Development of Alternative to Animal Testing on Cosmetics by Middle-out Strategy

The discussion on cosmetic animal testing ban started since 1990s, with the fnally implementation of full animal testing ban in both research and marketing in EU and Israel in 2013. Now it has been fully or partially banned by law in 33 countries or regions, with more and more countries lining up to do the same. Beyond animal welfare consideration, the need of mutual acceptance of data （MAD） and harmonization of global market have made non-animal testing an irresistible general trend for worldwide countries to made regulation and policy. Recently, China is in critical crossroad to shift the toxicity paradigm and explore a proper strategy to promote the development of cosmetic non-animal testing. 3R theory has been frstly introduced in Chinese legislation in 2006 that is an important step forward to seriously thinking of animal test. In the following 10 years, the alternative technology in China has been developed dramatically with the implementation of relevant legislations, holding various theoretical and hands-on training, exploration work on methods validation, adoption of internationally recognized methods, propagation of alternative standards and in-depth investigation in in vitro bioscience. The ultimate goal of alternative technology is the regulatory application, thus demands infrastructure constructing, technology capability building and national standard forming. However, concrete works should be carefully planned to facilitate the technology transformation and standardization. This paper will give a retrospective review on the progress in recent years and put forward a middle-out strategy to promote the development of cosmetics alternative in China.

Current Status of Global Ban on Cosmetic Tests on Animals

The article reviewed the cosmetic animal testing ban globally, with focusing on EU, United Kingdom, Korea, the United States, Russia, Australia, Canada and others total 15 regions and countries. The article also briefed the developments of the alternatives of animal testing in the world, and the cosmetic animal testing regulation in China as well. The article suggested China to adopt the alternatives which have been validated based on the development of technology, gradually ban animal testing for cosmetics.

Cognitive function among military veterans with STEM occupations

Dear Editor,There is limited research on the relationship between science,technology,engineering,and mathematics(STEM)occupational history and cognitive function in later life,especially among military veterans,who may be at greater risk for later-life cognitive decline.This study examines a nationally representative sample of military veterans to address this gap in knowledge.

Biomechanical features of Poly-D,L-lactic acid (PDLLA) rods through the degradation in vitro and in vivo

Objective：To observe the changing of biomechanical features during the degradation course of poly-D,L-lactic acid （PDLLA） rods in vivo and in vitro and to evaluate its value as an internal fixation material. Methods ：PDLLA rods were emerged into PBS simultaneous body fluid with constant temperature of 37℃ and the rods were embedded into muscle tissue of 20 rabbits for degradation in vitro and in vivo . The rods were taken out in 2, 4, 6, 8 and 12 weeks. Biomechanical features of bending, shearing and axial compression strength, rigidity and elastic modulus were observed during the degradation course. Statistical method was used to test the changes of biomechanical parameters. Results： （1）There was similar changes of bending, compressive, shearing strength and bending, compressive and shearing rigidity of the PDLLA rods between in vivo and in vitro. （2）Bending, compressive, shearing strength decreased 33%, 18 % and 43 % respectively within the first stage of the degradation, and after 6 weeks of degradation, they decreased slowly. （3）Elastic modulus, bending, compressive and shearing rigidity.decreased sharply during the 6 weeks of degradation, with a drop of 22%, 39% and 30% respectively, and after 8 weeks, they decreased slowly. Even after 12 weeks of degradation, the strength of the rods was still higher than that of sponge bone. Conclusion： During the degradation of the material, the strength and rigidity of PDLLA rods can meet the need of fracture fixation of cancellous bones.

Relationship between Host Survival and the Type of Immune Response in Different Organs during Disseminated Candidiasis

Summary: To examine the relationship between host survival and the type of immune response in different organs during disseminated candidiasis, the murine model of disseminated candidiasis was established by injection with Candida albicans via tail vein. The survival time was observed for up to 60 days. And the expression levels of cytokines in the spleen and kidney, including IFN-γ and IL-4, were determined with RT-PCR. Our results showed that in the spleen, both non-fatal and fatal inoculum caused a type Ⅱimmune response with steady expression levels of IFN-γ and the obviously increased levels of IL-4. While in the kidney, non-fatal inoculum induced a typeⅠimmune response with the obviously increased levels of IFN-γ and the steady expression levels of IL-4. However, fatal inoculum induced a type Ⅱ immune response with a constant expression of IFN-γ and the evidently increased levels of IL-4. It is concluded that in disseminated candidiasis, host survival is associated with the type of immune responses in the kidney, but not in the spleen.

A Novel Preparation of Artificial Bile Ducts for Clinical Application of Biliary Diseases

The aim of this paper was to prepare an artificial bile duct using polytetrafluoroethylene（PTFE） for the development of a new treatment for biliary diseases. The basic properties of the PTFE material, such as crystallization properties, were characterized; the surface structures of the sample tubes were observed by scanning electron microscope（SEM） and water permeability test of different tubes was evaluated by osmosis device. Six Shanghai white pigs were selected to do the implantation surgery of the artificial biIe ducts. After 90 days, the artifidai bile ducts were removed from the pigs and characterized by electron microscope in order to study the tissue compatibility. The results of animal test indicated that the artificial bile duct had good tissue compatibility. This new artificial bile duct shows great potential for the treatment of biliary diseases.

