Unraveling ETC complex I function in ferroptosis reveals a potential ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.

The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes cancer cells to GPX4-inactivation-induced ferroptosis. Furthermore, complex I inhibition synergizes with radiotherapy (RT) to selectively suppress the growth of LKB1-deficient tumors by inducing ferroptosis in mouse models. Our data demonstrate a multifaceted role of complex I in regulating ferroptosis and propose a ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.

Granulomas in Pediatric Liver Biopsies: Single Center Experience.

BACKGROUND: Granulomas in pediatric liver biopsies (GPLB) are rare with the largest pediatric cohort reported over 25 years ago. METHODS: Single-center retrospective study of GPLB. RESULTS: Seventeen liver biopsies from 16 patients with granulomas were identified (9 boys, 56%) with a median age of 13 years (range: 1-18) for which the most common indication was the presence of a nodule/mass (47%). Significant comorbidities were seen in 13 patients (81%) and included: liver transplant (25%), history of a neoplasm (25%), autoimmune hepatitis (6%), Crohn disease (6%), bipolar disorder (6%), severe combined immunodeficiency (6%), and sickle cell disease (6%). Eleven patients were taking multiple medications at the time of biopsy. Granulomas were more commonly pan-acinar (11 cases) followed by subcapsular (4 cases), portal (1 case), and periportal (1 case). Necrosis was seen in 10 cases (59%). GMS stain was positive in 2 cases for Histoplasma-like yeast; microbiological cultures were negative in all cases (no: 4). A 18S and 16S rRNA gene sequencing performed in 15 cases revealed only 1 with a pathogenic microorganism, Mycobacterium angelicum. CONCLUSION: In our experience, GPLB are heterogenous with only 3 cases having an identifiable infectious etiology and many of the remaining cases being associated to multiple medications, suggesting drug-induced liver injury as possible etiology.

Exploring Ferroptosis-Inducing Therapies for Cancer Treatment: Challenges and Opportunities.

Conventional cancer therapies typically aim to eliminate tumor cells by inducing cell death. The emergence of resistance to these standard treatments has spurred a shift in focus toward exploring alternative cell death pathways beyond apoptosis. Ferroptosis-an iron-dependent regulated cell death triggered by lipid peroxide accumulation-has gained prominence in cancer research in recent years. Ferroptosis-inducing therapies hold promise for overcoming resistance encountered with conventional treatments. However, challenges, including the lack of distinctive ferroptosis markers and the intricate role of ferroptosis within the tumor microenvironment, currently hinder the clinical translation of these therapies. This perspective article critically outlines these hurdles and highlights unexplored opportunities in ferroptosis research, aiming to refine its therapeutic utilization in combating cancer.

The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions.

In cancer treatment, the recurrent challenge of inducing apoptosis through conventional therapeutic modalities, often thwarted by therapy resistance, emphasizes the critical need to explore alternative cell death pathways. Ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides on cellular membranes, has emerged as one such promising frontier in oncology. Induction of ferroptosis not only suppresses tumor growth but also holds potential for augmenting immunotherapy responses and surmounting resistance to existing cancer therapies. This review navigates the role of ferroptosis in tumor suppression. Furthermore, we delve into the complex role of ferroptosis within the tumor microenvironment and its interplay with antitumor immunity, offering insights into the prospect of targeting ferroptosis as a strategic approach in cancer therapy.

Correlation between the TyG-BMI index and carotid plaque characteristics in middle-aged and elderly patients with acute myocardial infarction.

