Dioscin: Therapeutic potential for diabetes and complications.

Diabetes mellitus is a widespread metabolic disorder with increasing incidence worldwide, posing a considerable threat to human health because of its complications. Therefore, cost-effective antidiabetic drugs with minimal side effects are urgently needed. Dioscin, a naturally occurring compound, helps to reduce the complications of diabetes mellitus by regulating glucose and lipid metabolism, protecting islet ß cells, improving insulin resistance, and inhibiting oxidative stress and inflammatory response. Plant-derived dioscin reduces the risk of toxicity and side effects associated with chemically synthesized drugs. It is a promising option for treating diabetes mellitus because of its preventive and therapeutic effects, which may be attributed to a variety of underlying mechanisms. However, data compiled by current studies are preliminary. Information about the molecular mechanism of dioscin remains limited, and no high-quality human experiments and clinical trials for testing its safety and efficacy have been conducted. As a resource for research in this area, this review is expected to provide a systematic framework for the application of dioscin in the treatment of diabetes mellitus and its complications.

Wireless Electrical Signals Induce Functional Neuronal Differentiation of BMSCs on 3D Graphene Framework Driven by Magnetic Field.

Bone marrow mesenchymal stem cells (BMSCs) are suggested as candidates for neurodegeneration therapy by autologous stem cells to overcome the lack of neural stem cells in adults. However, the differentiation of BMSCs into functional neurons is a major challenge for neurotherapy. Herein, a methodology has been proposed to induce functional neuronal differentiation of BMSCs on a conductive three-dimensional graphene framework (GFs) combined with a rotating magnetic field. A wireless electrical signal of about 10 µA can be generated on the surface of GFs by cutting the magnetic field lines based on the well-known electromagnetic induction effect, which has been proven to be suitable for inducing neuronal differentiation of BMSCs. The enhanced expressions of the specific genes/proteins and apparent Ca2+ intracellular flow indicate that BMSCs cultured on GFs with 15 min/day rotating magnetic field stimulation for 15 days can differentiate functional neurons without any neural inducing factor. The animal experiments confirm the neural differentiation of BMSCs on GFs after transplantation in vivo, accompanied by stimulation of an external rotating magnetic field. This study overcomes the lack of autologous neural stem cells for adult neurodegeneration patients and provides a facile and safe strategy to induce the neural differentiation of BMSCs, which has potential for clinical applications of neural tissue engineering.

Controlling Local Thermalization Dynamics in a Floquet-Engineered Dipolar Ensemble.

Understanding the microscopic mechanisms of thermalization in closed quantum systems is among the key challenges in modern quantum many-body physics. We demonstrate a method to probe local thermalization in a large-scale many-body system by exploiting its inherent disorder and use this to uncover the thermalization mechanisms in a three-dimensional, dipolar-interacting spin system with tunable interactions. Utilizing advanced Hamiltonian engineering techniques to explore a range of spin Hamiltonians, we observe a striking change in the characteristic shape and timescale of local correlation decay as we vary the engineered exchange anisotropy. We show that these observations originate from the system's intrinsic many-body dynamics and reveal the signatures of conservation laws within localized clusters of spins, which do not readily manifest using global probes. Our method provides an exquisite lens into the tunable nature of local thermalization dynamics and enables detailed studies of scrambling, thermalization, and hydrodynamics in strongly interacting quantum systems.

The Role of Oxidative Stress in Multiple Exercise-Regulated Bone Homeostasis.

Bone is a tissue that is active throughout the lifespan, and its physiological activities, such as growth, development, absorption, and formation, are always ongoing. All types of stimulation that occur in sports play an important role in regulating the physiological activities of bone. Here, we track the latest research progress locally and abroad, summarize the recent, relevant research results, and systematically summarize the effects of different types of exercise on bone mass, bone strength and bone metabolism. We found that different types of exercise have different effects on bone health due to their unique technical characteristics. Oxidative stress is an important mechanism mediating the exercise regulation of bone homeostasis. Excessive high-intensity exercise does not benefit bone health but induces a high level of oxidative stress in the body, which has a negative impact on bone tissue. Regular moderate exercise can improve the body's antioxidant defense ability, inhibit an excessive oxidative stress response, promote the positive balance of bone metabolism, delay age-related bone loss and deterioration of bone microstructures and have a prevention and treatment effect on osteoporosis caused by many factors. Based on the above findings, we provide evidence for the role of exercise in the prevention and treatment of bone diseases. This study provides a systematic basis for clinicians and professionals to reasonably formulate exercise prescriptions and provides exercise guidance for patients and the general public. This study also provides a reference for follow-up research.

