Prevalence of group B streptococcus colonization in pregnant women in Jiangsu, East China.

BACKGROUND: Group B streptococcus (GBS) is the leading cause of early-onset neonatal sepsis. However, GBS was infrequently reported in the developing world in contrast to western countries. This study assessed the prevalence of GBS colonization among pregnant women in Jiangsu, East China, and revealed the difference of GBS infection between culture and PCR. METHODS: A total of 16,184 pregnant women at 34 to 37 weeks' gestation aged 16-47 years were recruited from Nanjing Kingmed Center for Clinical Laboratory. Nine thousand twenty-two pregnant women received GBS screening by PCR detection only. Seven thousand one hundred sixty-two pregnant women received GBS screening by bacterial culture and GBS-positive samples were tested for antibiotic resistance. RESULTS: The overall GBS positive rate was 8.7% by PCR and 3.5% by culture. Colonization rate was highest in the "25-29 years" age group. The 249 GBS-positive samples which detected by culture were all sensitive to penicillin. The prevalence of resistance to erythromycin, clindamycin, and levofloxacin was 77.5, 68.3, and 52.2%, respectively. CONCLUSIONS: This study revealed the data on the prevalence of GBS colonization in pregnant women at 34 to 37 weeks' gestation in Jiangsu, East China. It compared the difference of the sensitivity to detect GBS between PCR and culture. PCR was expected to become a quick method in pregnancy women conventional detection of GBS infection.

Terahertz MIMO communication performance analysis in exponentiated Weibull turbulence with pointing errors.

With the rapid growth in demand for high-speed wireless communication, terahertz (THz) has become one of the most promising techniques. Both atmospheric turbulence and pointing errors are important factors in degrading the performance of THz propagation. We study the performance of a multiple-input/multiple-output (MIMO) system in the THz band under the combined influences noted above. Especially, we take the impact on amplitude and phase caused by turbulence into consideration. We adopt the Padé approximation to analyze the probability density function of the channel coefficient in equal gain combining and derive the bit error rate by the Meijer-G function. The curve-fitting results of theoretical analysis are in good agreement with the actual measurements in the THz band. Therefore, it can be deduced that the exponentiated Weibull model can also be applied in the THz band. Then, we verify the theoretical results by Monte Carlo simulation. We find that turbulence is a more significant cause, which deteriorates communication performance in a larger scale of the MIMO system.

Functional ecology of congeneric variation in the leaf economics spectrum.

Variation in resource availability can lead to phenotypic plasticity in the traits comprising the world-wide leaf economics spectrum (LES), potentially impairing plant function and complicating the use of tabulated values for LES traits in ecological studies. We compared 14 Carex (Cyperaceae) species in a factorial experiment (unshaded/shaded × sufficient/insufficient P) to analyze how changes in the network of allometric scaling relationships among LES traits influenced growth under favorable and resource-limited conditions. Changes in leaf mass per area (LMA) shifted the scaling relationships among LES traits expressed per unit area vs mass in ways that helped to sustain growth under resource limitation. Increases in area-normalized photosynthetic capacity and foliar nitrogen (N) were correlated with increased growth, offsetting losses associated with mass-normalized dark respiration and foliar N. These shifts increased the contributions to growth associated with photosynthetic N-use efficiency and the N : P ratio. Plasticity in LMA is at the hub of the functional role of the LES as an integrated and resilient complex system that balances the relationships among area- and mass-based aspects of gas exchange and foliar nutrient traits to sustain at least some degree of plant growth under differing availabilities of above- and below-ground resources.

Not only phosphorus: dauciform roots can also influence aboveground biomass through root morphological traits and metal cation concentrations.

Background: Phosphorus in the soil is mostly too insoluble for plants to utilize, resulting in inhibited aboveground biomass, while Carex can maintain their aboveground biomass through the presence of dauciform roots. However, dauciform roots lead to both morphological and physiological changes in the root system, making their primary mechanism unclear. Methods: A greenhouse experiment was conducted on three Carex species, in which Al-P, Ca-P, Fe-P, and K-P were employed as sole phosphorus sources. The plants were harvested and assessed after 30, 60 and 90 days. Results: (1) The density of dauciform roots was positively correlated with root length and specific root length, positively influencing aboveground biomass at all three stages. (2) The aboveground phosphorus concentration showed a negative correlation with both dauciform root density and aboveground biomass in the first two stages, which became positive in the third stage. (3) Aboveground biomass correlated negatively with the aboveground Al concentration, and positively with Ca and Fe concentration (except Al-P). (4) Root morphological traits emerged as critical factors in dauciform roots' promotion of aboveground biomass accumulation. Conclusion: Despite the difference among insoluble phosphorus, dauciform roots have a contributing effect on aboveground growth status over time, mainly by regulating root morphological traits. This study contributes to our understanding of short-term variation in dauciform roots and their regulatory mechanisms that enhance Carex aboveground biomass under low available phosphorus conditions.

