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Abstract Chiral monodentate biaryl phosphines (MOPs) have attracted intense attention as chiral ligands over the past decades. However, the creation of structurally diverse chiral MOPs with both P- and axial chirality is still in high demand but challenging. Here, we show a distinct strategy for diversity-oriented synthesis of structurally diverse MOPs containing both P- and axial chirality enabled by enantioselective C-P bond cleavage. The key chiral PdII intermediates, generated through the stereoselective oxidative addition of C-P bond, could be trapped by alkynes, R3Si-Bpin, diboron esters or reduced by H2O/B2pin2, leading to enantioenriched structurally diverse MOPs in excellent diastereo- and enantioselectivities. Based on the outstanding properties of the parent scaffolds, the P- and axially chiral monodentate biaryl phosphines serve as excellent catalysts in asymmetric [3 + 2] annulation of MBH carbonate affording the chiral functionalized bicyclic imide.

Abstract Background Timely discharge to post-acute care (PAC) settings, such as skilled nursing facilities, requires early identification of eligible patients. We sought to develop and internally validate a model which predicts a patient’s likelihood of requiring PAC based on information obtained in the first 24 h of hospitalization. Methods This was a retrospective observational cohort study. We collected clinical data and commonly used nursing assessments from the electronic health record (EHR) for all adult inpatient admissions at our academic tertiary care center from September 1, 2017 to August 1, 2018. We performed a multivariable logistic regression to develop the model from the derivation cohort of the available records. We then evaluated the capability of the model to predict discharge destination on an internal validation cohort. Results Age (adjusted odds ratio [AOR], 1.04 [per year]; 95% Confidence Interval [CI], 1.03 to 1.04), admission to the intensive care unit (AOR, 1.51; 95% CI, 1.27 to 1.79), admission from the emergency department (AOR, 1.53; 95% CI, 1.31 to 1.78), more home medication prescriptions (AOR, 1.06 [per medication count increase]; 95% CI 1.05 to 1.07), and higher Morse fall risk scores at admission (AOR, 1.03 [per unit increase]; 95% CI 1.02 to 1.03) were independently associated with higher likelihood of being discharged to PAC facility. The c-statistic of the model derived from the primary analysis was 0.875, and the model predicted the correct discharge destination in 81.2% of the validation cases. Conclusions A model that utilizes baseline clinical factors and risk assessments has excellent model performance in predicting discharge to a PAC facility.

The high risk of postoperative mortality in lung adenocarcinoma (LUAD) patients is principally driven by cancer recurrence and low response rates to adjuvant treatment. Here, A combined cohort containing 1,026 stage I–III patients was divided into the learning (n = 678) and validation datasets (n = 348). The former was used to establish a 16-mRNA risk signature for recurrence prediction with multiple statistical algorithms, which was verified in the validation set. Univariate and multivariate analyses confirmed it as an independent indicator for both recurrence-free survival (RFS) and overall survival (OS). Distinct molecular characteristics between the two groups including genomic alterations, and hallmark pathways were comprehensively analyzed. Remarkably, the classifier was tightly linked to immune infiltrations, highlighting the critical role of immune surveillance in prolonging survival for LUAD. Moreover, the classifier was a valuable predictor for therapeutic responses in patients, and the low-risk group was more likely to yield clinical benefits from immunotherapy. A transcription factor regulatory protein–protein interaction network (TF-PPI-network) was constructed via weighted gene co-expression network analysis (WGCNA) concerning the hub genes of the signature. The constructed multidimensional nomogram dramatically increased the predictive accuracy. Therefore, our signature provides a forceful basis for individualized LUAD management with promising potential implications.

Abstract The solid-electrolyte interphase (SEI) plays crucial roles for the reversible operation of lithium metal batteries. However, fundamental understanding of the mechanisms of SEI formation and evolution is still limited. Herein, we develop a depth-sensitive plasmon-enhanced Raman spectroscopy (DS-PERS) method to enable in-situ and nondestructive characterization of the nanostructure and chemistry of SEI, based on synergistic enhancements of localized surface plasmons from nanostructured Cu, shell-isolated Au nanoparticles and Li deposits at different depths. We monitor the sequential formation of SEI in both ether-based and carbonate-based dual-salt electrolytes on a Cu current collector and then on freshly deposited Li, with dramatic chemical reconstruction. The molecular-level insights from the DS-PERS study unravel the profound influences of Li in modifying SEI formation and in turn the roles of SEI in regulating the Li-ion desolvation and the subsequent Li deposition at SEI-coupled interfaces. Last, we develop a cycling protocol that promotes a favorable direct SEI formation route, which significantly enhances the performance of anode-free Li metal batteries.

Objective Humeral fractures are common in arm wrestling and other sports and military activities requiring similar movements; however, the precise mechanism is poorly understood. Here, we present an overview of the characteristics, possible mechanisms, and treatment of humeral shaft fractures sustained during arm wrestling. Methods We reviewed 8 years (January 2013 to January 2021) of medical records and retrospectively analyzed data from 27 patients with humeral shaft fractures sustained during arm wrestling. The clinical data included sex, age, affected arm, alcohol consumption, muscle warm‐up, history of competitive participation, opponents' characteristics, wrist position, and post‐fracture radial nerve injuries. The fracture configurations were radiographically assessed and analyzed. Surgical management included single or dual plating. Scores on the Disability of the Arm, Shoulder, and Hand questionnaire (DASH) were evaluated preoperatively and postoperatively at the last follow‐up visit. Results All fractures sustained during arm wrestling were spiral fractures of the distal third of the humerus. Of these, 11 were 12‐A1 type and 16 were 12‐B2 type with a wedge fragment. The two subtypes differed in the total fracture line length (12‐A1: 0.18 ± 0.04; 12‐B2: 0.23 ± 0.04; P 2 years. Cold seasonal temperatures and a lack of warm‐ups increased the risk of injury. All patients showed improved DASH scores at the last follow‐up (12‐A1:77.82 ± 5.14 to 10.25 [5.38]; 12‐B2:78.91 ± 7.46 to 8.95 [3.17]; P

