Preparation, properties and in vitro osteogensis of self-reinforcing injectable hydrogel.

As an attractive biomaterial for bone reconstruction, injectable biomaterials have many prominent characteristics such as good biocompatibility and bone-filling ability. However, there are weak as load-bearing scaffolds. In this study, polyvinyl alcohol (PVA) and bioactive glass (BAG) were interpenetrated into sodium alginate (SA) network to obtain self-enhanced injectable hydrogel. The optimum ratio of PVA/SA/BAG hydrogel was determined based on injectability, gelation time and chemical characterization. Results showed that the selected ratio had the shortest gelation time of 3.5min, and the hydrogel had a rough surface and good coagulation property. The hydrogel was capable of carrying 1kg of weight by mineralization for 14 d The compressive strength, compressive modulus, and fracture energy of the hydrogel reached 0.12MPa, 0.376MPa and 17.750kJ m-2, respectively. Meanwhile, the hydrogel had high moisture content and dissolution rate, and it was sensitive to temperature and ionic strength. Hydroxyapatite was generated on the hydrogel surface, and the hydrogel pores increased, and the pore size enlarged. The biocompatibility of PVA/SA/BAG hydrogel was analyzed using hemolysis and cytotoxicity assays. Results revealed its good biocompatibility with low hemolysis rate and no cytotoxicity to MC3T3-E1 cells. The hydrogel was also found to promote the differentiation of MC3T3-E1 cells with significantly increased in ALP activity and expression of relevant differentiation factors. In vitro mineralization assay showed an increase in calcium nodules and calcification area, indicating the ability of hydrogel to promote mineralization MC3T3-E1 cells. These findings indicated that PVA/SA/BAG hydrogel had potential uses in the field of irregular bone-defect repair due to its injectability, cytocompatibility, and tailorable functionality.

Seasonal variations of macrozoobenthic community trophic structure in the waters adjacent to the seaweed beds of Dalian Island in the North Yellow Sea.

To investigate the effects of algal detritus export on the trophic structure of macrozoobenthic community in the adjacent benthic habitat during the bloom and decline of macroalgae, we collected macrozoobenthos from the adjacent sea area of Dalian Island in the North Yellow Sea in May (the algal bloom period) and August (the algal decay period) of 2020. We quantifyied the seasonal changes in the trophic structure of macrozoobenthic community by using carbon and nitrogen stable isotope techniques. Results showed that δ13C and δ15N values of macrozoo-benthos in May ranged from -23.14‰ to -14.24‰, 6.21‰ to 12.90‰, respectively, and -22.36‰ to -14.13‰, 5.33‰ to 12.00‰, respectively in August. Results of PERMANOVA analysis showed that δ13C values of macrozoobenthos differed significantly between the two months, while δ15N values were not significantly different. Based on the Euclidean distance, the macrozoobenthic communities in both months could be classified into five trophic functional groups. The trophic levels of macrozoobenthos ranged from 2.00 (Nitidotellina minuta) to 3.97 (Glycera onomichiensis) in May and from 2.00 (N. minuta) to 3.96 (G. onomichiensis) in August. The δ13C range, δ15N range, mean centroid distance, total area and corrected standard ellipse areas which represented community trophic structure indices in August were higher than those in May. Our results indicated that the trophic diversity level and trophic niche width of the macrozoobenthic community in the adjacent sea area of the seaweed bed were higher in the algal decline season.

The role of insulin-like growth factor-1 in bone remodeling: A review.

Insulin-like growth factor (IGF)-1 is a polypeptide hormone with vital biological functions in bone cells. The abnormal expression of IGF-1 has a serious effect on bone growth, particularly bone remodeling. Evidence from animal models and human disease suggested that both IGF-1 deficiency and excess cause changes in bone remodeling equilibrium, resulting in profound alterations in bone mass and development. Here, we first introduced the functions and mechanisms of the members of IGFs in bone. Subsequently, the critical role of IGF-1 in the process of bone remodeling were emphasized from the aspects of bone resorption and bone formation respectively. This review explains the mechanism of IGF-1 in maintaining bone mass and bone homeostasis to a certain extent and provides a theoretical basis for further research.

