Bi-LSTM), (2) jaywalker motion encoder (Bi-LSTM) and (3) background information encoder (MLP). Subsequently, features extracted by these three encoders are concatenated and transferred to the conflict severity decoder (MLP) to obtain the predicted severity level. We further conduct a case study using the surveyed video data at three mid-blocks without crossing facilities in Nanjing, China. The experimental results indicate that, compared to classical models, our proposed encoder-decoder (Proposed ED) model exhibits the best and stable predictive metrics. Furthermore, the results of the ablation study suggest that the incorporation of background information significantly enhances the four evaluative metrics of the Proposed ED model, with an average improvement of 24.291%. Additionally, the results of transferability analysis suggest that, when the ratio of added samples from the new mid-block reaches 40% to 50%, the predictive metrics of the updated models could stabilize at around 80% to 95%, indicating a notably good performance. Eventually, we derive several practical suggestions from the above findings, in order to help with J-V conflict prediction and jaywalking safety improvement.

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.