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Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhang, Guo, Bai, Tian and Luo.)

Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes ( BATF2 , PTPRJ , RGS1 , and VCAN ), is a reliable and independent biomarker for GC. PRS low is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRS low marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Seeking novel high-performance elastocaloric materials with low critical stress plays a crucial role in advancing the development of elastocaloric refrigeration technology. Here, as a first attempt, the elastocaloric effect of TiZrNbAl shape memory alloy at both room temperature and finite temperatures ranging from 245 K to 405 K, is studied systematically. Composition optimization shows that Ti-19Zr-14Nb-1Al (at.%), possessing excellent room-temperature superelasticity with a critical stress of around 100 MPa and a small stress hysteresis of around 70 MPa and outstanding fracture resistance with a compressive strain of 20% and stress of 1.7 GPa, demonstrates a substantial advantage as an elastocaloric refrigerant. At room temperature, a large adiabatic temperature change (ΔTad) of -6.7 K is detected, which is comparable to the highest value reported in the Ti-based alloys. A high elastocaloric cyclic stability, with almost no degradation of ΔTad after 4000 cycles, is observed. Furthermore, the sizeable elastocaloric effect can be steadily expanded from 255 K to 395 K with a temperature window of as large as 140 K. A maximum ΔTad of -7.9 K appears at 355 K. The present work demonstrates a promising potential of TiZrNbAl as a low critical stress and low hysteresis elastocaloric refrigerant.

The chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. However, at present, research on the role played by CCL5 in the occurrence and development of CRC is still limited, and whether CCL5 promotes the occurrence and development of CRC and its role remain controversial. This paper discusses the cells recruited by CCL5 in patients with CRC and the specific mechanism of this recruitment, as well as recent clinical studies of CCL5 in patients with CRC.Key MessagesCCL5 plays dual roles in colorectal cancer progression.CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action.CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.

Object: There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms., Methods: GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions., Results: Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software's MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p., Conclusion: Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhang, Fang, Li, Shu, Gong, Luo and Tian.)

Substance use disorders (SUD) can lead to serious health problems, and there is a great interest in developing new treatment methods to alleviate the impact of substance abuse. In recent years, the ketogenic diet (KD) has shown therapeutic benefits as a dietary therapy in a variety of neurological disorders. Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism, thereby reducing withdrawal symptoms and indicating the therapeutic potential of KD in SUD. Additionally, SUD often accompanies increased sugar intake, involving neural circuits and altered neuroplasticity similar to substance addiction, which may induce cross-sensitization and increased use of other abused substances. Reducing carbohydrate intake through KD may have a positive effect on this. Finally, SUD is often associated with mitochondrial damage, oxidative stress, inflammation, glia dysfunction, and gut microbial disorders, while KD may potentially reverse these abnormalities and serve a therapeutic role. Although there is much indirect evidence that KD has a positive effect on SUD, the small number of relevant studies and the fact that KD leads to side effects such as metabolic abnormalities, increased risk of malnutrition and gastrointestinal symptoms have led to the limitation of KD in the treatment of SUD. Here, we described the organismal disorders caused by SUD and the possible positive effects of KD, aiming to provide potential therapeutic directions for SUD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kong, Sun, Yang, Li, Bi, Zhang, Wang, Luo, Zhu and Xu.)

Background: Methamphetamine (METH) abuse causes serious health problems, including injury to the immune system, leading to increased incidence of infections and even making withdrawal more difficult. Of course, immune cells, an important part of the immune system, are also injured in methamphetamine abuse. However, due to different research models and the lack of bioinformatics, the mechanism of METH injury to immune cells has not been clarified., Methods: We examined the response of three common immune cell lines, namely Jurkat, NK-92 and THP-1 cell lines, to methamphetamine by cell viability and apoptosis assay in vitro, and examined their response patterns at the mRNA level by RNA-sequencing. Differential expression analysis of two conditions (control and METH treatment) in three types of immune cells was performed using the DESeq2 R package (1.20.0). And some of the differentially expressed genes were verified by qPCR. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of differentially expressed genes by the clusterProfiler R package (3.14.3). And gene enrichment analysis was also performed using MetaScape ( www.metascape.org )., Results: The viability of the three immune cells was differentially affected by methamphetamine, and the rate of NK-cell apoptosis was significantly increased. At the mRNA level, we found disorders of cholesterol metabolism in Jurkat cells, activation of ERK1 and ERK2 cascade in NK-92 cells, and disruption of calcium transport channels in THP-1 cells. In addition, all three cells showed changes in the phospholipid metabolic process., Conclusions: The results suggest that both innate and adaptive immune cells are affected by METH abuse, and there may be commonalities between different immune cells at the transcriptome level. These results provide new insights into the potential effects by which METH injures the immune cells., (© 2022. The Author(s).)

Spinal cord injury is a severe central nervous system disease, which will cause a series of complex pathophysiological changes and activate a variety of signaling pathways including Notch signaling. Studies have evidenced that activation of the Notch signaling pathway is not conducive to nerve repair and symptom improvement after spinal cord injury. Its mechanisms include inhibiting neuronal differentiation and axon regeneration, promoting reactive astrocyte proliferation, promoting M1 macrophage polarization and the release of proinflammatory factors, and inhibiting angiogenesis. Therefore, it has become a promising therapeutic strategy to inhibit Notch signal as a target in the treatment of spinal cord injury. In recent years, some researchers have used drugs, cell transplantation or genetic modification to regulate Notch signaling, which can promote the recovery of nerve function after spinal cord injury, thereby providing new treatment strategies for the treatment of spinal cord injury. This article will summarize the mechanism of Notch signaling pathway in spinal cord injury, and at the same time review the research progress in the treatment of spinal cord injury by modulating Notch signaling pathway in recent years, so as to provide new research ideas for further exploring new strategies for spinal cord injury.

