Tailoring d-p Orbital Hybridization to Decipher the Essential Effects of Heteroatom Substitution on Redox Kinetics.

The heteroatom substitution is considered as a promising strategy for boosting the redox kinetics of transition metal compounds in hybrid supercapacitors (HSCs) although the dissimilar metal identification and essential mechanism that dominate the kinetics remain unclear. It is presented that d-p orbital hybridization between the metal and electrolyte ions can be utilized as a descriptor for understanding the redox kinetics. Herein, a series of Co, Fe and Cu heteroatoms are respectively introduced into Ni3Se4 cathodes, among them, only the moderate Co-substituted Ni3Se4 can hold the optimal d-p orbital hybridization resulted from the formed more unoccupied antibonding states π*. It inevitably enhances the interfacial charge transfer and ensures the balanced OH- adsorption-desorption to accelerate the redox kinetics validated by the lowest reaction barrier (0.59 eV, matching well with the theoretical calculations. Coupling with the lower OH- diffusion energy barrier, the prepared cathode delivers ultrahigh rate capability (~68.7% capacity retention even the current density increases by 200 times), and an assembled HSC also presents high energy/power density. This work establishes the principles for determining heteroatoms and deciphers the underlying effects of the heteroatom substitution on improving redox kinetics and the rate performance of battery-type electrodes from a novel perspective of orbital-scale manipulation.

A robust vessel-labeling pipeline with high tissue clearing compatibility for 3D mapping of vascular networks.

The combination of vessel-labeling, tissue-clearing, and light-sheet imaging techniques provides a potent tool for accurately mapping vascular networks, enabling the assessment of vascular remodeling in vascular-related disorders. However, most vascular labeling methods face challenges such as inadequate labeling efficiency or poor compatibility with current tissue clearing technology, which significantly undermines the image quality. To address this limitation, we introduce a vessel-labeling pipeline, termed Ultralabel, which relies on a specially designed dye hydrogel containing lysine-fixable dextran and gelatins for double enhancement. Ultralabel demonstrates not only excellent vessel-labeling capability but also strong compatibility with all tissue clearing methods tested, which outperforms other vessel-labeling methods. Consequently, Ultralabel enables fine mapping of vascular networks in diverse organs, as well as multi-color labeling alongside other labeling techniques. Ultralabel should provide a robust and user-friendly method for obtaining 3D vascular networks in different biomedical applications.

Pangenome analysis of Shewanella xiamenensis revealed important genetic traits concerning genetic diversity, pathogenicity and antibiotic resistance.

BACKGROUND: Shewanella xiamenensis, widely distributed in natural environments, has long been considered as opportunistic pathogen. Recently, significant changes in the resistance spectrum have been observed in S. xiamenensis, due to acquired antibiotic resistance genes. Therefore, a pan-genome analysis was conducted to illuminate the genomic changes in S. xiamenensis. RESULTS: Phylogenetic analysis revealed three major clusters and three singletons, among which close relationship between several strains was discovered, regardless of their host and niches. The "open" genomes with diversity of accessory and strain-specific genomes took advantage towards diversity environments. The purifying selection pressure was the main force on genome evolution, especially in conservative genes. Only 53 gene families were under positive selection pressure. Phenotypic resistance analysis revealed 21 strains were classified as multi-drug resistance (MDR). Ten types of antibiotic resistance genes and two heavy metal resistance operons were discovered in S. xiamenensis. Mobile genetic elements and horizontal gene transfer increased genome diversity and were closely related to MDR strains. S. xiamenensis carried a variety of virulence genes and macromolecular secretion systems, indicating their important roles in pathogenicity and adaptability. Type IV secretion system was discovered in 15 genomes with various sequence structures, indicating it was originated from different donors through horizontal gene transfer. CONCLUSIONS: This study provided with a detailed insight into the changes in the pan-genome of S. xiamenensis, highlighting its capability to acquire new mobile genetic elements and resistance genes for its adaptation to environment and pathogenicity to human and animals.

Why small towns are shrinking: The spatial heterogeneity of small towns shrinkage and the impact of it from the perspective of rural-urban interaction in China.

