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Abstract Background In the family Trypanosomatidae, the genus Trypanosoma contains protozoan parasites that infect a diverse range of hosts, including humans, domestic animals, and wildlife. Wild rodents, as natural reservoir hosts of various pathogens, play an important role in the evolution and emergence of Trypanosomatidae. To date, no reports are available on the trypanosomatid infection of pikas (Lagomorpha: Ochotonidae). Methods In this study, Mongolian pikas and their fleas were sampled at the China–Mongolia border, northwestern China. The samples were analyzed with polymerase chain reaction (PCR) and sequencing for the presence of Trypanosomatidae on the basis of both the 18S ribosomal RNA (18S rRNA) gene and the glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) gene. The morphology of trypomastigotes was also observed in peripheral blood smears by microscopy. Results Molecular and phylogenetic analyses revealed a new genotype of the Trypanosoma lewisi clade that was found both in pika blood and flea samples. This genotype, which probably represents a new species, was provisionally designated as “Trypanosoma sp. pika”. In addition, a novel genotype belonging to the genus Blechomonas of Trypanosomatidae was detected in fleas. On the basis of its molecular and phylogenetic properties, this genotype was named Blechomonas luni-like, because it was shown to be the closest related to B. luni compared with other flea-associated trypanosomatids. Conclusions To the best of our knowledge, this is the first study to report any trypanosomatid species in Mongolian pikas and their fleas. Further studies are needed to investigate the epidemiology of these protozoan parasites, as well as to evaluate their pathogenicity for humans or domestic animals. Graphical Abstract

Green-blue spaces (GBS) are pivotal in mitigating thermal discomfort. However, their management lacks guidelines rooted in epidemiological evidence for specific planning and design. Here we show how various GBS types modify the link between non-optimal temperatures and cardiovascular mortality across different thermal extremes. We merged fine-scale population density and GBS data to create novel GBS exposure index. A case time series approach was employed to analyse temperature-cardiovascular mortality association and the effect modifications of type-specific GBSs across 1085 subdistricts in south-eastern China. Our findings indicate that both green and blue spaces may significantly reduce high-temperature-related cardiovascular mortality risks (e.g., for low (5%) vs. high (95%) level of overall green spaces at 99th vs. minimum mortality temperature (MMT), Ratio of relative risk (RRR) = 1.14 (95% CI: 1.07, 1.21); for overall blue spaces, RRR = 1.20 (95% CI: 1.12, 1.29)), while specific blue space types offer protection against cold temperatures (e.g., for the rivers at 1st vs MMT, RRR = 1.17 (95% CI: 1.07, 1.28)). Notably, forests, parks, nature reserves, street greenery, and lakes are linked with lower heat-related cardiovascular mortality, whereas rivers and coasts mitigate cold-related cardiovascular mortality. Blue spaces provide greater benefits than green spaces. The severity of temperature extremes further amplifies GBS's protective effects. This study enhances our understanding of how type-specific GBS influences health risks associated with non-optimal temperatures, offering valuable insights for integrating GBS into climate adaptation strategies for maximal health benefits.

Background: As large language models continue to expand in size and diversity, their substantial potential and the relevance of their applications are increasingly being acknowledged. The rapid advancement of these models also holds profound implications for the long-term design of stimulus-responsive materials used in drug delivery. Methods: The large model used Hugging Face’s Transformers package with BigBird, Gemma, and GPT NeoX architectures. Pre-training used the PubChem dataset, and fine-tuning used QM7b. Chemist instruction training was based on Direct Preference Optimization. Drug Likeness, Synthetic Accessibility, and PageRank Scores were used to filter molecules. All computational chemistry simulations were performed using ORCA and Time-Dependent Density-Functional Theory. Results: To optimize large models for extensive dataset processing and comprehensive learning akin to a chemist’s intuition, the integration of deeper chemical insights is imperative. Our study initially compared the performance of BigBird, Gemma, GPT NeoX, and others, specifically focusing on the design of photoresponsive drug delivery molecules. We gathered excitation energy data through computational chemistry tools and further investigated light-driven isomerization reactions as a critical mechanism in drug delivery. Additionally, we explored the effectiveness of incorporating human feedback into reinforcement learning to imbue large models with chemical intuition, enhancing their understanding of relationships involving -N=N- groups in the photoisomerization transitions of photoresponsive molecules. Conclusions: We implemented an efficient design process based on structural knowledge and data, driven by large language model technology, to obtain a candidate dataset of specific photoswitchable molecules. However, the lack of specialized domain datasets remains a challenge for maximizing model performance.

Background Glioblastoma (GBM) is a fatal primary brain malignancy in adults. Previous studies have shown that cytomegalovirus (CMV) is a risk factor for tumorigenesis and aggressiveness for glioblastoma. However, little is known about how CMV infection affects immune cells in the tumor microenvironment of GBM. Furthermore, there has been almost no engineered T-cell receptor (TCR)-T targeting CMV for GBM research to date.Methods We evaluated the CMV infection status of patients with GBM’s tumor tissue by immune electron microscopy, immunofluorescence, and droplet digital PCR. We performed single-cell RNA sequencing for CMV-infected GBM to investigate the effects of CMV on the GBM immune microenvironment. CellChat was applied to analyze the interaction between cells in the GBM tumor microenvironment. Additionally, we conducted single-cell TCR/B cell receptor (BCR) sequencing and Grouping of Lymphocyte Interactions with Paratope Hotspots 2 algorithms to acquire specific CMV-TCR sequences. Genetic engineering was used to introduce CMV-TCR into primary T cells derived from patients with CMV-infected GBM. Flow cytometry was used to measure the proportion and cytotoxicity status of T cells in vitro.Results We identified two novel immune cell subpopulations in CMV-infected GBM, which were bipositive CD68+SOX2+ tumor-associated macrophages and FXYD6+ T cells. We highlighted that the interaction between bipositive TAMs or cancer cells and T cells was predominantly focused on FXYD6+ T cells rather than regulatory T cells (Tregs), whereas, FXYD6+ T cells were further identified as a group of novel immunosuppressive T cells. CMV-TCR-T cells showed significant therapeutic effects on the human-derived orthotopic GBM mice model.Conclusions These findings provided an insight into the underlying mechanism of CMV infection promoting the GBM immunosuppression, and provided a novel potential immunotherapy strategy for patients with GBM.

