Developing Covalent Protein Drugs via Proximity-Enabled Reactive Therapeutics.

Small molecule covalent drugs provide desirable therapeutic properties over noncovalent ones for treating challenging diseases. The potential of covalent protein drugs, however, remains unexplored due to protein's inability to bind targets covalently. We report a proximity-enabled reactive therapeutics (PERx) approach to generate covalent protein drugs. Through genetic code expansion, a latent bioreactive amino acid fluorosulfate-L-tyrosine (FSY) was incorporated into human programmed cell death protein-1 (PD-1). Only when PD-1 interacts with PD-L1 did the FSY react with a proximal histidine of PD-L1 selectively, enabling irreversible binding of PD-1 to only PD-L1 in vitro and in vivo. When administrated in immune-humanized mice, the covalent PD-1(FSY) exhibited strikingly more potent antitumor effect over the noncovalent wild-type PD-1, attaining therapeutic efficacy equivalent or superior to anti-PD-L1 antibody. PERx should provide a general platform technology for converting various interacting proteins into covalent binders, achieving specific covalent protein targeting for biological studies and therapeutic capability unattainable with conventional noncovalent protein drugs.

Comparative analysis of the quality of platelet concentrates produced by apheresis procedures, platelet rich plasma, and buffy coat.

BACKGROUND: Platelet concentrates (PCs) could be prepared using either whole-blood processes or apheresis instruments. During collection, processing and storage, some biochemical and functional changes occur, which may result in quality reduction. Quality evaluation of PCs may be helpful for the precise control of platelet (PLT) inventory to reduce the risk of refractoriness and adverse effects caused by platelet transfusion. STUDY DESIGN AND METHODS: The study was aimed to evaluate the quality of PCs which were produced by five processes: apheresis (AP) procedures (using three different cell separators: Amicus, Trima Accel and MCS+ instruments), platelet rich plasma (PRP), and buffy coat (BC). A total of 100 PCs (20 of each group) were assessed in respect of routine quality control, morphology, size distribution, destroyed and activated platelets, and production of platelet-derived microparticles (PMPs). RESULTS: All PCs have satisfied the recommended quality of volume, platelet count, residual WBC count, residual RBC count, pH, and sterility according to the Chinese Technical Manual. There was no difference among the 5 groups in morphology and size of PLT and PMPs. Dynamic light scattering test showed that apheresis PCs showed peaks around 10-20 nm, but not whole blood-derived PCs. PCs prepared by Amicus had the relatively high percentage of destroyed platelet, activated platelets and PMPs than other groups. DISCUSSION: The data suggested high heterogeneity of PMPs, destroyed and activated platelets in PCs produced by different processes, which might be helpful to manage the platelet inventory for targeted use.

Association between clinical symptoms during the COVID-19 infection and SARS-CoV-2 immunoglobulin G titers in COVID-19 convalescent whole-blood donors in China.

BACKGROUND: Limited studies have explored the association between clinical symptoms and titers of SARS-CoV-2 antibodies. STUDY DESIGN AND METHODS: In this cross-sectional study, whole-blood donors who had experienced a confirmed or suspected COVID-19 infection completed questionnaires at the time of blood donation. Plasma SARS-CoV-2 immunoglobulin G (IgG) titers were measured using an enzyme-linked immunosorbent assay. Logistic regression models were used to calculate odds ratios (ORs) for high-titer COVID-19 convalescent plasma (CCP) for each variable. RESULTS: Among the total 386 donors, 120 (31%) donors with IgG titers ≥1:160 were classified as high-titer donors. The multivariable ORs (95% confidence intervals [CIs]) for high titers were 2.33 (1.45-3.75), 2.11 (1.29-3.43), 1.10 (1.01-1.21), 1.19 (1.00-1.43), and 1.97 (1.05-3.71) for sore throat, cough, symptom count, fever duration, and low fever (compared with non-fever), respectively. No significant association was observed between other symptoms and medical visits and the odds of high-titer CCP. The association between high-titer CCP and fever duration was restricted to confirmed COVID-19-infected donors, while associations with sore throat and cough remained significant in suspected infected donors. In addition, medical visit was positively associated with high-titer CCP in suspected donors, but not in confirmed donors. In bootstrapped logistic regression models, the associations remained significant and reproducible for medical visit in suspected donors and for sore throat and cough in both suspected donors and total donors. DISCUSSION: Experiencing a sore throat and cough were associated with high-titer CCP in overall donors. We also identified sore throat, cough, and medical visits as potential predictors of high-titer CCP for suspected donors during the pandemic.

