Co-Cu nanoparticles uniformly embedded in the intra-crystalline mesoporous Silicalite-1 for catalytic ammonia borane hydrolysis.

Zeolite-encaged metal nanoparticles (NPs) catalysts are emerging as a new frontier owing to their superior ability to stabilize the structure and catalytic performance in the thermal and environmental catalytic reaction. However, the pore size below 2 nm of the conventional zeolites usually limits the accessibility of metal active sites. Herein, Co-Cu NPs of about 2.5-3.5 nm were uniformly encapsulated in the intracrystalline mesoporous Silicalite-1 (S-1) through alkali-treatment ligand-assisted strategy. The obtained sample (termed CoxCu1-x@HS-1) exhibited efficient activity and stability in the ammonia borane hydrolysis with the highest TOF value of 21.46 molH2·molMe-1·min-1. UV-vis DRS spectra indicated that intracrystalline mesopores have greatly improved the openness and accessibility of the active sites, thus improving their catalytic performance. The introduction of Cu regulates the electronic properties of Co, further increasing hydrogen production activity. This research creates new prospects to design other high-performance hierarchical porous zeolite-confined metal/metal oxide catalysts.

Research on the Properties of Steel Slag with Different Preparation Processes.

To promote the resource utilization of steel slag and improve the production process of steel slag in steelmaking plants, this research studied the characteristics of three different processed steel slags from four steelmaking plants. The physical and mechanical characteristics and volume stability of steel slags were analyzed through density, water absorption, and expansion tests. The main mineral phases, morphological characteristics, and thermal stability of the original steel slag and the steel slag after the expansion test are analyzed with X-ray diffractometer (XRD), scanning electron microscope (SEM), and thermogravimetric analysis (TG) tests. The results show that the composition of steel slag produced by different processes is similar. The main active substances of other processed steel slags are dicalcium silicate (C2S), tricalcium silicate (C3S), CaO, and MgO. After the expansion test, the main chemical products of steel slag are CaCO3, MgCO3, and calcium silicate hydrate (C-S-H). Noticeable mineral crystals appeared on the surface of the steel slag after the expansion test, presenting tetrahedral or cigar-like protrusions. The drum slag had the highest density and water stability. The drum slag had the lowest porosity and the densest microstructure surface, compared with steel slags that other methods produce. The thermal stability of steel slag treated by the hot splashing method was relatively higher than that of steel slag treated by the other two methods.

Unraveling the role of CD24 in Hepatocellular carcinoma: Involvement of inactivated Hippo signaling and SOX4-mediated regulation.

Hepatocellular carcinoma (HCC) is a prevalent type of liver cancer, and CD24 gene is reportedly involved in HCC progression. However, the precise regulatory mechanisms of CD24 in HCC remain unclear. In this study, we established a primary HCC mouse model and observed that CD24, induced by inactivation of the Hippo pathway, was highly expressed in HCC. Using a systematic molecular and genomic approach, we identified the Hippo-YAP1-SOX4 pathway as the mechanism through which YAP1 induces CD24 upregulation in HCC cells. CD24 knockdown significantly attenuated YAP1 activation-induced HCC. These findings shed light on the link between CD24 and HCC progression, particularly in the Hippo-inactivated subclass of HCC. Therefore, CD24 may serve as a potential target for specific treatment of this HCC subclass.

Preparation of pH-sensitive alginate-based hydrogel by microfluidic technology for intestinal targeting drug delivery.

Hydrogel microspheres stand out in drug delivery due to their small particle size, biocompatibility and good internal stability. In this paper, pH-sensitive hydrogels are prepared by microfluidic technology for targeted drug delivery in the small intestine. A coaxial dual-channel microfluidic chip is constructed. By analyzing the effects of flow rates and three fracture stages (Rayleigh-Plateau instability crushing stage, pressure difference crushing stage and shear force crushing stage) on the size of hydrogel microspheres, the optimal control stage of the microsphere size is determined (shear force crushing stage). Based on this, the accurate control model of the hydrogel microsphere size is proposed. In addition, based on the coaxial dual channel microfluidic chip, a monolayer hydrogel microcapsule loaded with Indometacin is prepared. The core-shell hydrogel microcapsules loaded with Indometacin are prepared by an improved coaxial three channel microfluidic chip. The swelling rates of both microcapsules in simulated intestinal fluid are significantly higher than those in simulated gastric fluid. The results of in vitro simulated release experiments show that the two hydrogel microcapsules basically do not release in simulated gastric juice. In simulated intestinal fluid, single-layer hydrogel microcapsules show rapid release, while core-shell hydrogel microcapsules showed slow release. In conclusion, the alginate-based hydrogel microcapsules have good stability and pH sensitivity, and are suitable for targeted drug delivery in the small intestine.