Red foxes (Vulpes vulpes) have been recognized as natural reservoirs for multiple pathogens and a source of infection for domestic animals, wildlife and humans. To date, no reports are available on the Bartonella rochalimae and Hepatozoon canis infection in red foxes from China. In 2018–2022, a total of 16 red foxes were sampled in two counties and a city in Xinjiang Uygur Autonomous Region (XUAR) in northwest China. Subsequently analyzed by DNA extraction amplified by polymerase chain reaction (PCR). In the present study, based on nucleotide sequence and phylogenetic tree analyses, B. rochalimae and H. canis were molecularly identified in red foxes. Our findings provide the first molecular evidence of B. rochalimae and H. canis in red foxes from China.

Eurasian lynx (Lynx lynx) is widely distributed in various habitats in Asia and Europe, and it may harbor multiple pathogens. Currently, the information on protozoan infection in Eurasian lynx is scarce. In this study, we performed nested polymerase chain reaction (nPCR) analysis to detect intestinal protozoan infection in three dead Eurasian lynxes, in northwestern China. Three dead Eurasian lynxes, an adult female (#1), an adult male (#2), and a cub male (#3), were sampled in West Junggar Mountain, the northwestern region of Xinjiang Uyghur Autonomous Region. The intestine samples were analyzed using nPCR. We used primers targeting the cytochrome C oxidase subunit I gene (COI) for detection of Sarcocystis and Eimeria species and targeting the small subunit 18 S ribosomal RNA gene (18S rRNA) for detection of Cystoisospora species. The nPCR-positive products were sequenced, aligned, and phylogenetically analyzed. Three intestinal protozoa, Sarcocystis albifronsi, Eimeria alpacae, and Cystoisospora felis, were found in three Eurasian lynxes. The intestine sample of Eurasian lynx #2 was detected with S. albifronsi and E. alpacae. In addition, C. felis was only found in the intestine sample of Eurasian lynx #3. To the best of our knowledge, S. albifronsi and E. alpacae were detected in Eurasian lynx for the first time. In addition, C. felis was firstly found in Eurasian lynx in China. These findings extend our knowledge of the geographical distribution and host range of intestinal protozoa.

Abstract Background The incidence and mortality of early-onset colorectal cancer (EOCRC;

Abstract Supported metal clusters comprising of well-tailored low-nuclearity heteroatoms have great potentials in catalysis owing to the maximized exposure of active sites and metal synergy. However, atomically precise design of these architectures is still challenging for the lack of practical approaches. Here, we report a defect-driven nanostructuring strategy through combining defect engineering of nitrogen-doped carbons and sequential metal depositions to prepare a series of Pt and Mo ensembles ranging from single atoms to sub-nanoclusters. When applied in continuous gas-phase decomposition of formic acid, the low-nuclearity ensembles with unique Pt3Mo1N3 configuration deliver high-purity hydrogen at full conversion with unexpected high activity of 0.62 molHCOOH molPt −1 s−1 and remarkable stability, significantly outperforming the previously reported catalysts. The remarkable performance is rationalized by a joint operando dual-beam Fourier transformed infrared spectroscopy and density functional theory modeling study, pointing to the Pt-Mo synergy in creating a new reaction path for consecutive HCOOH dissociations.

Abstract Harvested wood/bamboo products (HWP/HBP) constitute a large global carbon stock. However, the contribution of HBP to carbon stocks has been neglected in mixed wood and bamboo data, especially in China. Therefore, the production approach and the first-order decay method were used to estimate the spatiotemporal carbon stock change in HWP/HBP based on provincial production data from the China Forestry Statistical Yearbooks for 1987–2020. The results showed that China’s total carbon stocks of HWP and HBP were 328.7 teragram carbon (TgC) and 129.7 TgC between 1987 and 2020. Of this, the HWP carbon stock was mainly sourced from three provinces across the north and south: Guangxi (60.8 TgC), Heilongjiang (37.2 TgC), and Fujian (24.2 TgC), and HBP carbon stock was mainly sourced from three southern provinces: Fujian (33.4 TgC), Guangxi (20.3 TgC), and Zhejiang (13.7 TgC). The proportion of the HBP carbon stock in the total carbon stock increased from 20% in 2010 to 28% in 2020, indicating that bamboo products play an important role in the accumulation of carbon stocks in China. The differences in contributions to spatiotemporal trends between the provinces provide more specific information to make precise decisions about forest management and carbon sequestration.

Abstract Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training in mice induces excitatory synapse formation onto a subset of anterior cingulate cortex neurons projecting to the dorsomedial striatum (ACC→DMS). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor α2δ−1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of α2δ−1 in the adult ACC→DMS circuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation does not impact learning but results in a significant increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC→DMS neurons rescues or phenocopies the behaviors of the α2δ−1 cKO mice, highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion.

Lipids are organic nonpolar molecules with essential biological and economic importance. While the genetic pathways and regulatory networks of lipid biosynthesis and metabolism have been extensively studied and thoroughly reviewed in oil crops such as soybeans, less attention has been paid to the biological roles of lipids in rice, a staple food for the global population and a model species for plant molecular biology research, leaving a considerable knowledge gap in the biological roles of lipids. In this review, we endeavor to furnish a current overview of the advancements in understanding the genetic foundations and physiological functions of lipids, including triacylglycerol, fatty acids, and very-long-chain fatty acids. We aim to summarize the key genes in lipid biosynthesis, metabolism, and transcriptional regulation underpinning rice’s developmental and growth processes, biotic stress responses, abiotic stress responses, fertility, seed longevity, and recent efforts in rice oil genetic improvement.

Low-carbon cities aim to minimize greenhouse gas emissions in the context of climate change in the process of urbanization. Maintaining these cities at an appropriate physical scale has been proven to contribute to carbon reduction. Therefore, this study extended the definition of the city scale to an integrated framework with three dimensions: the construction land area, population, and economy. The urban construction land of 258 cities in China during 2012 to 2019 was divided into commercial, industrial, residential, and traffic sectors, and carbon emissions were calculated for each. The regression relationship between carbon emissions and the urban scale revealed by panel data analysis showed the following conclusions: (1) carbon emissions were concentrated in north China, provincial capital cities, and municipalities directly under the central government during the research period, and the industrial sector was the main emission resource, accounting for more than 85% of the total emissions. (2) Carbon emissions per unit of land decreased with the increasing land scale, regardless of the land-use type. The growth rate of carbon emissions was slower than that of the population, and cities also became more efficient as their economic scale expanded. (3) Compared with small cities, the large ones benefited more from increasing commercial and traffic land areas, whereas industrial emissions for production needs exhibited significant agglomeration characteristics. Overall, low-carbon planning should focus on the driving role of provincial capital cities as large cities tend to be more efficient, and develop the emission reduction potential of major industrial cities as well.