The skin barrier of melasma is involved in the pathogenesis of melasma. Previous studies have shown that there are differences in the expression of epidermal lipid genes in melasma, but little is known about the epidermis lipid composition of melasma. Compared with the non-lesional skin, the content of total lipids, phosphatidic acid, phosphatidylserine, and ceramide (Cer) increased significantly in the lesional skin. Multivariate data analysis indicated that 40 individual Cer lipid species were responsible for the discrimination. In terms of acyl chain length in Cer, the expressions of very long chain (VLC) (C20-C26) and ultra-long chain (ULC) (>C26) increased significantly in the lesional skin. However, Cer[AH] had negative correlations with the activation of melanocytes in the lesional skin. Some lipid species had lower expression in lesional skin with high activation of melanocytes, as well as the high darkness. The epidermal thickness of lesional skin was higher compared with the non-lesional skin. These results suggest that Cer increased significantly in the lesional skin of melasma, possibly as a compensatory mechanism to maintain skin barrier function. Between different groups of darkness and activation of melanocytes, the change of ceramides might have correlation with the pigmentation progress of melasma., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Gastrointestinal probiotics play an important role in maintaining intestinal bacteria homeostasis. They might benefit people with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), which remains a global health challenge. However, there is a controversy regarding the efficacy of probiotics for the treatment of AIDS. This study systematically reviewed the evidence of the effects of existing probiotic interventions on AIDS and sought to provide information on the role of probiotics in the treatment of HIV/AIDS patients. A meta-analysis of studies identified by screening multiple databases was performed using a fixed-effects model in Review Manager 5.2 software. The meta-analysis showed that probiotics could reduce the incidence of AIDS-related diarrhea (RR = 0.60 (95% CI: 0.44-0.82), p = 0.001). The short-term use of probiotics (supplementation duration shorter than 30 days) did not reduce the incidence of diarrhea (RR = 0.76 (95% CI: 0.51-1.14), p = 0.19), while the long-term use of probiotics (supplementation duration longer than 30 days) reduced diarrhea (RR = 0.47 (95% CI: 0.29-0.76), p = 0.002). Probiotics had no effect on CD4 cell counts in HIV/AIDS patients (MD = 21.24 (95% CI: -12.95-55.39), p = 0.22). Our data support that probiotics were associated with an obvious reduction in AIDS-related diarrhea, which indicates the need for additional research on this potential preventive strategy for AIDS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Chen, Geng, Yu, Kuang, Luo and Wang.)

Melasma is a frequently acquired hyperpigmentary skin disorder, for which several therapies are available. Among them, 1064 nm QS Nd:YAG laser therapy is an effective method, but the recurrence rate of laser treatment is still high. The aim of the present study was to elucidate the mechanism of the high relapse rate of melasma after 1064 nm Nd:YAG laser treatment. Twenty-five female melasma patients were treated with 1064 nm Nd:YAG laser for 10 times. The lesional skin and non-lesional skin were evaluated by means of a reflectance confocal laser scanning microscope before and after laser treatment. Melanin content and transepidermal water loss (TEWL) were measured by an MPA9 skin multifunction tester accordingly. The melanin index value was significantly decreased in the lesional skin after laser treatment, while the non-lesional skin had no difference. The dendritic cells were observed at the level of the dermal-epidermal junction (DEJ) in the lesions of 8 patients before laser treatment, while after laser treatment, the dendritic cells were observed in all 25 subjects. Moreover, there was significant difference between the TEWL value of the lesions before and after laser treatment. Furthermore, the TEWL value was higher in lesions of the 8 subjects which had dendritic cells compared with other 17 subjects which had no dendritic cells, no matter before or after laser treatment. The relapse patients of melasma had higher TEWL value compared with the non-relapse patients. Melanocyte activation and skin barrier disruption may be related to the high relapse rate of melasma after laser treatment.

Sleep disturbance is a significant problem affecting around 50% of cancer patients. Non-pharmacological interventions can be used to improve sleep quality in cancer patients, but little is known about the feasibility, acceptability, and effectiveness of auricular point acupressure (APA) to reduce sleep disturbance in women with ovarian cancer undergoing chemotherapy. A pilot randomized controlled trial was conducted at a publicly funded hospital in southern Taiwan. Fifty-five eligible women were approached and 47 women participated. Women randomly assigned to the control group (n = 24) received sleep hygiene practices alone. Women in the intervention group (n = 23) received sleep hygiene practices and APA treatment which involved gentle fingertip pressure at acupoints on the external ear. The Pittsburgh Sleep Quality Index (PSQI) was completed at four time points. Forty women completed the trial giving a retention rate of 85%. Women receiving the intervention reported a 65% reduction in sleep disturbance according to PSQI global scores from Time 1 (mean = 13.2) to Time 2 (mean = 4.65) after 4 weeks of APA treatment. There was a further 10% decrease in PSQI scores at Time 3 (mean = 4.21) after 6 weeks of APA treatment. Compared to controls, women receiving APA had significantly lower PSQI mean global scores at both Time 2 and Time 3 (p < .001). APA treatment for women with ovarian cancer produced significantly improved sleep. Participants found the procedure easy to perform. Pilot findings support the feasibility of a longitudinal study with a larger, representative sample., (© 2018 Wiley Periodicals, Inc.)

Human immunodeficiency virus‑1 (HIV‑1) infection severely damages the gut‑associated lymphoid tissue (GALT), the immune system and the gut barrier, which leads to accelerating the disease progression for patients with acquired immune deficiency syndrome (AIDS). Dysregulation of microRNAs (miRNAs) may contribute to this process. However, few studies have investigated the importance of miRNAs in AIDS pathogenesis and progression. The whole miRNA profile of patients with HIV infection from southwest P.R. China and the mode of interaction between HIV‑1 and miRNAs remains to be elucidated. Colon mucosal samples were collected from HIV+ patients and HIV‑ healthy individuals, miRNAs were isolated and subjected to array hybridization in the present study. A total of 476 human and virus‑derived microRNAs were significantly altered in the HIV+ group when compared with the control group (P<0.05), which may be involved in the progression to AIDS. Target genes of the significantly altered miRNAs were predicted using the TargetScan, miRbase and miRanda databases and the 10 shared target genes of upregulated miRNAs and the 391 target genes of downregulated miRNAs were selected. As only 10 target genes were predicted for upregulated miRNAs, subsequent GO and KEGG pathway analyses were focused on the 391 target genes of the downregulated miRNAs. The findings of the present study identified a series of crucial pathways, including cell‑extracellular matrix interaction and chemokine regulation, which indicated close affinity with CD4+ T cell activation. These pathways, involving genes such as integrin α5, led to a gut barrier dysfunction of patients with HIV. Important miRNAs include hsa‑miRNA‑32‑5p, hsa‑miRNA‑195‑5p, hsa‑miRNA‑20b‑5p, hsa‑miRNA‑590‑5p. The expression levels of the miRNAs and their target genes were confirmed using RT‑qPCR. Taking into previous observations, the findings of the present study identified the importance of miRNAs for regulating gut barrier dysfunction via multiple regulatory molecules and signaling pathways, which elucidated the underlying molecular mechanism of gut barrier dysfunction in patients with HIV.

Falconiformes include most of the predatory birds, they play crucial role in maintaining the balance of ecology system. To further illustrate the phylogenetic status for the species of Falconiformes, the entire mitochondrial DNA (mtDNA) genome of Falco naumanni was amplified and sequenced, further phylogenetic analysis was performed by incorporating with other 8 entire mtDNA genomes representing 8 species of predatory birds by taking the Apus apus and Haematopus ater as out-groups. Our results indicated that the mtDNA genome of F. naumanni includes 17,370 base pairs in length, which has the similar organization and gene order with other mtDNA genomes of the species belonging to Falconiformes. Further phylogenetic analyses supported that the F. naumanni clustered with other species of Falconidae, which formed the sister group of Accipitridae, Cathartes aura located at the basal position with Haematopus ater. In addition, Pandion haliaetus was clustered with other species of Accipitridae, which was conflict with the traditional classification system by taking P. haliaetus as an independent Familia of Falconidae.