Small towns play a crucial role in bridging urban and rural territory systems. While numerous studies have identified the characteristics and causes of small town shrinkage (STS), there remains an unexplored perspective on the reasons for their shrinkage from the perspective of the rural-urban relationship. To address this research gap, we investigated the relationship between STS and rural-urban interaction (RUI) in China. We hypothesized that a negative relationship existed between the degree of STS and the intensity of RUI. Using geo-statistical methods, such as the multi-scale geographical weighted regression (MGWR) model, the hypothesis was tested using Henan Province in China as a case study. The results indicated that the phenomenon of STS was observed extensively across the study region, with a 59% geographical overlap between the high-value area of STS and the low-value area of urban-rural interaction. Three distinct sub-types of STS regions were identified: shrinking regions along geographical borders, shrinking regions adjacent to metropolitan areas, and shrinking regions in ecologically fragile areas. The factors influencing STS demonstrated spatial heterogeneity and multi-scale characteristics. The findings will improve our understanding of urban shrinkage from a multi-level perspective and offer policy makers guidance for the sustainable development of small towns based on local conditions.

Supply and demand of higher vocational education in China: Comprehensive evaluation and geographical representation from the perspective of educational equality.

The imbalanced regional development of higher vocational education, particularly the disparity between the supply and demand of educational resources, has emerged as the primary factor impeding the provision of high-quality higher education in China during the establishment of a universal education system. Based on the 1,482 higher vocational education institutions recognized by the Ministry of Education of China in 2021 as the research objects, the development of higher vocational education in China was explored from the perspective of supply and demand using the entropy weight TOPSIS method and coupling coordination degree model. It was found that China's higher vocational institutions were mainly located in provincial capitals, representing a point distribution pattern. From a comprehensive evaluation of the supply level, areas such as the Beijing-Tianjin-Hebei region, Yangtze River Delta, and central Henan Province have become the catchment areas for the development of higher vocational education, laying the foundation for regional network cooperation. From the perspective of educational equality, the higher vocational education in China was found to be sufficient to match the supply and demand, and a balance between supply and demand was apparent in provincial capitals. The coupling degree between supply and demand exhibited an "olive-type" spatial structure pattern, indicating that the development of higher vocational education in most cities in China is still in the transformation stage. The results provide a scientific basis for optimizing resources in the provision of higher vocational education.

Self-assembly of CXCR4 antagonist peptide-docetaxel conjugates for breast tumor multi-organ metastasis inhibition.

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

Protocol for fine casting, imaging, and analysis of murine vascular networks with VALID.

The majority of fluorescent vessel labeling techniques currently available are limited by their expense, incomplete labeling, or complexity. Here, we present VALID (vessel labeling via gelatin-based lipophilic dye solution)-a protocol for complete labeling of different vascular networks. We describe steps for preparing different dye hydrogels, murine vascular casting and tissue harvesting, immunolabeling, tissue clearing, and imaging, as well as detailed analysis of the vascular networks. This protocol is helpful for evaluating vascular lesions in studying different vessel-associated diseases. For complete details on the use and execution of this protocol, please refer to Zhu et al.1.

Impact of regional energy allocation distortion on carbon emission efficiency: Evidence from China.

The free flow of energy cannot be fully achieved in China's energy market because of incomplete market-oriented reform, resulting in energy allocation distortion, which has hampered carbon emissions reduction. However, the extent of energy allocation distortion and its role in carbon emission efficiency remain unexplored. Therefore, this study aims to measure energy allocation distortion and investigate its impact on carbon emission efficiency. For this purpose, first, we derive energy allocation distortion based on a production function and carbon emission efficiency using a meta-frontier non-radial Malmquist index. To effectively address the endogeneity issue, we use a generalized method of moments model to estimate the impact of energy allocation distortion on carbon emission efficiency. Second, we further explore the distortionary mechanism of carbon emission efficiency associated with energy allocation and analyze the asymmetric effect of energy allocation distortion on carbon emission efficiency. The results show a certain degree of energy allocation distortion throughout the country, and disparity exists among different regions. The average value of carbon emission efficiency in the eastern region is 1.0286, well ahead of the national average, demonstrating better performance than other regions. Energy allocation distortion negatively affects carbon emission efficiency, with a 1% increase in energy allocation distortion leading to a 0.251% decrease in carbon emission efficiency. Technological progress, the structure of energy consumption, and industrial structure are important transmission channels through which energy allocation affects carbon emission efficiency. The study contributes to uncovering regional energy allocation distortion and its impacts on carbon emission efficiency and providing strategic policy recommendations for improving energy allocation efficiency.