Photoresponsive drug delivery stands as a pivotal frontier in smart drug administration, leveraging the non-invasive, stable, and finely tunable nature of light-triggered methodologies. The generative pre-trained transformer (GPT) has been employed to generate molecular structures. In our study, we harnessed GPT-2 on the QM7b dataset to refine a UV-GPT model with adapters, enabling the generation of molecules responsive to UV light excitation. Utilizing the Coulomb matrix as a molecular descriptor, we predicted the excitation wavelengths of these molecules. Furthermore, we validated the excited state properties through quantum chemical simulations. Based on the results of these calculations, we summarized some tips for chemical structures and integrated them into the alignment of large-scale language models within the reinforcement learning from human feedback (RLHF) framework. The synergy of these findings underscores the successful application of GPT technology in this critical domain.

Microorganisms are important sources of various natural products that have been commercialized for human medicine and animal healthcare. Bacitracin is an important antibacterial natural product predominantly produced by Bacillus licheniformis and Bacillus subtilis, and it is characterized by a broad antimicrobial spectrum, strong activity and low resistance, thus bacitracin is extensively applied in animal feed and veterinary medicine industries. In recent years, various strategies have been proposed to improve bacitracin production. Herein, we systematically describe the regulation of bacitracin biosynthesis in genus Bacillus and its associated mechanism, to provide a theoretical basis for bacitracin overproduction. The metabolic engineering strategies applied for bacitracin production are explored, including improving substrate utilization, using an enlarged precursor amino acid pool, increasing ATP supply and NADPH generation, and engineering transcription regulators. We also present several approaches of fermentation process optimization to facilitate the industrial large-scale production of bacitracin. Finally, the challenges and prospects associated with microbial bacitracin synthesis are discussed to facilitate the establishment of high-yield and low-cost biological factories.

Introduction: Chinese Holstein in South China suffer heat stress for a long period, which leads to evolutionary differences from Chinese Holstein in North China. The aim of this study was to estimate the genetic parameters of fertility traits for Chinese Holstein in South China.Methods: A total of 167,840 Chinese Holstein heifers and cows from Guangming Animal Husbandry Co., LTD farms were used in this study. The fertility traits analyzed were calving interval (CI), days open (DO), age of first service (AFS), age of first calving (AFC), calving to first insemination (CTFS), first insemination to conception (FSTC), gestation length (GL), non-return rate to 56 days (NRR), and number of services (NS).Results: The descriptive statistics revealed that the same trait in heifers performed better than in cows, which was consistent with the other studies. The heritabilities of fertility traits in this study ranged from close to 0 (for NS of cows) to 0.2474 (for AFC of heifers). The genetic correlation of NRR between heifers and cows was 0.9993, which indicates that the NRR for heifers and cows could be treated as one trait in this population.Conclusion: The heritabilities of fertility traits in Chinese Holstein in south China were quite different from the heritabilities of fertility traits in North China. NRR56, NS, AFC, and CI were suggested to be included into the selection index to improve fertility performance of Chinsese Holstein of south China. The results of this study could provide genetic parameters for the animal breeding program of Chinese Holstein in the south of China.

Betalains provide Chenopodium quinoa bright color, and the key enzyme genes for betalain biosynthesis include CYP76AD, DODA, and GTs. In this study, 59 CqCYP76AD, CqDODA and CqGTs genes in quinoa were identified and characterized by gene structural characteristics, phylogenetic relationships and gene expression patterns. The CqCYP76AD genes were divided into ɑ, β and γ types, CqDODA into ɑ and β types, and CqGTs into CqcDOPA5GT, CqB5GT and CqB6GT types according to phylogenetic relationships. The analysis of co-linearity identified eight pairs of duplicated genes which were subjected to purifying selection during evolution. CqCYP76AD and CqDODA, as well as CqcDOPA5GT and CqB5GT may have been evolutionarily linked in genetic inheritance, based on gene location and gene structure study. The tissue expression specificity of CqCYP76AD, CqDODA, and CqGTs genes in response to seed germination and cold stress was studied by RNA-Seq data. The genes CqCYP76AD, CqDODA, and CqGTs were involved in betalain biosynthesis and cold stress. CqCYP76AD, CqDODA, CqcDOPA5GT and CqB5GT gene sequences were consistent in the eight quinoa samples and showed significant variations in expression. In contrast, the inconsistency between changes in gene expression and betalain accumulation indicates that other factors may influence betalain biosynthesis in quinoa. This study offers the theoretical basis for the roles of the CqCYP76AD, CqDODA, and CqGTs genes in betalain biosynthesis and cold stress in quinoa, as well as a guide for the full utilization of betalains in quinoa plants.

Tropane alkaloids (TAs) are synthesized by some species in Solanaceae. Here, the authors assemble the genomes of two representative TAs producing species, show that gene loss shapes uneven distribution of TAs in Solanaceae, and identify a cytochrome P450 gene catalyzing N-demethylation of hyoscyamine to generate norhyoscyamine.

Oxidative stress causes gut dysfunction and is a contributing factor in several intestinal disorders. Intestinal epithelial cell survival is essential for maintaining human and animal health under oxidative stress. 18beta-Glycyrrhetinic acid (GA) is known to have multiple beneficial effects, including antioxidant activity; however, the underlying molecular mechanisms have not been well established. Thus, the present study evaluated the therapeutic effects of GA on H2O2-induced oxidative stress in intestinal porcine epithelial cells. The results showed that pretreatment with GA (100 nM for 16 h) significantly increased the levels of several antioxidant enzymes and reduced corresponding intracellular levels of reactive oxidative species and malondialdehyde. GA inhibited cell apoptosis via activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, as confirmed by RNA sequencing. Further analyses demonstrated that GA upregulated the phosphorylation levels of PI3K and Akt and the protein level of B cell lymphoma 2, whereas it downregulated Cytochrome c and tumor suppressor protein p53 levels. Moreover, molecular docking analysis predicted the binding of GA to Vasoactive intestinal peptide receptor 1, a primary membrane receptor, to activate the PI3K/Akt signaling pathway. Collectively, these results revealed that GA protected against H2O2-induced oxidative damage and cell apoptosis via activating the PI3K/Akt signaling pathway, suggesting the potential therapeutic use of GA to alleviate oxidative stress in humans/animals.