Transmission of SARS-CoV-2 Omicron Variant under a Dynamic Clearance Strategy in Shandong, China.

SARS-CoV-2 Omicron caused a large wave of COVID-19 cases in China in spring 2022. Shandong was one of the most affected regions during this epidemic yet was also among those areas that were able to quickly contain the transmission. We aimed to investigate the origin, genetic diversity, and transmission patterns of the Omicron epidemic in Shandong under a dynamic clearance strategy. We generated 1,149 Omicron sequences, performed phylogenetic analysis, and interpreted results in the context of available epidemiological information. We observed that there were multiple introductions of distinct Omicron sublineages into Shandong from foreign countries and other regions in China, while a small number of introductions led to majority of local cases. We found evidence suggesting that some local clusters were potentially associated with foreign imported cases. Superspreading events and cryptic transmissions contributed to the rapid spread of this epidemic. We identified a BA.1.1 genome with the R493Q reversion mutation in the spike receptor binding domain, potentially associated with an escape from vaccine and Omicron infection elicited neutralizing immunity. Our findings illustrated how the dynamic clearance strategy constrained this epidemic's size, duration, and geographical distribution. IMPORTANCE Starting in March 2022, the Omicron epidemic caused a large wave of COVID-19 cases in China. Shandong was one of the most affected regions during this epidemic but was also among those areas that were able to quickly contain the transmission. We investigated the origin, genetic diversity, and transmission patterns of Omicron epidemic in Shandong under a dynamic clearance strategy. We found that there were multiple introductions of distinct Omicron sublineages into Shandong from foreign countries and other regions in China, while a small number of introductions led to most local cases. We found evidence suggesting that some local clusters were associated with foreign imported cases. Superspreading events and cryptic transmissions contributed to the rapid spread of this epidemic. Our study illustrated the transmission patterns of Omicron epidemic in Shandong and provided a looking glass onto this epidemic in China.

Interactive effects of elevated temperature and drought on plant carbon metabolism: A meta-analysis.

Elevated temperature (Te ) and drought often co-occur and interactively affect plant carbon (C) metabolism and thus the ecosystem C cycling; however, the magnitude of their interaction is unclear, making the projection of global change impacts challenging. Here, we compiled 107 journal articles in which temperature and water availability were jointly manipulated, and we performed a meta-analysis of interactive effects of Te and drought on leaf photosynthesis (Agrowth ) and respiration (Rgrowth ) at growth temperature, nonstructural carbohydrates and biomass of plants, and their dependencies on experimental and biological moderators (e.g., treatment intensity, plant functional type). Our results showed that, overall, there was no significant interaction of Te and drought on Agrowth . Te accelerated Rgrowth under well-watered conditions rather than under drought conditions. The Te × drought interaction on leaf soluble sugar and starch concentrations were neutral and negative, respectively. The effect of Te and drought on plant biomass displayed a negative interaction, with Te deteriorating the drought impacts. Drought induced an increase in root to shoot ratio at ambient temperature but not at Te . The magnitudes of Te and drought negatively modulated the Te × drought interactions on Agrowth . Root biomass of woody plants was more vulnerable to drought than that of herbaceous plants at ambient temperature, but this difference diminished at Te . Perennial herbs exhibited a stronger amplifying effect of Te on plant biomass in response to drought than did annual herbs. Te exacerbated the responses of Agrowth and stomatal conductance to drought for evergreen broadleaf trees rather than for deciduous broadleaf and evergreen coniferous trees. A negative Te × drought interaction on plant biomass was observed on species-level rather than on community-level. Collectively, our findings provide a mechanistic understanding of the interactive effects of Te and drought on plant C metabolism, which would improve the prediction of climate change impacts.