Neural Signatures of Hierarchical Linguistic Structures in Second Language Listening Comprehension.

Native speakers excel at parsing continuous speech into smaller elements and entraining their neural activities to the linguistic hierarchy at different levels (e.g., syllables, phrases, and sentences) to achieve speech comprehension. However, how a nonnative brain tracks hierarchical linguistic structures in second language (L2) speech comprehension and whether it relates to top-down attention and language proficiency remains elusive. Here, we applied a frequency-tagging paradigm in human adults and investigated the neural tracking responses to hierarchically organized linguistic structures (i.e., the syllabic rate of 4 Hz, the phrasal rate of 2 Hz, and the sentential rate of 1 Hz) in both first language (L1) and L2 listeners when they attended to a speech stream or ignored it. We revealed disrupted neural responses to higher-order linguistic structures (i.e., phrases and sentences) for L2 listeners in which the phrasal-level tracking was functionally related to an L2 subject's language proficiency. We also observed less efficient top-down modulation of attention in L2 speech comprehension than in L1 speech comprehension. Our results indicate that the reduced δ-band neuronal oscillations that subserve the internal construction of higher-order linguistic structures may compromise listening comprehension in a nonnative language.

Case report: Targeting the PD-1 receptor and genetic mutations validated in primary histiocytic sarcoma with hemophagocytic lymphohistiocytosis.

Histiocytic sarcoma (HS) is a rare hematological malignancy with limited treatment options, and it is also prone to complications such as hemophagocytic lymphohistiocytosis (HLH) in the later stages of the disease, leading to difficulties in treatment and poor prognosis. It highlights the importance of developing novel therapeutic agents. Herein, we present a case of a 45-year-old male patient who was diagnosed with PD-L1-positive HS with HLH. The patient was admitted to our hospital with recurrent high fever, multiple skin rashes with pruritus throughout the body and enlarged lymph nodes. Subsequently, pathological biopsy of the lymph nodes revealed high expression of CD163, CD68, S100, Lys and CD34 in the tumor cells and no expression of CD1a and CD207, confirming this rare clinical diagnosis. Concerning the low remission rate by conventional treatment in this disease, the patient was administered with sintilimab (an anti-programmed cell death 1 [anti-PD-1] monoclonal antibody) at 200 mg/d combined with a first-line chemotherapy regimen for one cycle. Further exploration of pathological biopsy by using next-generation gene sequencing led to the use of targeted therapy of chidamide. After one cycle of combination therapy (chidamide+sintilimab, abbreviated as CS), the patient achieved a favorable response. The patient showed remarkable improvement in the general symptoms and laboratory examination results (e.g., elevated indicators of inflammation); even the clinical benefits was not persistent, he survived one more month after his cessation of treatment by himself due to economic difficulty. Our case suggests that PD-1 inhibitor coupled with targeted therapy might constitute a potential therapeutic option for primary HS with HLH.

A versatile vessel casting method for fine mapping of vascular networks using a hydrogel-based lipophilic dye solution.

