Plexin B3 guides axons to cross the midline in vivo.

During the development of neural circuits, axons are guided by a variety of molecular cues to navigate through the brain and establish precise connections with correct partners at the right time and place. Many axon guidance cues have been identified and they play pleiotropic roles in not only axon guidance but also axon fasciculation, axon pruning, and synaptogenesis as well as cell migration, angiogenesis, and bone formation. In search of receptors for Sema3E in axon guidance, we unexpectedly found that Plexin B3 is highly expressed in retinal ganglion cells of zebrafish embryos when retinal axons are crossing the midline to form the chiasm. Plexin B3 has been characterized to be related to neurodevelopmental disorders. However, the investigation of its pathological mechanisms is hampered by the lack of appropriate animal model. We provide evidence that Plexin B3 is critical for axon guidance in vivo. Plexin B3 might function as a receptor for Sema3E while Neuropilin1 could be a co-receptor. The intracellular domain of Plexin B3 is required for Semaphorin signaling transduction. Our data suggest that zebrafish could be an ideal animal model for investigating the role and mechanisms of Sema3E and Plexin B3 in vivo.

Design, Synthesis and Biological Evaluation of Novel Phenyl-Substituted Naphthoic Acid Ethyl Ester Derivatives as Strigolactone Receptor Inhibitor.

Strigolactones (SLs) are plant hormones that regulate several key agronomic traits, including shoot branching, leaf senescence, and stress tolerance. The artificial regulation of SL biosynthesis and signaling has been considered as a potent strategy in regulating plant architecture and combatting the infection of parasitic weeds to help improve crop yield. DL1b is a previously reported SL receptor inhibitor molecule that significantly promotes shoot branching. Here, we synthesized 18 novel compounds based on the structure of DL1b. We performed rice tillering activity assay and selected a novel small molecule, C6, as a candidate SL receptor inhibitor. In vitro bioassays demonstrated that C6 possesses various regulatory functions as an SL inhibitor, including inhibiting germination of the root parasitic seeds Phelipanche aegyptiaca, delaying leaf senescence and promoting hypocotyl elongation of Arabidopsis. ITC analysis and molecular docking experiments further confirmed that C6 can interact with SL receptor proteins, thereby interfering with the binding of SL to its receptor. Therefore, C6 is considered a novel SL receptor inhibitor with potential applications in plant architecture control and prevention of root parasitic weed infestation.

Ultrafast restricted intramolecular rotation in molecules with aggregation induced emission.

In this work, the ultrafast intramolecular rotation behavior of 1,1,2,3,4,5-hexaphenylsilole has been investigated in several solutions with different viscosities using femtosecond transient absorption spectroscopy combined with density functional theory and time-dependent density functional theory calculations. It is demonstrated that the nonradiative process, which competes with radiative decay, involves two main stages, namely the restricted intramolecular rotation and internal conversion processes. The intramolecular rotation depends on viscosity and presents a significant restriction. The restricted rotational rate is determined to be dozens of picoseconds. The following nonradiative process is strongly dominated by intramolecular rotation. The nonradiative decay rate will decrease with the increase in viscosity, leading to a rise in the radiative probability and photoluminous yield. These results have borne out the mechanism of ultrafast restricted intramolecular rotation of aggregation induced emission and provided a detailed photophysical picture of nonradiative processes.

Steering Selectivity in Electrocatalytic Furfural Reduction via Electrode-Electrolyte Interface Modification.

Electrocatalytic reduction of biomass-derived furfural (FF) represents a sustainable route to produce furfuryl alcohol (FA) and 2-methylfuran (MF) as a value-added chemical and a biofuel, respectively. However, achieving high selectivity for MF as well as tuning the selectivity between FA and MF within one reaction system remain challenging. Herein, we have reported an electrode-electrolyte interface modification strategy, enabling FA and MF selectivity steering under the same reaction conditions. Specifically, by modifying copper (Cu) electrocatalysts with butyl trimethylammonium bromide (BTAB), we achieved a dramatic shift in selectivity from producing FA (selectivity: 83.8%; Faradaic efficiency, FE: 68.9%) to MF (selectivity: 80.1%; FE: 74.8%). We demonstrated that BTAB adsorption over Cu modulates the electrical double layer (EDL) structure, which repels interfacial water and weakens the hydrogen-bond (H-bond) network for proton transfer, thus impeding FF-to-FA conversion by suppression of the hydrogen atom transfer (HAT) process. On the contrary, FF-to-MF conversion was less affected. This work shows the potential of engineering of the electrode-electrolyte interface for selectivity control in electrocatalysis.