The acquired immunodeficiency syndrome (AIDS) in humans was one of the chronic infections caused by human immunodeficiency virus (HIV), and the interactions between viral infection and mitochondrial energetic implicated that mitochondrial DNA (mtDNA) variation(s) may effect genetic susceptibility to AIDS. Thus, to illustrate the maternal genetic structure and further identify whether mtDNA variation(s) can effect HIV infection among southwest Chinese AIDS group, the whole mtDNA control region sequences of 70 AIDS patients and 480 health individuals from southwest China were analyzed here. Our results indicated the plausible recent genetic admixture results of AIDS group; comparison of matrilineal components between AIDS and matched Han groups showed that mtDNA haplogroup A (p = 0.048, OR = 3.006, 95% CI = 1.109-8.145) has a significant higher difference between the two groups; further comparison illustrated that mtDNA mutations 16,209 (p = 0.046, OR = 2.607, 95% CI = 0.988-6.876) and 16,319 (p = 0.009, OR = 2.965, 95% CI = 1.278-6.876) have significant differences between AIDS and matched control groups, and both of which were the defining variations of mtDNA haplogroup A, they further confirmed that mtDNA haplogroup A may confer genetic susceptibility to AIDS. Our results suggested that haplogroup A may confer a genetic susceptibility to AIDS group from Southwest China.

Intratumor heterogeneity (ITH) leads to an underestimation of the mutational landscape portrayed by a single needle biopsy and consequently affects treatment precision. The extent of colorectal cancer (CRC) genetic ITH is not well understood in Chinese patients. Thus, we conducted deep sequencing by using the OncoGxOne™ Plus panel, targeting 333 cancer-specific genes in multi-region biopsies of primary and liver metastatic tumors from three Chinese CRC patients. We determined that the extent of ITH varied among the three cases. On average, 65% of all the mutations detected were common within individual tumors. KMT2C aberrations and the NCOR1 mutation were the only ubiquitous events. Subsequent phylogenetic analysis showed that the tumors evolved in a branched manner. Comparison of the primary and metastatic tumors revealed that PPP2R1A (E370X), SETD2 (I1608V), SMAD4 (G382T), and AR splicing site mutations may be specific to liver metastatic cancer. These mutations might contribute to the initiation and progression of distant metastasis. Collectively, our analysis identified a substantial level of genetic ITH in CRC, which should be considered for personalized therapeutic strategies.

Two examples of Co(II)-N-heterocyclic coordination polymers based on 1-hydroxyethylidenediphosphonic acid (H5L=CH3C(OH)(PO3H2)2), namely 0.5(H3NCH2CH2NH3)·[Co6(Cl2)(H3L)2(H2L)(HL)(2,2'-bipy)6] 1 and 2(NH4)·[Co3(HL)2(H2O)2(phen)2]·2(H2O) 2, have been solvothermally obtained by introducing the second ligands 2,2'-bipyridine/1,10-phenanthroline (2,2'-bipy/phen) and characterized by powder X-ray diffraction (PXRD), elemental analysis, IR, TG-DSC. The single-crystal X-ray diffractions show that compound 1 possesses a 0-D structure with hexa-nuclear cluster [Co6(O-P-O)8] built through single/double O-P-O bridges and compound 2 displays a 1-D ladder-like chain structure with magnetic topology building blocks [Co4(O-P-O)4]n. Then H-bonding and π-π stacking interactions further expand the two low-dimensional structures into three-dimensional supramolecular frameworks. Fluorescent measurements reveal that both the maximum emission peaks of 1-2 are centered at 423nm, mainly deriving from intraligand π*-π transition state of N-heterocyclic ligand 2,2'-bipy/phen, respectively. Magnetism data indicate that 1 exhibits antiferromagnetic behavior within hexa-nuclear Co(II) clusters, while 2 shows weak ferromagnetic interactions in 1-D topology Co(II)-chain, showing promising potential as magnetic materials., (Copyright © 2015 Elsevier B.V. All rights reserved.)

By introducing the second organic N-heterocyclic ligands 2,2'-bipyridine (2,2'-bipy)/1,10-phenanthroline (phen), two mono-/bi-nuclear examples of Cu(II)-diphosphonate coordination polymers based on 1-hydroxyethylidenediphosphonic acid (H5L=CH3C(OH)(PO3H2)2), [Cu(H4L)2(2,2'-bipy)]·H2O 1 and [Cu(H3L)(phen)]2·(HOCH2CH2OH)0.52, have been solvothermally obtained and characterized by powder X-ray diffraction, elemental analysis, IR, TG-DSC. The single-crystal X-ray diffractions show that both the two compounds possess zero-dimensional structures, built from mononuclear unit [CuO4N2]n for 1 and binuclear unit [-Cu-O-P-O-]2n with a double O-P-O bridge for 2 in syn-anti fashion. Then H-bond or/and π-π interactions further expand the two zero-dimensional structures into the three-dimensional supramolecular frameworks. Fluorescent measurements reveal that the maximum emission peaks of 1-2 centered at 433.5nm for 1 and 434.5nm for 2, respectively, are mainly caused by intraligand π(*)-π emission state of N-heterocyclic ligands (λex=235nm). The further magnetic study shows the two coordination polymers exhibit antiferromagnetic behavior for 1 between the mononuclear units, while ferromagnetic behavior for 2 derived from double O-P-O bridges in syn-anti mode between the metal centers., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A novel broadband emission phosphor Sr(3-2x) Li(1+ x) MgV3 O12 : xEu3+ was synthesized by a solid-state reaction method. Then discussed the luminous property under the influence of temperature and doping density of Eu3+, was discussed. X-ray diffraction (XRD), scanning electron microscopy (SEM), and photoluminescence spectra were used to characterize the feature of Sr(3-2x)Li(1+x)MgV3O12 : xEu3+. The excitation and emission spectra exhibit that the phosphor of Sr(3-2x) Li(1 + x) MgV3O12 : xEu3+ matches with nearly ultraviolet chip. The emission band covers from 450 to 630 nm, which shows that the phosphor is promising single-phase phosphors for white LED.