Enhancing understanding of healthy aging based on time-varying dependencies among multidimensional health, life satisfaction, and health behaviors of older adults aged 60 years and over.

BACKGROUND: Healthy aging is a process of not only achieving good health but also increasing the life satisfaction of older adults aged 60 years and over, in which health behaviors play an important role. There is a lack of research on the time-varying dependencies between health, life satisfaction, and health behaviors, impeding a deeper understanding of healthy aging. PURPOSE: To develop an integrated framework for modeling the interrelationships among the components of healthy aging between multiple time slices. METHODS: Based on the Chinese Longitudinal Healthy Living Survey (CLHLS) data in the three waves of 2011/2012, 2014, and 2017/2018, Bayesian network and dynamic Bayesian network are jointly employed to study the relationships among the components of healthy aging within one time slice, as well as to explore the time-varying dependencies among the components between time slices. RESULTS: The results of structure learning reveal the direction of effects between different dimensions of health, with mental health and social health affecting physical health and self-rated health affecting both physical and mental health. In addition, health behaviors are found to affect mental health and social health, while self-rated health can influence life satisfaction. The parameters learned from the data show the magnitude and direction of concurrent effects, one-period lagged effects and two-period lagged effects between the factors, which find that the time-varying dependencies vary but are generally positive, long-term, and accumulative over time. In addition, the results of autoregressive effects show the positive predictive effects of health and life satisfaction. CONCLUSIONS: It confirms the influence pathway from health behaviors to multidimensional health to life satisfaction, and the time-varying dependencies among the components of healthy aging, which facilitates a deeper understanding of healthy aging. Combining the results of autoregressive effects and descriptive statistics, it further indicates that healthy aging is a comprehensive result arising from interactions of multiple factors. Policymakers should guide older adults aged 60 years and over to adopt healthier behaviors and ensure the long-term sustainability and continuity of policies.

Size-dependent bending of a rectangular polymer film.

Inhomogeneous swelling of polymer films in liquid environments may find applications in soft actuators and sensors. Among them, fluoroelastomer based films bend up spontaneously once they are placed on an acetone-soaked filter paper. The stretchability and dielectric properties of a fluoroelastomer is attractive in the fields of soft actuators and sensors, making in-depth studies on and understanding of fluoroelastomer bending behaviors important. Here, we report an abnormal size-dependent bending phenomenon of rectangular fluoroelastomer films, which transform the bending direction from the long-side bending to the short-side bending as their length or width increases or the thickness decreases. By using finite element analysis and an analytical expression obtained using a bilayer model, we reveal the key role of gravity in determining the size-dependent bending behavior. In the bilayer model, an energy quantity is obtained to characterize the role of each material and geometrical parameters in determining the size-dependent bending behavior. We further construct phase diagrams to correlate the bending modes and the film sizes based on the finite element results, which are in good agreement with experimental results. These findings can be useful for the design of future swelling-based polymer actuators and sensors.

Genome-Wide Identification and Expression Analysis of the bHLH Transcription Factor Family in Wintersweet (Chimonanthus praecox).