This study investigated the effects of thermosonication (TS) on the quality of blackcurrant juice, along with its physicochemical properties, bioactive compounds, antioxidant capacity, and microbiological and sensory qualities. The treatments included raw juice (RJ), pasteurized juice (90 °C, 1 min, PJ), and thermosonicated juice (480 W, 40 kHz at 40, 50, or 60 °C, for 10, 20, 30, or 40 min, TJ). The results indicated that the effects of pasteurization and thermosonication on the pH, total soluble solids, and titratable acidity of the juice were not significant (p > 0.05). However, the cloudiness, browning index, and viscosity were significantly increased (p < 0.05), and the color properties of the blackcurrant juice were improved. The total phenolic, flavonoid, and anthocyanin contents of TJ (treated at 50 °C for 30 min) were increased by 12.6%, 20.9%, and 40.4%, respectively, and there was a notable decline in ascorbic acid content after the pasteurization treatment, while the loss was minor in all TJ samples compared with RJ. The scavenging ability of 1,1-diphenyl-2-pyridyl and hydroxyl radicals increased to 52.77% and 50.52%, respectively, which were significantly (p < 0.05) higher than those in the RJ and PJ samples. In addition, both pasteurization and thermosonication resulted in a significant (p < 0.05) reduction in microbial counts, while there were no significant (p > 0.05) differences in the sensory parameters compared with the RJ samples. In conclusion, this study suggests that TS is an effective method that can be used as an alternative to pasteurization to improve the quality of blackcurrant juice.

Marine actinomycetes produce a substantial number of natural products with cytotoxic activity. Actinomycete strains have been isolated from sources including fishes, coral, sponges, seaweeds, mangroves and sediments. These cytotoxic compounds can be broadly categorized into four classes: polyketides; non-ribosomal peptides and hybrids; isoprenoids and hybrids; and others, among which the majority are polyketides (146 of 254). Twenty-two of the 254 compounds show potent cytotoxicity, with IC50 values at the ng/mL or nM level. This review highlights the sources, structures and antitumor activity of 254 natural products isolated from marine actinomycetes and first reported between 1989 and 2020.

Laryngeal carcinoma (LC) is the second most common malignant tumor of the head and neck. Due to its insidious nature, most patients have developed to the middle and late stages by the time they are diagnosed, missing the best treatment period. Thus, early detection, diagnosis and treatment are crucial to improve the prognosis of LC and enhance the quality of life of patients. In this study, a surface-enhanced Raman (SERS) sensing platform was developed by combining the magnetic beads (MBs) enrichment strategy and the antibody-DNA-mediated catalytic hairpin self-assembly (CHA) signal amplification technology. 4-Mercaptobenzoic acid (4-MBA) and hairpin DNA 1 (hpDNA1) were modified onto the surface of gold nanobipyramids (GNBPs) as SERS nanotags. Hairpin DNA 2 (hpDNA2) modified MBs were used as capture nanoprobes. Under the action of CHA and magnet-induced MBs enrichment, GNBPs can be assembled on the surface of MBs, forming high-density “hot spots” for the SERS signal enhancement. The results showed that the SERS sensing platform has the advantages of high sensitivity, high specificity and high reproducibility, with the limit of detection (LOD) low to pg/mL level. The expression level of CYFRA21-1 in serum of LC patients and healthy controls was successfully detected by the SERS sensing platform. The accuracy of the SERS results was verified by enzyme linked immunosorbent assay (ELISA). Therefore, this SERS sensor can be used for the detection of CYFRA21-1 in serum, providing a simple and reliable new method for the early diagnosis of LC.

The control of Aspergillus niger (A. niger) is of great significance for the agricultural economy and food safety. In this study, the antifungal effect and mechanism of iturin A from Bacillus amyloliquefaciens (CGMCC No. 8473) against A. niger (ATCC 16404) were investigated using biochemical analyses and proteomics. Changes in a mycelium treated with iturin A were observed using scanning electron microscopy and transmission electron microscopy, including mycelial twisting and collapse, organelle disintegration, and intracellular vacuolization. The cytomembrane integrity of A. niger was affected by iturin A, as detected by propidium iodide staining. In addition, the generation of excess reactive oxygen species, the hyperpolarization of the mitochondrial membrane potential and malondialdehyde accumulation also indicated that iturin A induced apoptosis in A. niger through the oxidative stress pathway. Proteomics results showed that 310 proteins were differentially expressed in the A. niger mycelium exposed to iturin A, including 159 upregulated proteins and 151 downregulated proteins, which were mainly associated with energy metabolism of A. niger. We propose that iturin A might inhibit the growth of A. niger by disrupting cytomembrane integrity, via oxidative stress, and by interfering with glycolysis/gluconeogenesis and the tricarboxylic acid cycle. Overall, iturin A is a promising antifungal agent that provides a rationale for controlling A. niger contamination in food.

Subarachnoid hemorrhage (SAH) is a cerebrovascular accident with an acute onset, severe disease characteristics, and poor prognosis. Within 72 hours after the occurrence of SAH, a sequence of pathological changes occur in the body including blood-brain barrier breakdown, cerebral edema, and reduced cerebrovascular flow that are defined as early brain injury (EBI), and it has been demonstrated that EBI exhibits an obvious correlation with poor prognosis. Ferroptosis is a novel programmed cell death mode. Ferroptosis is induced by the iron-dependent accumulation of lipid peroxides and reactive oxygen species (ROS). Ferroptosis involves abnormal iron metabolism, glutathione depletion, and lipid peroxidation. Recent study revealed that ferroptosis is involved in EBI and is significantly correlated with poor prognosis. With the gradual realization of the importance of ferroptosis, an increasing number of studies have been conducted to examine this process. This review summarizes the latest work in this field and tracks current research progress. We focused on iron metabolism, lipid metabolism, reduction systems centered on the GSH/GPX4 system, other newly discovered GSH/GPX4-independent antioxidant systems, and their related targets in the context of early brain injury. Additionally, we examined certain ferroptosis regulatory mechanisms that have been studied in other fields but not in SAH. A link between death and oxidative stress has been described. Additionally, we highlight the future research direction of ferroptosis in EBI of SAH, and this provides new ideas for follow-up research.

Objective: In critically ill patients, the change of pathophysiological status may affect the pharmacokinetic (PK) process of drugs. The purpose of this study was to develop a PK model for tigecycline in critically ill patients, identify the factors influencing the PK and optimiz dosing regimens.Method: The concentration of tigecycline was measured LC-MS/MS. We established population PK model with the non-linear mixed effect model and optimized the dosing regimens by Monte Carlo simulation.Result: A total of 143 blood samples from 54 patients were adequately described by a one-compartment linear model with first-order elimination. In the covariate screening analysis, the APACHEII score and age as significant covariates. The population-typical values of CL and Vd in the final model were 11.30 ± 3.54 L/h and 105.00 ± 4.47 L, respectively. The PTA value of the standard dose regimen (100 mg loading dose followed by a 50 mg maintenance dose at q12 h) was 40.96% with an MIC of 2 mg/L in patients with HAP, the ideal effect can be achieved by increasing the dosage. No dose adjustment was needed for Klebsiella pneumoniae for AUC0–24/MIC targets of 4.5 and 6.96, and the three dose regimens almost all reached 90%. A target AUC0–24/MIC of ≥17.9 reached 100% in patients with cSSSI in the three tigecycline dose regimens, considering MIC ≤ 0.25 mg/L.Conclusion: The final model indicated that APACHEII score and age could affect the Cl and Vd of tigecycline, respectively. The standard dose regimen of tigecycline was often not able to obtain satisfactory therapeutic effects for critically ill patients. For patients with HAP and cIAI caused by one of three pathogens, the efficacy rate can be improved by increasing the dose, but for cSSSI infections caused by Acinetobacter baumannii and K. pneumoniae, it is recommended to change the drug or use a combination of drugs.