Porcine IGF-1R synonymous mutations in the extracellular domain affect proliferation and differentiation of skeletal muscle cells.

OBJECTIVE: Miniature pigs are considered ideal organ donors for xenotransplantation in humans, but the mechanism underlying their dwarfism remains to be elucidated. IGF-1R is a crucial factor in body size formation in mammals, including skeletal muscle formation and development. The extracellular domain (ECD) binds to the ligand, a phenomenon that results in the activation of downstream pathways. METHODS: In this study, the coding sequences of two IGF-1R ECD haplotypes of the large Landrace (LP) pig and the small Bama Xiang (BM) pig were cloned into pcDNA3.1 vectors to generate pcDNA3.1-LP and pcDNA3.1-BM. The two recombinant vectors were then transfected into skeletal muscle cells. RESULTS: IGF-1R transcript was found to be expressed at higher levels in the pcDNA3.1-LP group than in the pcDNA3.1-BM group. The IGF-1R ECD from LP promoted cell proliferation and CyclinD1 expression, and promoted the phosphorylation of protein kinase B (to yield p-AKT). Moreover, the IGF-1R ECD from LP increased cell differentiation and the expression of myogenic determination factor (MyoD). CONCLUSION: Our data indicated that the IGF-1R ECD haplotypes between pig breeds with different body sizes affect IGF-1R expression, in turn affecting the proliferation and differentiation of skeletal muscle cells by activating downstream signalling pathways.

Co-expression of recombinant human collagen α1(III) chain with viral prolyl 4-hydroxylase in Pichia pastoris GS115.

The Collagen α1(Ш) chain (COL3A1) is an important structural protein on the surface of human skin. The activity of prolyl 4-hydroxylase (P4H) is crucial to maintaining the stable triple-helix structure and function of human COL3A1. To obtain hydroxylated human COL3A1, virus-derived P4H A085R was co-expressed with human COL3A1 in Pichia pastoris GS115. Colony PCR analysis and sequencing after transfection confirmed that the target gene was successfully inserted. Quantitative reverse transcription PCR (RT-qPCR) indicated that human COL3A1 and P4H A085R were expressed at mRNA levels in the clones. SDS-PAGE and Western blot analysis of supernatant from the recombinant methylotrophic yeast culture showed that recombinant human COL3A1 (rhCOL3A1) was secreted into the culture medium with an apparent molecular mass of approximately 130 kDa. It was observed that the amount of secreted rhCOL3A1 was highest at 120 h after induction. Furthermore, mass spectrometry analysis demonstrated that rhCOL3A1 was successfully expressed in P. pastoris. The His-tagged rhCOL3A1 protein was purified by Ni-affinity column chromatography.

Genome-wide DNA methylation analysis of middle-aged and elderly monozygotic twins with age-related hearing loss in Qingdao, China.

OBJECTIVE: To explore the differences in DNA methylation associated with age-related hearing loss in a study of 57 twin pairs from China. DESIGN: Monozygotic twins were identified through the Qingdao Twin Registration system. The median age of participants was > 50 years. Their hearing thresholds were measured using a multilevel pure-tone audiometry assessment. The pure-tone audiometry was calculated at low frequencies (0.5, 1.0, and 2.0 kHz), speech frequencies (0.5, 1.0, 2.0, and 4.0 kHz), and high frequencies (4.0 and 8 kHz). The CpG sites were tested using a linear mixed-effects model, and the function of the cis-regulatory regions and ontological enrichments were predicted using the online Genomic Regions Enrichment of Annotations Tool. The differentially methylated regions were identified using a comb-p python library approach. RESULTS: In each of the PTA categories (low-, speech-, high-frequency), age-related hearing loss was detected in 25.9%, 19.3%, and 52.8% of participants. In the low-, speech- and high-frequency categories we identified 18, 42, and 12 individual CpG sites and 6, 11, and 6 differentially methylated regions. The CpG site located near DUSP4 had the strongest association with low- and speech-frequency, while the strongest association with high-frequency was near C21orf58. We identified associations of ALG10 with high-frequency hearing, C3 and LCK with low- and speech-frequency hearing, and GBX2 with low-frequency hearing. Top pathways that may be related to hearing, such as the Notch signaling pathway, were also identified. CONCLUSION: Our study is the first of its kind to identify these genes and their associated with DNA methylation may play essential roles in the hearing process. The results of our epigenome-wide association study on twins clarify the complex mechanisms underlying age-related hearing loss.