GPR50 regulates neuronal development as a mitophagy receptor.

Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.

Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus.

The development of hippocampal circuitry depends on the proper assembly of correctly specified and fully differentiated hippocampal neurons. Little is known about factors that control the hippocampal specification. Here, we show that zinc finger protein Zbtb20 is essential for the specification of hippocampal CA1 field identity. We found that Zbtb20 expression was initially activated in the hippocampal anlage at the onset of corticogenesis, and persisted in immature hippocampal neurons. Targeted deletion of Zbtb20 in mice did not compromise the progenitor proliferation in the hippocampal and adjacent transitional ventricular zone, but led to the transformation of the hippocampal CA1 field into a transitional neocortex-like structure, as evidenced by cytoarchitectural, neuronal migration, and gene expression phenotypes. Correspondingly, the subiculum was ectopically located adjacent to the CA3 in mutant. Although the field identities of the mutant CA3 and dentate gyrus (DG) were largely maintained, their projections were severely impaired. The hippocampus of Zbtb20 null mice was reduced in size, and exhibited increased apoptotic cell death during postnatal development. Our data establish an essential role of Zbtb20 in the specification of CA1 field identity by repressing adjacent transitional neocortex-specific fate determination.

What role do dauciform roots play? Responses of Carex filispica to trampling in alpine meadows based on functional traits.

In China, dauciform roots were hardly studied and only reported in alpine meadows, where sedges showed a different tendency from other functional groups such as grasses and forbs with degradation. In addition, Carex species were proved to have shifting scaling relationships among LES (leaf economics spectrum) traits under disturbance. So, are these unique performances of sedges related to the presence of dauciform roots, and if so, how? An alpine meadow dominated by Carex filispica in Baima Snow Mountain was selected, and quantitative trampling was performed (0, 50, 200, and 500 passes). The cover and dauciform root properties of Carex filispica were measured, as well as the morphological, chemical traits and biomass of leaves and roots, their correlations and the differences between individuals with and without dauciform roots were analyzed. After the trampling, individuals with dauciform roots showed multiple resource-acquisitive traits: Larger, thicker leaves, more aboveground biomass, higher efficiency of nutrient utilization, and slenderer roots. Additionally, they had a tighter correlation among belowground biomass, morphological and chemical traits, as well as dauciform root properties and morphology of leaves, suggesting that their traits were more related than those without dauciform roots. The presence of dauciform roots in Carex filispica was related to advantages in multiple traits after trampling, which is consistent with and might be responsible for the unique performances of sedges.

Dauciform roots affect functional traits of Carex filispica under nitrogen and phosphorus fertilization in alpine meadow.

Over recent decades, there has been a severe nitrogen-deposition in alpine meadows which often leads to phosphorus limitation of plant productivity. In these high-altitude localities, Cyperaceae have an increasing biomass while other functional groups decrease. Meanwhile, Cyperaceae are known to have the ability of producing dauciform roots, which are formed under phosphorus limitation, but in China, are only described in these high-altitude places. So, is the superiority of Cyperaceae and the formation of dauciform roots in high-altitude localities related to the accumulation of nitrogen? And is there a link between them? A Carex filispica dominated community in Baima Snow Mountain was selected and quantitative fertilization with four levels of nitrogen and three levels of phosphorus was performed. After 2 weeks, Carex filispica individuals with and without dauciform roots were separated and analyzed for their regular root properties, dauciform root properties, biomass and chemical traits of above- and belowground parts. The total cover of the community declined under phosphorus limitation with increasing nitrogen supply, while the relative cover difference of Carex filispica increased with increasing nitrogen supply and decreased with increasing phosphorus supply. Dauciform roots had a more significant response to nitrogen supply than to phosphorus supply and they were formed the most at a low supply of nitrogen. The biomass and root properties of individuals with dauciform roots were enhanced by nitrogen supply and inhibited by phosphorus supply, while those of individuals without dauciform roots were often enhanced by phosphorus supply. Individuals with and without dauciform roots showed two different mechanisms, and were limited by significantly different factors, which can explain the opposite performance of Cyperaceae after nitrogen and phosphorus supply in previous studies.