Aiming at the complex and changeable channel characteristics in high-speed mobile environment, and the influence of additive noise and nonlinear effects, a residual mixing network (RM-Net) for massive MIMO CSI feedback was proposed.By learning the spatial structure and temporal correlation of high-speed mobile channel, the network was able to remove massive MIMO channel noise, and the CSI compression rate and recovery quality could be significantly improved.System simulation results show that RM-Net can eliminate the influence of additive noise in high-speed mobile scenarios, learn and adapt to the channel characteristics of sparse and double-selective fading channels, and still has good performance under the conditions of high compression rate and low signal-to-noise ratio.The proposed algorithm performance is much better than other CS-based and DL-based CSI feedback algorithms.

V937 is an oncolytic virus immunotherapy clinical drug candidate consisting of a proprietary formulation of Coxsackievirus A21 (CVA21). V937 specifically binds to and lyses cells with over-expressed ICAM-1 receptors in a range of tumor cell types and is currently in phase I and II clinical trials. Infectious V937 particles consist of a ∼30 nm icosahedral capsid assembled from four structural viral proteins that encapsidate a viral RNA genome. Rapid and robust analytical methods to quantify and characterize CVA21 virus particles are important to support the process development, regulatory requirements, and validation of new manufacturing platforms. Herein, we describe a size-exclusion chromatography (SEC) method that was developed to characterize the V937 drug substance and process intermediates. Using a 4-in-1 combination of multi-detectors (UV, refractive index, dynamic and static light scattering), we demonstrate the use of SEC for the quantification of the virus particle count, the determination of virus size (molecular weight and hydrodynamic diameter), and the characterization of virus purity by assessing empty-to-full capsid ratios. Through a SEC analysis of stressed V937 samples, we propose CVA21 thermal degradation pathways that result in genome release and particle aggregation.

Objective: We performed a case-control study to investigate the correlation between DNA methylation and mRNA expression of the glutathione S-transferase alpha 4 (GSTA4) gene and the risk of intracranial aneurysm (IA) in the Chinese Han population.Methods: After propensity score matching, 44 pairs of cases and controls were collected in this study. Fasting blood samples were collected for DNA and RNA extraction within 24 h of admission. Nine CpG dinucleotides were selected from the GSTA4 promoter region for DNA methylation pyrosequencing. mRNA expression of GSTA4 was measured by quantitative real-time polymerase chain reaction (RT-qPCR). In vitro cell experiments were conducted to verify the association between 5-aza-2′-deoxycytidine induced DNA hypomethylation and GSTA4 mRNA expression.Results: The mean methylation level of GSTA4 was much lower in IA patients, especially in IA patients, especially in unruptured IA (UIA), than that in controls (IA vs. Control, p < .001; ruptured IA (RIA) vs. Control, p = .005; UIA vs. Control, p < .001). With sex stratification, we further found that the association between GSTA4 methylation and IA risk presented only in women (mean methylation level: IA vs. Control, p < .001; RIA vs. Control, p = .009; UIA vs. Control, p < .001). GSTA4 mRNA expression was significantly higher in the IA group than in the control group (p < .01) and negatively correlated with DNA methylation in all individuals (r = −.746, p < .001). DNA hypomethylation can increase GSTA4 mRNA expression in human primary artery smooth muscle cells. The receiver operating characteristic (ROC) curve showed that GSTA4 mean methylation (AUC = .80, p < .001) was a reliable predictor of women intracranial aneurysm, among which CpG 1 exhibited the best predictive value (AUC = .89, p < .001). In addition, GSTA4 expression levels could also predict the risk of IA in women (AUC = .87, p = .005).Conclusion: Decreased DNA methylation and increased mRNA expression of the GSTA4 gene are associated with the risk of IA in women.

We aim to detect the presence of Tacheng tick virus 2 (TcTV-2) in ticks of southeastern Kazakhstan. A total of 205 ticks were collected and separated into four species, namely Hyalomma scupense, Dermacentor marginatus, Hyalomma asiaticum and Hyalomma anatolicum. The partial S segment of TcTV-2 was detected in individual RNA of separated ticks by reverse transcriptase polymerase chain reaction. 11.22% (23/205) of ticks were positive to the viral S segment. This is first report of presence of the TcTV-2 in Hy. scupense and Hy. anatolicum from Kazakhstan. This finding extends tick species and the geographic distribution of TcTV-2.

The aim of this study was to investigate the genetic parameters and genetic architectures of six milk production traits in the Shanghai Holstein population. The data used to estimate the genetic parameters consisted of 1,968,589 test-day records for 305,031 primiparous cows. Among the cows with phenotypes, 3,016 cows were genotyped with Illumina Bovine SNP50K BeadChip, GeneSeek Bovine 50K BeadChip, GeneSeek Bovine LD BeadChip v4, GeneSeek Bovine 150K BeadChip, or low-depth whole-genome sequencing. A genome-wide association study was performed to identify quantitative trait loci and genes associated with milk production traits in the Shanghai Holstein population using genotypes imputed to whole-genome sequences and both fixed and random model circulating probability unification and a mixed linear model with rMVP software. Estimated heritabilities (h2) varied from 0.04 to 0.14 for somatic cell score (SCS), 0.07 to 0.22 for fat percentage (FP), 0.09 to 0.27 for milk yield (MY), 0.06 to 0.23 for fat yield (FY), 0.09 to 0.26 for protein yield (PY), and 0.07 to 0.35 for protein percentage (PP), respectively. Within lactation, genetic correlations for SCS, FP, MY, FY, PY, and PP at different stages of lactation estimated in random regression model were ranged from -0.02 to 0.99, 0.18 to 0.99, 0.04 to 0.99, 0.04 to 0.99, 0.01 to 0.99, and 0.33 to 0.99, respectively. The genetic correlations were highest between adjacent DIM but decreased as DIM got further apart. Candidate genes included those related to production traits (DGAT1, MGST1, PTK2, and SCRIB), disease-related (LY6K, COL22A1, TECPR2, and PLCB1), heat stress–related (ITGA9, NDST4, TECPR2, and HSF1), and reproduction-related (7SK and DOCK2) genes. This study has shown that there are differences in the genetic mechanisms of milk production traits at different stages of lactation. Therefore, it is necessary to conduct research on milk production traits at different stages of lactation as different traits. Our results can also provide a theoretical basis for subsequent molecular breeding, especially for the novel genetic loci.