Wintersweet (Chimonanthus praecox (L.) Link, Calycanthaceae) is an esteemed ornamental flowering shrub known for its distinct blooming period in winter, vibrant color petals, and captivating floral fragrance. Basic helix-loop-helix (bHLH) transcription factors (TFs) play pivotal roles as key regulators in secondary metabolites biosynthesis, growth, and development in plants. However, the systematic analysis of the bHLH family members and their role in the regulation of floral traits in Wintersweet remains insufficiently understood. To bridge this knowledge gap, we conducted a comprehensive genome-wide analysis of the C. praecox bHLH (CpbHLH) gene family, identifying a total of 131 CpbHLH genes across 11 chromosomes. Phylogenetic analysis classified these CpbHLH genes into 23 subfamilies, wherein most members within the same subfamily exhibited analogous intron/exon patterns and motif composition. Moreover, the expansion of the CpbHLH gene family was primarily driven by segmental duplication, with duplicated gene pairs experiencing purifying selection during evolution. Transcriptomic analysis revealed diverse expression patterns of CpbHLH genes in various tissues and distinct stages of Wintersweet flower development, thereby suggesting their involvement in a diverse array of physiological processes. Furthermore, yeast 2-hybrid assay demonstrated interaction between CpbHLH25 and CpbHLH59 (regulators of floral scent and color) as well as with CpbHLH112 and CpMYB2, suggesting potential coordinately regulation of secondary metabolites biosynthesis in Wintersweet flowers. Collectively, our comprehensive analysis provides valuable insights into the structural attributes, evolutionary dynamics, and expression profiles of the CpbHLH gene family, laying a solid foundation for further explorations of the multifaceted physiological and molecular roles of bHLH TFs in Wintersweet.

Enhancement and manipulation of group delay based on topological edge state in one-dimensional photonic crystal with graphene.

In this paper, the reflected and transmitted group delay from a one-dimensional photonic crystal heterostructure with graphene at communication band are investigated theoretically. It is shown that the negative reflected group delay of the beam in this structure can be significantly enhanced and can be switched to positive. The large reflected group delay originates from the sharp phase change caused by the excitation of topological edge state at the interface between the two one-dimensional photonic crystals. Besides, the introduction of graphene provides an effective approach for the dynamic control of the group delay. It is clear that the positive and negative group delay can be actively manipulated through the Fermi energy and the relaxation time of the graphene. In addition, we also investigate the transmitted group delay of the structure, which is much less than the reflected one. The enhanced and tunable delay scheme is promising for fabricating optical delay devices like optical buffer, all-optical delays and other applications at optical communication band.

Synthesis and Optical Properties of Unique Pt1Ag24 Nanoclusters with Mixed Exterior Motif Structures.

The atomic arrangement of metal nanoclusters plays a significant role in the structure-property correlation. Herein, we present a novel Pt1Ag24(SR)16(PPh3)3 nanocluster with a unique structure, different from two reported Pt1Ag24 nanoclusters. The nanocluster was prepared via one-pot synthesis and solvent extraction. It has a centered icosahedral Pt1Ag12 kernel and an open shell composed of three Ag2(SR)3(PPh3) staple motifs and a unique trefoil-like Ag6(SR)7 motif. The three kinds of Pt1Ag24 nanoclusters have the same kernel but different shell configurations. The fine-tuning of structures is necessary and significant for the investigation of the relationship of structures and properties. The different UV-vis absorption spectra indicate that the optical properties of three Pt1Ag24 nanoclusters mainly depend on the exterior shell configuration and the metal-ligand interface. This work provides insights toward growth mechanism and the structure-property correlation of metal nanoclusters.

Emergency response to COVID-19 epidemic: One Chinese blood centre's experience.