OBJECTIVE: The aim of this study is to investigate the correlation between the triglyceride-glucose-body mass index (TyG-BMI) and the characteristics of various carotid plaques in middle-aged and elderly patients with acute myocardial infarction (AMI). METHODS: A retrospective study was conducted on 380 patients with AMI hospitalized in the Cardiology Department of Kaifeng Central Hospital. Based on carotid ultrasound results, patients were divided into the following two groups: the stable plaque group and the unstable plaque group. Additionally, a control group comprising 380 healthy individuals visiting the hospital's physical examination center during the same timeframe was established. Fasting venous blood samples were collected from all participants to measure blood glucose and triglyceride. The baseline TyG-BMI index was calculated using the formula Ln [fasting triglyceride (mg/dL)×fasting blood glucose (mg/dL)/2]×BMI. The correlation between different plaque groups and the TyG-BMI index was analyzed. RESULTS: The TyG-BMI index was significantly higher in the unstable plaque group compared to the stable plaque group, with values of 252.81±29.99 and 201.92±28.72, respectively (P = 0.034). Spearman's correlation analysis showed a positive correlation between the instability of carotid plaques and the TyG-BMI index in patients with AMI (r = 0.521, P = 0.003). Logistic regression analysis indicated that the TyG-BMI index was an important risk factor for unstable carotid plaques in patients with AMI (OR = 2.691, 95% CI: 1.169-4.123). CONCLUSION: The findings of this study suggest that an elevated TyG-BMI index significantly increases the risk of unstable carotid plaques in patients with AMI, making it an important risk factor for carotid plaque instability.

Determination of the cycle threshold value of the Xpert Xpress SARS-CoV-2/Flu/RSV test that corresponds to the presence of infectious SARS-CoV-2 in anterior nasal swabs.

Despite having high analytical sensitivities and specificities, qualitative SARS-CoV-2 nucleic acid amplification tests (NAATs) cannot distinguish infectious from non-infectious virus in clinical samples. In this study, we determined the highest cycle threshold (Ct) value of the SARS-CoV-2 targets in the Xpert Xpress SARS-CoV-2/Flu/RSV (Xpert 4plex) test that corresponded to the presence of detectable infectious SARS-CoV-2 in anterior nasal swab samples. A total of 111 individuals with nasopharyngeal swab specimens that were initially tested by the Xpert Xpress SARS-CoV-2 test were enrolled. A healthcare worker subsequently collected anterior nasal swabs from all SARS-CoV-2-positive individuals, and those specimens were tested by the Xpert 4plex test, viral culture, and laboratory-developed assays for SARS-CoV-2 replication intermediates. SARS-CoV-2 Ct values from the Xpert 4plex test were correlated with data from culture and replication intermediate testing to determine the Xpert 4plex assay Ct value that corresponded to the presence of infectious virus. Ninety-eight of the 111 (88.3%) individuals initially tested positive by the Xpert Xpress SARS-CoV-2 test. An anterior nasal swab specimen collected from positive individuals a median of 2 days later (range, 0-9 days) tested positive for SARS-CoV-2 by the Xpert 4plex test in 39.8% (39/98) of cases. Of these samples, 13 (33.3%) were considered to contain infectious virus based on the presence of cultivable virus and replication intermediates, and the highest Ct value observed for the Xpert 4plex test in these instances was 26.3. Specimens that yielded Ct values of ≤26.3 when tested by the Xpert 4plex test had a likelihood of containing infectious SARS-CoV-2; however, no infectious virus was detected in specimens with higher Ct values.IMPORTANCEUnderstanding the correlation between real-time PCR test results and the presence of infectious SARS-CoV-2 may be useful for informing patient management and workforce return-to-work or -duty. Further studies in different patient populations are needed to correlate Ct values or other biomarkers of viral replication along with the presence of infectious virus in clinical samples.

Cell cycle arrest induces lipid droplet formation and confers ferroptosis resistance.

How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)-dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some slow-cycling antimitotic drug-resistant cancer cells, such as 5-fluorouracil-resistant cells, have accumulation of lipid droplets and that combined treatment with ferroptosis inducers and DGAT inhibitors effectively suppresses the growth of 5-fluorouracil-resistant tumors by inducing ferroptosis. Together, these results reveal a role for cell cycle arrest in driving ferroptosis resistance and suggest a ferroptosis-inducing therapeutic strategy to target slow-cycling therapy-resistant cancers.

