Alterations of the blood-brain barrier during aging.

The blood-brain barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules and cells between the blood and the central nervous system. It undergoes structural and functional changes during aging, which may compromise its integrity and contribute to the pathogenesis of neurodegenerative diseases. In recent years, advances in microscopy and high-throughput bioinformatics have allowed a more in-depth investigation of the aging mechanisms of BBB. This review summarizes age-related alterations of the BBB structure and function from six perspectives: endothelial cells, astrocytes, pericytes, basement membrane, microglia and perivascular macrophages, and fibroblasts, ranging from the molecular level to the human multi-system level. These basic components are essential for the proper functioning of the BBB. Recent imaging methods of BBB were also reviewed. Elucidation of age-associated BBB changes may offer insights into BBB homeostasis and may provide effective therapeutic strategies to protect it during aging.

Result of a year-long animal survey in a state-owned forest farm in Beijing, China.

Background Artificial forest can have great potential in serving as habitat to wildlife, depending on different management methods. As the state-owned forest farms now play a new role in ecological conservation in China, the biological richness of this kind of land-use type is understudied. Once owned by a mining company, a largest state-owned forest farm, Jingxi Forest Farm, has been reformed to be a state-owned forest farm with the purpose of conservation since 2017. Although this 116.4 km2 forest farm holds a near-healthy montaine ecosystem very representative in North China, a large proportion of artificial coniferous forest in the forest farm has been proven to hold less biodiversity than natural vegetation. This situation, however, provides a great opportunity for ecological restoration and biodiversity conservation. Therefore, from November 2019 to December 2020, we conducted a set of biodiversity surveys, whose results will serve as a baseline for further restoration and conservation. New information Here, we report the result of a multi-taxa fauna diversity survey conducted in Jingxi Forest Farm mainly in year 2020 with explicit spatial information. It is the first survey of its kind conducted in this area, revealing a total of 19 species of mammals, 86 birds, four reptiles, two amphibians and one fish species, as well as 101 species of insects. Four species of mammals are identified as data-poor species as they have less than 100 occurrence records with coordination in the GBIF database. One species of insect, representing one new provincial record genus of Beijing, is reported.

Regulating Percolation Threshold via Dual Conductive Phases for High-Efficiency Microwave Absorption Performance in C and X Bands.

The development of high-efficiency microwave absorbers for C and X bands still remains a challenge, limiting the settlement of corresponding electromagnetic pollution and radar stealth. In this work, a reduced graphene oxide (RGO)/Cu/Fe3O4 composite is successfully proposed by a one-step solvothermal method with a GO dispersion content of 5 mL, where Fe3O4 exhibits high magnetic loss from natural resonance at the C band, and Cu nanorods and RGO are introduced as dual conductive phases to produce suitable dielectric properties by regulating the percolation threshold. The results show that the existence of Cu nanorods significantly reduces the conductivity and dielectric loss of the composites, optimizing the coordination of attenuation capacity and impedance matching in the C and X bands. Consequently, the obtained RGO/Cu/Fe3O4 composite shows outstanding microwave absorption performance with the maximum effective absorption bandwidth (EAB) value of 5.2 GHz at a thin thickness of 3.1 mm, which covers 84% of the C band and 46% of the X band (4.64-9.84 GHz). The performance is superior to the vast majority of previous absorbers in the corresponding bands.

Evaluation of Lethal Giant Larvae as a Schistosomiasis Vaccine Candidate.

Schistosomiasis is a neglected tropical disease of humans, and it is considered to be the second most devastating parasitic disease after malaria. Eggs produced by normally developed female worms are important in the transmission of the parasite, and they responsible for the pathogenesis of schistosomiasis. The tumor suppressor gene lethal giant larvae (lgl) has an essential function in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. In our earlier study, downregulation of the lgl gene induced a significant reduction in the egg hatching rate of Schistosoma japonicum (Sj) eggs. In this study, the Sjlgl gene was used as a vaccine candidate against schistosomiasis, and vaccination achieved and maintained a stable reduction of the egg hatching rate, which is consistent with previous studies, in addition to reducing the worm burden and liver egg burden in some trials.

Improvement of alkalophilicity of an alkaline xylanase Xyn11A-LC from Bacillus sp. SN5 by random mutation and Glu135 saturation mutagenesis.