Ovarian cancer patients frequently develop resistance to chemotherapy regiments using Taxol and carboplatin. One of the resistance factors that protects cancer cells from Taxol-based therapy is multidrug resistance 1 (MDR1). micro(mi)RNAs are small noncoding RNAs that negatively regulate protein expression. Members of the let-7 family of miRNAs are downregulated in many human cancers, and low let-7 expression has been correlated with resistance to microtubule targeting drugs (Taxanes), although little is known that would explain this activity. We now provide evidence that, although let-7 is not a universal sensitizer of cancer cells to Taxanes, it affects acquired resistance of cells to this class of drugs by targeting IMP-1, resulting in destabilization of the mRNA of MDR1. Introducing let-7g into ADR-RES cells expressing both IMP-1 and MDR1 reduced expression of both proteins rendering the cells more sensitive to treatment with either Taxol or vinblastine without affecting the sensitivity of the cells to carboplatin, a non-MDR1 substrate. This effect could be reversed by reintroducing IMP-1 into let-7g high/MDR1 low cells causing MDR1 to again become stabilized. Consistently, many relapsed ovarian cancer patients tested before and after chemotherapy were found to downregulate let-7 and to co-upregulate IMP-1 and MDR1, and the increase in the expression levels of both proteins after chemotherapy negatively correlated with disease-free time before recurrence. Our data point at IMP-1 and MDR1 as indicators for response to therapy, and at IMP-1 as a novel therapeutic target for overcoming multidrug resistance of ovarian cancer., (Copyright © 2011 UICC.)

1,2-Annulated pyrrolo[2,1,5-de]quinolizin-5-ones (cycl[3.3.2]azin-5-ones) 6a-6k, 8a-8b and 9 have been synthesized by one pot tandem reactions of 2-acetyl-N-phenacylpyridinium bromides (1a-1d) with electron-deficient cyclic alkenes (N-alkyl(aryl)maleimides, benzoquinones and naphthoquinone) in the presence of sodium carbonate as a base and tetrakispyridinecobalt(II) dichromate (TPCD) as an oxidant. These products are formed by 1.3-dipolar cycloaddition of the 1-oxoquinolizinium ylides generated in situ from 1a-1d with the alkene followed by dehydrogenation of the primary cycloadduct under the action of TPCD. Similar reactions of the ylides generated in situ from 1a-1f with maleic anhydride gave the 1,2-unsubstituted pyrrolo[2,1,5-de]quinolizin-5-ones 7a-7f via oxidative bisdecarboxylation and dehydrogenation of the primary cycloadducts under the action of TPCD.

This study was aimed to investigate the characteristics of RHCE genotyping of Xinjiang Uygur nationality population in China. Primers for detecting RHCE genes were designed according to the references, 89 Uygur nationality RhD-negative samples, 233 Han nationality RhD-negative samples and 109 Han nationality RhD-positive samples were detected by sequence-specific primer-polymerase chain reaction (SSP-PCR) for RHCE genotyping. All above-mentioned samples were unrelated. The results indicated that RHE/e genotyping results were consistent with the serological test results in the samples of Uygur and Han nationality, regardless of the RhD-negative samples or the RhD-positive samples. The RHC/c genotyping results from 89 RhD-negative samples of Uygur nationality were consistent with serological test results. However, total error of RHC/c genotyping from 233 RhD-negative and 109 RhD-positive samples of Han nationality was 5.05%. In conclusion, this method of RHCE genotyping is suitable for the analysis of the RHE/e genotyping of Uygur nationality, no erroneous RHC/c genotyping of Uygur nationality was found in this study, but this method needs to be further studied.

To understand how molecular damage under harsh environmental conditions can be controlled, we investigated the properties of ATPase activity of the chaperonin molecular machinery from the hyperthermophilic archaeon Pyrococcus furiosus (PfCPN). PfCPN ATPase activity depended on K(+) and Mg(2+) and its optimal pH was 7.5. PfCPN had almost no ADPase activity. ADP strongly competitively inhibited PfCPN ATPase activity. Inhibition of PfCPN ATPase decreased its chaperonin activity in protecting lysozyme from heat-induced inactivation.

Recent miRNA transfection experiments show strong evidence that miRNAs influence not only their target but also non-target genes; the precise mechanism of the extended regulatory effects of miRNAs remains to be elucidated. A hypothetical two-layer regulatory network in which transcription factors (TFs) function as important mediators of miRNA-initiated regulatory effects was envisioned, and a comprehensive strategy was developed to map such miRNA-centered regulatory cascades. Given gene expression profiles after miRNA-perturbation, along with putative miRNA-gene and TF-gene regulatory relationships, highly likely degraded targets were fetched by a non-parametric statistical test; miRNA-regulated TFs and their downstream targets were mined out through linear regression modeling. When applied to 53 expression datasets, this strategy discovered combinatorial regulatory networks centered around 19 miRNAs. A tumor-related regulatory network was diagrammed as an example, with the important tumor-related regulators TP53 and MYC playing hub connector roles. A web server is provided for query and analysis of all reported data in this article. Our results reinforce the growing awareness that non-coding RNAs may play key roles in the transcription regulatory network. Our strategy could be applied to reveal conditional regulatory pathways in many more cellular contexts.

We performed this study to reassess the prognostic factors of diffuse large B-cell lymphoma (DLBCL) in the era of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Chinese population. One hundred and twenty-five consecutive patients with DLBCL were enrolled in this study from February 2000 to September 2006. They had received six courses of R-CHOP regimen consisting of rituximab 375 mg/m(2), intravenously, D1; cyclophosphamide 750 mg/m(2), bolus infusion, D2; doxorubicin 50 mg/m(2), bolus infusion, D2; vincristine 1.4 mg/m(2), bolus infusion, D2; and prednisone 60 mg, orally, D2-6. All the patients were evaluated and followed-up after the treatment. Eighty-six out of 125 enrolled patients (68.8%) achieved complete response (CR), 16 patients (12.8%) achieved partial response (PR), 11 patients (12.8%) achieved stable disease, and 12 patients (9.6%) experienced progressive disease (PD). In univariate analysis, IPI factors, except for age, was correlated with the treatment outcome of complete remission; however, only early clinical stages and absence of bulky disease was statistically significantly associated with the better CR rate. Lactate dehydrogenase (LDH), extranodal diseases, bulky disease, and obtaining CR after completion of four courses of treatment was correlated with TTF (P = 0.038, 0.044, 0.034, and 0.000, respectively); performance status, LDH level, number of extranodal diseases, and obtaining CR after completion four courses of treatment significantly influenced OS (P = 0.027, 0.000, 0.019, and 0.000, respectively); and presence of bulky disease and obtaining CR at the end of fourth cycle of treatment were significantly correlated with DFS in multivariate analysis (P = 0.006 and 0.001, respectively) in Cox regression. IPI is still important in predicting the prognosis in the R-CHOP era in DLBCL; however, obtaining CR after four cycles of R-CHOP and presence of bulky disease should be considered together.