Two-Point Localization Algorithm of a Magnetic Target Based on Tensor Geometric Invariant.

Currently, magnetic gradient tensor-based localization methods face challenges such as significant errors in geomagnetic field estimation, susceptibility to local optima in optimization algorithms, and inefficient performance. In addressing these issues, this article propose a two-point localization method under the constraint of overlaying geometric invariants. This method initially establishes the relationship between the target position and the magnetic gradient tensor by substituting an intermediate variable for the magnetic moment. Exploiting the property of the eigenvector corresponding to the minimum absolute eigenvalue being perpendicular to the target position vector, this constraint is superimposed to formulate a nonlinear system of equations of the target's position. In the process of determining the target position, the Nara method is employed for obtaining the initial values, followed by the utilization of the Levenberg-Marquardt algorithm to derive a precise solution. Experimental validation through both simulations and experiments confirms the effectiveness of the proposed method. The results demonstrate its capability to overcome the challenges faced by a single-point localization method in the presence of some errors in geomagnetic field estimation. In comparison to traditional two-point localization methods, the proposed method exhibits the highest precision. The localization outcomes under different noise conditions underscore the robust noise resistance and resilience of the proposed method.

Substrate-Selective Catalysis Enabled Synthesis of Azaphilone Natural Products.

Achieving substrate-selectivity is a central element of nature's approach to synthesis. By relying on the ability of a catalyst to discriminate between components in a mixture, control can be exerted over which molecules will move forward in a synthesis. This approach can be powerful when realized but can be challenging to duplicate in the laboratory. In this work, substrate-selective catalysis is leveraged to discriminate between two intermediates that exist in equilibrium, subsequently directing the final cyclization to arrive at either the linear or angular tricyclic core common to subsets of azaphilone natural products. By using a flavin-dependent monooxygenase (FDMO) in sequence with an acyl transferase (AT), the conversion of several orcinaldehyde substrates directly to the corresponding linear tricyclic azaphilones in a single reaction vessel was achieved. Further, mechanistic studies support that a substrate equilibrium together with enzyme substrate selectivity play an import role in the selectivity of the final cyclization step. Using this strategy, five azaphilone natural products were synthesized for the first time as well as a number of unnatural derivatives thereof.

MV-SHIF: Multi-view symmetric hypothesis inference fusion network for emotion-cause pair extraction in documents.

Emotion-cause pair extraction (ECPE) is a challenging task that aims to automatically identify pairs of emotions and their causes from documents. The difficulty of ECPE lies in distinguishing valid emotion-cause pairs from many irrelevant ones. Most previous methods have primarily focused on utilizing multi-task learning to extract semantic information solely from documents without explicitly encoding the relations between clauses. We propose a new approach that incorporates textual entailment paradigm aiming to infer the entailment relationship between the original document as the premise and the clauses or pairs described as the hypothesis. Our approach designs label-view hypothesis templates to improve ECPE by filtering out irrelevant emotion and cause clauses. Furthermore, we formulate candidate emotion-cause pairs as hypothesis statements, and define explicit multi-view symmetric templates to capture the emotion-cause relation semantics. The text entailment recognition for ECPE is finally implemented by fusing multi-view semantic information using a simplified capsule network. Our proposed model achieves state-of-the-art performance on ECPE compared to previous baselines. More importantly, this work demonstrates a novel effective way of applying the textual entailment paradigm to ECPE or clause-level causal discovery by designing multi-view hypothesis inference and information fusion.

The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer.

Background: This study aimed to construct a nomogram based on CAF features to predict the cancer-specific survival (CSS) rates of locally advanced rectal cancer (LARC) patients. Methods: The EPIC algorithm was employed to calculate the proportion of CAFs. based on the differentially expressed genes between the high and low CAF proportion subgroups, prognostic genes were identified via LASSO and Cox regression analyses. They were then used to construct a prognostic risk signature. Moreover, the GSE39582 and GGSE38832 datasets were used for external validation. Lastly, the level of immune infiltration was evaluated using ssGSEA, ESTIMATE, CIBERSORTx, and TIMER. Results: A higher level of CAF infiltration was associated with a worse prognosis. Additionally, the number of metastasized lymph nodes and distant metastases, as well as the level of immune infiltration were higher in the high CAF proportion subgroup. Five prognostic genes (SMOC2, TUBAL3, C2CD4A, MAP1B, BMP8A) were identified and subsequently incorporated into the prognostic risk signature to predict the 1-, 3-, and 5-year CSS rates in the training and validation sets. Differences in survival rates were also determined in the external validation cohort. Furthermore, independent prognostic factors, including TNM stage and risk score, were combined to established a nomogram. Notably, our results revealed that the proportions of macrophages and neutrophils and the levels of cytokines secreted by M2 macrophages were higher in the high-risk subgroup. Finally, the prognostic genes were significantly associated with the level of immune cell infiltration. Conclusion: Herein, a nomogram based on CAF features was developed to predict the CSS rate of LARC patients. The risk model was capable of reflecting differences in the level of immune cell infiltration.