Efficient labeling of the vasculature is important for understanding the organization of vascular networks. Here, we propose VALID, a vessel-labeling method that enables visualization of vascular networks with tissue clearing and light-sheet microscopy. VALID transforms traditional lipophilic dye solution into hydrogel by introducing gelatin and restrains the dye aggregation, resulting in complete and uniform vessel-labeling patterns with high signal-to-background ratios. VALID also enhances the compatibility of lipophilic dyes with solvent-based tissue-clearing protocols, which was hard to achieve previously. Using VALID, we combined lipophilic dyes with solvent-based tissue-clearing techniques to perform 3D reconstructions of vasculature within mouse brain and spinal cord. We also employed VALID for 3D visualization and quantification of microvascular damage in a middle cerebral artery occlusion mouse model. VALID should provide a simple, cost-effective vessel-labeling protocol that would significantly widen the applications of lipophilic dyes in research on cerebrovascular complications.

Optimal combinations of fluorescent vessel labeling and tissue clearing methods for three-dimensional visualization of vasculature.

Significance: Visualization of intact vasculatures is crucial to understanding the pathogeneses of different neurological and vascular diseases. Although various fluorescent vessel labeling methods have been used in combination with tissue clearing for three-dimensional (3D) visualization of different vascular networks, little has been done to quantify the labeling effect of each vessel labeling routine, as well as their applicability alongside various clearing protocols, making it difficult to select an optimal combination for finely constructing different vasculatures. Therefore, it is necessary to systematically assess the overall performance of these common vessel labeling methods combined with different tissue-clearing protocols. Aim: A comprehensive evaluation of the labeling quality of various vessel labeling routines in different organs, as well as their applicability alongside various clearing protocols, were performed to find the optimal combinations for 3D reconstruction of vascular networks with high quality. Approach: Four commonly-used vessel labeling techniques and six typical tissue optical clearing approaches were selected as candidates for the systematic evaluation. Results: The vessel labeling efficiency, vessel labeling patterns, and compatibility of each vessel labeling method with different tissue-clearing protocols were quantitatively evaluated and compared. Based on the comprehensive evaluation results, the optimal combinations were selected for 3D reconstructions of vascular networks in several organs, including mouse brain, liver, and kidney. Conclusions: This study provides valuable insight on selecting the proper pipelines for 3D visualization of vascular networks, which may facilitate understanding of the underlying mechanisms of various neurovascular diseases.

Fatty Acid Profiles and Their Association With Autoimmunity, Insulin Sensitivity and ß Cell Function in Latent Autoimmune Diabetes in Adults.

Background: The pathogenesis of the progressive loss of beta cell function latent autoimmune diabetes in adults (LADA) remains still elusive. We aim to study the fatty acid (FA) profile in LADA. Subjects and methods: Data from 116 patients with diabetes and GADA and 249 diabetes controls without GADA selected by Propensity Score Matching were collected. FA was analyzed with liquid chromatography-tandem mass spectrometry analysis. Results: Principal factor analysis found component 1 explains 82.6% of total variance contained fatty acids from a mixed of lard oil, seafood, and vegetable diet, followed by diet predominantly from vegetable oil, a diet of high fat diet, and a diet of seafood diet. The FA heatmap looked clearly different among the three groups with more similar type 1 (t1dm) and LADA fatty acid profile. n-3 α-linolenic acid (ALA), n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), such as Eicosapentaenoic Acid and Docosapentaenoic Acid, n-3/n-6 ratio and triene/tetraene ratio were higher in patients with type 2 diabetes (t2dm) compared with LADA and t1dm. Saturated FAs were lower in t2dm than t1dm and LADA. Arachidic acid and n-6 LC-PUFAs were lower in t2dm than in t1dm and LADA. The characteristics of FAs in LADA were in between of classical t1dm and t2dm. Patients were classified into 6 clusters by FA clusters. Only cluster 2, 3, 5 contained enough patients to be analyzed. Cluster 5 showed an insulin deficient phenotype containing more than 60% of patients with t1dm and LADA and only 12.8% of t2dm. Cluster 2 and 3 were similar. ß cell function and glycemic control was better in cluster 3 homing 25% of t2dm. Cluster 2 held 28% of t1dm and LADA, in this cluster more than 60% of patients was t2dm. n-3 linolenic acid, n-3 LC-PUFAs, some n-6 LC-PUFAs, n-3/n-6 ratio and triene/tetraene ratio were negatively associated with GADA positivity while n-6 Arachidonic Acid was associated positively with GADA. Similar findings were found for insulin sensitivity and beta cell function. Conclusion: PUFA are associated with insulin sensitivity and beta cell function, and like other clinical features, FA profile distributed differently, but could not be used as makers to differentiate LADA from t1dm and t2dm. Ethics and Dissemination: This study has been approved by the Ethical Review Committee of Second Hospital of Dalian Medical University (approval number: 2021-005). Clinical Trial Registration: none.