Recovering from trampling: The role of dauciform roots to functional traits response of Carex filispica in alpine meadow.

In the natural habitats of China, dauciform roots were only described in degraded alpine meadows. It was found that the presence of dauciform roots of Carex filispica was related to the advantage of multiple functional traits after trampling, reflecting short-term resistance. However, the long-term response of dauciform roots to trampling and the recovery of C. filispica with and without dauciform roots to trampling require further studies. In this study, different intensities of trampling (0, 50, 200 and 500 passages) were performed in an alpine meadow. One year later, individuals with and without dauciform roots were separated and their functional traits related to the economic spectrum of leaves and roots were measured as a reflection of recovery from trampling. The results showed that: (1) 1 year after trampling, the number of dauciform roots showed an increase with trampling intensity; (2) 1 year later, there was no significant difference in the response of economic spectrum traits among trampling intensities, or between plants with and without dauciform roots; (3) the number of dauciform roots was positively correlated with the leaf area of both individuals with and without dauciform roots, as well as with the biomass of those without dauciform roots; and (4) plants with more resource-conservative roots showed an advantage after trampling recovery: specifically, plants with dauciform roots showed such an advantage in the control group, which was lost with a leaning towards resource-acquisitive roots and an increased density of dauciform roots once trampled. In contrast, plants without dauciform roots showed a significant advantage of conservative roots only after trampling. In conclusion, the presence of dauciform roots is related to the plants' position on the root economic spectrum, thereby influencing the recovery of C. filispica from trampling. Carex filispica showed strong recovery from trampling after 1 year, which makes it an adequate choice for ecological restoration in alpine meadows. Dauciform roots showed a positive correlation with the aboveground growth of both plants with and without them, however, it requires a lab-controlled study to confirm whether there is indeed a positive effect on the growth of neighbouring plants.

Dauciform roots affect the position of the neighboring plants on the economic spectrum in degraded alpine meadows.

Background and aims: Special root structures that can dissolve insoluble phosphorus locked in soil are supposed to contribute not only to the growing status of themselves but also to the neighbouring plants. However, whether dauciform roots have any effect on the neighbouring plants and how does it respond to meadow degradation had not been studied. Methods: Alpine meadows with different degradation statuses were selected and the functional traits of Carex filispica and the co-occurring species Polygonum viviparum were measured to explore their response to degradation, as well as the response of Polygonum viviparum to the dauciform roots of Carex filispica. Results: The results showed that 1) the number of dauciform roots decreased with the intensifying degradation, positively related to available phosphorus in the soil and negatively related to the aboveground phosphorus of Carex filispica. 2) Carex filispica and Polygonum viviparum are similar in specific leaf area and specific root area, yet different in the phosphorus content. The available phosphorus in the soil was negatively related to the aboveground phosphorus of Carex filispica and positively related to that of Polygonum viviparum. 3) When lightly degraded, the proportion of dauciform roots had positive effects on the aboveground resource-acquiring traits of Polygonum viviparum, which were no longer significant at heavy degradation. 4) Polygonum viviparum and Carex filispica without dauciform roots have similar performance: a decrease of belowground carbon with the increasing degradation, and a trend toward resource conservation with the increasing proportion of dauciform roots, which did not exist in Carex filispica with dauciform roots. Conclusion: Our study found that dauciform roots had a beneficial effect on the resource acquisition of their neighbouring plants. However, due to the uncontrollable nature of natural habitats, whether this effect is stable and strong enough to be performed in ecological restoration requires further lab-controlled studies.

Response of Carex breviculmis to phosphorus deficiency and drought stress.