Verifying AXL and putative proteins as SARS-CoV-2 receptors by DnaE intein-based rapid cell-cell fusion assay.

As the understanding of the mechanisms of SARS-CoV-2 infection continues to grow, researchers have come to realize that ACE2 and TMPRSS2 receptors are not the only way for the virus to invade the host, and that there are many molecules that may serve as potential receptors or cofactors. The functionality of these numerous receptors, proposed by different research groups, demands a fast, simple, and accurate validation method. To address this issue, we here established a DnaE intein-based cell-cell fusion system, a key result of our study, which enables rapid simulation of SARS-CoV-2 host cell infection. This system allowed us to validate that proteins such as AXL function as SARS-CoV-2 spike protein receptors and synergize with ACE2 for cell invasion, and that proteins like NRP1 act as cofactors, facilitating ACE2-mediated syncytium formation. Our results also suggest that mutations in the NTD of the SARS-CoV-2 Delta variant spike protein show a preferential selection for Spike-AXL interaction over Spike-LDLRAD3. In summary, our system serves as a crucial tool for the rapid and comprehensive verification of potential receptors, screening of SARS-CoV-2-neutralizing antibodies, or targeted drugs, bearing substantial implications for translational clinical applications.

Magnetically actuated hydrogel-based capsule microrobots for intravascular targeted drug delivery.

Microrobots for targeted drug delivery in blood vessels have attracted increasing interest from researchers. In this work, hydrogel-based capsule microrobots are used to wrap drugs and deliver drugs in blood vessels. In order to prepare capsule microrobots of different sizes, a triaxial microfluidic chip is designed and built, and the formation mechanism of three flow phases including the plug flow phase, bullet flow phase and droplet phase during the preparation of capsule microrobots is studied. The analysis and simulation results show that the size of the capsule microrobots can be controlled by the flow rate ratio of two phases in the microfluidic chip, and when the flow rate of the outer phase is 20 times that of the inner phase in the microfluidic chip, irregular multicore capsule microrobots can be prepared. On this basis, a three degree of freedom magnetic drive system is developed to drive the capsule microrobots to reach the destination along the predetermined trajectory in the low Reynolds number environment, and the magnetic field performance of the magnetic drive system is simulated and analyzed. Finally, in order to verify the feasibility of targeted drug delivery of the capsule microrobots in the blood vessel, the motion process of the capsule microrobots in the vascular microchannel is simulated, and the relationship between the motion performance of the capsule microrobots and the magnetic field is studied. The experimental results show that the capsule microrobots can reach a speed of 800 µm s-1 at a low frequency of 0.4 Hz. At the same time, the capsule microrobots can reach a peak speed of 3077 µm s-1 and can continuously climb over a 1000 µm high obstacle under a rotating magnetic field of 2.4 Hz and 14.4 mT. Experiments show that the capsule microrobots have excellent drug delivery potential in similar vascular curved channels driven by this system.

The Value of Ecosystem Services from Giant Panda Reserves.

Ecosystem services (the benefits to humans from ecosystems) are estimated globally at $125 trillion/year [1, 2]. Similar assessments at national and regional scales show how these services support our lives [3]. All valuations recognize the role of biodiversity, which continues to decrease around the world in maintaining these services [4, 5]. The giant panda epitomizes the flagship species [6]. Its unrivalled public appeal translates into support for conservation funding and policy, including a tax on foreign visitors to support its conservation [7]. The Chinese government has established a panda reserve system, which today numbers 67 reserves [8, 9]. The biodiversity of these reserves is among the highest in the temperate world [10], covering many of China's endemic species [11]. The panda is thus also an umbrella species [12]-protecting panda habitat also protects other species. Despite the benefits derived from pandas, some journalists have suggested that it would be best to let the panda go extinct. With the recent downlisting of the panda from Endangered to Vulnerable, it is clear that society's investment has started to pay off in terms of panda population recovery [13, 14]. Here, we estimate the value of ecosystem services of the panda and its reserves at between US$2.6 and US$6.9 billion/year in 2010. Protecting the panda as an umbrella species and the habitat that supports it yields roughly 10-27 times the cost of maintaining the current reserves, potentially further motivating expansion of the reserves and other investments in natural capital in China.

Inbreeding and inbreeding avoidance in wild giant pandas.