Dynamic assessment of cerebral blood flow (CBF) is crucial for guiding personalized management and treatment strategies, and improving the prognosis of stroke. However, a safe, reliable, and effective method for dynamic CBF evaluation is currently lacking in clinical practice. In this study, we developed a CBF monitoring system utilizing electromagnetic coupling sensing (ECS). This system detects variations in brain conductivity and dielectric constant by identifying the resonant frequency (RF) in an equivalent circuit containing both magnetic induction and electrical coupling. We evaluated the performance of the system using a self-made physical model of blood vessel pulsation to test pulsatile CBF. Additionally, we recruited 29 healthy volunteers to monitor cerebral oxygen (CO), cerebral blood flow velocity (CBFV) data and RF data before and after caffeine consumption. We analyzed RF and CBFV trends during immediate responses to abnormal intracranial blood supply, induced by changes in vascular stiffness, and compared them with CO data. Furthermore, we explored a method of dynamically assessing the overall level of CBF by leveraging image feature analysis. Experimental testing substantiates that this system provides a detection range and depth enhanced by three to four times compared to conventional electromagnetic detection techniques, thereby comprehensively covering the principal intracranial blood supply areas. And the system effectively captures CBF responses under different intravascular pressure stimulations. In healthy volunteers, as cerebral vascular stiffness increases and CO decreases due to caffeine intake, the RF pulsation amplitude diminishes progressively. Upon extraction and selection of image features, widely used machine learning algorithms exhibit commendable performance in classifying overall CBF levels. These results highlight that our proposed methodology, predicated on ECS and image feature analysis, enables the capture of immediate responses of abnormal intracranial blood supply triggered by alterations in vascular stiffness. Moreover, it provides an accurate diagnosis of the overall CBF level under varying physiological conditions.

Due to the impact of climate change on agriculture and the emergence of water security issues, proper irrigation management has become increasingly important to overcome the challenges. The Internet of Things (IoT) technology is being utilized in agriculture for collecting field information and sharing it through websites in real time. This study discusses the efforts taken to develop an IoT-based sensor station, a user-friendly website, and a smartphone app for irrigation management. In addition, the demonstration of the IoT-based sensor station and its effectiveness are discussed. Before deploying the sensor station, soil moisture sensor calibration was conducted using a laboratory experiment. Overall, the calibrated soil moisture sensors met the statistical criteria for both sand [root mean squared error (RMSE) = 0.01 cm3/cm3, index of agreement (IA) = 0.97, and mean bias error (MBE) = 0.01] and loamy sand (RMSE = 0.023 cm3/cm3, IA = 0.98, and MBE = −0.02). This article focuses on case studies from corn, blueberry, and tomato fields in Michigan, USA. In the corn and blueberry fields, the evaluation of irrigation practices of farmer's using an IoT-based sensor technology was considered. In the tomato field, a demonstration of automation irrigation was conducted. Overirrigation was observed using the IoT-based sensor station in some fields that have sandy soil and use a drip irrigation system. In the blueberry demonstration field, the total yield per plant (p = 0.025) and 50-berry weights (p = 0.013) were found to be higher with the recommended irrigation management than the farmer's existing field. In the tomato demonstration field, there were no statistical differences in the number of marketable tomatoes (p = 0.382) and their weights (p = 0.756) between the farmer's existing method and the recommended irrigation strategy. However, 30% less water was applied to the recommended irrigation strategy plot. Thus, the result showed that the IoT-based sensor irrigation strategy can save up to 30% on irrigation while maintaining the same yields and quality of the product.

To tackle the common issue of imbalanced data classes in the fault diagnosis of avionics equipment, this study proposes a method that integrates the Synthetic Minority Oversampling Technique (SMOTE) with Boosting (SMOTEWB) and the Light Gradient Boosting Machine (LGBM). Initially, SMOTEWB is refined through a “successive one-vs-many balancing strategy,” which effectively addresses multiclass sample balance issues. The enhanced data is then employed for pattern recognition and classification using LGBM. Additionally, this study utilizes the Tree-structured Parzen Estimator (TPE) method and five-fold cross-validation to optimize the model’s hyperparameters, thus improving diagnostic accuracy. Experimental validation using University of California Irvine (UCI) public datasets and real-world avionics equipment fault data shows that the proposed SMOTEWB-LGBM method outperforms other common methods in handling multiclass imbalanced datasets. This new approach not only enhances fault diagnosis efficiency but also offers a potent solution for similar multiclass imbalance challenges.

Accurately estimating the duration of freeway incidents can enhance emergency management practices and reduce the likelihood of secondary incidents. To investigate the mechanisms through which key factors influence incident duration, this study sorted out the characteristics and variables of the incident duration on a special freeway in Zhejiang Province, that is, the ring road, and developed a latent class accelerated hazard model. Heterogeneity was incorporated into the model. Three distributions (Weibull, Log-normal, and Log-logistic) were compared, and the Log-logistic distribution exhibited superior performance. The analysis revealed two distinct latent classes: Latent Class 1 and Class 2, had class membership probability of 0.53 and 0.47, respectively, with a total of 11 variables being statistically significant at the 0.05 significance level. It is worth noting that, some neglected explanatory variables are discussed in depth in this study. For example, the mechanism of which specific lane is closed has an impact on the incident duration, rather than a general discussion of the number of lane closures. Furthermore, the way in which the driver involved in the incident reports to the police has a significant impact on the duration of incidents. Notably, potential heterogeneity and its influencing mechanism are captured in the model. Additionally, by predicting class membership using posterior probabilities, it was determined that most data points were more likely to belong to Class 1, and the incident duration primarily ranged between 0 and 60 minutes. These findings are helpful to reduce the duration of incidents on ring-roads and freeways in China, and provide theoretical support for the formulation of freeway incident management and treatment policies.

Abstract The impact of mid‐Pliocene boundary conditions on Afro‐Asian summer monsoon (AfroASM) rainfall is examined using the fully coupled Earth System Model EC‐Earth3‐LR. Our focus lies on the effects of varying CO2 concentration, diminished ice sheets and vegetation dynamics. We find that the enhanced AfroASM rainfall is predominantly caused by the “warmer‐gets‐wetter” mechanism due to elevated CO2 levels. Additionally, the ice sheet, similar in size to that of the mid‐Pliocene era, creates several indirect effects. These include sea ice‐albedo feedback and inter‐hemispheric atmosphere energy transport. Such influences result in the southward shift of Hadley circulation and formation of Pacific‐Japan pattern, leading to reduced rainfall in North African and South Asian monsoon regions but increased rainfall in East Asian monsoon region. Interestingly, while dynamic vegetation feedback has a minimal direct effect on AfroASM rainfall, it significantly influences rainfall in the mid‐high latitudes of the North Hemisphere by enhancing water vapor feedback.