A genome and single-nucleus cerebral cortex transcriptome atlas of the short-finned pilot whale Globicephala macrorhynchus.

Cetaceans (dolphins, whales, and porpoises) have large and anatomically sophisticated brains. To expand our understanding of the cellular makeup of cetacean brains and the similarities and divergence between the brains of cetaceans and terrestrial mammals, we report a short-finned pilot whale (Globicephala macrorhynchus) single-nucleus transcriptome atlas. To achieve this goal, we assembled a chromosome-scale reference genome spanning 2.25 Gb on 22 chromosomes and profiled the gene expression of five major anatomical cortical regions of the short-finned pilot whale by single-nucleus RNA-sequencing (snRNA-seq). We identified six major cell lineages in the cerebral cortex (excitatory neurons, inhibitory neurons, oligodendrocytes, oligodendrocyte precursor cells, astrocytes, and endothelial cells), eight molecularly distinct subclusters of excitatory neurons, and four subclusters of inhibitory neurons. Finally, a comparison of snRNA-seq data from the short-finned pilot whale, human, and rhesus macaque revealed a broadly conserved cellular makeup of brain cell types. Our study provides genomic resources and molecular insights into cetacean brain evolution.

Establishment and identification of an animal model of long-term exercise-induced fatigue.

In competitive sports, the training load is close to the human physiological limit, which will inevitably lead to exercise-induced fatigue. If fatigue cannot be recovered in time, it will eventually lead to excessive training and affect sport performance. Therefore, fatigue has become an important part of the physical function assessment for athletes. This paper will review animal models of long-term exercise-induced fatigue, modeling schemes of mice under treadmill and swimming training, phenotypes of long-term exercise-induced fatigue (e.g., nervous system damage, myocardial cell damage, bone mineral density changes, and skeletal muscle damage), and fatigue indicators. The relationship between physiological indicators and biomarkers and long-term exercise-induced fatigue is analyzed to promote exercise-induced fatigue monitoring. This paper attempts to provide a reference for the selection of animal models of long-term exercise-induced fatigue and provide a new theoretical basis for medical supervision and recovery of exercise-induced fatigue.

Research Progress on Transorgan Regulation of the Cardiovascular and Motor System through Cardiogenic Exosomes.

The heart is the core organ of the circulatory system. Through the blood circulation system, it has close contact with all tissues and cells in the body. An exosome is an extracellular vesicle enclosed by a phospholipid bilayer. A variety of heart tissue cells can secrete and release exosomes, which transfer RNAs, lipids, proteins, and other biomolecules to adjacent or remote cells, mediate intercellular communication, and regulate the physiological and pathological activities of target cells. Cardiogenic exosomes play an important role in regulating almost all pathological and physiological processes of the heart. In addition, they can also reach distant tissues and organs through the peripheral circulation, exerting profound influence on their functional status. In this paper, the composition and function of cardiogenic exosomes, the factors affecting cardiogenic exosomes and their roles in cardiovascular physiology and pathophysiology are discussed, and the close relationship between cardiovascular system and motor system is innovatively explored from the perspective of exosomes. This study provides a reference for the development and application of exosomes in regenerative medicine and sports health, and also provides a new idea for revealing the close relationship between the heart and other organ systems.

Stemness Maintenance and Massproduction of Neural Stem Cells on Poly L-Lactic Acid Nanofibrous Membrane Based on Piezoelectriceffect.

Neural stem cells (NSCs) therapy is promising for treating neurodegenerative disorders and neural injuries. However, the limited in vitro expansion, spontaneous differentiation, and decrease in stemness obstruct the acquisition of high quantities of NSCs, restricting the clinical application of cell-based therapies and tissue engineering. This article reports a facile method of promoting NSCs expansion and maintaining stemness using wireless electrical stimulation triggered by piezoelectric nanomaterials. A nanofibrous membrane of poly L-lactic acid (PLLA) is prepared by electrostatic spinning, and the favorable piezoelectric property of PLLA facilitates the freeing of electrons after transformation. These self-powered electric signals generated by PLLA significantly enhance NSCs proliferation. Further, an undifferentiated cellular state is maintained in the NSCs cultured on the surfaces of PLLA nanofibers exposed to ultrasonic vibration. In addition, the neural differentiation potencies and functions of NSCs expanded by piezoelectric-driven localized electricity are not attenuated. Moreover, cell stemness can be maintained by wireless electric stimulation. Taken together, the electronic signals mediated by PLLA nanofibers facilitate NSCs proliferation. This efficient and simple strategy can maintain the stemness of NSCs during proliferation, which is essential for their clinical application, and opens up opportunities for the mass production of NSCs for use in cell therapy.