Inbreeding can have negative consequences on population and individual fitness, which could be counteracted by inbreeding avoidance mechanisms. However, the inbreeding risk and inbreeding avoidance mechanisms in endangered species are less studied. The giant panda, a solitary and threatened species, lives in many small populations and suffers from habitat fragmentation, which may aggravate the risk of inbreeding. Here, we performed long-term observations of reproductive behaviour, sampling of mother-cub pairs and large-scale genetic analyses on wild giant pandas. Moderate levels of inbreeding were found in 21.1% of mating pairs, 9.1% of parent pairs and 7.7% of panda cubs, but no high-level inbreeding occurred. More significant levels of inbreeding may be avoided passively by female-biased natal dispersal rather than by breeding dispersal or active relatedness-based mate choice mechanisms. The level of inbreeding in giant pandas is greater than expected for a solitary mammal and thus warrants concern for potential inbreeding depression, particularly in small populations isolated by continuing habitat fragmentation, which will reduce female dispersal and increase the risk of inbreeding.

Expression profiling of abundant genes in pulmonary and cardiac muscle tissues of Tibetan Antelope (Pantholops hodgsonii).

The Tibetan Antelope (TA), which has lived at high altitude for millions of years, was selected as the model species of high hypoxia-tolerant adaptation. Here we constructed two cDNA libraries from lung and cardiac muscle tissues, obtained EST sequences from the libraries, and acquired extensive expression data related energy metabolism genes. Comparative analyses of synonymous (Ks) and nonsynonymous (Ka) substitution rates of nucleus-encoded mitochondrial unigenes among different species revealed that many antelope genes have undergone rapid evolution. Surfactant-associated protein A (SP-A) and surfactant-associated protein B (SP-B) genes in the AT lineage experienced accelerated evolution compared to goat and sheep, and these two genes are highly expressed in the lung tissue. This study suggests that many specific genes of lung and cardiac muscle tissues showed unique expression profiles and may undergo fast adaptive evolution in TA. These data provide useful information for studying on molecular adaptation to high-altitude in humans as well as other mammals.

Sequencing of 50 human exomes reveals adaptation to high altitude.

Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP's association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude.

Gene conversion in the rice genome.

BACKGROUND: Gene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes increases opportunities for gene conversion. RESULTS: To characterize gene conversion in rice, we have defined 626 multigene families in which 377 gene conversions were detected using the GENECONV program. Over 60% of the conversions we detected were between chromosomes. We found that the inter-chromosomal conversions distributed between chromosome 1 and 5, 2 and 6, and 3 and 5 are more frequent than genome average (Z-test, P < 0.05). The frequencies of gene conversion on the same chromosome decreased with the physical distance between gene conversion partners. Ka/Ks analysis indicates that gene conversion is not tightly linked to natural selection in the rice genome. To assess the contribution of segmental duplication on gene conversion statistics, we determined locations of conversion partners with respect to inter-chromosomal segment duplication. The number of conversions associated with segmentation is less than ten percent. Pseudogenes in the rice genome with low similarity to Arabidopsis genes showed greater likelihood for gene conversion than those with high similarity to Arabidopsis genes. Functional annotations suggest that at least 14 multigene families related to disease or bacteria resistance were involved in conversion events. CONCLUSION: The evolution of gene families in the rice genome may have been accelerated by conversion with pseudogenes. Our analysis suggests a possible role for gene conversion in the evolution of pathogen-response genes.

High altitude adaptation and phylogenetic analysis of Tibetan horse based on the mitochondrial genome.

To investigate genetic mechanisms of high altitude adaptations of animals living in the Tibetan Plateau, three mitochondrial genomes (mt-genome) of Tibetan horses living in Naqu (4,500 m) of Tibetan, Zhongdian (3,300 m) and Deqin (3,100 m) of Yunnan province were sequenced. The structures and lengths of these three mt-genomes are similar to the Cheju horse, which is related to Tibetan horses, but little shorter than the Swedish horse. The pair-wise identity of these three horses on nucleotide level is more than 99.3%. When the gene encoding the mitochondrial protein of Tibetan horses was analyzed, we found that NADH6 has higher non-synonymous mutation rate in all of three Tibetan horses. This implies that NADH6 may play a role in Tibetan horses' high altitude adaptation. NADH6 is one of the subunits of the complex I in the respiratory chain. Furthermore, 7 D-loop sequences of Tibetan horse from different areas were sequenced, and the phylogeny tree was constructed to study the origin and evolutionary history of Tibetan horses. The result showed that the genetic diverse was high among Tibetan horses. All of Tibetan horses from Naqu were clustered into one clade, and Tibetan horses from Zhongdian and Deqin were clustered into others clades. The first molecular evidence of Tibetan horses indicated in this study is that Tibetan horse population might have multiple origins.

Phylogenetic relationships in genus Niviventer (Rodentia: Muridae) in China inferred from complete mitochondrial cytochrome b gene.