Cell division plays an indispensable role in leaf morphogenesis, which is regulated via the complexes formed by cyclin and cyclin-dependent kinase (CDK). In this study, gene family analysis, exogenous auxin stimulation, RNA-seq and WGCNA analysis were all used to investigate the molecular mechanisms by which cell-cycle-related factors participated in the auxin signaling pathway on leaf morphogenesis. Sixty-three cyclin members and seventeen CDK members in Populus alba were identified and systematically analyzed. During the evolution, WGD was the main reason that resulted in the expansion of cyclin and CDK genes. Firstly, after a short time treating with auxin to matured leaves of seedlings, genes related to cell division including GRF and ARGOS were both upregulated to restart the transition of cells from G1-to-S phase. Secondly, with three days of continuous auxin stimulation to leaves at different developmental stages, leaves area variation, transcriptomes and hormones were analyzed. By PCA, PCoA and WGCNA analyses, the turquoise module was both positively related to leaf development and auxin. Based on the co-expression analysis and Y2H experiment, PoalbCYCD1;4, PoalbCYCD3;3 and PoalbCYCD3;5 were supposed to interact with PoalbCDKA;1, which could be the trigger to promote the G1-to-S phase transition. The ARF transcription factor might play the key role of connecting the auxin signaling pathway and cell division in leaf morphogenesis by affecting CYC–CDK complexes.

Cross-modal sentiment analysis is an emerging research area in natural language processing. The core task of cross-modal fusion lies in cross-modal relationship extraction and joint feature learning. The existing research methods of cross-modal sentiment analysis focus on static text, video, audio, and other modality data but ignore the fact that different modality data are often unaligned in practical applications. There is a long-term time dependence among unaligned data sequences, and it is difficult to explore the interaction between different modalities. The paper proposes a sentiment analysis model (UA-BFET) based on feature enhancement technology in unaligned data scenarios, which can perform sentiment analysis on unaligned text and video modality data in social media. Firstly, the model adds a cyclic memory enhancement network across time steps. Then, the obtained cross-modal fusion features with interaction are applied to the unimodal feature extraction process of the next time step in the Bi-directional Gated Recurrent Unit (Bi-GRU) so that the progressively enhanced unimodal features and cross-modal fusion features continuously complement each other. Secondly, the extracted unimodal text and video features taken jointly from the enhanced cross-modal fusion features are subjected to canonical correlation analysis (CCA) and input into the fully connected layer and Softmax function for sentiment analysis. Through experiments executed on unaligned public datasets MOSI and MOSEI, the UA-BFET model has achieved or even exceeded the sentiment analysis effect of text, video, and audio modality fusion and has outstanding advantages in solving cross-modal sentiment analysis in unaligned data scenarios.

BackgroundThe reported rate of cardiovascular adverse events (CAE) caused by immune checkpoint inhibitors (ICI) is low but potentially fatal. Assess the risk of CAE in cancer patients and compare the incidence of CAE between Chinese developed ICIs and imported ICIs.MethodsA retrospective analysis was performed on cancer patients treated with ICI for at least four cycles in the Second Affiliated Hospital of Dalian Medical University from January 2018 to March 2022. Baseline characteristics, physiological and biochemical values, electrocardiographic and echocardiographic findings were compared between patients with and without CAE.ResultsAmong 495 patients treated with ICIs, CAEs occurred in 64 patients (12.93%). The median time to the event was 105 days (61–202). The patients with low neutrophil-to-lymphocyte ratio (L-NLR) were significantly associated with the risk of developing CAE (hazard ratio HR 3.64, 95% confidence ratio CI 1.86–7.15, P = 0.000). Patients with higher comorbidity burden significantly increased the risk of developing CAE (HR 1.30, 95% CI 1.05–1.61, P = 0.014). Those who received a combination of ICI and vascular endothelial growth factor receptor (VEGFR) inhibitors (HR 2.57, 95% CI 1.37–4.84, P = 0.003) or thoracic radiation therapy (HR 32.93, 95% CI 8.81–123.14, P = 0.000) were at a significantly increased risk of developing CAE. Compared to baseline values, creatine kinase is -oenzymes (CK-MB) (95% CI -9.73 to -2.20, P = 0.003) and cardiac troponin I (cTnI) (95% CI -1.06 to -0.06, P = 0.028) were elevated, and the QTc interval prolonged (95% CI -27.07 to -6.49, P = 0.002). Using nivolumab as a control, there was no difference in CAE risk among the eight ICIs investigated. However, the results of the propensity matching showed that programmed death-ligand 1 (PD-L1) inhibitors had lower CAE occurrence compared with programmed cell death protein 1 (PD-1) inhibitors (adjusted HR = 0.38, P = 0.045).ConclusionPatients who received concurrent VEGFR inhibitors and ICIs had a history of thoracic radiation therapy, L-NLR, and higher comorbidity burden had an increased risk of CAEs. Elevated cTnI, CK-MB, and QTc, can be used to monitor CAEs. There was no significant difference in CAE risks between Chinese domestic and imported ICIs. PD-L1 inhibitors had lower CAE occurrence than PD-1 inhibitors.

Abstract Diabetic retinopathy (DR) as a retinal neovascularization‐related disease is one of the leading causes of irreversible blindness in patients. The goal of this study is to determine the role of a G‐protein‐coupled chemoattractant receptor (GPCR) FPR2 (mouse Fpr2) in the progression of DR, in order to identify novel therapeutic targets. We report that Fpr2 was markedly upregulated in mouse diabetic retinas, especially in retinal vascular endothelial cells, in associated with increased number of activated microglia and Müller glial cells. In contrast, in the retina of diabetic Fpr2−/− mice, the activation of vascular endothelial cells and glia was attenuated with reduced production of proinflammatory cytokines. Fpr2 deficiency also prevented the formation of acellular capillary during diabetic progression. Furthermore, in oxygen‐induced retinopathy (OIR) mice, the absence of Fpr2 was associated with diminished neovasculature formation and pathological vaso‐obliteration region in the retina. These results highlight the importance of Fpr2 in exacerbating the progression of neuroglial degeneration and angiogenesis in DR and its potential as a therapeutic target.