OBJECTIVE: The COVID-19 epidemic has caused a significant global social and economic impact since December 2019. The objective of this study was to demonstrate the emergency response of a Chinese blood centre on maintaining both the safety and the sufficiency of blood supply during large, emerging, infectious epidemics. MATERIALS AND METHODS: Early on in the outbreak of COVID-19, the Chengdu Blood Center developed strategies and implemented a series of measures, including enhanced recruitment efforts, addition of new donation deferral criteria and notification after donation, optimisation of donor experience, development and implementation of a new coronavirus nucleic acid detection technology platform for blood screening and screening all donations for SARS-CoV-2 RNA to maximumly protect the safety of blood supply during a time of unclear risk. RESULTS: Starting on February 20, the immediate satisfaction rate of blood product orders in Chengdu city's clinical settings reached 100%, and there was no case of blood transfusion infection. CONCLUSION: The recent experience during the outbreak of SARS-CoV-2 reminded us that improvement in the areas of national and international collaborative programmes for dealing with blood availability and safety concerns during early stages of a disaster and regional and national mechanisms for timely communication with the general public on behalf of blood services should help to better prepare us for future disasters.

The apheresis platelet donation was increased after a nationwide ban on family/replacement donation in China.

BACKGROUND: A nationwide ban on family/replacement donation (FRD) went into effect on April 1, 2018 in China. To date, no reports relevant to the trend of plateletpheresis donations before and after a nationwide ban on FRD were found. METHODS: We used two independent full samples, consisting of 135,851 and 82,129 plateletpheresis donors from Guangzhou and Chengdu between October 2012 and September 2019, respectively. A pseudo-panel data approach was applied by grouping three time-invariant covariates - gender, blood donation history, and birth year across 14 cross-sections (a 6-month interval each) to form a total of 24 cohort groups (14 × 24 = 336 cohorts, i.e., cells) with each having common covariates. The outcome was average apheresis platelet units per donor in each cell. We performed a two-piecewise linear mixed model with the cross-section (i.e., time) just right before the ban as a time breakpoint (i.e., 11th cross-section) to examine the trend of outcome with the adjustment of three time-invariant covariates. We removed the FRDs in each of the first 11 cross-sections to detect its possible influence on the trend. RESULTS: The final model for the samples from Guangzhou presented a two-piecewise linear trend of the outcome over time with a horizontal line to the left of the breakpoint (ßtimeBefore11 = 0.0111, p = 0.0976) and a significantly positive linear trend to the right (ßtimeAfter11 = 0.0404, p < 0.0001). The male donors and the donors with plateletpheresis donation history had an increased baseline outcome and a significant outcome change over time after the ban. Such a two-piecewise linear trend pattern can be replicated using the samples from Chengdu with some minor variations. Removing the FRD before the ban can change the pattern. CONCLUSION: The significant increase of the average apheresis platelet units per donor over time after the FRD ban may be related to the implement of the FRD ban and the improved donation behavior of male donors and/or donors with platelet donation history after the ban. Our findings may potentially motivate the policymakers in other countries where the FRD for plateletpheresis donation is still legitimate to phase out their FRD strategy and ultimately achieve 100% voluntary plateletpheresis donation.

IDO1 Maintains Pluripotency of Primed Human Embryonic Stem Cells by Promoting Glycolysis.

Human embryonic stem cells (hESCs) depend on glycolysis for energy supply and pluripotency and switch to oxidative phosphorylation upon differentiation. The underlying mechanisms remain unclear. Here, we demonstrate that indoleamine 2,3-dioxygenase 1 (IDO1) is expressed in primed hESCs and its expression rapidly downregulated upon hESC differentiation. IDO1 is required to maintain pluripotency by suppressing mitochondria activity and promoting glycolysis through the increase of NAD+ /NADH ratio. The upregulation of IDO1 during hESC differentiation suppresses the differentiation of hESCs into certain lineages of cells such as cardiomyocytes, which depend on oxidative phosphorylation to satisfy their high energy demand. Therefore, IDO1 plays important roles in maintaining the pluripotency of hESCs. Stem Cells 2019;37:1158-1165.