Introduction: The drought and phosphorus deficiency have inevitably become environmental issues globally in the future. The analysis of plants functional trait variation and response strategies under the stress of phosphorus deficiency and drought is important to explore their ability to respond to potential ecological stress. Methods: In this study, Carex breviculmis was selected as the research object, and a 14-week pot experiment was conducted in a greenhouse, with two phosphorus treatment (add 0.5mmol/L or 0.05µmol/L phosphorus) and four drought treatment (add 0-5%PEG6000), totaling eight treatments. Biomass allocation characteristics, leaf anatomical characteristics, biochemical parameters, root morphology, chemical element content, and photosynthetic parameters were measured. Results: The results showed that the anatomical characteristics, chemical elements, and photosynthetic parameters of Carex breviculmis responded more significantly to main effect of phosphorus deficiency. Stomatal width, leaf phosphorus content and maximum net photosynthetic rate decreased by 11.38%, 59.39%, 38.18% significantly (p<0.05), while the change in biomass was not significant (p>0.05). Biomass allocation characteristics and root morphology responded more significantly to main effect of drought. Severe drought significantly decreased leaf fresh weight by 61% and increased root shoot ratio by 223.3% compared to the control group (p<0.05). The combined effect of severe drought and phosphorus deficiency produced the highest leaf N/P ratio (291.1% of the control) and MDA concentration (243.6% of the control). Correlation analysis and redundancy analysis showed that the contributions of phosphorus and drought to functional trait variation were similar. Lower epidermal cell thickness was positively correlated with maximum net photosynthetic rate, leaf phosphorus, chlorophyll ab, and leaf fresh weight (p<0.05). Discussion: In terms of response strategy, Carex breviculmis was affected at the microscopic level under phosphorus deficiency stress, but could maintain the aboveground and underground biomass well through a series of mechanisms. When affected by drought, it adopted the strategy of reducing leaf yield and improving root efficiency to maintain life activities. Carex breviculmis could maintain its traits well under low phosphorus and moderate drought, or better conditions. So it may have good ecological service potential in corresponding areas if promoted. This study also provided a reference for plant response to combined drought and phosphorus deficiency stresses.

Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

Ubiquitin-conjugating enzyme E2T promotes tumor stem cell characteristics and migration of cervical cancer cells by regulating the GRP78/FAK pathway.

Ubiquitin-conjugating enzyme E2T (UBE2T) functions as an E2 ubiquitin-conjugating enzyme in the ubiquitin-proteasome degradation system and mediates cellular processes, such as cell cycle, proliferation, and differentiation. UBE2T has been considered to be an oncogene in a variety of tumors. However, the oncogenic role of UBE2T in cervical cancer remains unclear. In this study, our results first showed that the expression of UBE2T was higher in both of cervical cancer tissues and cells than that in the normal tissues and cells. Knockdown of UBE2T reduced cervical cancer cell viability and suppressed the proliferation, invasion, and migration. However, overexpression of UBE2T contributed to cervical cancer cell growth and metastasis. Moreover, UBE2T overexpression cervical cancer cells demonstrated enhanced self-renewal capacity with upregulation of SOX2, Oct-4, and Nanog protein. Silencing of UBE2T downregulated protein expression of SOX2, Oct-4, and Nanog in cervical cancer cells reduced self-renewal capacity. Furthermore, ectopic UBE2T expression promoted protein expression of glucose-regulated protein 78 (GRP78) and focal adhesion kinase (FAK) phosphorylation in cervical cancer cells. The knockdown of UBE2T reduced protein expression of GRP78 and FAK phosphorylation. Collectively, UBE2T promoted cervical cancer stem cell traits and exerted an oncogenic role through activation of the GRP78/FAK pathway.

Intranasal Transplantation of Human Neural Stem Cells Ameliorates Alzheimer's Disease-Like Pathology in a Mouse Model.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory impairments, which has no effective therapy. Stem cell transplantation shows great potential in the therapy of various disease. However, the application of stem cell therapy in neurological disorders, especially the ones with a long-term disease course such as AD, is limited by the delivery approach due to the presence of the brain blood barrier. So far, the most commonly used delivery approach in the therapy of neurological disorders with stem cells in preclinical and clinical studies are intracranial injection and intrathecal injection, both of which are invasive. In the present study, we use repetitive intranasal delivery of human neural stem cells (hNSCs) to the brains of APP/PS1 transgenic mice to investigate the effect of hNSCs on the pathology of AD. The results indicate that the intranasally transplanted hNSCs survive and exhibit extensive migration and higher neuronal differentiation, with a relatively limited glial differentiation. A proportion of intranasally transplanted hNSCs differentiate to cholinergic neurons, which rescue cholinergic dysfunction in APP/PS1 mice. In addition, intranasal transplantation of hNSCs attenuates ß-amyloid accumulation by upregulating the expression of ß-amyloid degrading enzymes, insulin-degrading enzymes, and neprilysin. Moreover, intranasal transplantation of hNSCs ameliorates other AD-like pathology including neuroinflammation, cholinergic dysfunction, and pericytic and synaptic loss, while enhancing adult hippocampal neurogenesis, eventually rescuing the cognitive deficits of APP/PS1 transgenic mice. Thus, our findings highlight that intranasal transplantation of hNSCs benefits cognition through multiple mechanisms, and exhibit the great potential of intranasal administration of stem cells as a non-invasive therapeutic strategy for AD.