Abstract Background Topical isotretinoin is commonly used to treat acne. However, topical isotretinoin has side effects and can hardly permeate through the stratum corneum, the most important skin barrier. Therefore, this study aimed to demonstrate the efficacy of nanoparticles as stable carriers with great curative effects, low side effects, and strong transdermal ability. Results In a rabbit model of hyperkeratinization, STCM-ATRA-NPs showed significant therapeutic efficacy. By contrast, negative therapeutic efficacy was observed in a golden hamster model of hyper sebum production. Scanning electron microscopy and Fourier transform infrared spectral analyses showed that nanoparticles could penetrate the stratum corneum. Western blotting demonstrated that the nanoparticles could enhance the transdermal efficacy of isotretinoin by reducing the effect of keratin and tight junction proteins. Further, nanoparticles enhanced endocytosis, thereby promoting drug penetration and absorption into the skin. Conclusion STCM-ATRA-NPs were demonstrated to control isotretinoin release, reducing its side effects, and efficiently permeating through the skin by reducing the effect of keratin and tight junction proteins and enhancing endocytosis.

Abstract Background Despite the fact that the overwhelming majority of mental health services are delivered in outpatient settings, the effect of changes in non-hospital-based mental health care on increased suicide rates is largely unknown. This study examines the association between changes in community mental health center (CMHC) supply and suicide mortality in the United States. Methods Retrospective analysis was performed using data from National Mental Health Services Survey (N-MHSS) and the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) (2014–2017). Population-weighted multiple linear regressions were used to examine within-state associations between CMHCs per capita and suicide mortality. Models controlled for state-level characteristics (i.e., number of hospital psychiatric units per capita, number of mental health professionals per capita, age, race, and percent low-income), year and state. Results From 2014 to 2017, the number of CMHCs decreased by 14% nationally (from 3406 to 2920). Suicide increased by 9.7% (from 15.4 to 16.9 per 100,000) in the same time period. We find a small but negative association between the number of CMHCs and suicide deaths (− 0.52, 95% CI − 1.08 to 0.03; p = 0.066). Declines in the number of CMHCs from 2014 to 2017 may be associated with approximately 6% of the national increase in suicide, representing 263 additional suicide deaths. Conclusions State governments should avoid the declining number of CMHCs and the services these facilities provide, which may be an important component of suicide prevention efforts.

Titanium oxide nanotubes prepared by anodization are widely used in many fields due to their excellent properties, but the formation mechanism is still under discussion. This paper focuses on the formation of TiO2 nanotubes in different electrolytes. We explored the influence of electrolyte components on anodization process and results through analysing the current–time curves and SEM images. The results showed that the addition of ionizable sodium salt to the electrolyte increased the conductivity of electrolytes, and then promoted the growth of nanotubes with improving the properties. In this paper, we explained the interesting experimental results by the oxygen bubble model theory and double current(ionic current and electronic current) theory.

In an electroencephalogram- (EEG-) based brain–computer interface (BCI), a subject can directly communicate with an electronic device using his EEG signals in a safe and convenient way. However, the sensitivity to noise/artifact and the non-stationarity of EEG signals result in high inter-subject/session variability. Therefore, each subject usually spends long and tedious calibration time in building a subject-specific classifier. To solve this problem, we review existing signal processing approaches, including transfer learning (TL), semi-supervised learning (SSL), and a combination of TL and SSL. Cross-subject TL can transfer amounts of labeled samples from different source subjects for the target subject. Moreover, Cross-session/task/device TL can reduce the calibration time of the subject for the target session, task, or device by importing the labeled samples from the source sessions, tasks, or devices. SSL simultaneously utilizes the labeled and unlabeled samples from the target subject. The combination of TL and SSL can take advantage of each other. For each kind of signal processing approaches, we introduce their concepts and representative methods. The experimental results show that TL, SSL, and their combination can obtain good classification performance by effectively utilizing the samples available. In the end, we draw a conclusion and point to research directions in the future.

In this study, a superhydrophobic surface was constructed on a copper substrate through dealloying-forming and solution-immersion methods. The dealloying process for nanostructures on a copper surface involved the electrodeposition of zinc atoms, and the thermal alloying and chemical dealloying of zinc atoms. Then, a dealloyed copper surface was subsequently modified with low-surface-energy copper stearate to produce a superhydrophobic surface. Scanning electron microscopy, X-ray diffractometry, and Fourier transform infrared spectrometry were employed to characterize the morphological features and composition components of the surface in the fabrication process. The static contact angles of the copper surfaces were compared and evaluated based on various fabrication parameters, including electric current density, corrosive solution concentration, and nanostructures. The results indicated that a leaf-like copper stearate could be constructed through immersing a dealloyed copper plate into a 0.005 mol/L ethanol solution of stearic acid for 5 min. Nanostructures provided more attachment areas on the copper surface to facilitate the formation of copper stearate. The resulting as-prepared surface presented excellent superhydrophobic properties with a contact angle of over 156.5°, and showed the potential properties of non-sticking, self-cleaning, anti-corrosion, and stability. This study provides an efficient approach to fabricate superhydrophobic surfaces for engineering copper metals.

Compound 1 (SMTP-7, also FGFC1), an isoindolone alkaloid from marine fungi Starchbotrys longispora FG216 and fungi Stachybotrys microspora IFO 30018, possessed diverse bioactivities such as thrombolysis, anti-inflammatory and anti-oxidative properties, and so on. It may be widely used for the treatment of various diseases, including cerebral infarction, stroke, ischemia/reperfusion damage, acute kidney injury, etc. Especially in cerebral infarction, compound 1 could reduce hemorrhagic transformation along with thrombolytic therapy, as the traditional therapies are accompanied with bleeding risks. In the latest studies, compound 1 selectively inhibited the growth of NSCLC cells with EGFR mutation, thus demonstrating its excellent anti-cancer activity. Herein, we summarized pharmacological activities, preparation of staplabin congeners—especially compound 1—and the mechanism of compound 1, with potential therapeutic applications.

With increasing life expectations, more and more patients suffer from fractures either induced by intensive sports or other bone-related diseases. The balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption is the basis for maintaining bone health. Osterix (Osx) has long been known to be an essential transcription factor for the osteoblast differentiation and bone mineralization. Emerging evidence suggests that Osx not only plays an important role in intramembranous bone formation, but also affects endochondral ossification by participating in the terminal cartilage differentiation. Given its essentiality in skeletal development and bone formation, Osx has become a new research hotspot in recent years. In this review, we focus on the progress of Osx’s function and its regulation in osteoblast differentiation and bone mass. And the potential role of Osx in developing new therapeutic strategies for osteolytic diseases was discussed.