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Bone defects have long been a major healthcare issue because of the difficulties in regenerating bone mass volume and the high cost of treatment. G protein-coupled receptor kinase 2 interacting protein 1 (GIT1) has been proven to play an important role both in vascular development and in bone fracture healing. In this study, a type of thermoresponsive injectable hydrogel from oligoethylene glycol-based dendronized chitosan (G1-CS) was loaded with GIT1-plasmids (G1-CS/GIT1), and used to fill unicortical bone defects. RT-PCR analysis confirmed that G1-CS/GIT1 enhanced DNA transfection in MSCs both in vitro and in vivo. From the results of micro-CT, RT-PCR and histological analysis, it can be concluded that G1-CS/GIT1 accelerated the bone healing rate and increased the amount of neovascularization around the bone defects. In addition, an adeno-associated virus (AAV)-GIT1 was constructed to transfect mesenchymal stem cells. The results of capillary tube formation assay, immunofluorescence staining and western blot analysis proved that high expression of GIT1 induces mesenchymal stem cells to differentiate into endothelial cells. RT-PCR analysis and capillary tube formation assay confirmed that the Notch signaling pathway was activated in the differentiation process. Overall, we developed an efficient strategy through combination of injectable hydrogel and G1T1 for bone tissue engineering.

Through the use of the material test system (MTS), bending fatigue tests are conducted in this work in order to investigate the attenuation law of fatigue performance of asphalt pavement in the end-stage of service. Response surface methodology (RSM) is used to analyze the effects of strain, frequency, and temperature on the asphalt surface layer's initial stiffness, fatigue life, phase angle, and cumulative dissipated energy when there is a 50 % reduction in the initial stiffness. Through multi-factor coupling analysis, the optimal combination is found and verified by the MTS-810 test system. Based on this, the data of the initial stiffness declining to 20 % was used for analysis on the AC-13C asphalt surface mixture of the APT full-size test road in the laboratory. At 15 °C and 10 Hz, the evolution law of the flexural stiffness, the residual stiffness, phase angle, and cumulative dissipated energy of the asphalt mixture was investigated. Analysis of the asphalt mixture's damage evolution under the single stage of loading and various strain levels revealed changes in the fatigue cracking crack. Beam specimens were made from asphalt mixture field test beams of AC-13C (laboratory accelerated pavement test road), AC-20C, and AC-25C (Ji-Qing expressway) to conduct four-point bending fatigue test (4PB). According to the constant strain fatigue prediction equation, and the residual fatigue life of prediction localized model was established. The results show that the influence of frequency and temperature on the initial stiffness and phase angle is more significant than strain, and the influence of strain on number of fatigue is more significant. The flexural stiffness of the asphalt mixture shows an obvious S-curve, and larger the tensile strain at the bottom of the asphalt layer, shorter the time needed to reach the termination condition, that is, the faster the fatigue failure occurs. When the damage termination condition is reached, under the strain level of 200–300 με, 60 % of the number of loading produce about 35–40 % damage, and the remaining 20 % of the number of loading lead to 10–20 % damage.

Herein, two types of Fc-based hypercrosslinked polymers (HHCP and DHCP) with high BET surface area (953.9 and 1062.7 m2 g−1) were prepared by direct one-step phenolic polycondensation aiming at high uptake capacity towards H2. As expected, the hydrogen uptake values of HHCP and DHCP were notably higher than those of porous polymers with a higher surface area under the same conditions. The maximum H2 uptake of HCPs at 77 K/1.0 bar are determined to be 2.51 wt % for HHCP and 2.74 wt % for DHCP, respectively. Despite the pore structure playing a determinant role in hydrogen adsorption, the adsorption sites in the polymer framework can be another essential factor to influence the hydrogen adsorption capacity. The interactions between the Fc building block and H2 are revealed by DFT calculation to fully illustrate the role of Fc in H2 adsorption. The results indicate that both iron atoms and benzene rings in Fc-based HCPs contribute to the adsorption of hydrogen. Moreover, it is interesting to find that the most stable adsorption site around the Fc building unit is the position directly above the Cp ring. The results in this work may more reasonably explain the phenomenon that the introduction of Fc units could enhance the adsorption of H2 in many studies, which also provides possible insights into the application of metallocene compounds in H2 adsorption.

Abstract Purpose To develop a bidirectional slide guide to assist screw placement in the axial lamina and to preliminarily discuss the accuracy and feasibility of auxiliary screw placement. Methods CT data from 40 randomly selected patients were imported into the software for modelling, and cross-pinning was used to simulate pinning. According to the different crossing methods of the upper and lower laminar screws, they are divided into two groups. In the software, the position of the needlepoint of each screw is accurately measured, and the needle point is kept unchanged to simulate the movable range of the screw tail under the condition that the body does not penetrate the cortical bone. The data were compared by grouping and gender. Finally, the guide was designed by combining the screw exit point and fine adjustment angle data of all patients with the centripetal principle of the slide rail. Results The needle exit data L1/L2/L3/L4 were 6.44 ± 0.52 mm, 7.05 ± 0.48 mm, 3.55 ± 0.75 mm and 5.09 ± 0.74 mm, respectively, and the fine adjustment angle of the slide rail was 10.51° ± 0.87°. There was no significant difference between the two groups or between men and women (p > 0.05). Conclusion In this experiment, using the data obtained from the simulation of screw insertion, a two-way slide guide was designed to assist the insertion of axial laminar screws. The guide locks the screw outlet point to position and guides the screw inlet point, which improves the accuracy and safety of screw placement.

The unique motion styles of flagella and cilia (i.e., planar/helical waveform propulsion of flagella and two-dimensional (2D)/three-dimensional (3D) asymmetric ciliary beating), play a key role in many biological activities and inspire lots of bionic designs, especially miniature robotic systems. However, quite different to the fact in nature that microorganisms can evolve diverse motions from the homologous bio-structure (9 + 2 axoneme structure), current bionics can still not find an effective engineering solution to achieve such wisdom. Herein, by investigating the inner structure of flagella/cilia and their intrinsic driven mechanisms, we derive a unified physical model to describe the microtubules’ bending and the constructed external motions. Then, we propose a three-channel based tubular actuation concept and correspondingly fabricate an actuator via a rod-embedded casting process. By sequencing the actuation of each channel, our design can not only reproduce the diverse 2D/3D flagellar/ciliary motility in nature, but also extrapolate a variety of symmetry-breaking ciliary beating modes for effective propulsion at low Reynolds number. This study deepens our understanding of the propulsion mechanism of microorganisms and provides new inspirations for the design of biomimetic systems, which may find significant applications in a wide spectrum of engineering fields.