Regulation of Neural Differentiation of ADMSCs using Graphene-Mediated Wireless-Localized Electrical Signals Driven by Electromagnetic Induction.

Although adipose-derived mesenchymal stem cells (ADMSCs) isolated from patients' fat are considered as the most important autologous stem cells for tissue repair, significant difficulties in the neural differentiation of ADMSCs still impede stem cell therapy for neurodegenerative diseases. Herein, a wireless-electrical stimulation method is proposed to direct the neural differentiation of ADMSCs based on the electromagnetic effect using a graphene film as a conductive scaffold. By placing a rotating magnet on the top of a culture system without any inducer, the ADMSCs cultured on graphene differentiate into functional neurons within 15 days. As a conductive biodegradable nanomaterial, graphene film acts as a wireless electrical signal generator driven by the electromagnetic induction, and millivolt-level voltage generated in situ provokes ADMSCs to differentiate into neurons, proved by morphological variation, extremely high levels of neuron-specific genes, and proteins. Most importantly, Ca2+ intracellular influx is observed in these ADMSC-derived neurons once exposure to neurotransmitters, indicating that these cells are functional neurons. This research enhances stem cell therapy for neurodegenerative diseases using autologous ADMSCs and overcomes the lack of neural stem cells. This nanostructure-mediated physical-signal simulation method is inexpensive, safe, and localized, and has a significant impact on neural regeneration.

Out-of-equilibrium criticalities in graphene superlattices.

In thermodynamic equilibrium, current in metallic systems is carried by electronic states near the Fermi energy, whereas the filled bands underneath contribute little to conduction. Here, we describe a very different regime in which carrier distribution in graphene and its superlattices is shifted so far from equilibrium that the filled bands start playing an essential role, leading to a critical-current behavior. The criticalities develop upon the velocity of electron flow reaching the Fermi velocity. Key signatures of the out-of-equilibrium state are current-voltage characteristics that resemble those of superconductors, sharp peaks in differential resistance, sign reversal of the Hall effect, and a marked anomaly caused by the Schwinger-like production of hot electron-hole plasma. The observed behavior is expected to be common to all graphene-based superlattices.

A TTP-incorporated scoring model for predicting mortality of solid tumor patients with bloodstream infection caused by Escherichia coli.

BACKGROUND: Few mortality-scoring models are available for solid tumor patients who are predisposed to develop Escherichia coli-caused bloodstream infection (ECBSI). We aimed to develop a mortality-scoring model by using information from blood culture time to positivity (TTP) and other clinical variables. METHODS: A cohort of solid tumor patients who were admitted to hospital with ECBSI and received empirical antimicrobial therapy was enrolled. Survivors and non-survivors were compared to identify the risk factors of in-hospital mortality. Univariable and multivariable regression analyses were adopted to identify the mortality-associated predictors. Risk scores were assigned by weighting the regression coefficients with corresponding natural logarithm of the odds ratio for each predictor. RESULTS: Solid tumor patients with ECBSI were distributed in the development and validation groups, respectively. Six mortality-associated predictors were identified and included in the scoring model: acute respiratory distress (ARDS), TTP ≤ 8 h, inappropriate antibiotic therapy, blood transfusion, fever ≥ 39 °C, and metastasis. Prognostic scores were categorized into three groups that predicted mortality: low risk (< 10% mortality, 0-1 points), medium risk (10-20% mortality, 2 points), and high risk (> 20% mortality, ≥ 3 points). The TTP-incorporated scoring model showed excellent discrimination and calibration for both groups, with AUC being 0.833 vs 0.844, respectively, and no significant difference in the Hosmer-Lemeshow test (6.709, P = 0.48) and the chi-square test (6.993, P = 0.46). Youden index showed the best cutoff value of ≥ 3 with 76.11% sensitivity and 79.29% specificity. TTP-incorporated scoring model had higher AUC than no TTP-incorporated model (0.837 vs 0.817, P < 0.01). CONCLUSIONS: Our TTP-incorporated scoring model was associated with improving capability in predicting ECBSI-related mortality. It can be a practical tool for clinicians to identify and manage bacteremic solid tumor patients with high risk of mortality.