How does power technology innovation affect carbon productivity? A spatial perspective in China.

Power technology innovation has been positioned as an effective way to contribute to China's carbon productivity. However, limited empirical evidence exists on the impact of power technology innovation on carbon productivity. Thus, based on the annual panel dataset of 30 China's provinces from 2001 to 2019, this study explored whether and how power technology innovation promotes or impedes the improvement of carbon productivity. First, carbon productivity in the framework of total factor was calculated based on the metafrontier Malmquist-Luenberger productivity index. Second, the effect of power technology innovation on carbon productivity was investigated using the spatial Durbin model. And we also examined whether heterogeneous power technology innovations have a synergistic effect on carbon productivity. Third, influence mechanism of power technology innovation affecting carbon productivity was identified. Results show that (1) there are notable differences in China's provincial carbon productivity, which is characterized by the spatial correlation. (2) Local power technology innovation has a promotion effect on carbon productivity in both local and neighboring provinces. Moreover, the promotion effect of breakthrough power technology innovation is stronger than that of incremental power technology innovation. (3) Catching-up Effect and Innovation Effect are important transmission channels through which power technology innovation improves carbon productivity. Finally, policy recommendations are provided.

Tissue optical clearing for 3D visualization of vascular networks: A review.

Reconstruction of the vasculature of intact tissues/organs down to the capillary level is essential for understanding the development and remodeling of vascular networks under physiological and pathological conditions. Optical imaging techniques can provide sufficient resolution to distinguish small vessels with several microns, but the imaging depth is somewhat limited due to the high light scattering of opaque tissue. Recently, various tissue optical clearing methods have been developed to overcome light attenuation and improve the imaging depth both for ex-vivo and in-vivo visualizations. Tissue clearing combined with vessel labeling techniques and advanced optical tomography enables successful mapping of the vasculature of different tissues/organs, as well as dynamically monitoring vessel function under normal and pathological conditions. Here, we briefly introduce the commonly-used labeling strategies for entire vascular networks, the current tissue optical clearing techniques available for various tissues, as well as the advanced optical imaging techniques for fast, high-resolution structural and functional imaging for blood vessels. We also discuss the applications of these techniques in the 3D visualization of vascular networks in normal tissues, and the vascular remodeling in several typical pathological models in clinical research. This review is expected to provide valuable insights for researchers to study the potential mechanisms of various vessel-associated diseases using tissue optical clearing pipeline.

The Role of Exosomes and Their Cargos in the Mechanism, Diagnosis, and Treatment of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common persistent arrhythmia, but the mechanism of AF has not been fully elucidated, and existing approaches to diagnosis and treatment face limitations. Recently, exosomes have attracted considerable interest in AF research due to their high stability, specificity and cell-targeting ability. The aim of this review is to summarize recent literature, analyze the advantages and limitations of exosomes, and to provide new ideas for their use in understanding the mechanism and improving the diagnosis and treatment of AF.

Identification of 14-3-3 epsilon as a regulator of the neural apoptotic pathway for chronic-stress-induced depression.

Major depression is a prevalent and long-lasting psychiatric illness with severe functional impairment and high suicide rate. We have previously shown that the ventrolateral orbital cortex (VLO) plays a key role in the stress responses in mice, but the underlying mechanisms remains unclear. Here, we used proteomic method to identify differentially expressed proteins in VLO of chronic unpredictable mild stress (CUMS) mice. Of 4,953 quantified proteins, 45 proteins were differentially expressed following CUMS. The integrated pathway analyses identified 14-3-3ε and TrkB signaling as differentially downregulated in association with stress-induced depressive-like behaviors. 14-3-3ε overexpression in VLO relieved the depressive-like behaviors by rescue of Bad-mediated apoptosis. Moreover, treatment with the 14-3-3ε stabilizer FC-A precluded neuronal apoptotic signaling in VLO of depressed mice. Because 14-3-3ε provides significant protection against chronic stress, boosting 14-3-3ε expression, pharmacological stabilization of 14-3-3s (e.g. with FC-A) is identified as an exciting therapeutic target for major depression.