Abstract Background Cas12a (formerly known as Cpf1), the class II type V CRISPR nuclease, has been widely used for genome editing in mammalian cells and plants due to its distinct characteristics from Cas9. Despite being one of the most robust Cas12a nucleases, LbCas12a in general is less efficient than SpCas9 for genome editing in human cells, animals, and plants. Results To improve the editing efficiency of LbCas12a, we conduct saturation mutagenesis in E. coli and identify 1977 positive point mutations of LbCas12a. We selectively assess the editing efficiency of 56 LbCas12a variants in human cells, identifying an optimal LbCas12a variant (RVQ: G146R/R182V/E795Q) with the most robust editing activity. We further test LbCas12a-RV, LbCas12a-RRV, and LbCas12a-RVQ in plants and find LbCas12a-RV has robust editing activity in rice and tomato protoplasts. Interestingly, LbCas12a-RRV, resulting from the stacking of RV and D156R, displays improved editing efficiency in stably transformed rice and poplar plants, leading to up to 100% editing efficiency in T 0 plants of both plant species. Moreover, this high-efficiency editing occurs even at the non-canonical TTV PAM sites. Conclusions Our results demonstrate that LbCas12a-RVQ is a powerful tool for genome editing in human cells while LbCas12a-RRV confers robust genome editing in plants. Our study reveals the tremendous potential of these LbCas12a variants for advancing precision genome editing applications across a wide range of organisms.

Mechanisms of sleep remain elusive. Here, authors developed mouse sleep fMRI based on simultaneous electrophysiology and mapped global and sequential state transition patterns, together with global patterns triggered by SWRs in NREM and awake states.

Abstract Objectives This study aimed to explore differences between psychological resilience and problem-solving ability in grade one junior middle school adolescents with and without suicidal ideation, focusing on the relationship between these factors and suicidal ideation. Methods Ninety-nine adolescents (aged 10 to 14) were divided into Suicidal Ideation (SI, n = 49) and Non-Suicidal Ideation (NSI, n = 50) grouped by the Self-rating Idea of Suicide Scale (SIOSS). The Psychological Resilience Scale (PRS) and Tower of Hanoi task (TOH) were applied to assess psychological resilience and problem-solving ability, respectively. Results The SI group scored significantly lower than the NSI group on PRS (p

AgNbO3 has a potential for high power capacitors due to its antiferroelectric characteristics. Here, the authors achieve multilayer capacitors with energy-storage density of 14 J·cm−3 by heterovalent-doping-enabled atom-displacement fluctuation.

Abstract Metastable ε-Fe2O3 was discovered on a ceramic ware of Deqing kiln of the Tang Dynasty, which coexists with α-Fe2O3 in the brown area between adjacent black glaze areas, and it is the earliest known artificially synthesized ε-Fe2O3. Based on the composition analysis of α-Fe2O3, ε-Fe2O3 and the glass phase around them, it is speculated that some Fe3+ ions were replaced by Al3+ ions during the formation of ε-Fe2O3, and a relatively low CaO content may be required for its crystallization. This work may promote researchers' understanding of ε-Fe2O3 crystals, and provide clues for the artificial synthesis of large ε-Fe2O3 crystals.

The work in this paper is applied to the Zhangbei Power grid. In the flexible direct current (DC) power system, the fault current rises extremely fast when a DC fault occurs. The requirements for the peak of breaking current and fault energy absorption of DC circuit breakers (DCCBs) increase linearly, which significantly increases the cost of the equipment. Therefore, in order to reduce the design difficulty of DCCBs, this paper proposes a strategy to control energy after the fault occurs. Firstly, the energy dimension is added on the basis of the traditional vector control of MMC, which constitutes a three-dimensional energy direct control. Subsequently, the architectures of energy fluctuation control and feedforward control are proposed. The influencing mechanisms for the peak fault current, peak fault voltage and energy dissipation are analyzed. Finally, the simulation of energy fluctuation control and feedforward control is constructed on PSCAD/EMTDC. The simulation results show that the energy fluctuation control is obviously better than the conventional three-dimensional energy control, and the feedforward energy control is further improved on this basis. Compared with the conventional vector control, the peak energy is reduced by 45.43% and the peak current is reduced by 25.39%, which helps to simplify the equipment design and reduce the equipment cost.

Long-term, automated fish detection provides invaluable data for deep-sea aquaculture, which is crucial for safe and efficient seawater aquafarming. In this paper, we used an infrared camera installed on a deep-sea truss-structure net cage to collect fish images, which were subsequently labeled to establish a fish dataset. Comparison experiments with our dataset based on Faster R-CNN as the basic objection detection framework were conducted to explore how different backbone networks and network improvement modules influenced fish detection performances. Furthermore, we also experimented with the effects of different learning rates, feature extraction layers, and data augmentation strategies. Our results showed that Faster R-CNN with the EfficientNetB0 backbone and FPN module was the most competitive fish detection network for our dataset, since it took a significantly shorter detection time while maintaining a high AP50 value of 0.85, compared to the best AP50 value of 0.86 being achieved by the combination of VGG16 with all improvement modules plus data augmentation. Overall, this work has verified the effectiveness of deep learning-based object detection methods and provided insights into subsequent network improvements.

Accurate 3D localization of the mandibular canal is crucial for the success of digitally-assisted dental surgeries. Damage to the mandibular canal may result in severe consequences for the patient, including acute pain, numbness, or even facial paralysis. As such, the development of a fast, stable, and highly precise method for mandibular canal segmentation is paramount for enhancing the success rate of dental surgical procedures. Nonetheless, the task of mandibular canal segmentation is fraught with challenges, including a severe imbalance between positive and negative samples and indistinct boundaries, which often compromise the completeness of existing segmentation methods. To surmount these challenges, we propose an innovative, fully automated segmentation approach for the mandibular canal. Our methodology employs a Transformer architecture in conjunction with cl-Dice loss to ensure that the model concentrates on the connectivity of the mandibular canal. Additionally, we introduce a pixel-level feature fusion technique to bolster the model’s sensitivity to fine-grained details of the canal structure. To tackle the issue of sample imbalance and vague boundaries, we implement a strategy founded on mandibular foramen localization to isolate the maximally connected domain of the mandibular canal. Furthermore, a contrast enhancement technique is employed for pre-processing the raw data. We also adopt a Deep Label Fusion strategy for pre-training on synthetic datasets, which substantially elevates the model’s performance. Empirical evaluations on a publicly accessible mandibular canal dataset reveal superior performance metrics: a Dice score of 0.844, click score of 0.961, IoU of 0.731, and HD95 of 2.947 mm. These results not only validate the efficacy of our approach but also establish its state-of-the-art performance on the public mandibular canal dataset.