Comparative genomics provides insights into the aquatic adaptations of mammals.

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.

A Chromosomal-scale Reference Genome of the Kelp Grouper Epinephelus moara.

The kelp grouper, Epinephelus moara, is a carnivorous coral reef fish widely distributing in the Indo-Pacific Oceans. Compared to other grouper species, E. moara is featured for its wide tolerance to environmental stresses, such as temperature and salinity. In addition, it is popularly used as a breeding species for hybrid grouper production. Here, we report the de novo sequencing and assembly of E. moara genome using a combination of Illumina pair-ended, PacBio and Hi-C technologies. We generated a 1.08 Gb genome assembly with a scaffold N50 of 44.93 Mb and contig N50 of 2.22 Mb. The scaffolds and contigs were clustered and oriented into 24 chromosomes, and 24,135 protein-coding genes were predicted, among which 96.8% were annotated. More than 95.6% of the conserved complete genes were successfully retrieved by BUSCO analysis. Comparative genomic analyses showed that some expanded gene families in the E. moara genome were significantly enriched in innate immune pathways. The E. moara genome provides a valuable resource for genetic improvement and genomic breeding of groupers, as well as evolutionary and comparative study with other grouper species.

Fabrication of a Sensitive Strain and Pressure Sensor from Gold Nanoparticle-Assembled 3D-Interconnected Graphene Microchannel-Embedded PDMS.

Manufacture of uniform, sensitive, and durable microtextured sensing materials is one of the greatest challenges for pressure sensors and electronic skins. Reported in this article is a gold nanoparticle-assembled, 3D-interconnected, graphene microchannel-embedded PDMS (3D GMC-PDMS) film for strain and pressure sensors. The film consists of porous nickel foam with its inner walls coated by multilayer graphene. Embedding in PDMS with etching removal of the Ni yields a 3D GMC-PDMS. Coating the inner walls with Au nanoparticles yields an Au nanoparticle-assembled 3D GMC-PDMS (AuNPs-GMC-PDMS) film, which is useful as an ultrasensitive pressure and strain sensor. This sensor exhibits a wide detection range (∼50 kPa) and ultrahigh sensitivity of 5.37, 1.56, and 0.5 kPa-1 in the ranges of <1, 1-10, and 10-50 kPa, respectively. Its lower detection limit is 4.4 Pa, its response time is 20 ms, and its strain factor is up to 15. Comparison of a AuNPs-GMC-PDMS film with a 3D GMC-PDMS film reveals a sensitivity improvement of 40 times in the 0-1 kPa pressure range and a gauge factor of more than 4 times in the 0-30% tensile strain range. The device has broad applications as a traditional or wearable medical sensor.

The White-Spotted Bamboo Shark Genome Reveals Chromosome Rearrangements and Fast-Evolving Immune Genes of Cartilaginous Fish.

Chondrichthyan (cartilaginous fish) occupies a key phylogenetic position and is important for investigating evolutionary processes of vertebrates. However, limited whole genomes impede our in-depth knowledge of important issues such as chromosome evolution and immunity. Here, we report the chromosome-level genome of white-spotted bamboo shark. Combing it with other shark genomes, we reconstructed 16 ancestral chromosomes of bamboo shark and illustrate a dynamic chromosome rearrangement process. We found that genes on 13 fast-evolving chromosomes can be enriched in immune-related pathways. And two chromosomes contain important genes that can be used to develop single-chain antibodies, which were shown to have high affinity to human disease markers by using enzyme-linked immunosorbent assay. We also found three bone formation-related genes were lost due to chromosome rearrangements. Our study highlights the importance of chromosome rearrangements, providing resources for understanding of cartilaginous fish diversification and potential application of single-chain antibodies.

Decomposition performance of hypochlorite on bead-type NiOx(OH)y catalyst: improving applicability of catalysts.

An easy-to-use, pollution-free and reusable beaded NiOx(OH)y catalyst for improving hypochlorite oxidation was prepared by impregnating the mixture of persulfate and alkali over alumina and then reduced it with Ni2+. The effects of catalyst preparation conditions and reaction parameters on NaClO conversion rate and Ni2+ dissolution rate were studied. Impregnating the γ-Al2O3 beads in PS/OH- mixed solution with 0.59 M PS and PS/OH- molar ratio of 1.1, and then reducing with 0.8 M Ni2+ solution is the best condition for preparing catalyst. The catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The best catalytic layer is characterized by high content of chemisorbed oxygen which can be converted into atomic oxygen. The hypochlorite conversion rate increased with the catalyst dosage and reuse times, and decreased with available chlorine, while pH of hypochlorite solution had little effect on the conversion rate. After running stably for 120 h in continuous flow test, the chemisorbed oxygen content in the optimal catalytic layer decreased slightly. Atomic oxygen plays an important role in the decolorization of dye solution by NaClO/NiOx(OH)y system. The oxidant consumption cost of this process is much cheaper than Fenton reagent. The prepared catalyst has great potential in hypochlorite decomposition and wastewater treatment.