Paeonol can improve hypoxic-induced H9c2 cells injury and ion channel activity by up-regulating the expression of CKIP-1.

BACKGROUND: Paeonol is a representative active ingredient of the traditional Chinese medicinal herbs Cortex Moutan, which has a well-established cardioprotective effect on ischemic heart disease. However, there is little evidence of the protective effect of paeonol, and its pharmacological mechanism is also unclear. This study aims to explore the protective effect and mechanism of Paeonol on myocardial infarction rat and hypoxic H9c2 cells. METHODS: Myocardial ischemia/reperfusion (I/R) was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion, and then gavage with Paeonol for 7 days. H9c2 cells were applied for the in vitro experiments and hypoxia/reoxygenation (H/R) model was established. CKIP-1 expression was evaluated by qPCR and western blot. The expression of genes involved in apoptosis, inflammation and ion channel was measured by western blot. The currents levels of Nav1.5 and Kir2.1 were measured by whole-cell patch-clamp recording. RESULTS: CKIP-1 expression was decreased in H/R-induced H9c2 cells, which was inversely increased after Paeonol treatment. Paeonol treatment could increase the viability of H/R-induced H9c2 cells and diminish the apoptosis and inflammation of H/R-induced H9c2 cells, while si-CKIP-1 treatment inhibited the phenomena. Moreover, the currents levels of Nav1.5 and Kir2.1 were reduced in H/R-induced H9c2 cells, which were inhibited after Paeonol treatment. Intragastric Paeonol can reduce the ventricular arrhythmias in rats with myocardial infarction. CONCLUSIONS: The protective effects of Paeonol on myocardial infarction rats and hypoxic H9c2 cells were achieved by up-regulating CKIP-1.

In Situ Reconstruction of Active Heterointerface for Hydrocarbon Combustion through Thermal Aging over Strontium-Modified Co3O4 Nanocatalyst with Good Sintering Resistance.

The issue of catalyst deactivation due to sintering has gained significant attention alongside the rapid advancement of thermal catalysts. In this work, a simple Sr modification strategy was applied to achieve highly active Co3O4-based nanocatalyst for catalytic combustion of hydrocarbons with excellent antisintering feature. With the Co1Sr0.3 catalyst achieving a 90% propane conversion temperature (T90) of only 289 °C at a w8 hly space velocity of 60,000 mL·g-1·h-1, 24 °C lower than that of pure Co3O4. Moreover, the sintering resistance of Co3O4 catalysts was greatly improved by SrCO3 modification, and the T90 over Co1Sr0.3 just increased from 289 to 337 °C after thermal aging at 750 °C for 100 h, while that over pure Co3O4 catalysts increased from 313 to 412 °C. Through strontium modification, a certain amount of SrCO3 was introduced on the Co3O4 catalyst, which can serve as a physical barrier during the thermal aging process and further formation of Sr-Co perovskite nanocrystals, thus preventing the aggregation growth of Co3O4 nanocrystals and generating new active SrCoO2.52-Co3O4 heterointerface. In addition, propane durability tests of the Co1Sr0.3 catalysts showed strong water vapor resistance and stability, as well as excellent low-temperature activity and resistance to sintering in the oxidation reactions of other typical hydrocarbons such as toluene and propylene. This study provides a general strategy for achieving thermal catalysts by perfectly combining both highly low-temperature activity and sintering resistance, which will have great significance in practical applications for replacing precious materials with comparative features.

Reconsidering gas as clean energy: Switching to electricity for household cooking to reduce NO2-attributed disease burden.

Nitrogen dioxide (NO2) is a prevalent air pollutant in urban areas, originating from outdoor sources, household gas consumption, and secondhand smoke. The limited evaluation of the disease burden attributable to NO2, encompassing different health effects and contributions from various sources, impedes our understanding from a public health perspective. Based on modeled NO2 exposure concentrations, their exposure-response relationships with lung cancer, chronic obstructive pulmonary disease, and diabetes mellitus, and baseline disability-adjusted life years (DALYs), we estimated that 1,675 (655-2,624) thousand DALYs were attributable to NO2 in urban China in 2019 [138 (54-216) billion Chinese yuan (CNY) economic losses]. The transition from gas to electricity for household cooking was estimated to reduce the attributable economic losses by 35%. This reduction falls within the range of reductions achieved when outdoor air meets the World Health Organization interim target 3 and air quality guidelines for annual NO2, highlighting the significance of raising awareness of gas as a polluting household energy for cooking. These findings align with global sustainable development initiatives, providing a sustainable solution to promote public health while potentially mitigating climate change.