Background Higher social support protects people from developing mental disorders. Limited evidence is available on the mechanism through which social support plays this protective role.Objective To investigate the stress-buffering process of social support on depressive symptoms using a novel longitudinal dynamic symptom network approach.Methods A total of 4242 adult participants who completed the first two waves (from May to October 2020) of the International Covid Mental Health Survey were included in the study. Cross-lagged panel network modelling was used to estimate a longitudinal network of self-reported social support, loneliness and depressive symptoms. Standardised regression coefficients from regularised cross-lagged regressions were estimated as edge weights of the network.Findings The results support a unidirectional protective effect of social support on key depressive symptoms, partly mediated through loneliness: A higher number of close confidants and accessible practical help was associated with decreased anhedonia (weight=−0.033) and negative self-appraisal symptoms (weight=−0.038). Support from others was also negatively associated with loneliness, which in turn associated with decreased depressed mood (weight=0.086) and negative self-appraisal (weight=0.077). We identified a greater number of direct relationships from social support to depressive symptoms among men compared with women. Also, the edge weights from social support to depression were generally stronger in the men’s network.Conclusions Reductions in negative self-appraisal might function as a bridge between social support and other depressive symptoms, and, thus, it may have amplified the protective effect of social support. Men appear to benefit more from social support than women.Clinical implications Building community-based support networks to deliver practical support, and loneliness reduction components are critical for depression prevention interventions after stressful experiences.

Summary: The purpose of the present study was to examine the effects of 6 weeks of 40-, 60-, or 80-cm drop jump (DJ) training on lower limb explosive and change of direction (CoD) performance in collegiate Sanda athletes. Repeated-measure ANOVA revealed that there was a significant group × time interaction for standing long jump test (p = 0.006), counter movement jump test (p = 0.026), Illinois agility test (p = 0.003), square test (p = 0.018), Nebraska test (p = 0.027), t test (p = 0.032), and hexagon test (p = 0.012) due to the best performance observed at post-test compared with pre-test for DJ60 (effect size = 0.89–2.89), and the improvement was higher than that of the other groups. These findings suggest that 6 weeks of DJ training could improve the lower limb explosive and CoD performance in collegiate Sanda athletes and that 60 cm may be the optimal drop height.

ABSTRACT Rabies kills more than 59,000 people annually, mainly in developing countries. Previous studies on the evolution and distribution of rabies viruses (RABVs) were scattered. Here, we explore the evolution and distribution of this deadly virus from a novel panorama view. Multiple bioinformatic software tools were employed to analyze the phylogenetic diversity, evolution, spatiotemporal, and distribution of RABVs. The analyses were based on 1,202 qualified full-length genomes of RABVs and numerous literatures. Of the 10 distinct phylogenetic clades of RABV that we identified, more frequent intra- and inter-clade recombination occurs in the sequences of Asian-SEA, Arctic, and Cosmopolitan clades isolated from China, while according to existing sequence information, RABV might originate from bats (posterior probability, PP = 0.75, PP = 0.60 inferred from N and L genes, separately) in North America (PP = 0.57, PP = 0.62 inferred from N and L genes, separately). Due to the difference in evolutionary rate of N (2.22 × 10−4 subs/site/year, 95% HPD 1.99–2.47 × 10−4 subs/site/year) and L genes (1.67 × 10−4 subs/site/year, 95% HPD 1.59–1.74 × 10−4 subs/site/year), the root age was 1,406.6 (95% HPD 1,291.2–1,518.2) and 1,122.7 (95% HPD 1,052.4–1,193.9) inferred from N and L genes, separately. Among other findings, Mephitidae plays an important role in the interspecific transmission and communication of RABV, which we found tends to spread to populations genetically proximate to the host. We also identified amino acids under positive selection in different genes of different clades as well as single nucleotide variation sites important for different lineages. IMPORTANCE Rabies virus is widely distributed all over the world, and wild animals are its largest potential reservoir. Our study offers a panorama view about evolution and distribution of rabies viruses and emphasizes the need to monitor the transmission dynamics of animal rabies.

Cas12a, also known as Cpf1, is a highly versatile CRISPR-Cas enzyme that has been widely used in genome editing. Unlike its well-known counterpart, Cas9, Cas12a has unique features that make it a highly efficient genome editing tool at AT-rich genomic regions. To enrich the CRISPR-Cas12a plant genome editing toolbox, we explored 17 novel Cas12a orthologs for their genome editing capabilities in plants. Out of them, Ev1Cas12a and Hs1Cas12a showed efficient multiplexed genome editing in rice and tomato protoplasts. Notably, Hs1Cas12a exhibited greater tolerance to lower temperatures. Moreover, Hs1Cas12a generated up to 87.5% biallelic editing in rice T0 plants. Both Ev1Cas12a and Hs1Cas12a achieved effective editing in poplar T0 plants, with up to 100% of plants edited, albeit with high chimerism. Taken together, the efficient genome editing demonstrated by Ev1Cas12a and Hs1Cas12a in both monocot and dicot plants highlights their potential as promising genome editing tools in plant species and beyond.

Introduction Post-tuberculosis lung damage (PTLD) refers to the residual pulmonary impairment following the completion of antituberculosis (TB) therapy, characterised by persistent respiratory symptoms and abnormal pulmonary function. The risk factors and biomarkers for PTLD have been scarcely investigated. More importantly, whether and to what extent cigarette smoking is involved in PTLD remain to be known.Methods and analysis This prospective observational study will enrol 400 male smoking or non-smoking patients aged 25–65 years, with newly confirmed active TB between 2022 and 2024, from the Department of Respiratory and Critical Care Medicine at Peking University Third Hospital and the Tuberculosis Department at Beijing Geriatric Hospital. Because females rarely smoke in China, we will enrol only males in this study. Demographic data, smoking history and amount, clinical symptoms, lung function, and chest CT findings will be prospectively collected. Respiratory questionnaires, lung function measurements and chest CT examinations will be performed immediately after, and 1 year, 2 years and 3 years after the completion of TB treatment. Peripheral blood samples will be obtained at baseline and at the end of anti-TB therapy, and a Luminex xMAP-based multiplex immunoassay will be used to measure inflammatory mediators and cytokines in serum. The collected data will be analysed to determine the incidence and factors/biomarkers of PTLD according to smoking status.Ethics and dissemination The study was approved by the Ethics Committee of Peking University Third Hospital (approval number: (2022)271-03; approval date: 8 June 2022). The research results will be disseminated through scientific and medical conferences and will be published in an academic journal.Trial registration number NCT04966052.