Development and evaluation of a Novel RT-PCR system for reliable and rapid SARS-CoV-2 screening of blood donations.

BACKGROUND: The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused great global concerns. In contrast to SARS, some SARS-CoV-2-infected people can be asymptomatic or have only mild nonspecific symptoms. Furthermore, there is evidence that SARS-CoV-2 may be infectious during an asymptomatic incubation period. With the discovery that SARS-CoV-2 can be detected in plasma or serum, blood safety is worthy of consideration. STUDY DESIGN AND METHODS: We developed a nucleic acid test (NAT) screening system for SARS-CoV-2 targeting nucleocapsid protein (N) and open reading frame 1ab (ORF 1ab) gene that could screen 5076 samples every 24 hours. The 2019 novel coronavirus RNA standard was used to evaluate linearity of standard curves. Diagnostic sensitivity and reproducibility were evaluated using artificial SARS-CoV-2. Specificity was evaluated with 61 other respiratory pathogens. Diagnostic performance was evaluated by testing two sputum and nine oropharyngeal swab specimens. The reverse transcription polymerase chain reaction (RT-PCR) assay was used to screen SARS-CoV-2 RNA in blood donor specimens collected during the outbreak of SARS-CoV-2 in Chengdu. RESULTS: Limits of detection of the SARS-CoV-2 RT-PCR assay for N and ORF 1ab gene were 12.5 and 27.58 copies/mL, respectively. Intra-assay and interassay for the SARS-CoV-2 RT-PCR assay based on cycle threshold were acceptably low. No cross-reactivity was observed with other respiratory virus and bacterial isolates. The overall agreement value between the SARS-CoV-2 RT-PCR assay and clinical diagnostic results was 100%. A total of 16 287 blood specimens collected from blood donors during SARS-CoV-2 surveillance were tested negative. CONCLUSIONS: A high-throughput NAT screening system was developed for SARS-CoV-2 screening of blood donations during the outbreak of SARS-CoV-2.

Structure of the Au23-x Agx (S-Adm)15 Nanocluster and Its Application for Photocatalytic Degradation of Organic Pollutants.

Ligands play an important role in determining the atomic arrangement within the metal nanoclusters. Here, we report a new nanocluster [Au23-x Agx (S-Adm)15 ] protected by bulky adamantanethiol ligands which was obtained through a one-pot synthesis. The total structure of [Au23-x Agx (S-Adm)15 ] comprises an Au13-x Agx icosahedral core, three Au3 (SR)4 units, and one AgS3 staple motif in contrast to the 15-atom bipyramidal core previously seen in [Au23-x Agx (SR)16 ]. UV/Vis spectroscopy indicates that the HOMO-LUMO gap of [Au23-x Agx (S-Adm)15 ] is 1.5 eV. DFT calculations reveal that [Au19 Ag4 (S-Adm)15 ] is the most stable structure among all structural possibilities. Benefitting from Ag doping, [Au23-x Agx (S-Adm)15 ] exhibits drastically improved photocatalytic activity for the degradation of rhodamine B (RhB) and phenol under visible-light irradiation compared to Au23 nanoclusters.

Effects of microRNA-292-5p on myocardial ischemia-reperfusion injury through the peroxisome proliferator-activated receptor-α/-γ signaling pathway.