Successful treatment of gastric cancer 10 years after heart transplantation: A case report.

BACKGROUND: While survival rates among cardiac allograft recipients have improved, there has been a rise in post-transplant malignancies, with gastric cancer being less commonly reported. This study presented a successful treatment of gastric cancer in an individual 10 years after undergoing a heart transplant. CASE PRESENTATION: A 66-year-old Chinese man presented to the gastrointestinal clinic with a complaint of diagnosis of gastric cancer for 4 months and treated with neoadjuvant therapy for 1 month. He has undergone orthotopic heart transplantation 10 years earlier due to a myocardial infarction. Physical examination and laboratory tests did not reveal any significant abnormalities. Abdominal contrast-enhanced computed tomography (CT) imaging indicated a gastric mass near the greater curvature, with gastroscopy suggesting a carcinoma at the esophagogastric junction, Siewert III. An echocardiogram indicated left atrial enlargement with mild mitral and tricuspid regurgitation. The diagnosis suggested that his gastric cancer at the esophagogastric junction was a consequence of long-term immunosuppressive therapy. A multidisciplinary team (MDT) consultation recommended a proximal radical gastrectomy. Postoperatively, the patient received 4 cycles of adjuvant chemotherapy with XELOX combined with Herceptin, initiated a month after surgery. During the 1-year follow-up, the patient showed commendable recovery, with no signs of tumor recurrence or metastasis. CONCLUSION: This case underscores the potential risk of malignancy from immunosuppressive agents in transplant recipients. The successful management of this complex scenario underscores the indispensable role of an MDT approach in treating such unique and challenging cases.

Astragaloside-IV promotes autophagy via the Akt/mTOR pathway to improve cellular lipid deposition.

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.

Machine Learning Molecular Dynamics Shows Anomalous Entropic Effect on Catalysis via Surface Pre-melting of Nanoclusters.

Due to the superior catalytic activity and efficient utilization of noble metals, nanocatalysts are extensively used in the modern industrial production of chemicals. The surface structures of these materials are significantly influenced by reactive adsorbates, leading to dynamic behavior under experimental conditions. The dynamic nature poses significant challenges in studying the  structure-activity relations of catalysts. Herein, we unveil an anomalous entropic effect on catalysis via surface pre-melting of nanoclusters through machine learning accelerated molecular dynamics and free energy calculation. We find that due to the pre-melting of shell atoms, there exists a non-linear variation in the catalytic activity of the nanoclusters with temperature. Consequently, two notable changes in catalyst activity occur at the respective temperatures of melting for the shell and core atoms. We further study the nanoclusters with surface point defects, i.e. vacancy and ad-atom, and observe significant decrease in the surface melting temperatures of the nanoclusters, enabling the reaction to take place under more favorable and milder conditions. These findings not only provide novel insights into dynamic catalysis of nanoclusters  but also offer new understanding of the role of point defects in catalytic processes.

Inhibition of mtDNA-PRRs pathway-mediated sterile inflammation by astragalus polysaccharide protects against transport stress-induced cardiac injury in chicks.

Transport stress (TS) not only weakens poultry performance but also affects animal welfare. Additionally, TS can evoke cardiac damage by triggering sterile inflammation in chicks, but the underlying mechanism is not fully understood. Here, we aimed to elucidate how TS induces sterile inflammation and heart injury and to clarify the antagonism effect of astragalus polysaccharides (APS). We randomly divided 60 chicks (one-day-old female) into 5 groups (n = 12): Control_0h (Con_0h) group (chicks were slaughtered at initiation), Control group (stress-free control), TS group (simulated TS exposure for 8 h), TS plus water (TS+W) group, and TS plus APS (TS+APS) group. Before simulation transport, the chicks of TS+W and TS+APS groups were, respectively, dietary with 100 µL of water or APS (250 µg/mL). H&E staining was employed for cardiac histopathological observation. ELISA assay was used to measure oxidative stress marker levels (GSH, GPX, GST, and MDA). A commercial kit was used to isolate the mitochondrial portion, and qRT-PCR was employed to measure the mitochondrial DNA (mtDNA) levels. Furthermore, we evaluated the activity of mtDNA-mediated NF-κB, NLRP3 inflammasome, and cGAS-STING inflammatory pathways and the expression of downstream inflammatory factors by Western Blotting or qRT-PCR. Our findings revealed that APS notably relieved TS-induced myocardial histopathological lesions and infiltrations. Likewise, the decrease in proinflammatory factors (TNF-α, IL-1ß, and IL-6) and IFN-ß by APS further supported this result. Meanwhile, TS caused severe oxidative stress in the chick heart, as evidenced by decreased antioxidant enzymes and increased MDA. Importantly, APS prevented mtDNA stress and leakage by reducing oxidative stress. Interestingly, TS-induced mtDNA leakage caused a series of inflammation events via mtDNA-PRRs pathways, including TLR21-NF-κB, NLRP3 inflammasome, and cGAS-STING signaling. Encouragingly, all these adverse changes related to inflammation events induced by mtDNA-PRRs activation were all relieved by APS treatment. In summary, our findings provide the first evidence that inhibition of mtDNA-PRRs pathway-mediated sterile inflammation by APS could protect against TS-induced cardiac damage in chicks.