Sheath currents in high voltage cable circuits have proven to be one of the most convenient indicators for assessing cable health. The sheath currents are regularly distributed with fluctuation in a certain range under normal conditions, while the principle of distribution characteristics is still unclear when the cross-bonded grounding system of the cable circuit is abnormal. This paper classifies the common defects of grounding system into three types of circuit topologies and analyzes the correspondence between grounding system conditions and sheath currents. A fault diagnosis method is proposed to detect irregular distribution of sheath currents by quantifying the difference of sheath currents in each of the minor sections and the average currents of each sheath loop. Sensitive analyses are provided to evaluate the criteria, clarifying the influence of fault resistance in each defect. The results show that the method can be very effective when the ratio of the fault resistance to the earth resistance is less than 7.6 for a short-circuit defect in metallic sheath, or less than 1.2 for a short-circuit defect between metallic sheath and ground. The performance of the method is also shown to be very efficient by evaluation with the data collected on site.

Training a high-quality image classification model often requires a large number of labeled datasets. However, in real-world business scenarios or production environments, the cost of obtaining labeled samples can be prohibitively high. Therefore, finding ways to obtain valuable labeled data at a lower cost is essential to improve the effectiveness of the algorithm. In this paper, we propose an effective and novel image selection strategy for active learning called Competence-based Active Learning. Our approach selects informative source images to strengthen the model’s generalization ability while minimizing the cost of manual labeling. Our experiments on MNIST, FashionMNIST, CIFAR10, and CIFAR100 demonstrate that our selection approach outperforms random selection and conventional selection methods. Moreover, Competence-based Active Learning not only enhances the generalization ability of the model but also reduces the training time.

In this paper, it is proved that every pair of large positive even integers satisfying some necessary conditions can be represented in the form of a pair of eight cubes of primes and 287 powers of 2. This improves the previous result.

Research has shown that long-chain noncoding RNAs (lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury.

Abstract Previous studies have shown that aerobic exercise is an effective way to improve symptoms of Parkinson’s disease (PD). The aim of this study [PROSPERO CRD42022340730] was to explore the effects of aerobic exercises on balance, gait, motor function, and quality of life in PD patients. Searches were performed in PubMed, Web of Science, and EBSCO electronic databases. The Cochrane risk assessment tool was used to evaluate the methodological quality of the included literature. From 1287 search records initially identified, 20 studies were considered eligible for systematic review and meta-analysis. There was a significant effect of aerobic exercise on improving timed up and go test [standardized mean difference (SMD), −0.41 (95% CI, −0.61 to −0.22), p

Abstract Background Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown. Results We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma. Conclusion INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.

Walnut (Juglans regia L.) is a good source of lipids and polyunsaturated fatty acids (PUFAs). In order to explore the biosynthesis molecular mechanism of oil accumulation and fatty acid (FA) synthesis in walnut, the samples at different development periods of three walnut cultivars, ‘Zhipi’ (ZP), ‘Xinwu 417’ (W417) and ‘Xinwen 81’ (W81) were collected for transcriptomic analysis. The analysis of oil accumulation and FA profiles showed that the oil content in mature walnut kernel was nearly 70 %, and over 90 % of FAs were PUFAs. We identified 126 candidate genes including 64 genes for FA de novo synthesis, 45 genes for triacylglycerol assembly, and 17 genes for oil bodies involved in lipid biosynthesis by RNA-sequencing. Ten key enzymes including ACCase, LACS6, LACS8, SAD, FAD2, FAD3, LPAAT1, DGAT2, PDAT2, and PLC encoded by 19 genes were highly associated with lipid biosynthesis. Quantitative PCR analysis further validated 9 important genes, and the results were well consistent with our transcriptomic data. Finally, 5 important transcription factors including WRI1, ABI3, FUS3, PKL and VAL1 were identified, and their main regulatory genes might contain ACCase, KASⅡ, LACS, FAD3 and LPAAT which were determined through correlation analysis of expression levels for 27 walnut samples. These findings will provide a comprehensive understanding and valuable information on the genetic engineering and molecular breeding in walnut.

The goal of the research was to find alternative protein sources for animal farming that are efficient and cost-effective. The researchers focused on distillers dried grains with solubles (DDGS), a co-product of bioethanol production that is rich in protein but limited in its use as a feed ingredient due to its high non-starch polysaccharides (NSPs) content, particularly for monogastric animals. The analysis of the Paenibacillus pabuli E1 genome revealed the presence of 372 genes related to Carbohydrate-Active enzymes (CAZymes), with 98 of them associated with NSPs degrading enzymes that target cellulose, hemicellulose, and pectin. Additionally, although lignin is not an NSP, two lignin-degrading enzymes were also examined because the presence of lignin alongside NSPs can hinder the catalytic effect of enzymes on NSPs. To confirm the catalytic ability of the degrading enzymes, an in vitro enzyme activity assay was conducted. The results demonstrated that the endoglucanase activity reached 5.37 U/mL, while beta-glucosidase activity was 4.60 U/mL. The filter paper experiments did not detect any reducing sugars. The xylanase and beta-xylosidase activities were measured at 11.05 and 4.16 U/mL, respectively. Furthermore, the pectate lyase and pectin lyase activities were found to be 8.19 and 2.43 U/mL, respectively. The activities of laccase and MnP were determined as 1.87 and 4.30 U/mL, respectively. The researchers also investigated the effect of P. pabuli E1 on the degradation of NSPs through the solid-state fermentation of DDGS. After 240 h of fermentation, the results showed degradation rates of 11.86% for hemicellulose, 11.53% for cellulose, and 8.78% for lignin. Moreover, the crude protein (CP) content of DDGS increased from 26.59% to 30.59%. In conclusion, this study demonstrated that P. pabuli E1 possesses various potential NSPs degrading enzymes that can effectively eliminate NSPs in feed. This process improves the quality and availability of the feed, which is important for animal farming as it seeks alternative protein sources to replace traditional nutrients.