Ischemia-reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes, such as free radical damage and cell apoptosis. This study aims to investigate whether microRNA-292-5p (miR-292-5p) protects against myocardial ischemia-reperfusion injury (IRI) via the peroxisome proliferator-activated receptor (PPAR)-α/-γ signaling pathway in myocardial IRI mice models. Mouse models of myocardial IRI were established. Adult male C57BL/6 mice were divided into different groups. The hemodynamic indexes, levels of related inflammatory factors and serum myocardial enzymes, and malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was applied to determine infarct size. TUNEL staining was used to detect cardiomyocyte apoptosis. RT-qPCR and western blotting were performed to measure the related gene expressions. Compared with the model group and the T0070907 + miR-292-5p inhibitor, the miR-292-5p inhibitor group exhibited decreased incidence and duration time of ventricular tachycardia and ventricular fibrillation, serum myocardial enzymes, TNF-α, IL-6, IL-1ß, MDA, cardiomyocyte apoptosis, expressions of Bax and p53 in addition to increased SOD and GSH-Px activity, and increased expressions of Bcl-2, PPARα, PPARγ, PLIN5, AQP7, and PCK1. The T0070907 group exhibited opposite results compared to the miR-292-5p inhibitor group. The results indicate that miR-292-5p downregulation protects against myocardial IRI through activation of the PPAR-α/PPAR-γ signaling pathway.

Multicolor, Fluorescent Supercapacitor Fiber.

Fiber-shaped supercapacitors have attracted broad attentions from both academic and industrial communities due to the demonstrated potentials as next-generation power modules. However, it is important while remains challenging to develop dark-environment identifiable supercapacitor fibers for enhancement on operation convenience and security in nighttime applications. Herein, a novel family of colorful fluorescent supercapacitor fibers has been produced from aligned multi-walled carbon nanotube sheets. Fluorescent dye particles are introduced and stably anchored on the surfaces of aligned multi-walled carbon nanotubes to prepare hybrid fiber electrodes with a broad range of colors from red to purple. The fluorescent component in the dye introduces fluorescent indication capability to the fiber, which is particularly promising for flexible and wearable devices applied in dark environment. In addition, the colorful fluorescent supercapacitor fibers also maintain high electrochemical performance under cyclic bending and charge-discharge processes.

A Safety Checkpoint to Eliminate Cancer Risk of the Immune Evasive Cells Derived from Human Embryonic Stem Cells.

Human embryonic stem cells (hESCs) hold great promise in the regenerative therapy of many currently untreatable human diseases. One of the key bottlenecks is the immune rejection of hESC-derived allografts by the recipient. To overcome this challenge, we have established new approaches to induce immune protection of hESC-derived allografts through the coexpression of immune suppressive molecules CTLA4-Ig and PD-L1. However, this in turn raises a safety concern of cancer risk because these hESC-derived cells can evade immune surveillance. To address this safety concern, we developed a safety checkpoint so that the immune evasive hESC-derived cells in the graft can be effectively eliminated if any cellular transformation is detected. In this context, we knock-in the suicidal gene herpes simplex virus thymidine kinase (HSVTK) into the constitutive HPRT locus of CP hESCs (knock-in hESCs expressing CTLA4-Ig and PD-L1), denoted CPTK hESCs. Employing humanized mice (Hu-mice) reconstituted with human immune system, we demonstrated that the CPTK hESC-derived cells are protected from immune rejection. In addition, CPTK hESC-derived cells can be efficiently eliminated in vitro and in vivo with FDA approved TK-targeting drug ganciclovir. Therefore, this new safety checkpoint improves the feasibility to use the immune evasive hESC-derived cells for regenerative medicine. Stem Cells 2017;35:1154-1161.

Bifunctional bamboo-like CoSe2 arrays for high-performance asymmetric supercapacitor and electrocatalytic oxygen evolution.

Bifunctional bamboo-like CoSe2 arrays are synthesized by thermal annealing of Co(CO3)0.5OH grown on carbon cloth in Se atmosphere. The CoSe2 arrays obtained have excellent electrical conductivity, larger electrochemical active surface areas, and can directly serve as a binder-free electrode for supercapacitors and the oxygen evolution reaction (OER). When tested as a supercapacitor electrode, the CoSe2 delivers a higher specific capacitance (544.6 F g-1 at current density of 1 mA cm-2) compared with CoO (308.2 F g-1) or Co3O4 (201.4 F g-1). In addition, the CoSe2 electrode possesses excellent cycling stability. An asymmetric supercapacitor (ASC) is also assembled based on bamboo-like CoSe2 as a positive electrode and active carbon as a negative electrode in a 3.0 M KOH aqueous electrolyte. Owing to the unique stucture and good electrochemical performance of bamboo-like CoSe2, the as-assembled ACS can achieve a maximum operating voltage window of 1.7 V, a high energy density of 20.2 Wh kg-1 at a power density of 144.1 W kg-1, and an outstanding cyclic stability. As the catalyst for the OER, the CoSe2 exhibits a lower potential of 1.55 V (versus RHE) at current density of 10 mA cm-2, a smaller Tafel slope of 62.5 mV dec-1 and an also outstanding stability.