Comparison of the Profile and Management of Chronic Pancreatitis between China and Western Countries: A Single-Center Experience and Literature Review.

OBJECTIVE: The etiology, clinical presentation, diagnosis, and treatment strategies of chronic pancreatitis (CP) vary significantly between countries. Specifically, the etiology and surgical approaches to treating CP differ between China and Western countries. Therefore, this study aims to compare the disparities in CP profiles and management based on our single-center experience and recent data from the West. METHODS: From January 2007 to December 2017, a total of 130 consecutive patients with histologically confirmed chronic pancreatitis (CP) underwent surgical treatment at the First Affiliated Hospital of Nanjing Medical University. The clinical features, etiology, risk factors, and operative procedures of these CP patients were analyzed and compared with recent data from Western countries. RESULTS: Our patient cohort was predominantly male (3.19:1), with a median age of 50.2 ± 9.8 years. Upper abdominal pain was the most common symptom, present in 102 patients (78.5%). The most common etiology was obstructive factors (47.7%), followed by alcohol (34.6%). The incidence of genic mutation was 2%, significantly lower than rates reported in Western research. Steatorrhea, weight loss, and jaundice were present in 6.9%, 18.5%, and 17.7% of patients, respectively. Pancreatic cysts or pseudocysts were diagnosed in 7 patients (5.4%). The following procedures were performed: Partington procedure in 33 patients (25.4%), Frey procedure in 17 patients (13.2%), Berne procedure in 5 patients (3.9%), Beger procedure in 1 patient (0.8%), pancreaticoduodenectomy in 17 patients (13.1%), pylorus-preserving pancreaticoduodenectomy in 18 patients (13.9%), middle pancreatectomy in 1 patient (0.8%), and distal pancreatectomy in 9 patients (6.9%). Choledochojejunostomy was performed in 14 patients (10.8%), gastroenterostomy in 2 (1.5%), and 15 patients (11.5%) underwent aspiration biopsy. CONCLUSION: Our study confirms that, etiologically, obstructive chronic pancreatitis (CP) is more frequent in the Chinese population than in Western populations. Although diagnostic instruments and operative procedures in China and Western countries are roughly comparable, slight differences exist in relation to diagnostic flowcharts/criteria and the indications and optimal timing of surgery.

Convolutional Neural Network with Attention Mechanism and Visual Vibration Signal Analysis for Bearing Fault Diagnosis.

Bearings, as widely employed supporting components, frequently work in challenging working conditions, leading to diverse fault types. Traditional methods for diagnosing bearing faults primarily center on time-frequency analysis, but this often requires expert experience for accurate fault identification. Conversely, intelligent fault recognition and classification methods frequently lack interpretability. To address this challenge, this paper introduces a convolutional neural network with an attention mechanism method, denoted as CBAM-CNN, for bearing fault diagnosis. This approach incorporates an attention mechanism, creating a Convolutional Block Attention Module (CBAM), to enhance the fault feature extraction capability of the network in the time-frequency domain. In addition, the proposed method integrates a weight visualization module known as the Gradient-Weighted Class Activation Map (Grad-CAM), enhancing the interpretability of the convolutional neural network by generating visual heatmaps on fault time-frequency graphs. The experimental results demonstrate that utilizing the dataset employed in this study, the CBAM-CNN achieves an accuracy of 99.81%, outperforming the Base-CNN with enhanced convergence speed. Furthermore, the analysis of attention weights reveals that this method exhibits distinct focus of attention under various fault types and degrees. The interpretability experiments indicate that the CBAM module balances the weight allocation, emphasizing signal frequency distribution rather than amplitude distribution. Consequently, this mitigates the impact of the signal amplitude on the diagnostic model to some extent.