Background: There is no clear agreement regarding the ideal rest interval and training intensity to optimize post-activation performance enhancement (PAPE) after barbell squat (BS). Therefore, the aim of this study was to investigate the effects of rest interval and training intensity on jumping performance due to PAPE.Methods: Searches were performed in PubMed, Web of Science, and EBSCO databases. We included studies that satisfied the following criteria: (1) eligible studies should be randomized controlled trials; (2) eligible studies should investigate the acute effect of barbell squat-induced PAPE on jump performance; (3) eligible studies should use countermovement jump, squat jump, or vertical jump as the outcome measure.Results: From 2518 search records initially identified, 19 studies were eligible for meta-analysis. Our meta-analysis results showed that BS had no significant effect on improving jumping performance due to PAPE (Cohen’s d = 0.09, p = 0.08). Subgroup analysis showed that rest interval between 0–1 min was detrimental to jumping performance (Cohen’s d = −0.33, p < 0.01), while rest intervals between 4–7 min (Cohen’s d = 0.31, p < 0.01) and 8-9 min (Cohen’s d = 0.26, p = 0.02) provided favorable jumping performance outcomes. In addition, low-intensity and moderate-intensity BS had no significant effect on jump performance, while high-intensity BS showed results consistent with rest interval.Conclusion: Our study indicated that both low-intensity and moderate-intensity BS failed to induce PAPE, and it is recommended that future studies use high-intensity BS to induce PAPE. A rest interval of 4–9 min had a beneficial impact on jump height, and an interval range of 4–7 min seems to be the best rest interval between conditioning activity and jumping performance.

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR) nucleases like Cas9 and Cas12a are revolutionizing plant basic research and crop breeding. A major advantage of CRISPR over earlier nucleases systems is its capability of multiplexed genome editing. However, it remains unknown about the potential off‐target effects when multiple concurrent DNA double‐strand breaks (DSBs) are induced in a crop genome. Here, we investigated this important question in rice (Oryza sativa) using a highly multiplexed CRISPR‐Cas12a system. With whole‐genome sequencing, we first revealed high genome editing specificity of Mb2Cas12a and protospacer adjacent motif promiscuity of LbCas12a. We discovered large chromosomal rearrangement events in edited rice plants that endured many (e.g., >50) simultaneous DSBs, but not in plants that endured lower order DSBs (e.g.,

The available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-treated rats) and observed an immediate (within seconds to minutes) alleviation of depressive-like symptoms with a high-response rate. Simultaneous functional MRI (fMRI) conducted on the same sets of depressive rats used in behavioral tests revealed DBS-induced activation of multiple regions in afferent and efferent circuitry of the LHb. The activation levels of brain regions connected to the medial LHb (M-LHb) were correlated with the extent of behavioral improvements. Rats with more medial stimulation sites in the LHb exhibited greater antidepressant effects than those with more lateral stimulation sites. These results indicated that the antidromic activation of the limbic system and orthodromic activation of the monoaminergic systems connected to the M-LHb played a critical role in the rapid antidepressant effects of LHb-DBS. This study indicates that M-LHb-DBS might act as a valuable, rapid-acting antidepressant therapeutic strategy for treatment-resistant depression and demonstrates the potential of using fMRI activation of specific brain regions as biomarkers to predict and evaluate antidepressant efficacy.

An ad hoc calculation is presented to interpret the growth of sideband waves during lower hybrid current drive (LHCD) experiments on Experimental Advanced Superconducting Tokamak (EAST). We adopt the solution of the non-linear dispersion relation for parametric instabilities to describe the growth rate of ion cyclotron quasi-modes (ICQMs) in the peripheral plasma, and use the WKB solution of the propagation of electrostatic waves in two dimensions to model the variation of the electric field in the scrape-off-layer (SOL). We then calculate the growth rates and amplification factors of the sideband waves associated with ICQM in the parallel and perpendicular coupling limits. The onset and substantial growth of the first down-shifted sideband of lower hybrid waves (LHWs) are associated with elevation of the plasma density in the outer SOL where the growth rate of ICQM in the parallel coupling limit increases sharply after the density is elevated. The peak frequencies associated with the first harmonic of ICQM obtained from calculating the amplification factors in the parallel coupling limit ( ${A_{{\text{para}}}}$ ) agree very well with the observed frequencies of the first down-shifted sideband of 2.45 GHz LHWs in EAST pulse 43 772 and 86 521. The consistency between the calculation and the observation indicates that the sideband waves are associated with parametric decay instability of ICQM excited in the outer SOL through parallel coupling. The amplitude of ${A_{{\text{para}}}}$ obtained from a single pass of LHWs through the SOL of EAST is, however, one order of magnitude smaller than unity, meaning that it remains elusive whether the substantial growth of sideband waves mainly occurs in front of the antenna or requires multiple passes of LHWs across the SOL region.

The long-term presence of PPCPs in the aqueous environment poses a potentially significant threat to human life and physical health and the safety of the water environment. In our previous work, we investigated low-cost pitch-based HCP adsorbents with an excellent adsorption capacity and magnetic responsiveness through a simple one-step Friedel–Crafts reaction. In this work, we further investigated the adsorption behavior of the prepared pitch-based adsorbents onto three PPCP molecules (DFS, AMP, and antipyrine) in detail. The maximum adsorption capacity of P-MPHCP for DFS was 444.93 mg g−1. The adsorption equilibrium and kinetic processes were well described through the Langmuir model and the proposed secondary kinetic model. The negative changes in Gibbs free energy and enthalpy reflected that the adsorption of HCPs onto PPCPs was a spontaneous exothermic process. The recoverability results showed that the adsorption of MPHCP and P-MPHCP onto DFS remained above 95% after 10 adsorption–desorption cycles. The present work further demonstrates that these pitch-based adsorbents can be used for multiple applications, which have a very extensive practical application prospect.