A case of catheter related bloodstream infection by Corynebacterium striatum.

BACKGROUND: C. striatum is an innocuous inhabitant of the normal human epithelial and mucosal surfaces. The C. striatum ´s thogenic potential is increasingly recognized in our time. METHODS: We present a rare case of CRBSI by C. striatum in a 57-yr-old male patient. The patient suffered from many basic diseases and was admitted to hospital of shock. RESULTS: The patient finally died of septic shock caused by CRBSI due to multidrug-resistant C. striatum which responded neither to empiric nor to targeted treatment. CONCLUSIONS: C. striatum can cause CRBSI in immunocompromised patients when they were treated by intravenous catheters.

Transplantation of GABAergic Interneuron Progenitor Attenuates Cognitive Deficits of Alzheimer's Disease Model Mice.

Excitatory (E) and inhibitory (I) balance of neural network activity is essential for normal brain function and of particular importance to memory. Disturbance of E/I balance contributes to various neurological disorders. The appearance of neural hyperexcitability in Alzheimer's disease (AD) is even suggested as one of predictors of accelerated cognitive decline. In this study, we found that GAD67+, Parvalbumin+, Calretinin+, and Neuropeptide Y+ interneurons were progressively lost in the brain of APP/PS1 mice. Transplanted embryonic medial ganglionic eminence derived interneuron progenitors (IPs) survived, migrated, and differentiated into GABAergic interneuron subtypes successfully at 2 months after transplantation. Transplantation of IPs hippocampally rescued impaired synaptic plasticity and cognitive deficits of APP/PS1 transgenic mice, concomitant with a suppression of neural hyperexcitability, whereas transplantation of IPs failed to attenuate amyloid-ß accumulation, neuroinflammation, and synaptic loss of APP/PS1 transgenic mice. These observations indicate that transplantation of IPs improves learning and memory of APP/PS1 transgenic mice via suppressing neural hyperexcitability. This study highlights a causal contribution of GABAergic dysfunction to AD pathogenesis and the potentiality of IP transplantation in AD therapy.

Mitochondrial Dysfunction in Neural Injury.

Mitochondria are the double membrane organelles providing most of the energy for cells. In addition, mitochondria also play essential roles in various cellular biological processes such as calcium signaling, apoptosis, ROS generation, cell growth, and cell cycle. Mitochondrial dysfunction is observed in various neurological disorders which harbor acute and chronic neural injury such as neurodegenerative diseases and ischemia, hypoxia-induced brain injury. In this review, we describe how mitochondrial dysfunction contributes to the pathogenesis of neurological disorders which manifest chronic or acute neural injury.

Inhibition of sphingomyelin synthase 1 ameliorates alzheimer-like pathology in APP/PS1 transgenic mice through promoting lysosomal degradation of BACE1.

Sphingolipids emerge as essential modulators in the etiology of Alzheimer's disease (AD) with unclear mechanisms. Elevated levels of SM synthase 1 (SMS1), which catalyzes the synthesis of SM from ceramide and phosphatidylcholine, have been observed in the brains of Alzheimer's disease (AD), where expression of ß-site APP cleaving enzyme 1 (BACE1), a rate limiting enzyme in amyloid-ß (Aß) generation, are upregulated. In the present study, we show knockdown of SMS1 via andeno associated virus (serotype 8, AAV8) in the hippocampus of APP/PS1 transgenic mice, attenuates the densities of Aß plaques, neuroinflammation, synaptic loss and thus rescuing cognitive deficits of these transgenic mice. We further describe that knockdown or inhibition of SMS1 decreases BACE1 stability, which is accompanied with decreased BACE1 levels in the Golgi, whereas enhanced BACE1 levels in the early endosomes and the lysosomes. The reduction of BACE1 levels induced by knockdown or inhibition of SMS1 is prevented by inhibition of lysosomes. Therefore, knockdown or inhibition of SMS1 promotes lysosomal degradation of BACE1 via modulating the intracellular trafficking of BACE1. Knockdown of SMS1 attenuates AD-like pathology through promoting lysosomal degradation of BACE1.