Simulation Method for Blockchain Systems with a Public Chain.

The potential security problems of blockchain technology are constantly restricting the development process of related industrial applications. The cost of deploying a blockchain system in a real environment to conduct research on security issues is relatively high, and the related security analysis and verification are also destructive and irreproducible. Therefore, based on the idea of layered design, this paper proposes a blockchain system simulation platform. The blockchain system is divided into four layers in the simulation platform: the consensus layer, network layer, contract layer, and storage layer. In the consensus layer, the problem of computing resource waste is solved. In the network layer, a peer-to-peer network topology simulation is implemented. In the storage layer, the problem of redundant storage is solved. In the contract layer, the contract replay speed is accelerated. Finally, a prototype of an efficient blockchain simulation system is implemented based on the above methods.

Identification of Potential miRNA-mRNA Regulatory Network Associated with Pig Growth Performance in the Pituitaries of Bama Minipigs and Landrace Pigs.

Pig growth performance is one of the criteria for judging pork production and is influenced by genotype and external environmental factors such as feeding conditions. The growth performance of miniature pigs, such as Bama minipigs, differs considerably from that of the larger body size pigs, such as Landrace pigs, and can be regarded as good models in pig growth studies. In this research, we identified differentially expressed genes in the pituitary gland of Bama minipigs and Landrace pigs. Through the pathway enrichment analysis, we screened the growth-related pathways and the genes enriched in the pathways and established the protein-protein interaction network. The RNAHybrid algorithm was used to predict the interaction between differentially expressed microRNAs and differentially expressed mRNAs. Four regulatory pathways (Y-82-ULK1/CDKN1A, miR-4334-5p-STAT3/PIK3R1/RPS6KA3/CAB39L, miR-4331-SCR/BCL2L1, and miR-133a-3p-BCL2L1) were identified via quantitative real-time PCR to detect the expression and correlation of candidate miRNAs and mRNAs. In conclusion, we revealed potential miRNA-mRNA regulatory networks associated with pig growth performance in the pituitary glands of Bama minipigs and Landrace pigs, which may help to elucidate the underlying molecular mechanisms of growth differences in pigs of different body sizes.

Health Effects of Peptides Extracted from Deer Antler.

Deer antler is widely used as a nutraceutical in Asian countries. In the past decades, deer antler peptides (DAPs) have received considerable attention because of their various biological properties such as antioxidant, anti-inflammatory, anti-bone damage, anti-neurological disease, anti-tumor and immunomodulatory properties. This review describes the production methods of DAPs and the recent progress of research on DAPs, focusing on the physiological functions and their regulatory mechanisms.

Peptides Isolated from Amphibian Skin Secretions with Emphasis on Antimicrobial Peptides.

The skin of amphibians is a tissue with biological functions, such as defense, respiration, and excretion. In recent years, researchers have discovered a large number of peptides in the skin secretions of amphibians, including antimicrobial peptides, antioxidant peptides, bradykinins, insulin-releasing peptides, and other peptides. This review focuses on the origin, primary structure, secondary structure, length, and functions of peptides secreted from amphibians' skin. We hope that this review will provide further information and promote the further study of amphibian skin secretions, in order to provide reference for expanding the research and application of amphibian bioactive peptides.