Dual-functional ionic liquids additive enables dendrite-free Zn anode with ultra-long cycle life over one year.

Zn anodes suffer from the formation of uncontrolled dendrites aggravated by the uneven electric field and the insulating by-product accumulation in aqueous zinc-ion batteries (AZIBs). Here, an effective strategy implemented by 1-butyl-3-methylimidazolium hydrogen sulfate (BMIHSO4) additive is proposed to synergistically tune the crystallographic orientation of zinc deposition and suppress the formation of zinc hydroxide sulfate for enhancing the reversibility on Zn anode surface. As a competing cation, BMI+ is proved to preferably adsorb on Zn-electrode compared with H2O molecules, which shields the "tip effect" and inhibits the Zn-deposition agglomerations to inducing the horizontal growth along Zn (002) crystallographic texture. Simultaneously, the protonated BMIHSO4 additives could remove the detrimental OH- in real-time to fundamentally eliminate the accumulation of 6Zn(OH)2·ZnSO4·4H2O and Zn4SO4(OH)6·H2O on Zn anode surface. Consequently, Zn anode exhibits an ultra-long cycling stability of one year (8762 h) at 0.2 mA cm-2/0.2 mAh cm-2, 3600 h at 2 mA cm-2/2 mAh cm-2 with a high plating cumulative capacity of 3.6 Ah cm-2, and a high average Coulombic efficiency of 99.6 % throughout 1000 cycles. This work of regulating Zn deposition texture combined with eliminating notorious by-products could offer a desirable way for stabilizing the Zn-anode/electrolyte interface in AZIBs.

Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing.

Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

Macrophage-derived extracellular vesicles regulate skeletal stem/progenitor Cell lineage fate and bone deterioration in obesity.

Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.

BRCA1-Mediated Dual Regulation of Ferroptosis Exposes a Vulnerability to GPX4 and PARP Co-Inhibition in BRCA1-Deficient Cancers.

Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i co-treatment. Finally, we show that xenograft tumors derived from patients with BRCA1-mutant breast cancer with PARPi resistance exhibit decreased GPX4 expression and high sensitivity to PARP and GPX4 co-inhibition. Our results show that BRCA1 deficiency induces a ferroptosis vulnerability to PARP and GPX4 co-inhibition and inform a therapeutic strategy for overcoming PARPi resistance in BRCA1-deficient cancers. Significance: BRCA1 deficiency promotes resistance to erastin-induced ferroptosis via blocking VDAC3 yet renders cancer cells vulnerable to GPX4i-induced ferroptosis via inhibiting GPX4. NCOA4 induction and defective GPX4 further synergizes GPX4i with PARPi to induce ferroptosis in BRCA1-deficient cancers and targeting GPX4 mitigates PARPi resistance in those cancers. See related commentary by Alborzinia and Friedmann Angeli, p. 1372.

Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats.

Bats carry many zoonotic pathogens without showing pronounced pathology, with a few exceptions. The underlying immune tolerance mechanisms in bats remain poorly understood, although information-rich omics tools hold promise for identifying a wide range of immune markers and their relationship with infection. To evaluate the generality of immune responses to infection, we assessed the differences and similarities in serum proteomes of wild vampire bats (Desmodus rotundus) across infection status with five taxonomically distinct pathogens: bacteria (Bartonella spp., hemoplasmas), protozoa (Trypanosoma cruzi), and DNA (herpesviruses) and RNA (alphacoronaviruses) viruses. From 19 bats sampled in 2019 in Belize, we evaluated the up- and downregulated immune responses of infected versus uninfected individuals for each pathogen. Using a high-quality genome annotation for vampire bats, we identified 586 serum proteins but found no evidence for differential abundance nor differences in composition between infected and uninfected bats. However, using receiver operating characteristic curves, we identified four to 48 candidate biomarkers of infection depending on the pathogen, including seven overlapping biomarkers (DSG2, PCBP1, MGAM, APOA4, DPEP1, GOT1, and IGFALS). Enrichment analysis of these proteins revealed that our viral pathogens, but not the bacteria or protozoa studied, were associated with upregulation of extracellular and cytoplasmatic secretory vesicles (indicative of viral replication) and downregulation of complement activation and coagulation cascades. Additionally, herpesvirus infection elicited a downregulation of leukocyte-mediated immunity and defense response but an upregulation of an inflammatory and humoral immune response. In contrast to our two viral infections, we found downregulation of lipid and cholesterol homeostasis and metabolism with Bartonella spp. infection, of platelet-dense and secretory granules with hemoplasma infection, and of blood coagulation pathways with T. cruzi infection. Despite the small sample size, our results suggest that vampire bats have a similar suite of immune mechanisms for viruses distinct from responses to the other pathogen taxa, and we identify potential biomarkers that can expand our understanding of pathogenesis of these infections in bats. By applying a proteomic approach to a multi-pathogen system in wild animals, our study provides a distinct framework that could be expanded across bat species to increase our understanding of how bats tolerate pathogens.