Background: MicroRNAs (miRNAs) are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs., Results: In order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values < 0.05. The results indicated that the miRNA profiles were different in neural and non-neural tissues. In total, we found 30 miRNAs that were specifically expressed in neural tissues. For example, miR-199a was specifically expressed in neural tissues. Of these, the expression patterns of four miRNAs were comparable with those of Landgraf et al., Bak et al., and Kapsimani et al. Thirty neural tissue-specific miRNAs were chosen to predict target genes. A total of 1,475 target mRNA were predicted based on the intersection of three public databases, and target mRNA's pathway, function, and regulatory network analysis were performed. We focused on target enrichments of the dorsal root ganglion (DRG) and olfactory bulb. There were four Gene Ontology (GO) functions and five KEGG pathways significantly enriched in DRG. Only one GO function was significantly enriched in the olfactory bulb. These targets are all predictions and have not been experimentally validated., Conclusion: Our work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.

The title compound, C(20)H(19)NO, is a substructure of CP-640186, a potent inhibitor of mammalian acetyl-coenzyme A carboxyl-ases. In the crystal structure, the amide group forms a dihedral angle of 87.0 (1)° with the plane of the anthracene unit and the piperidine ring adopts a chair conformation. Mol-ecules are arranged into layers parallel to (100) and adjacent anthracene units within layers form dihedral angles of 13.2 (1)°. C-H⋯O inter-actions from the piperidine rings to the C=O group of the amide are observed between layers.

MicroRNAs (miRNAs) are a group of RNAs that play important roles in regulating gene expression and protein translation. In a previous study, we established an oligonucleotide microarray platform to detect miRNA expression. Because it contained only hundreds of probes, data normalization was difficult. In this study, the microarray data for eight miRNAs extracted from inflamed rat dorsal root ganglion (DRG) tissue were normalized using 15 methods and compared with the results of real-time polymerase chain reaction. It was found that the miRNA microarray data normalized by the print-tip loess method were the most consistent with results from real-time polymerase chain reaction. Moreover, the same pattern was also observed in 14 different types of rat tissue. This study compares a variety of normalization methods and will be helpful in the preprocessing of miRNA microarray data.

Objective: To genotype the RHCE gene of Hans, Xinjiang's Uigurs and Kazakstans in China, and to compare the results of RHCE genotyping with that of RhCc/Ee phenotyping., Methods: RHCE genes of 98 Hans with RhD positive and 230 Hans, 72 Uigurs and 18 Kazakstans with RhD/RHD negative were genotyped with PCR-sequence specific primer (SSP) technique., Results: The results of RHE/RHe genotyping from samples with RhD positive and negative were in accord with that of phenotyping. It would result in 4.44% error using C-->G polymorphism at nt48 of RHCE gene to genotype RHCE, and 4.05% failure of detection using the 109 bp insertion to detectRHCE gene in Chinese Hans. The results of RHE/RHe genotyping in unrelated 72 Uigurs and 18 Kazakstans with RhD phenotype were consistent with that of phenotyping, and false positive and false negative were not found in genotyping in Uigurs and Kazakstans tested., Conclusion: The results of RHE/RHe and RHc genotyping were correct with PCR-SSP and accordant with that of phenotyping. Using the C48G polymorphism in exon 1 of RHCE to genotype RHC gene would result in false positive resulting from RHc mutation at this locus, and using the 109 bp insertion to genotype RHC gene would result in false negative because of the absence of the 109 bp. Therefore it is necessary to genotype RHC gene using more than two polymorphic loci.

The study was to investigate the characteristics of Rh blood group of Uygur nationality in Xinjiang. 1 230 blood samples of Uygur nationality were studied by Rh serological typing, modified antiglobulin test, chloroform/trichloroethylene absorption elution test, upstream, downstream and hybrid Rhesus boxes, 10 exons of D gene, RHD(psi) pseudogene. The results showed that the frequency of RHD negative was 5.8%, and no Del type was found. The further investigation of 72 samples of RhD (-) found that ccee (57.02%) and Ccee (29.08%) phenotype as well as RHD(-)/RHD(-) genotype (94.44%) and complete deletion type of D gene exon (91.12%) were all in high frequency, no RHD(psi) pseudugene was detected. In conclusion, the Rh blood group of Uygurs nationality in Xinjiang possesses both oriental and caucasian Rh characteristics, which enriches the diversity of blood types in chinesenation.

The chaperonin molecular machine from hyperthermophilic archaeon Pyrococcus furiosus was studied in this paper. The Pyrococcus furiosus chaperonin gene (PfCPN) was amplified by PCR from the Pyrococcus furiosus genomic DNA, and expressed in Escherichia coli BL21-Codonplus(DE)(3)-RIL. The recombinant PfCPN was purified to homogeneity by using ion-exchange and size-exclusion chromatography. It was found that the ATPase activity of the PfCPN was highest at 88 degrees C, and there existed a nested cooperativity of the ATPase activity of the PfCPN. This result suggested that nested allosteric behavior may be common to chaperonin molecular machines from archaea. The half-life (t(1/2)) of the ATPase activity of the PfCPN at 100 degrees C was about 60 min. The PfCPN displayed chaperone activity in preventing lysozyme from thermal inactivation. This chaperone activity was in an ATP-dependent manner.

Objects: Our objective was to develop an oligonucleotide DNA microarray (OMA) for genome-wide microRNA profiling and use this method to find miRNAs, which control organic development especially for nervous system., Materials and Methods: Eighteen organic samples included cerebrum and spinal cord samples from two aborted human fetuses. One was 12 gestational weeks old (G12w) and the other was 24 gestational weeks old (G24w). Global miRNA expression patterns of different organs were investigated using OMA and Northern blot., Conclusion: The OMA revealed that 72-83% of miRNAs were expressed in human fetal organs. A series of microRNAs were found specifically and higher-expressed in the human fetal nervous system and confirmed consistently by Northern blot, which may play a critical role in nervous system development.