Peptide-Calcium Chelate from Antler (Cervus elaphus) Bone Enhances Calcium Absorption in Intestinal Caco-2 Cells and D-gal-Induced Aging Mouse Model.

Antler bone calcium (AB-Ca) and bioactive peptides (ABPs) were extracted from antler bones (Cervus elaphus) to maximize their value. In this study, 0.14 g calcium was obtained from 1 g antler bone. The peptide-calcium chelate rate was 53.68 ± 1.80%, and the Gly, Pro, and Glu in ABPs were identified to donate most to the increased calcium affinity through the mass spectrometry. Fourier transform infrared spectroscopy showed that calcium predominantly interacted with amino nitrogen atoms and carboxyl oxygen atoms, thereby generating a peptide-calcium chelate. The peptide-calcium chelates were characterized using scanning electron microscopy. A Caco-2 cell monolayer model showed that ABPs significantly increased calcium transport. Furthermore, the D-gal-induced aging mouse model indicated that the ABPs + AB-Ca group showed higher Ca and PINP levels, lower P, ALP, and CTX-1content in serum, and considerably higher tibia index and tibia calcium content. Results showed that ABPs + AB-Ca increased bone formation and inhibited bone resorption, thereby providing calcium supplements for ameliorating senile osteoporosis (SOP).

Epidemiologic and clinical characteristics of human bocavirus infection in children hospitalized for acute respiratory tract infection in Qingdao, China.

Persistent infection and prolonged shedding of human bocavirus 1 (HBoV1) in children have been reported, and the role of HBoV1 as a sole causative pathogen in acute respiratory infection (ARI) is yet to be established. While the reported prevalence of HBoV infection varies due to different detection methods and sampling criteria, determining the viral and bacterial etiology of HBoV infection using multiplex real-time PCR is yet to be reported. Herein, we aimed to further explore the pathogenicity of HBoV in patients with ARI by screening the viral and bacterial infections in children with ARI in Qingdao and comparing the epidemiological, clinical characteristics, and etiological results. Human bocavirus was identified in 28.1% of the samples, and further sequencing analysis of the detected HBoV confirmed 96.4% as HBoV1. The rate of HBoV as a single viral infection was 75%, and the rate of coinfection with bacteria was 66.1%, suggesting the need for continued monitoring of HBoV in children with ARIs. Clinical characterization suggested that HBoV infection may affect the function of organs, such as the liver, kidney, and heart, and the blood acid-base balance. Additionally, it is essential to promote awareness about the importance of disinfection and sterilization of the hospital environment and standardizing operations. The interactions between HBoV and other pathogens remain to be investigated in further detail in the future.

An injectable thermosensitive hydrogel with a self-assembled peptide coupled with an antimicrobial peptide for enhanced wound healing.

A wound dressing based on a thermosensitive hydrogel shows advantages over performed traditional dressings, such as rapid reversible sol-gel-sol transition properties and the capacity to fill an irregular-shaped wound area. Herein, RA-Amps was fabricated by coupling a self-assembled peptide RADA16 with an antibacterial peptide (Amps) and incorporated into a PNIPAM hydrogel containing an MGF E peptide to develop a multi-functional composite hydrogel with thermo-response properties, good biocompatibility, good mechanical properties, and antibacterial and carrier functions for wound healing. PNI/RA-Amps is an injectable thermo-reversible system with a phase transition temperature of ∼32 °C, and exhibits a rapid reversible sol-gel-sol transition of ∼23 s, which makes it conducive to sealing the wound area and avoiding sol diffusion caused by a lengthy gel time. MGF E peptide was loaded into a hydrogel and released continuously to promote fibroblast proliferation. Rat full-thickness skin experiments revealed that the PNI/RA-Amps/E hydrogel accelerates wound healing significantly by accelerating epithelialization, the generation of new blood vessels and promoting the generation of collagen fiber compared with commercial dressing. Thus, our findings establish a new candidate for use as an injectable wound dressing for the clinical treatment of wounds.