125I seed implantation enhances arsenic trioxide-induced apoptosis and anti-angiogenesis in lung cancer xenograft mice

Background and Purpose Arsenic trioxide (ATO) exerts anticancer effects on lung cancer. However, the clinical use of ATO is limited due to its systemic toxicity and resistance of lung cancer cells. The present study aimed to investigate the effects of ATO, alone and in combination with 125I seed implantation on tumor growth and proliferation in lung cancer xenograft mice, and investigate the possible molecular mechanisms. Methods The transmission electron microscope observed the tumor ultrastructure of lung cancer xenograft mice. The proliferation index of Ki-67 and the number and morphology of tumor microvessels were detected with immunohistochemical staining. The protein and mRNA expression were examined by western blot and real-time PCR assay. Results The in vivo results demonstrated that ATO combined with 125I seed significantly inhibited tumor growth and proliferation, as well as promoted apoptosis, and decreased the Ki-67 index and microvessel density in lung cancer xenograft mice. Moreover, ATO combined with 125I seed decreased the protein and mRNA expression levels of HIF-1α, VEGF, and BCL-2, and increased those of BAX and P53. Conclusions ATO combined with 125I seed significantly inhibited tumor growth and proliferation in lung cancer, which may be accomplished by inhibiting tumor angiogenesis and inducing apoptosis (AU)

Effect of zoledronic acid combined with Jintiange capsule on treatment of postmenopausal osteoporosis / 中华内分泌外科杂志

Objective To explore the effect of Jintiange capsule on treatment of postmenopausal osteoporosis (PMOP) and its mechanism.Method 133 patients diagnosed as PMOP and meeting the standard were collected from Oct.2011 to Aug.2015 in our hospital.They were randomly divided into two groups:treatment group and the control group.The control group received calcium and alendronate,while the treatment group received 3 Jintiange capsules 3 times daily on the basis of the control group.The lumbar bone densit (BMD),greater trochanter BMD,femoral neck BMD,Ward triangle BMD,visual analogue score (VAS) of knee and back,the serum levels of bone glaprotein (BGP),alkaline phosphatase (ALP),β-C-terminal telopeptide of type Ⅰ collagen (β-CTX),N-terminal propeptide of type Ⅰ procollagen (PINP) and adverse reactions were recorded before and after treatment.Results The lumbar BMD,greater trochanter BMD,femoral neck BMD,ward triangle BMD of treatment group after treatment were higher than those before treatment and those of the control group (P＜0.05).VAS score of knee and back of treatment group were lower than those of the control group (P＜0.05).The serum levels of BGP,ALP,β-CTX,PINP of treatment group were lower than those of the control group (P＜0.05).The adverse reactions rate of two groups had no significant difference (P＞0.05).Conclusion Jintiange capsule can significantly reduce bone metabolism level,increasing BMD,reducing bone loss,relieving knee and back pain of PMOP,without increasing complication rates,which is worthy to be promoted due to high safety and efficacy.