Objective: To research comparatively on the RHD gene structures in unrelated RhD negative individuals of Chinese Uigur and Han population., Methods: The upstream, downstream, hybrid box and 10 exons of RHD gene were detected with sequence specific primer-PCR technique., Results: The results showed the genotypes of RhD negative individuals to have the significant difference between Chinese Uigur and Han population, that 94.44% Uigur individuals were with RHD(-)/RHD(-) genotype but just 61.40% Han population were with this genotype(94.44% versus 61.40%, P<0.01); 2.78% Uigur individuals were with RHD(+)/RHD(-) genotype but 34.21% Han population were with this genotype(2.78% versus 34.21%, P<0.01). However, there was significantly no RHD(+)/RHD(+) genotype difference between Chinese Uigur and Han population(2.78% versus 4.39%, P>0.05). In 78 cases of RhD negative Chinese Hans with single RHD gene, of which the RHD gene structure showed that 53(67.95%) cases were RHD(1-10) allele(of 53 RHD(1-10) alleles, 14 alleles were unexpressed); 15(19.23%) were RHD-CE(2-9)-D(2) allele; 5(6.41%) cases were RHD-CE(2-7)-D(2) allele; 2(2.56%) were similar to RHD-CE(3-6)D allele; 1(1.28%) case was RHD-CE(5-6)-D allele; and 2(2.56%) were RHD-CE(6)-D or point mutation respectively. Of 2 RhD negative Chinese Uigurs with RhD(-)/RHD(+) genotype, one carried RHD(1-10) allele, another carried RHD-CE(2-9)-D(2) allele., Conclusion: The most frequently unexpressed RHD alleles were RHD-CE(2-9)-D(2), RHD(1-10) and RHD-CE(2-7)-D(2) respectively in Chinese Han population who carried single RHD allele with RHD(-) phenotype and RHD(+) genotype. It showed the confluent character of RH gene in Chinese Han and Uigur population that there existed unexpressed RHD-CE(2-9)-D(2) allele in Chinese Uigur nationality, which was infrequent in Chinese Uigur population but frequent in Chinese Han population.

To study the method for Rhesus box test and its significance, the sequence specific primers of upstream, downstream and hybrid Rhesus boxes were designed according to RhD gene sequence; the upstream, downstream and hybrid Rhesus boxes were determined by PCP-SSP and mismatched PCR. The results showed that this method was confirmed by DNA Standard test. It was shown that in unrelative RhD positive individuals RHD(+)/RHD(-), RHD(+)/RHD(+) genotype accounted for 9.00%, 91.00% respectively, and in RhD negative individuals RHD(+)/RHD(-), RHD(+)/RHD(+), RHD(-)/RHD(-) genotype were 26.14%, 3.92%, 69.94% respectively. It is concluded that the method of Rhesus box test was confirmed to be reliable and can be used for the identification of RhD haplotype gene structure, as well as for study on inheritance, clinical transfusion and neonatal hemolytic diseases.

Umbilical cord blood stem cell transplantation (CBSCT) has made significant progress in treatment of lethal congenital or malignant disorders. Both the incidence and severity of GVHD from CBSCT were lower than that from bone marrow and peripheral blood stem cell transplantation, particularly for adult patients, but these advantages were also associated with higher rates of relapse. The immune-mediated effect of natural killer and cytotoxic T cells against residual tumor cells were shown to prevent relapse and to induce remission after bone marrow transplantation. To explore possibility of ex vivo expansion of T, NK and CD34(+) cells from umbilical cord blood, cord blood was expanded ex vivo with different combinations of cytokines, T and NK cells proliferation and differentiation were observed. CB MNCs were separated in Ficoll-Isopaque column and cultured in IMDM for 14 days with different recombinant cytokines. Cultured cells were collected and analyzed for progenitor/stem cell immunophenotyping at day 0, 3, 7, and 14 by using flow cytometry. The results indicated that all test groups cultured with different combinations of SCF, IL-3, IL-6, IL-7, IL-2 showed significant expansion of UCB MNC, compared with the group without cytokines. All test groups showed expansion effects on CD34(+) cells, CD34(+) percentage went up from 1.6% in fresh CB to the highest 11.9% in group D (SCF + IL-3, IL-6, IL-2). The CD34(+) cells peak displayed at day 7 of culture in group A and D, while in other two groups B and C appeared at day 14 of culture. The expansion multiple of CD34(+) cells in all test groups at day 7 of culture were from 10 to 50. The average value of CD3(+) T cell in fresh UCB was 18.7 +/- 4.3%, the CD3(+) T cells decreased sharply in the medium without any interleukin, while obvious increase were observed in the other test groups containing different combinations of cytokines. The maximal expansion multiple of CD3(+) T cells reached 2 times of the fresh UCB level. CD56(+) cells amounted to 3.6 +/- 1.9% of fresh UCB, CD56(+) cell number increased significantly only in medium containing IL-2. It is concluded that T cells, NK cells as well as stem/progenitor cells can be expanded in the same time from CB-MNC with the combinations of cytokines.

Objective: To study the difference and similarity between Hans and Uighurs in regard to Rhesus box and its significance., Methods: The sequence specific primers of upstream, downstream and hybrid Rhesus boxes were designed on the basis of RHD gene sequence. The upstream, downstream and hybrid Rhesus boxes were determined by polymerase chain reaction-sequence specific primer(PCP-SSP) and mismatched PCR., Results: The percentage of RHD-/RHD-, RHD+/RHD- and RHD+/RHD+ genotypes ascertained in the unrelated Hans with RhD(-) were 61.40%, 34.21% and 4.39% respectively, while those in the unrelated Chinese Uighurs with RhD(-) were 94.44%, 2.78% and 2.78% respectively. Furthermore, all 6 cases of some other minorities were RHD-/RHD- types. The percentage of RHD-/RHD- and RHD+/RHD- genotypes ascertained in the unrelated Chinese Uighurs were significantly higher than those in Chinese Hans (P < 0.01), whereas no statistically significant difference in the percentage of RHD+/RDH+ genotype between the two groups was observed (P > 0.05)., Conclusion: The Rh blood group of Uighurs in Xingjiang possesses both Oriental and Caucasian characteristics, which embodies a special ethnical aspect of the Chinese nation and is in accord with the anthropologic research results.

To study the detection of weak D and Del from samples initially screened RhD(-), RhD phenotype was initially screened by routine serological test, out of which weak D phenotype was detected by indirect antiglobulin test (IAT) and Del phenotype was detected by chloroform-trichloroethylene absorption-elution test. The results showed that 56 samples were RhD(-) confirmed by routine serology test, which were screened out of 26 200 donors, among them 5 samples were typed as weak D by IAT and 9 cases samples were typed as Del by absorption-elution test. In conclusion, the samples which typed as RhD(-) by routine serological test must be identified by IAT and chloroform-trchloroethylene absorption test is order to detect weak D and Del phenotype. It is important for clinical transfusion safely.

[reaction: see text] Photoinduced reactions of 1-acetylisatin (IS) with diphenylacetylenes 1a-c, 1-(p-methoxyphenyl)propyne 2, and 1,4-diphenyl-1,3-butadiyne 3 gave beta,beta-disubstituted 3-alkylidene oxindoles 6-12 respectively via [2+2] cycloaddition of 3IS* with the alkyne and subsequent oxetene ring opening. Photoreactions of IS with phenylacetylenes 4a-d and cyclopropylacetylene 5 furnished the dispiroindole[3,2']furan[3',3' ']indoles 13 and 14. Compounds 13 and 14 are formed in tandem reactions initiated by [2+2] cycloaddition of 3IS* with the alkynes to give spirooxetenes Va and Vb, which upon spontaneous ring opening gave the alpha,beta-unsaturated aldehydes IVa and IVb. It is proposed that hydrogen abstraction of 3IS* from the C(O)-H functionality in IV followed by dissociation of the triplet isatin ketyl (A)-aldehyde acyl (B) radical pair and an oxygenphilic attack of the acyl radical B at the C3 carbonyl oxygen atom of a neutral IS gave the 2:1 (IS:4) radical C, which took part in an intramolecular radical cyclization to give the dispiroindole[3,2']furan[3',3' ']indoles 13 and 14. The regioselectivity in the [2+2] photocycloadditions of IS with 4 to afford the oxetene Va depends on the intervening of the more stable 1,4-diradical intermediates VI, which have a linear alpha-phenyl-substituted vinyl radical where the phenyl provides spin delocalization of the radical center at the sp carbon atom.