BACKGROUND: Family 11 alkaline xylanases have great potential economic applications in the pulp and paper industry. In this study, we would improve the alkalophilicity of family 11 alkaline xylanase Xyn11A-LC from Bacillus sp. SN5, for the better application in this field. RESULTS: A random mutation library of Xyn11A-LC with about 10,000 clones was constructed by error-prone PCR. One mutant, M52-C10 (V116A and E135V), with improved alkalophilicity was obtained from the library. Site-directed mutation showed that the mutation E135V was responsible for the alkalophilicity of the mutant. The variant E135V shifted the optimum pH of the wild-type enzyme from 7.5 to 8.0. Compared to the relative activities of the wild type enzyme, those of the mutant E135V increased by 17.5, 18.9, 14.3 and 9.5 % at pH 8.5, 9.0, 9.5 and 10.0, respectively. Furthermore, Glu135 saturation mutagenesis showed that the only mutant to have better alkalophilicity than E135V was E135R. The optimal pH of the mutant E135R was 8.5, 1.0 pH units higher than that of the wild-type. In addition, compared to the wild-type enzyme, the mutations E135V and E135R increased the catalytic efficiency (k cat/K m) by 57 and 37 %, respectively. Structural analysis showed that the residue at position 135, located in the eight-residue loop on the protein surface, might improve the alkalophilicity and catalytic activity by the elimination of the negative charge and the formation of salt-bridge. CONCLUSIONS: Mutants E135V and E135R with improved alkalophilicity were obtained by directed evolution and site saturation mutagenesis. The residue at position 135 in the eight-residue loop on the protein surface was found to play an important role in the pH activity profile of family 11 xylanases. This study provided alkalophilic mutants for application in bleaching process, and it was also helpful to understand the alkaline adaptation mechanism of family 11 xylanases.

Distribution of lethal giant larvae (Lgl) protein in the tegument and negative impact of siRNA-based gene silencing on worm surface structure and egg hatching in Schistosoma japonicum.

Lethal giant larvae (Lgl) are an evolutionarily conserved tumor suppressor present in fungi and animals. It plays an essential role in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. Here, we report the presence of Lgl gene in the blood fluke Schistosoma japonicum (SjLgl) (GenBank: KF246684). SjLgl protein was mainly distributed in the unique surface tegument structure by immunofluorescence microscopic staining. Using a simple soaking method, a short interfering RNA (siRNA)-based RNA interference approach knocked down the expression of SjLgl in schistosomula in vitro by up to 89.0%. Moreover, tail vein injection of SjLgl-siRNA into the infected mice reduced SjLgl mRNA levels in vivo by 48.6-85.3%, depending on the duration of treatments. SjLgl-specific siRNA treatment during the infection in mice significantly altered the surface structure of adult worm, featured by the disappearance or significant reduction of sharp spines on the inner all of oral and ventral suckers. The siRNA also reduced the hatching rates in eggs produced by treated mice by up to 85.3%. These observations implied that Lgl plays an important role in the development of tegument in schistosomes, and may be explored as a novel target for developing immuno- and/or small molecule-based therapeutics to control and treat the infections caused by schistosome and other flatworms.

Schistosoma japonicum UDP-glucose 4-epimerase protein is located on the tegument and induces moderate protection against challenge infection.

Schistosomiasis is an important global public health problem, as millions of people are at risk of acquiring this infection. An ideal method for sustainable control of schistosomiasis is using a vaccine alone or in combination with drugs. In the present study, we cloned the SjGALE gene and generated the expression product in E. coli. The expression level of SjGALE during different developmental stages of S. japonicum was evaluated by real-time RT-PCR and western blotting. Immunolocalization indicated that the protein was mainly located on the tegument of the parasite. Infection of rSjGALE-immunized mice demonstrated a 34% and 49% reduction of the mean worm burden and liver egg burden, respectively, in two independent experiments, indicating immune protection. The liver egg count from each female adult worm was significantly reduced by 63% in the two trials. The cytokine profile and IgG isotype analysis demonstrated the induction of a Th1 immune profile in response to immunization with this protein, further suggesting protection against infection. In conclusion, these findings indicated that SjGALE is a potential vaccine against S. japonicum.

RNAi silencing of type V collagen in Schistosoma japonicum affects parasite morphology, spawning, and hatching.

Type V collagen is a component of non-cartilaginous tissues and is important in the determination of fibril structure and matrix organization, although its functions are still poorly understood. In this report, RNA interference (RNAi) approaches were used to investigate the effects of knockdown of the schistosome type V collagen (SjColV) gene. In this study, three different short interfering (si) RNAs targeting different regions of the gene were designed to suppress the expression of SjColV in Schistosoma japonicum using a soaking method. By establishing controls for measuring off-target RNAi effects, we found that different siRNA sequences had different levels of effectiveness. Although all the siRNAs tested reduced SjColV transcript levels, the S1 siRNA consistently reduced SjColV expression to >99 % of the control. In the following experiments, S1 siRNA was adapted to inhibit SjColV expression, and the silencing effects were detected by real-time PCR and Western blot. The spawning and egg hatching of parasites were calculated, while the worms' morphology was taken by scanning electron microscopy. The results show that silencing the expression of SjColV significantly affects the spawning and egg hatching of S. japonicum, and it also affects the worms' morphology.