Effects of insulin-like peptide 6 on renal fibrosis and calcification in unilateral ureteral obstruction mice / 上海交通大学学报（医学版）

Objective·To investigate the effects of insulin-like peptide 6 (Insl6) on renal fibrosis and calcification in unilateral ureteral obstruction (UUO) mice. Methods·Twenty-four SPF male mice with genotypic background of C57BL/6 were divided into Sham (n=8), UUO+saline (n=8) and UUO+Insl6 (n=8) groups randomly. Mice were sacrificed 10 days after operation and renal tissues of surgical side were obtained. Sirus red staining, Masson staining and alizarin red S staining were used to verify the level of collagen and calcium deposition. TGF-β1 expression was determined by Western blotting. Realtime-PCR was used for determining TGF-β1, BMP2, Col1a1, and Col2a1 mRNA expression. Results·Compared with sham group, fibrotic area especially collagen Ⅰ , calcium deposition, TGF-β1 protein, and TGF-β1, BMP2, Col1a1, and Col2a1 mRNA expression in UUO+saline group significantly increased (all P<0.05). As compared with UUO+saline group, fibrotic area especially collagen Ⅰ, calcium deposition, TGF-β1 protein, and TGF-β1, BMP2, Col1a1, and Col2a1 mRNA expression in UUO+Insl6 group significantly decreased (all P<0.05). Conclusion·Insl6 inhibits UUO-induced renal fibrosis and calcification, which may be related to regulation of TGF-β1, collagen Ⅰ , BMP2 and collagen Ⅱ expression levels.

Safety evaluation of coenzyme Q10 on central nervous system / 药物评价研究

Objective To investigate the effect of high-dose coenzyme Q10 on the central nervous system in mice,and to provide experimental basis for clinical safety evaluation.Methods Mice were randomly divided into vehicle control group,perillartine control group,positive control group (chlorpromazine or diazepam) and coenzyme Q10 low,medium and high dose groups (1.5,3.0 and 6.0 g/kg,equivalent to 75,150,and 300 times of clinical dosage,respectively).The corresponding drugs were ig given to mice with the volume of 40 mL/kg.The general behavior of mice was observed directly,the motor coordination ability was observed by rotating stick method,and Anymaze animal behavior video analysis system was used to observe the spontaneous activity of mice and synergistic reaction with sub-threshold dose of pentobarbital sodium.Results There were no significant differences in the general behavioral activity,and the number of spontaneous activity times,mean resident time,and ratio of sleeping were found in all coenzyme Q10 groups,compared with the vehicle and perillartine control groups.Conclusion High dose of coenzyme Q10 has no significantly toxic effect on the central nervous system in mice,which could provide a reliable experimental basis for further medication study and clinical application of high-dose coenzyme Q 10.

Safety evaluation of coenzyme Q10 on central nervous system / 药物评价研究

Objective To investigate the effect of high-dose coenzyme Q10 on the central nervous system in mice,and to provide experimental basis for clinical safety evaluation.Methods Mice were randomly divided into vehicle control group,perillartine control group,positive control group (chlorpromazine or diazepam) and coenzyme Q10 low,medium and high dose groups (1.5,3.0 and 6.0 g/kg,equivalent to 75,150,and 300 times of clinical dosage,respectively).The corresponding drugs were ig given to mice with the volume of 40 mL/kg.The general behavior of mice was observed directly,the motor coordination ability was observed by rotating stick method,and Anymaze animal behavior video analysis system was used to observe the spontaneous activity of mice and synergistic reaction with sub-threshold dose of pentobarbital sodium.Results There were no significant differences in the general behavioral activity,and the number of spontaneous activity times,mean resident time,and ratio of sleeping were found in all coenzyme Q10 groups,compared with the vehicle and perillartine control groups.Conclusion High dose of coenzyme Q10 has no significantly toxic effect on the central nervous system in mice,which could provide a reliable experimental basis for further medication study and clinical application of high-dose coenzyme Q 10.