Chromosome-level genome assembly of Tarim red deer, Cervus elaphus yarkandensis.

Tarim red deer (Cervus elaphus yarkandensis) is the only subspecies of red deer (of 22 subspecies) from Central Asia. This species is a desert dweller of the Tarim Basin of southern Xinjiang, China, and exhibits some unique adaptations to the dry and extreme hot climate. We report here the assembly of a Tarim red deer genome employing a 10X Genomics library, termed CEY_v1. Our genome consisted of 2.6 Gb with contig N50 and scaffold N50 of 275.5 Kb and 31.7 Mb, respectively. Around 96% of the assembled sequences were anchored onto 34 chromosomes based on the published high-quality red deer genetic linkage map. More than 94% BUSCOs complete genes (including 90.5% single and 3.6% duplicated ones) were detected in the CEY_v1 and 20,653 genes were annotated. The CEY_v1 is expected to contribute to comparative analysis of genome biology, to evolutionary studies within Cervidae, and to facilitating investigation of mechanisms underlying adaptation of this species to the extreme dry and hot climate.

De novo sequencing and chromosomal-scale genome assembly of leopard coral grouper, Plectropomus leopardus.

The leopard coral grouper, Plectropomus leopardus, belonging to the family Epinephelinae, is a carnivorous coral reef fish widely distributed in tropical and subtropical waters of the Indo-Pacific. Due to its appealing body appearance and delicious taste, P. leopardus has become a popular commercial fish for aquaculture in many countries. However, the lack of genomic and molecular resources for P. leopardus has hindered study of its biology and genomic breeding programmes. Here we report the de novo sequencing and assembly of the P. leopardus genome using a combination of 10 × Genomics, high-throughput chromosome conformation capture (Hi-C) and PacBio long-read sequencing technologies. The genome assembly has a total length of 881.55 Mb with a scaffold N50 of 34.15 Mb, consisting of 24 pseudochromosome scaffolds. busco analysis showed that 97.2% of the conserved single-copy genes were retrieved, indicating the assembly was almost entire. We predicted 25,248 protein-coding genes, among which 96.5% were functionally annotated. Comparative genomic analyses revealed that gene family expansions in P. leopardus were associated with immune-related pathways. In addition, we identified 5,178,453 single nucleotide polymorphisms based on genome resequencing of 54 individuals. The P. leopardus genome and genomic variation data provide valuable genomic resources for studies of its genetics, evolution and biology. In particular, it is expected to benefit the development of genomic breeding programmes in the farming industry.

A chromosome-level genome assembly of the giant grouper (Epinephelus lanceolatus) provides insights into its innate immunity and rapid growth.

The giant grouper (Epinephelus lanceolatus) is the largest coral reef teleost, with a native range that spans temperate and tropical waters in the Pacific and the Indian Oceans. It is cultured artificially and used as a breeding species in aquaculture due to its rapid growth rate. Here we report a giant grouper genome assembled at the chromosome scale from sequences generated using Illumina and high-throughput chromatin conformation capture (Hi-C) technology. The assembly comprised 1.086 Gb, with 98.4% of the scaffold sequences anchored into 24 chromosomes. The contig and scaffold N50 values were 119.9 kb and 46.2 Mb, respectively. The assembly is of high integrity, including 96.4% universal single-copy orthologues based on BUSCO analysis. Through chromosome-scale evolution analysis, we identified alignments of six giant grouper chromosomes to three stickleback chromosomes and some of the genes located within the breakpoints of reshuffling events may related to development and growth. From the 24,718 protein-coding genes, we found that several gene families related to innate immunity and glycan biosynthesis were significantly expanded in the giant grouper genome compared to other teleost genomes. In addition, we identified several genes related to the hormone signalling pathway and innate immunity that have experienced positive selection or accelerated evolution, implicating their roles in immune defence and fast growth of the species. The high-quality genome assembly will provide a valuable genomic resource for further biological and evolutionary studies, and useful genomic tools for breeding of the giant grouper.