Chinese species of the genus Niviventer, predominantly distributed in the southeastern Tibetan Plateau and in Taiwan, are a diverse group and have not yet received a thorough molecular phylogenetic analysis. Here, we reconstructed the phylogenetic relationships of 32 specimens representing nine Chinese species of Niviventer, based on sequences of the complete mitochondrial cytochrome b gene. Maximum parsimony, maximum likelihood and Bayesian analysis resulted in three consistent trees, each supported by high bootstrap values. The results showed that the Niviventer species included here are monophyletic. The nine species were classified into three distinct clades: clade A with Niviventer brahma, N. confucianus, N. coxingi, N. culturatus, N. eha and N. fulvescens; clade B with N. andersoni and N. excelsior; clade C with N. cremoriventer. Our results also suggested that N. culturatus should be a valid species rather than a subspecies of N. confucianus. Divergence times among species were calibrated according to the middle-late Pleistocene (1.2-0.13 Mya) fossil records of N. confucianus. The results demonstrated that the first radiation event of the genus Niviventer occurred in early Pleistocene (about 1.66 Mya), followed by the divergence of clades A and B at about 1.46 Mya. Most of the extant Niviventer species appeared during early to middle Pleistocene (about 1.29-0.67 Mya). These divergence times are coincidental with the last uplift events of the Tibetan Plateau, Kun-Huang movement, Pleistocene glaciations and the vicariant formation of Taiwan Strait. Consequently geographical events and Pleistocene glaciations have played a great role in the diversification of Niviventer.

Detection of HPV-2 and identification of novel mutations by whole genome sequencing from biopsies of two patients with multiple cutaneous horns.

BACKGROUND: Human papillomavirus-2 (HPV-2) is generally associated with common warts. The association of cutaneous horns with HPV-2 infection has never been reported. OBJECTIVES: To identify the papillomavirus (PV) type(s) involved in cutaneous horns and analysis the genomes of these viruses. STUDY DESIGN: We screened biopsies from two patients with multiple cutaneous horns using PV type-specific PCR assays, and sequenced the whole genomes of the viruses by a PCR-by-PCR strategy. Sequence comparison with the reference genome and its closely related PVs in the same phylogenetic group was performed to identify sequence variation across the genome(s) of newly detected PV(s). RESULTS: Two strains of HPV-2 were identified from the biopsies of two patients respectively. No double or multiple infections were detected. Novel mutations were found in the HPV-2 genome, located both in the coding and non-coding regions. Amino acid changes occurred only in E1 and E7 ORFs. The two strains also shared several mutations at the same positions. CONCLUSIONS: Each patient was infected with a single strain of HPV-2 that developed unique mutations; HPV-2 may play a role in the onset and development of cutaneous horns; amino acid changes in functionally significant viral proteins may confer differential pathogenic risks.

[Complete sequence and gene organization of the Tibetan chicken mitochondrial genome].

Using PCR amplification, sequencing and assembling, we obtained the complete mitochondrial genome of Tibetan chicken. The complete mitochondrial genome was 16 783 bp in length. It contained 37 genes (13 protein coding genes, 2 rRNA, 22 tRNA) and a control region. The deduced restriction map revealed a unique pattern of Dra I restriction in Tibetan chicken. Phylogenetic trees based on the D-loop locus and the 13 protein coding genes by Neighbor-joining and Maximum Parsimony analysis indicated that the red junglefowl was the direct ancestor of Tibetan chicken and Tibetan chicken was closest to white leghorn and white plymouth rock, although the evolution of Tibetan chicken appeared to be relatively independent from them. A possible explanation is that the ancestor of Tibetan chicken lived in a relatively isolated environment after entering into the high altitude area and developed unique genetic characters.

Historical demography and genetic structure of sister species: deermice (Peromyscus) in the North American temperate rain forest.

To investigate the evolutionary and biogeographical history of Peromyscus keeni and P. maniculatus within the coastal forest ecosystem of the Pacific Northwest of North America, we sampled 128 individuals from 43 localities from southeastern Alaska through Oregon. We analysed mitochondrial DNA variation using DNA sequence data from the mitochondrial cytochrome-b (cyt-b) gene and control region, and we found two distinct clades consistent with the morphological designation of the two species. The sequence divergence between the two clades was 0.0484 substitutions per site for cyt-b and 0.0396 for the control region, suggesting that divergence of the two clades occurred during the middle to late Pleistocene. We also examined the historical demography of the two clades using stepwise and exponential expansion models, both of which indicated recent rapid population growth. Furthermore, using the program migrate we found evidence of migration from populations north of the Fraser River (British Columbia) to the south in both clades. This study demonstrates the utility of these model-based demographic methods in illuminating the evolutionary and biogegographic history of natural systems.