The compound surfactant system has considerable development prospects for improving oil recovery. A synergistic effect can be achieved through the orderly arrangement of the two surfactants on the interface, which can make up for the performance defects of a single surfactant. In this paper, the effects of the number of propylene oxides (PO) in composite surfactants on interfacial tension and emulsion stability were systematically studied. The results showed that the solubility of composite surfactants was significantly improved under high-salinity conditions by adding anionic–nonionic surfactants to a single anionic surfactant. The interfacial tension of composite surfactants shows a V-shaped change of first decreasing and then increasing with the increase in PO groups. As the number of PO groups increases, the emulsion first increases and then decreases. Among the series of composite surfactants, LBAS/C12PO10S has the lowest interfacial tension, reaching the order of 10−3 mN/m, and the emulsion formed by it exhibits superior stability. This indicates that the synergistic effect of the two surfactants can be improved by adjusting the number of PO groups. Furthermore, the LBAS/C12PO10S composite system can be mixed with crude oil to form Winsor III microemulsion, which has great potential for application in enhanced oil recovery via chemical flooding.

Abstract Essential tremor (ET) is the most common movement disorder and share overlapping symptoms with Parkinson’s disease (PD), making differential diagnosis challenging. Gut dysbiosis is regarded crucial in the pathogenesis of PD. Since ET patients also has comorbidity in gastrointestinal disorders, the relationship between gut microbiota and ET really worth investigating and may help distinguishing ET from PD. Fecal samples from 54 ET, 67 de novo PD and 54 normal controls (NC) were collected for 16S ribosomal RNA gene sequencing and quantitative real-time PCR. ET showed lower species richness (Chao1 index) than NC and PD. ET was with Bacteroides-dominant enterotype, while PD was with Ruminococcus-dominant enterotype. Compared with NC, 7 genera were significantly reduced in ET, 4 of which (Ruminococcus, Romboutsia, Mucispirillum, and Aeromonas) were identified to be distinctive with an area under the curve (AUC) of 0.705. Compared to PD, 26 genera were found significantly different from ET, 4 of which (Bacteroides, Fusobacterium, Phascolarctobacterium, and Lachnospira) were found distinguishable with an AUC of 0.756. Clinical association results indicated that Proteus was associated with disease severity (TETRAS) of ET, while Klebsiella was linked to depression and anxiety in ET. Functional predictions revealed that 4 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were altered in ET. This study reveals gut dysbiosis in ET and it provides new insight into the pathogenesis of ET and helps distinguishing ET from PD.

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain. Cite this article: Bone Joint Res 2022;11(7):439–452.

Abstract Background Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types. In this study, we explored super-enhancer profiling through ChIP-Seq analysis of AML samples and AML cell lines, followed by functional analysis. Methods ChIP-seq analysis for H3K27ac was performed in 11 AML samples, 7 T-ALL samples, 8 B-ALL samples, and in NB4 cell line. Genes and pathways affected by GNE-987 treatment were identified by gene expression analysis using RNA-seq. One of the genes associated with super-enhancer and affected by GNE-987 treatment was LYL1 basic helix-loop-helix family member (LYL1). shRNA mediated gene interference was used to down-regulate the expression of LYL1 in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Results We identified a total of 200 genes which were commonly associated with super-enhancers in ≧10 AML samples, and were found enriched in regulation of transcription. Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells. Moreover, 20 candidate genes were selected by super-enhancer profile and gene expression profile and among which LYL1 was observed to promote cell growth and survival in human AML cells. Conclusions In summary, we identified 200 common super-enhancer-associated genes in AML samples, and a series of those genes are cancer genes. We also found GNE-987 treatment downregulates the expression of super-enhancer-associated genes in AML cells, including the expression of LYL1. Further functional analysis indicated that LYL1 is required for AML cell growth and survival. These findings promote understanding of AML pathophysiology and elucidated an important role of LYL1 in AML progression.

A challenge for developing acoustic metamaterials (AMMs) is considering the application of broadband muffling and load bearing capacity simultaneously. In this paper, a honeycomb based graded AMM muffler is proposed, which can widen the attenuation band and improve the structural stiffness without any external device by means of integrated design. Firstly, the acoustic and mechanical characteristics of the muffler unit cell are theoretically and numerically studied, and the graded muffler is designed based on these characteristics. The numerical results show that the graded muffler widens the attenuation bandwidth of the unit cell, and the simulation also shows that the graded muffler has greater stiffness than the uniform one. The stiffness driven muffler provides new possibilities for the design of advanced metamaterial with simultaneous sound insulation and load bearing performances.

Abstract Background Medulloblastoma (MB) is the most common malignant brain tumor in children. Approximately one-third of MB patients remain incurable. Understanding the molecular mechanism of MB tumorigenesis is, therefore, critical for developing specific and effective treatment strategies. Our previous work demonstrated that astrocytes constitute the tumor microenvironment (TME) of MB and play an indispensable role in MB progression. However, the underlying mechanisms by which astrocytes are regulated and activated to promote MB remain elusive. Methods By taking advantage of Math1-Cre/Ptch1 loxp/loxp mice, which spontaneously develop MB, primary MB cells and astrocytes were isolated and then subjected to administration and coculture in vitro. Immunohistochemistry was utilized to determine the presence of C3a in MB sections. MB cell proliferation was evaluated by immunofluorescent staining. GFAP and cytokine expression levels in C3a-stimulated astrocytes were assessed by immunofluorescent staining, western blotting, q-PCR and ELISA. C3a receptor and TNF-α receptor expression was determined by PCR and immunofluorescent staining. p38 MAPK pathway activation was detected by western blotting. Transplanted MB mice were treated with a C3a receptor antagonist or TNF-α receptor antagonist to investigate their role in MB progression in vivo. Results We found that complement C3a, a fragment released from intact complement C3 following complement activation, was enriched in both human and murine MB tumor tissue, and its receptor was highly expressed on tumor-associated astrocytes (TAAs). We demonstrated that C3a activated astrocytes and promoted MB cell proliferation via the p38 MAPK pathway. Moreover, we discovered that C3a upregulated the production of proinflammatory cytokines, such as IL-6 and TNF-α in astrocytes. Application of the conditioned medium of C3a-stimulated astrocytes promoted MB cell proliferation, which was abolished by preincubation with a TNF-α receptor antagonist, indicating a TNF-α-dependent event. Indeed, we further demonstrated that administration of a selective C3a receptor or TNF-α receptor antagonist to mice subcutaneously transplanted with MB suppressed tumor progression in vivo. Conclusions C3a was released during MB development. C3a triggered astrocyte activation and TNF-α production via the p38 pathway, which promoted MB cell proliferation. Our findings revealed the novel role of C3a-mediated TNF-α production by astrocytes in MB progression. These findings imply that targeting C3a and TNF-α may represent a potential novel therapeutic approach for human MB.