The A2c111nt-dup variants of human metapneumovirus predominantly circulating in Qingdao, China, during 2018 and 2019.

Human metapneumovirus (HMPV) plays an important role in acute respiratory tract infections (ARTIs), especially in children. We investigated the epidemiology of HMPV associated with ARTIs among pediatric inpatients and identified HMPV genetic variations in Qingdao, China, from January 2018 to June 2019. HMPV-positive samples were identified from throat swabs by multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR). The G gene sequences of HMPV were obtained, followed by phylogenetic analysis. As a result, 71 out of 1051 (6.76%) patients were HMPV positive, and the HMPV-positive rate in children under 5 years of age was three times higher than that in those aged 5-17 years. The epidemic season of HMPV was in spring, with a peak mainly in March. Thirty-two nucleotide sequences of the HMPV G gene successfully obtained were clustered into three genotypes, A2c (25/32, 78.13%), B1 (3/32, 9.38%) and B2 (4/32, 12.50%). In addition, 76% (19/25) of A2c viruses were identified as the emerging A2c111nt-dup variants, which were predominantly circulating among pediatric inpatients with ARTIs between January 2018 and June 2019 in Qingdao. The emerging A2c111nt-dup variants have spread between countries and cities and might spread more widely in the future. Further prevalence monitoring of this duplication variant is needed to clarify the potentially expanding transmission and to provide a scientific basis for disease control and vaccine development.

Evaluation of Potential for Nature-Based Recreation in the Qinghai-Tibet Plateau: A Spatial-Temporal Perspective.

Nature-based recreation (NBR) is an important cultural ecosystem service providing human well-being from natural environments. As the most concentrated and high-quality wilderness in China, the Qinghai-Tibet Plateau (QTP) has unique advantages for NBR. In this study, we designed an integrated nature-based recreation potential index (INRPI) based on four aspects: nature-based recreation resources, landscape attractiveness, recreation comfort and opportunity, and recreation reception ability. A combination of the analytic hierarchy process (AHP) and entropy evaluation method was adopted to assess the NBR potential in the QTP from 2000 to 2020. The research shows that: (i) The INRPI for the QTP decreases gradually from southeast to northwest and increases slightly from 2000 to 2020. (ii) The INRPI displays a pronounced difference on either side of the Qilian-Gyirong line. The areas with very high and high potentials mainly distributed in the southeast of the line, while areas with very low and low potentials distributed in the northwest. (iii) The construction of protected areas effectively improves NBR potential. Areas of INRPI at diverse levels within protected areas obviously increased in 2020. (iv) Increasing altitude has a notable effect on INRPI, and 3000 m is a critical dividing line for the NBR in the QTP. These findings can contribute to decision-makers in guiding rational use and spatial planning of natural land and promoting sustainable recreational development.

Key pituitary miRNAs mediate the expression of pig GHRHR splice variants by regulating splice factors.

The growth hormone releasing hormone receptor (GHRHR) is well documented in organism growth and its alternative splicing may generate multiple functional GHRHR splice variants (SVs). Our previous study has demonstrated the key pituitary miRNAs (let-7e and miR-328-5p) in pig regulated the expression of GHRHR SVs by directly targeting to them. And according to recent reports, the interplay between miRNA-based silencing of mRNAs and alternative splicing of pre-mRNAs is a crucial post-transcriptional mechanism. In this study, SF3B3 and CPSF4 were firstly excavated as the splice factors that involved in the formation of GHRHR SVs mediated by let-7e and miR-328-5p through the comparation of the expression relations of GHRHR SVs, let-7e/miR-328-5p and SF3B3/CPSF4 in pituitary tissues between Landrace pigs and BaMa pigs, as well as the prediction of the target relations of let-7e/miR-328-5p with SF3B3 and/or CPSF4. SF3B3 and CPSF4 targeted by let-7e and miR-328-5p were further verified by performing dual-luciferase reporter assays and detecting the expression of target transcripts. Then the RT-PCR, RT-qPCR and Western blot assays were used to confirm SF3B3 and CPSF4 were involved in the formation of the GHRHR SVs, and in this process, let-7e and miR-328-5p mediated GHRHR SVs by regulating SF3B3 and CPSF4. Finally, the target site of SF3B3 on pre-GHRHR was on the Exon 12 to Exon14, while CPSF4 acted on the other fragments of the pre-GHRHR, which were explored by dual-luciferase reporter system preliminarily. To the best of our knowledge, this paper is the first to report the miRNAs regulate GHRHR SVs indirectly by splice factors.