To expand the range of daphnetin-based inhibitors/activators used for targeting G protein-coupled receptors (GPCRs) in disease treatment, twenty-five coumarin derivatives 1–25, including 7,8-dihydroxycoumarin and 7-hydroxycoumarin derivatives with various substitution patterns/groups at C3-/4- positions, were synthesized via mild Pechmann condensation and hydroxyl modification. The structures were characterized by 1H NMR, 13C NMR and ESI-MS. Their inhibition or activation activities relative to GPCRs were evaluated by double-antibody sandwich ELISA (DAS–ELISA) in vitro. The results showed that most of the coumarin derivatives possessed a moderate GPCR activation or inhibitory potency. Among them, derivatives 14, 17, 18, and 21 showed a remarkable GPCR activation potency, with EC50 values of 0.03, 0.03, 0.03, and 0.02 nM, respectively. Meanwhile, derivatives 4, 7, and 23 had significant GPCR inhibitory potencies against GPCRs with IC50 values of 0.15, 0.02, and 0.76 nM, respectively. Notably, the acylation of hydroxyl groups at the C-7 and C-8 positions of 7,8-dihydroxycoumarin skeleton or the etherification of the hydroxyl group at the C-7 position of the 7-hydroxycoumarin skeleton could successfully change GPCRs activators into inhibitors. This work demonstrated a simple and efficient approach to developing coumarin derivatives as remarkable GPCRs activators and inhibitors via molecular diversity-based synthesis.

The method of moments (MoM) is an efficient electromagnetic numerical method for the accurate prediction of light scattering from plasmonic nanostructures. In practice, the light-scattering properties in different incident directions are often concerning. However, traditional MoM generally resorts to the iterative method, which suffers from the problems of convergence rate and redundant computations for multiple incident excitations. Nanoarray structures will further aggravate these problems due to a large number of unknowns. In this article, an efficient numerical method based on MoM and a hierarchical matrix (H-matrix) algorithm is proposed to solve these problems. Numerical experiments demonstrate the efficiency and accuracy of the proposed method for the prediction of light scattering from plasmonic nanoarrays in multiple directions.

Supported nickel catalysts represent a class of important catalytic materials in selective hydrogenations, but applications are frequently limited by metal agglomeration or active-site blocking induced by the presence of hydrogen halides. Herein, we report a novel pre-coking strategy, exposing the nickel nanoparticles under methane dry reforming conditions to manipulate performance in the continuous-flow hydrogenation of 1,2-dichloro-4-nitrobenzene. Compared with the pristine nickel catalyst, the nanotube-like coke-modified nickel catalyst showed weakened hydrogenating ability, but much improved stability and slightly better selectivity to the target product, 3,4-dichloroaniline. Characterization results revealed that the strengthened stability performance can be mainly linked to the reduced propensity to retain chlorine species, which seems to block the access of the substrate molecules to the active sites, and thus is a major cause of catalyst deactivation on the pristine nickel catalyst. Coke deposition can occur on the pre-coked nickel catalyst but not on the pristine analog; however, the impact on the stability performance is much milder compared with that on chlorine uptake. In addition, the presence of coke is also beneficial in restraining the growth of the nickel nanoparticles. Generally, the developed method might provide an alternative perspective on the design of novel transition-metal-based catalytic materials for other hydrogenation applications under harsh conditions.

The synthesis of ester compounds is one of the most important chemical processes. In this work, Zn-Mg-Al mixed oxides with different Zn2+/Mg2+ molar ratios were prepared via co-precipitation method and supported gold nanoclusters to study the direct oxidative esterification of aldehyde and alcohol in the presence of molecular oxygen. Various characterization techniques such as N2-physical adsorption, X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and CO2 temperature programmed desorption (TPD) were utilized to analyze the structural and electronic properties. Based on the results, the presence of small amounts of Zn2+ ions (~5 wt.%) provoked a remarkable modification of the binary Mg-Al system, which enhanced the interaction between gold with the support and reduced the particle size of gold. For oxidative esterification reaction, the Au25/Zn0.05MgAl-400 catalyst showed the best performance, with the highest turnover frequency (TOF) of 1933 h−1. The active center was believed to be located at the interface between metallic gold with the support, where basic sites contribute a lot to transformation of the substrate.

Rapamycin (Rap) and its derivatives, called rapalogs, are being explored in clinical trials targeting cancer and neurodegeneration. The underlying mechanisms of Rap actions, however, are not well understood. Mechanistic target of rapamycin (mTOR), a lysosome-localized protein kinase that acts as a critical regulator of cellular growth, is believed to mediate most Rap actions. Here, we identified mucolipin 1 (transient receptor potential channel mucolipin 1 [TRPML1], also known as MCOLN1), the principle Ca2+ release channel in the lysosome, as another direct target of Rap. Patch-clamping of isolated lysosomal membranes showed that micromolar concentrations of Rap and some rapalogs activated lysosomal TRPML1 directly and specifically. Pharmacological inhibition or genetic inactivation of mTOR failed to mimic the Rap effect. In vitro binding assays revealed that Rap bound directly to purified TRPML1 proteins with a micromolar affinity. In both healthy and disease human fibroblasts, Rap and rapalogs induced autophagic flux via nuclear translocation of transcription factor EB (TFEB). However, such effects were abolished in TRPML1-deficient cells or by TRPML1 inhibitors. Hence, Rap and rapalogs promote autophagy via a TRPML1-dependent mechanism. Given the demonstrated roles of TRPML1 and TFEB in cellular clearance, we propose that lysosomal TRPML1 may contribute a significant portion to the in vivo neuroprotective and anti-aging effects of Rap via an augmentation of autophagy and lysosomal biogenesis.

LRP6 is known for its role as a Wnt co-receptor essential for the canonical Wnt/β-catenin signaling. Here, Li et al. show that LRP6 exerts a Wnt-independent scaffold function and regulates connexin 43 gap junction formation and coupling of cardiomyocytes in mouse hearts.

Distributed computing for large-scale graph data need to partition the graph firstly. The current methods of large-scale graph partitioning is to reduce the edge cut in order to lessen communication overhead by using vertex transfer strategies，but easily to fall into local optimum. Simulated annealing has a great probability to avoid the trap of local optimum and prevent vertices from invalid transfer which was introduced to transfer vertices. This method decreased communication overhead greatly. Comparative experiments show that the proposed algorithm has made a great improvement in reducing edge cut rates in large scale graph partition field. PageRank algorithm was also used to verify the effectiveness and feasibility of this method.

The large-scale graph partitioning algorithms were summarized and graph computing models in the distributed environment were introduced. Firstly the large-scale static graph partitioning algorithms and the dynamic graph partitioning algorithms were discussed. Then the advantages and disadvantages of these algorithms and its adaptability conscientiously were sumed up. Finally, some meaningful research subjects about the distributed graph partition, which have not been explored were pointed out.