Disrupted-in-schizophrenia-1 protects synaptic plasticity in a transgenic mouse model of Alzheimer's disease as a mitophagy receptor.

Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD). Accumulated damaged mitochondria, which are associated with impaired mitophagy, contribute to neurodegeneration in AD. We show levels of Disrupted-in-schizophrenia-1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aß-treated cultured cells. Disrupted-in-schizophrenia-1 contains a canonical LC3-interacting region (LIR) motif (210 FSFI213 ), through which DISC1 directly binds to LC3-I/II. Overexpression of DISC1 enhances mitophagy through its binding to LC3, whereas knocking-down of DISC1 blocks Aß-induced mitophagy. We further observe overexpression of DISC1, but not its mutant (muFSFI) which abolishes the interaction of DISC1 with LC3, rescues Aß-induced mitochondrial dysfunction, loss of spines, suppressed long-term potentiation (LTP). Overexpression of DISC1 via adeno-associated virus (serotype 8, AAV8) in the hippocampus of 8-month-old APP/PS1 transgenic mice for 4 months rescues cognitive deficits, synaptic loss, and Aß plaque accumulation, in a way dependent on the interaction of DISC1 with LC3. These results indicate that DISC1 is a novel mitophagy receptor, which protects synaptic plasticity from Aß accumulation-induced toxicity through promoting mitophagy.

The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance.

BACKGROUND: According to recent clinical observations, deficient DNA mismatch repair (dMMR) is capable of improving antitumor effects of the PD-1/PD-L1 pathway, suggesting that dMMR may act as a prognostic indicator of PD-1/PD-L1 antibody drugs. In this study, we examined the dMMR and PD-1/PD-L1 expression, as well as explored the correlation of dMMR status with PD-1/PD-L1 expression in cervical cancer patients, in order to optimize cervical cancer patient selection for PD-1/PD-L1 antibody drug treatment, which is helpful to avoid adverse effects and keep costs manageable. METHODS: Sixty-six tissue samples from patients with squamous cell carcinoma were collected, and data of their clinical characteristics were also gathered. Based on these samples, the expression levels of MLH1, MSH2, and PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Moreover, PD-1/PD-L1 expression in tumor-invading lymphocytes (TILs) was detected by IHC as well. Six single-nucleotide-repeat markers of microsatellite instability (MSI), including NR-27, MONO-27, BAT-25, NR-24, NR-21, and BAT-26, were tested by capillary electrophoresis sequencer analysis. According to expression of MLH1, MSH2 and the MSI test, all 66 cases were divided into dMMR or proficient DNA mismatch repair (pMMR) groups. The comparisons of dMMR and PD-L1 in cancer cells and of PD-1/PD-L1 in TILs were conducted categorized by age, childbearing history, history of abortion, ethnicity, and cancer cell differentiation subgroup. Furthermore, PD-L1 levels in cancer cells and PD-1/PD-L1 in TILs were analyzed and compared in both dMMR and pMMR subgroups. RESULTS: Of the patient samples, 25.8% were associated with dMMR. PD-L1 in cancer cells, PD-L1 in TILs, and PD-1 in TILs took up 59.1%, 47.0%, and 60.6%, respectively. The data indicated that both dMMR and PD-L1 overexpression resulted from lower cancer differentiation, more incidences of childbearing, and a history of abortion. Abortion could significantly increase PD-1 expression levels in TILs. Additionally, more incidence of childbearing or older age (35-55 years) was able to upregulate PD-L1 expression in TILs. Statistical difference of PD-L1 in cancer cells could be observed between dMMR and pMMR subgroups. In the dMMR group, PD-L1 in cancer cells and PD-1 in TILs had no correlation (rs=0.161, p=0.537), but in the pMMR group, they had good correlation (rs=0.645, p<0.001). CONCLUSION: According to prior studies and our own experiments, PD-L1 in both cancer cells and TILs and PD-1 in TILs are widely observed in cervical cancer patients, indicating that there may be potential to apply PD-1/PD-L1 antibody drugs in cervical cancer. dMMR patients are associated with higher PD-L1 expression compared with pMMR ones, which suggested that PD-1/PD-L1 antibody drugs may work well in dMMR cervical cancer patients. Moreover, in patients with more incidences of childbearing or abortion, dMMR may be a molecular detection target for clinical application of PD-1/PD-L1 antibody drugs.