The aim was to determine RHD zygosity, further to investigate genetic structure of RHD gene, and to predict hemolytic disease of newborn (HDN). The upstream box, downstream box, and hybrid box of RHD gene were determined by PCR-SSP with 4 primers under the same conditions. The results showed that only hybrid box could be determined in RHD(-)/RHD(-) homozygosity. All the upstream box, downstream box, and hybrid box could be determined in RHD(+)/RHD(-) heterozygosity, while upstream box and downstream box except hybrid box could be determined in RHD(+)/RHD(+) homozygosity. Out of 50 cases of RhD(+), 5 cases (10%) were RHD(+)/RHD(-) heterozygosity, and the others (90%) were RHD(+)/RHD(+) homozygosity. 54 cases (55.1%), 36 cases (36.7%) and 8 cases (8.2%) were RHD(-)/RHD(-) homozygosity, RHD(+)/RHD(-) heterozygosity, and RHD(+)/RHD(+) homozygosity respectively in 98 unrelated cases of RhD(-) Chinese Hans. 2 cases of weak D were proved to be RHD(+)/RHD(-) heterozygosity. Out of 16 D(el) types, the upstream box, downstream box, and hybrid box could be determined in 10 cases (37.5%) and the upstream box and downstream box except hybrid box could be determined in 6 cases. Results detecting of RHD 10 exons in above samples proved the correctness of the method. It is concluded that the method is suitable for clinical application with its simplicity and veracity. There are many noneffective RHD genes (44.9%) in Chinese Hans with RhD(-) phenotype.

Aim of this study was to develop the detection method of soluble human leukocyte antigens I (sHLA-I) and to explore sHLA-I level alteration in storage blood and its significance. sHLA-I level in sera of 60 Guangdong normal individuals and sHLA-I concentration in blood components from 20 donors quantitatively were detected by sandwich ELISA. The results showed that sensitivity of this assay was 2.84 ng/ml. Coefficients of variation were 5.80% within assays and 9.00% between assays respectively. The recovery rate was >/= 98.57%. The sHLA-I level of normal individuals in Guangdong was (699.54 +/- 360.10) ng/ml. sHLA-I in red blood cells stored for 28 days and in random-donor platelets were significantly higher than that in other blood components and their amount was proportionate to the number of residual donor leukocytes and to the length of storage. In conclusion, sandwich ELISA assay for detection of sHLA-I is a sensitive, specific and stable technique. Blood components with different concentration of sHLA-I may be chosen for clinical transfusion.

Objective: To study exon polymorphism of human RHD gene and investigate the genetic mechanism of RhD-negative individuals., Methods: PCR using sequence-specific primers (PCR-SSP) was performed on 40 RhD-positive, 120 RhD-negative and 2 weak D blood samples., Results: All 10 exons could be detected in the 40 RhD-positive and 2 weak D samples. Out of the 120 RhD-negative samples, 28 (23.33%) carried 10 exons, 19 (15.83%) lost most of the 10 exons (with mainly intermediate deletion), and 73 (60.83%) had deletion of all the 10 exons; 19 samples of Del phenotype identified from the 120 RhD-negative samples had all the 10 exons., Conclusion: Polymorphism of the exon structure of RHD gene is present in RhD-negative individuals, characterized chiefly by gross deletion, partial deletion and non-deletion.

Photooxygenations of 1,2-, 1,3-, and 2,3-di- and 1,2,3-trisubstituted indolizines 1a-1f under different reaction conditions in methanol and acetonitrile have been investigated to establish the general reaction pattern and mechanism in indolizine photooxygenation in view of the influence of the ring substituents and substitution pattern. Photooxygenations of 1-acyl-2-phenylindolizines 1a and 1b and 1,3-dibenzoyl-2-phenylindolizine (1d) are self-sensitized, while those of 1-(p-nitrobenzoyl)-2-phenylindolizine (1c) and 2-phenyl-3-(p-chlorobenzoyl)indolizine (1e) need to be sensitized by rose bengal (RB) or methylene blue (MB). These reactions proceed via a singlet oxygen mechanism yet follow different pathways in methanol and in acetonitrile, with peroxidic zwitterion D (in methanol) and dioxetane E across the indolizine C2-C3 bond (in acetonitrile) as the intervening intermediates. Methanol trapping of the peroxidic zwitterion results in C3-N bond cleavage and pyrrole ring opening to give the corresponding (E)- and (Z)-3-(2-pyridinyl)-3-benzoylpropenoic acid methyl esters (2 and 3) and 4-(2-pyridinyl)-3-phenyl-5-aryl-5-hydroxyfuran-2-one (4) as products in methanol, while O-O bond homolysis of the dioxetane furnishes 3-(2-pyridinyl)-3-benzoyl-2-phenyloxirane-2-carboxaldehyde (6) and 1-(6-methyl-2-pyridinyl)-2-phenylethanedione (5) as products in acetonitrile. 3-Benzoyl-1-indolizinecarboxylic acid methyl ester (1f) is unreactive toward singlet oxygen; however, it could be photooxygenated under electron transfer conditions with 9,10-dicyanoanthracene (DCA) as a sensitizer. This reaction takes place by the combination of the indolizine cation radical with the superoxide anion radical (or molecular oxygen) to give the pyridine ring oxidized methyl 3-benzoyl-5-methoxy-8-hydroxy-1-indolizinecarboxylate (9f), dimethyl 2-(2-pyridinyl)fumarate (8f), and dimethyl 2-(2-pyridinyl)maleate (7f) as products.

Objectives: To investigate the reversal effect of gene MDR1 and MRP with combinational antisense phosphorothioate oligonucleotide on Drug-resistant human hepatocellular carcinoma cells SMMC-7721/ADM., Methods: SMMC-7721/ADM was transfected with synthetic antisense phosphorothioate oligonucleotides complementary to gene MDR1 and MRP mediated by Lipofectamine. Drug sensitivity was measured by MTT assay, Fluorescence intensity of cells was determined by flow cytometric analysis, RH123 and DNR retention was assayed by confocal scanning laser microscopy., Results: ASODN of MDR1+MRP increased the sensitivity of SMMC-7721/ADM to chemotherapeutic drug more significantly than that any of MDR1 and MRP did separately. But they did not enhance the inhibition expression of protein of p190 or p170., Conclusion: Drug-resistance could be reversed significantly when antisense phosphorothioate oligonucleotide of MDR1+MRP were transfected into drug-resistant human hepatocellular carcinoma cells SMMC-7721/ADM together.