The complete chloroplast genome sequence of Citrus maxima (Burm.) Merr. 'Guanximiyou'.

Citrus maxima (Burm.) Merr. 'Guanximiyou' is a major citrus tree largely cultivated in China. A previous study has reported the complete chloroplast genome of C. maxima, but there may be some differences between wild species and cultivating variety. In this study, the complete chloroplast genome sequence of 'Guanximiyou' pummelo was characterized using BGISEQ-500 sequencing. The chloroplast genome was 160,186 bp in length and separated into four distinct regions such as large single-copy region (87,939 bp), small single-copy region (18,395 bp), and a pair of inverted repeat regions (26,926 bp). The genome contained a total of 109 genes including 79 protein-coding genes, 29 tRNA genes, and 4 rRNA genes. Phylogenetic maximum-likelihood analysis revealed that 'Guanximiyou' pummelo was clustered with other Rutaceae species with high bootstrap values.

pH-triggered morphological change in a self-assembling amphiphilic peptide used as an antitumor drug carrier.

The geometry of nanoparticles plays an important role in the process of drug encapsulation and release. In this study, an acid-responsive amphiphilic polypeptide consisting of lysine and leucine was prepared. In neutral media, the amphiphilic peptide L6K4 self-assembled to form spherical nanoparticles and encapsulated fat-soluble antitumor drugs. The intratumoral accumulation of the drug-loaded nanoparticles was improved in HeLa cells compared with normal cells. Compared to a neutral environment, increasingly acidic solutions changed the secondary structure of the peptide. In addition, the drug-loaded nanoparticles expanded and decomposed, rapidly releasing the poorly soluble antitumor drug doxorubicin (DOX). In addition, the amphiphilic peptide L6K4 had antitumor properties, and the antitumor performance of the combination of L6K4 and DOX was better than that of free DOX. Our results indicate that the use of acid responsiveness to induce geometric changes in drug-loaded peptide nanoparticles could be a promising strategy for antitumor drug delivery.

3D-QSAR, molecular docking, and molecular dynamics simulation of a novel thieno[3,4-d]pyrimidine inhibitor targeting human immunodeficiency virus type 1 reverse transcriptase.

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is one of the most attractive drug targets for the treatment of AIDS. In this study, 67 thieno[3,4-d]pyrimidine derivatives were selected as novel HIV-1 RT inhibitors to combat viral resistance, and were subjected to 3 D-QSAR studies using CoMFA, CoMSIA, and T-CoMFA. In the 3 D-QSAR study, two methods of ligand-based alignment and pharmacophore-based alignment were used. The results showed that CoMFA (n = 8; q2 = 0.594; r2 = 0.974) and CoMSIA (n = 7; q2 = 0.528; r2 = 0.965) have good stability and predictability. The molecular docking study showed that the hydrogen bonding and van der Waals interactions of key residues such as Leu100, Lys101, Val106, Phe227 and Pro236 play an important role in ligand-receptor binding. Based on these results, 12 new thieno[3,4-d]pyrimidines were designed and their activities were predicted; the results indicated that these compounds have good predictive activity and reasonably good ADME/T profiles. MD simulation analysis of 50 ns showed that compound 23j formed four hydrogen bonds with the residues (Lys101, Lys104, Val106 and Thr318), and binds more closely to HIV-1 RT than compound 23j. Furthermore, the group at the R1 position and the horseshoe-like conformation of these compounds are critical for the inhibitory activity and stability. These results provide useful insights for the discovery and design of a new generation of HIV-1 RT inhibitors.Communicated by Ramaswamy H. Sarma.