Breakpoints located by sequence tagged sites of AZFc microdeletion in Chinese Han population / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the breakpoints of the azoospermia factor c (AZFc) microdeletion in Chinese Han population.</p><p><b>METHODS</b>We detected 9 sequence tagged sites (sY84, sY86, sY127, sY134, sY152, sY145, sY255, sY254 and sY157) to confirm AZFc microdeletions in the Y chromosome for patients with severe oligozoospermia or non-obstructive azoospermia by multiplex polymerase reaction. To locate the breakpoints of AZFc microdeletions, we analyzed 192 patients with sY255, sY254 and sY157 dele- ted by detecting sY1191, sY1197, sY1054, sY1125 and sY1206, respectively.</p><p><b>RESULTS</b>Five breaking patterns were found in the 192 patients with sY255, sY254 and sY157 deleted, among which the common ones were sY1197(+), sY1191(-), sY1054(-), sY1206(-) and sY1125(+), which accounted fro 54.17% (104/192), sY1197(+), sY1191(+), sY1206(-), sY1054(-) and sY1125(+), which constituted 28.12% (54/192), sY1197(+), sY1191(-), sY1206(-), sY1054(+) and sY1125 (+), which made up 14.58% (28/192). The proximal breakpoint located between sY1197 and sY1191 was 70.83% of AZFc microdeletions, and the distant breakpoint located between sY1054 and sY1125 was 82.29%.</p><p><b>CONCLUSION</b>There are 5 breaking patterns of AZFc microdeletions in Chinese Han population, the proximal and distant breakpoints mostly located at the replicons b2 and b4, respectively.</p>

Oxidative damage to DNA and its relationship with diabetic complications / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To detect the oxidative DNA damage in diabetic patients and to investigate the relationship of oxidative DNA damage with diabetes and diabetic nephropathy.</p><p><b>METHODS</b>Single cell gel electrophoresis (SCGE) was used to detect the DNA strand breaks in peripheral blood lymphocytes, and oxidative DNA damage product and serum 8-OHdG were determined by a competitive ELISA in 47 cases, including 25 patients without diabetic complications, 22 patients with diabetic nephropathy and 25 normal control subjects.</p><p><b>RESULTS</b>Diabetic patients showed greater oxidative damage to DNA. The percentage of comet cells and the length of DNA migration (comet tail length) of peripheral blood lymphocytes were significantly increased in patients with diabetes, and significantly higher in patients with diabetic nephropathy than in diabetic patients without vascular complications (P < 0.05). There was a significant increase in serum 8-OHdG in diabetic patients compared with normal subjects (P < 0.05). Moreover, serum 8-OHdG was much higher in patients with diabetic nephropathy than in diabetic patients without vascular complications (P < 0.05).</p><p><b>CONCLUSION</b>There is severe oxidative DNA damage in diabetic patients. Enhanced oxidative stress may be associated with diabetes, especially in patients with diabetic nephropathy.</p>

Recordings of The Hippocampal Field Potentials and Unit Activity by Using Linear Silicon Electrode Array / 生物化学与生物物理进展

The rapid development of silicon microelectrode arrays provides an ideal means for the study of spatio-temporal features of neuronal activity in the brain. The stability of the linear silicon electrode array (LSEA) in recording neuronal potentials and its validity in recording unit activity are investigated. The experimental results showed that during the recording of field potentials in the hippocampal CA1 region of anesthetized rats, upward and downward movements of the recording probe for a distance of 200 ?m did not affect the orthordromic and antidromic evoked potentials significantly. The data indicated that the probe movements caused very small damage to the neurons, and the recording was stable. The contact sites that located in the pyramidal cell layer acquired CA1 neuronal unit activity validly. Different types of unit activity from independent neurons were easily distinguished in epochs of recording from a same recording site. These results demonstrated the features of the LSEA, including the facility of probe manipulation, the stability of recording and the abundance of data acquirement. The data will be helpful to the researchers involved in the application of microelectrode array for neuroscience researches.