Correlative CD4 and CD8 T-cell immunodominance in humans and mice:Implications for preclinical testing

Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex(MHC)molecules,and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully understood.In this study,we addressed this matter by analyzing experimentally identified epitopes based on published data curated in the Immune Epitopes DataBase(IEDB)database.We first analyzed SARS-CoV-2 spike(S)and nucleoprotein(N),which are two common targets of the immune response and well studied in both human and mouse systems.We observed a weak but statistically significant correlation between human and H-2^(b)mouse T-cell responses(CD8 S specific(r=0.206,p=1.37×10^(−13));CD4 S specific(r=0.118,p=2.63×10^(−5))and N specific(r=0.179,p=2.55×10^(−4))).Due to intrinsic differences in MHC molecules across species,we also investigated the association between the immunodominance of common Human Leukocyte Antigen(HLA)alleles for which HLA transgenic mice are available,namely,A*02:01,B*07:02,DRB1*01:01,and DRB1*04:01,and found higher significant correlations for both CD8 and CD4(maximum r=0.702,p=1.36×10^(−31)and r=0.594,p=3.04−122,respectively).Our results further indicated that some regions are commonly immunogenic between humans and mice(either H-2^(b)or HLA transgenic)but that others are human specific.Finally,we noted a significant correlation between CD8 and CD4 S-(r=0.258,p=7.33×10^(21))and N-specific(r=0.369,p=2.43×10^(14))responses,suggesting that discrete protein subregions can be simultaneously recognized by T cells.These findings were confirmed in other viral systems,providing general guidance for the use of murine models to test T-cell immunogenicity of viral antigens destined for human use.

Isolation and Identification of a High-pathogenicity Strepto- coccus suis Serotype 7 Strain

In order to diagnose the diseased pigs in a certain large pig farm in Binzhou City, Shandong Province, the dead piglets with joint swelling were subjected to necroscopy, and the pathogenic bacterium was isolated and identified. One Gram-positive Streptococcus was isolated. The strain was subjected to characteristic culture, microscopic examination and molecular biological identification, and resistance detection, animal regression experiment and mouse pathogenicity test were carried out. The results showed that the isolate was identified to be Streptococcus suis serotype 7, which was resistant to multiple drugs; and the pathogenicity test showed that the strain had high pathogenicity to pigs, resulting in neurosis on partial pigs, and the strain had no pathogenicity to Kunming and BALB/c mice but certain pathogenicity to CD1 mice.

Study of Analgesic and Anti-inflammatory Effects of Lappaconitine Gelata

Objective: To explore the analgesic and anti-inflammatory effects of lappaconitine gelata (LA). Methods: The writhing response induced by acetic acid, the pain response induced by formaldehyde and hot plate method in the mouse, and the paw edema induced by egg albumen in the rat and the ear edema induced by xylene in the mouse were used for investigation on the analgesic and anti-inflammatory effects of LA. Results: The writhing response induced by acetic acid, the pain response induced by formaldehyde and hot plate methods was significantly inhibited by LA. In addition, the paw edema induced by egg albumen in the rat and the ear edema induced by xylene in the mouse were all significantly suppressed by LA. Conclusion: LA has the analgesic and anti-inflammatory effects.

An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair

The aim of this study was to evaluate injectable,in situ cross-linkable elastin-like recombinamers(ELRs)for osteochondral repair.Both the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells(rMSCs)were tested for the regeneration of critical subchondral defects in 10 New Zealand rabbits.Thus,cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4months for histological and gross evaluation of features of biomaterial performance,including integration,cellular infiltration,surrounding matrix quality and the new matrix in the defects.Although both approaches helped cartilage regeneration,the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration,whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline cartilage.In conclusion,the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.

Determining the critical size of a rabbit rib segmental bone defect model

In order to establish and standardize the rabbit rib segmental bone defect model,it is of vital importance to determine rabbit rib critical size defect(CSD).According to the general time needed for spontaneous long-bone regeneration,three-month observation period was set to determine the CSD.The rabbit rib segmental bone defects with different sizes from 1 to 5cm with or without periosteum were performed in the eighth rib of 4-month-old male New Zealand rabbits and underwent Xray examinations at the 4th,8th and 12th weeks postoperatively.The gross and histological examinations at postoperative week 12 were evaluated,which showed that the critical sizes in the rabbit rib models with and without periosteum were 5 and 2 cm,respectively.This study provides prerequisite data for establishing rabbit rib CSD model and evaluating bonematerials using this model.

Fighting and aggressive sound determines larger male to win male-male competition in a bark beetle

Intrasexual selection occurs in male-male competition over access to females and usually results in the larger male winning.While much research has documented that size matters,little is known about how the larger male wins.Dendroctonus vale ns is an aggregating monogamous bark beetle in which males have large variation in body size and display intense competition over females.Behavioral observation showed two males fight each other within the gallery by pushing/shoving and stridulated more when two males encountered each other.Experiments using two different-sized males synchronously competing showed that larger males won 95%of contests.Reciprocal displacement experiments using muted and intact males of different or equal size were used to simulate male-male competition.Larger males displaced the smaller resident male in 90%of contests,while smaller males prevailed over larger residents in 6.7%of contests.With both males silenced,larger males displaced smaller males in 80%of con tests,while smaller males prevailed in 8%of con tests.Further experiments using equal-sized males showed aggressive soundemitting males displaced muted males in 67%of contests,yet intact males displaced other intact males in only 37.5%of con tests.Sound analysis showed sound pressure level is an honest signal of body size and males chose soft sounds over loud aggressive sounds in assays.Therefore,D.valens males have evolved dual behaviors,fighting and aggressive sounds associated with body size,to assess rivals to compete for a partner,gaining insights in male-male competition for this species and for other animals.