Metabonomics Study on Naotaifang Extract Alleviating Neuronal Apoptosis after Cerebral Ischemia-Reperfusion Injury.

Naotaifang extract (NTE) is a clinically effective traditional Chinese medicine compound for cerebral ischemia-reperfusion injury. Although NTE can achieve neuroprotective function through different mechanisms, the pharmacodynamic substances of NTE corresponding to these mechanisms have rarely been reported. Alleviating or inhibiting neuronal apoptosis is an important way to achieve neuroprotection. Accordingly, this study has evaluated the effects of NTE on alleviating neuronal apoptosis after cerebral ischemia-reperfusion injury from two levels of cells and tissues. Meanwhile, the serum pharmacochemistry of NTE was analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with the guidance of Chinmedomics. The results included three aspects: (1) NTE could significantly alleviate neuronal apoptosis caused by in vitro cellular models and in vivo animal models; (2) a total of 21 serum differential metabolites was discovered, including adenosine, inosine, ferulic acid, calycosin, salidroside, 6-gingerol, 2-methoxycinnamaldehyde, and so on; (3) the metabolic pathway regulated by NTE was mainly purine metabolism. From these results, it can be concluded that alleviating neuronal apoptosis by NTE after cerebral ischemia-reperfusion injury is one of the important mechanisms to achieve neuroprotection. The pharmacodynamic substances of NTE for alleviating neuronal apoptosis on the one hand are related to components directly absorbed into blood, such as ferulic acid, calycosin, salidroside, 6-gingerol, and 2-methoxycinnamaldehyde and on the other hand are also closely linked to its indirect regulation of purine metabolism in the body to produce adenosine and inosine. Therefore, our research not only identified the main pharmacodynamic substances of NTE that alleviated neuronal apoptosis but also provided a methodological reference for studying other neuroprotective effects of NTE.

Long Distance Transmission of SARS-CoV-2 from Contaminated Cold Chain Products to Humans - Qingdao City, Shandong Province, China, September 2020.

What is already known about this topic? Though coronavirus disease 2019 (COVID-19) has largely been controlled in China, several outbreaks of COVID-19 have occurred from importation of cases or of suspected virus-contaminated products. Though several outbreaks have been traced to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated on the outer packaging of cold chain products, live virus has not been obtained. What is added by this report? In September 2020, two dock workers were detected as having asymptomatic SARS-CoV-2 infection using throat swabs during routine screening in Qingdao, China. Epidemiological information showed that the two dock workers were infected after contact with contaminated outer packaging, which was confirmed by genomic sequencing. Compared to the Wuhan reference strain, the sequences from the dock workers and the package materials differed by 12-14 nucleotides. Furthermore, infectious virus from the cold chain products was isolated by cell culture, and typical SARS-CoV-2 particles were observed under electron microscopy. What are the implications for public health practice? The international community should pay close attention to SARS-CoV-2 transmission mode through cold chain, build international cooperative efforts in response, share relevant data, and call on all countries to take effective prevention and control measures to prevent virus contamination in cold-chain food production, marine fishing and processing, transportation, and other operations.