To observe the gene polymorphism of Rh blood group in unrelated random individuals and families for Chinese Han nationality, polymerase chain reaction-sequence specific primer (PCR-SSP) was used to amplify the Rh C/E gene, RhD gene, exons, intron 2 and 10, insert and Rh Box in 160 blood samples of RhD positive unrelated individuals and 71 samples of RhD negative unrelated individuals and 7 samples of families whose probands were RhD-negative. The results showed that RhD genes of RhD-negative individuals with C antigens were polymorphism, three forms were found for D exon including intact, partial deletion and complete deletion exons. Insert fragments and Rh Box were found in most cases of families whose probands were RhD-negative and its inheritance accorded with the Mendel's Law, and it did not affect the expression of RhD gene. "Normal" RhD exon 4 amplifying product was not found in all of the samples. It was concluded that gene structure of the RhD-negative in Chinese was polymorphism, intact, partial deletion and complete deletion exons were found in the individuals with C antigen and probably existed specific D (nf) Ce haplotype. The function of insert was uncertain. The Rh gene sequences of Chinese Han nationality are different from those of Caucasian and the Rh gene library based on Han nationality should be established.

The objective of this study was to investigate the method and effect of blocking the specific reaction between lymphocyte HLA-I antigen and its antibody. The lymphocytes were disposed with 12 mmol/L methoxypolyethelene glycol benzotriazol carbonate (mPEG-BTC) in concentration gradient in PBS (pH 7.4) at 22 degrees C. The effect of the modified lymphocytes was detected by microlymphocytotoxicity assay. The results showed that lymphocytes modified by mPEG-BTC did not react with related HLA-I antibodies in microcytotoxicity test. It is suggested that the specific reaction between HLA-I antigen of lymphocyte and HLA-I antibodies can be completely camouflaged by mPEG-BTC in PBS (pH 7.4) under 22 degrees C room temperature.

Objective: To modify the HLA-A2 antigen on the lymphocytes with methoxypolyethylene glycol (mPEG) so as to block the specific binding site for antibody., Method: Different types of mPEG (all with final concentration of 12 mmol/L) were used at different temperatures in PBS with varied pH values for the modification of the HLA-A2 antigen., Result: The modification of the antigen was not obviously affected when it was carried out at 4 degrees Celsius or room temperature, but higher temperatures of 30 and 37 degrees Celsius significantly hampered the modification. Better antigen modification was observed with high-concentration mPEG in basic PBS, depending also on the type of mPEGs used for this purpose., Conclusion: The specific HLA-A2 binding on the lymphocytes is completely blocked by benzotriazole carbonate-mPEG(mPEG-BTC), which is superior to N-hydroxysuccinimidyl ester of mPEG(mPEG-SPA). Maleimide-mPEG(mPEG-MAL) is incapable of blocking the HLA-A2 ligand-binding site with antibody.

To study the correct method for determining ABO blood types in infants and its influencing factors, blood types of 33 infants under 6 months old were determined by routine serological method, micro-column gel typing system and PCR-SSP genotyping method. Of the 33 cases with discrepant results of ABO blood type by different methods, the blood types of 32 cases were discrepant between red cell and serological typings in the routine serological method, and a false coincidence in 1 case was caused by bacterial infection resulting in B-like antigen. Correct blood typing was obtained in 27 cases with a correct rate of 84.4% (27/32) by using micro-column gel typing system. PCR-SSP method gave correct results in all of 33 cases. There was a significant difference between the results of micro-column gel typing system and PCR-SSP. It is concluded that to determine ABO blood type for infants < 6 months old, it is recommended to adopt micro-column gel typing system method, and what must be taken into account is the possible false coincidence caused by bacterial infection resulting in B-like antigen. In micro-column gel typing system, if the results of red cell and serological typing are identical, the principle is that blood transfusion must be performed with same ABO blood type between recipient and donor. If not, washed O red blood cells should be used for infants, and then change to transfusion with identical blood group according to PCR-SSP typing results.

Aim: To investigate the correlation between subcellular daunorubicin distribution and the multidrug resistance phenotype in drug-resistant cell line SMMC-7721/R., Methods: The multidrug resistant cell line SMMC-7721/R, a human hepatocellular carcinoma cell line, was established. Antisense oligonucleotides (AS-ODN) were used to obtain different multidrug resistance phenotypes by inhibiting the expression of mdr1 gene and/or multidrug resistance-related protein gene(mrp) using Lipofectamine as delivery agent. Expression of mdr1 and mrp genes was evaluated by RT-PCR and Western blotting. Intracellular daunorubicin (DNR) concentration was measured by flow cytometry. Subcellular DNR distribution was analyzed by confocal laser scanning microscopy. Adriamycin (ADM) and DNR sensitivity was examined by MTT method., Results: Low level expression of mdr1 and mrp mRNAs and no expression of P-Glycoprotein(P-gp) and multidrug resistance-related protein (P(190)) were detected in parental sensitive cells SMMC-7721/S, but over-expression of these two genes was observed in drug-resistant cell SMMC-7721/R. The expression of mdr1 and mrp genes in SMMC-7721/R cells was down-regulated to the level in the SMMC-7721/S cells by AS-ODN. Intracellular DNR concentration in SMMC-7721/S cells was 10 times higher than that in SMMC-7721/R cells. In SMMC7721/S cells intracellular DNR distributed evenly in the nucleus and cytoplasm, while in SMMC-7721/R cells DNR distributed in a punctate pattern in the cytoplasm and was reduced in the nucleus. DNR concentration in SMMC-7721/R cells co-transfected with AS-ODNs targeting to mdr1 and mrp mRNAs recovered to 25 percent of that in SMMC7721/Scells. Intracellular DNR distribution pattern in drug-resistant cells treated by AS-ODN was similar to drug-sensitive cell, and the cells resistance index (RI) to DNR and ADM decreased at most from 88.0 and 116.0 to 4.0 and 2.3, respectively. Co-Transfection of two AS-ODNs showed a stronger synergistic effect than separate transfection., Conclusions: P-gp and P(190) are two members mediating MDR in cell line SMMC7721/R. Intracellular drug concentration increase and subcellular distribution change are two important factors in multidrug resistance (MDR) formation. The second factor, drugs transport by P-gp and P(190) from cell nucleus to organell in cytoplasm, may play a more important role.