DNA repair mechanisms in embryonic stem cells.

Embryonic stem cells (ESCs) can undergo unlimited self-renewal and retain the pluripotency to differentiate into all cell types in the body. Therefore, as a renewable source of various functional cells in the human body, ESCs hold great promise for human cell therapy. During the rapid proliferation of ESCs in culture, DNA damage, such as DNA double-stranded breaks, will occur in ESCs. Therefore, to realize the potential of ESCs in human cell therapy, it is critical to understand the mechanisms how ESCs activate DNA damage response and DNA repair to maintain genomic stability, which is a prerequisite for their use in human therapy. In this context, it has been shown that ESCs harbor much fewer spontaneous mutations than somatic cells. Consistent with the finding that ESCs are genetically more stable than somatic cells, recent studies have indicated that ESCs can mount more robust DNA damage responses and DNA repair than somatic cells to ensure their genomic integrity.

Distribution of hepatitis C virus genotypes in volunteer blood donors from Chengdu, China.

Hepatitis C virus (HCV) is a significant pathogen of global concern. The virus is usually spread through blood contact, such as transfusion, hemodialysis and injection of illegal drugs. HCV genotypes have a geographic distribution in different areas. In this paper, we focus on the distribution of HCV genotypes from volunteer blood donors in Chengdu. The prevalence of genotypes was analyzed using phylogenetic analysis. Phylogenetic trees were constructed based on the HCV core and NS5B regions from 313 sequences. HCV sequences were classified into six subtypes, and HCV genotypes were determined with the following results: 1b in 283, 2a in 14, 3b in seven, 3a in three, 6a in five and 6u in one. Subtype 1b was the most common and accounted for approximately 90.41 % (283/313), and a virus of subtype 6u was isolated for the first time from the Chengdu area. Genotypes 4 and 5 were not detected.

Transplantation of olfactory ensheathing cells promotes the recovery of neurological functions in rats with traumatic brain injury associated with downregulation of Bad.

BACKGROUND AIMS: The neuroprotective effects of olfactory ensheathing cells (OECs) after transplantation have largely been known in the injured nervous system. However, the underlying mechanisms still must be further elucidated. We explored the effects of OEC transplantation on the recovery of neurophysiologic function and the related anti-apoptosis mechanism in acute traumatic brain injury. METHODS: The OECs from neonatal Sprague-Dawley rats were isolated, identified and labeled and then were immediately transplanted into the regions surrounding the injured brain site that is resulted from free-weight drop injury. RESULTS: Nerve growth factor and it's recepor, p75 was expressed in cultured OECs. Transplanted OECs survived, migrated around the injury site and significantly improved the neurological severe scores compared with the control group (P < 0.05). OEC transplantation significantly increased the number of GAP-43-immunopositive fibers and synaptophysin-positive vesicles (P < 0.05) but significantly decreased the number of apoptotic cells (P < 0.05). On the molecular level, the expression of Bad in the OEC transplantation group was significantly downregulated (P < 0.05). CONCLUSIONS: OEC transplantation could effectively improve neurological deficits in TBI rats; the underlying mechanism may be related with their effects on neuroprotection and regeneration induction, which is associated with the downregulation of the apoptotic molecule Bad.