Chemical Flexibility of Atomically Precise Metal Clusters.

Ligand-protected metal clusters possess hybrid properties that seamlessly combine an inorganic core with an organic ligand shell, imparting them exceptional chemical flexibility and unlocking remarkable application potential in diverse fields. Leveraging chemical flexibility to expand the library of available materials and stimulate the development of new functionalities is becoming an increasingly pressing requirement. This Review focuses on the origin of chemical flexibility from the structural analysis, including intra-cluster bonding, inter-cluster interactions, cluster-environments interactions, metal-to-ligand ratios, and thermodynamic effects. In the introduction, we briefly outline the development of metal clusters and explain the differences and commonalities of M(I)/M(I/0) coinage metal clusters. Additionally, we distinguish the bonding characteristics of metal atoms in the inorganic core, which give rise to their distinct chemical flexibility. Section 2 delves into the structural analysis, bonding categories, and thermodynamic theories related to metal clusters. In the following sections 3 to 7, we primarily elucidate the mechanisms that trigger chemical flexibility, the dynamic processes in transformation, the resultant alterations in structure, and the ensuing modifications in physical-chemical properties. Section 8 presents the notable applications that have emerged from utilizing metal clusters and their assemblies. Finally, in section 9, we discuss future challenges and opportunities within this area.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

Pigmentiphaga kullae CHJ604 improved the growth of tobacco by degrading allelochemicals and xenobiotics in continuous cropping obstacles.

Plant autotoxicity is considered to be one of the important causes of continuous cropping obstacles in modern agriculture, which accumulates a lot of allelochemicals and xenobiotics and is difficult to solve effectively. To overcome tobacco continuous obstacles, a strain Pigmentiphaga kullae CHJ604 isolated from the environment can effectively degrade these compounds in this study. CHJ604 strain can degrade 11 types of autotoxicity allelochemicals and xenobiotics (1646.22 µg/kg) accumulated in the soil of ten-years continuous cropping of tobacco. The 11 allelochemicals and xenobiotics significantly reduced Germination Percentage (GP), Germination Index (GI), and Mean Germination Time (MGT) of tobacco seeds, and inhibited the development of leaves, stems, and roots. These negative disturbances can be eliminated by CHJ604 strain. The degradation pathways of 11 allelochemicals and xenobiotics were obtained by whole genome sequence and annotation of CHJ604 strain. The heterologous expression of a terephthalate 1,2-dioxygenase can catalyze 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid, 4-hydroxybenzaldehyde, and 4-hydroxy-3-methoxy-benzaldehyde, respectively. The phthalate 4,5-dioxygenase can catalyze phthalic acid, diisobutyl phthalate, and dibutyl phthalate. These two enzymes are conducive to the simultaneous degradation of multiple allelochemicals and xenobiotics by strain CHJ604. This study provides new insights into the biodegradation of autotoxicity allelochemicals and xenobiotics as it is the first to describe a degrading bacterium of 11 types of allelochemicals and xenobiotics and their great potential in improving tobacco continuous obstacles.

A novel AIE material for sensing of Erythromycin in pure water by hydrogen bond in portable test strips and cellular imaging applications.

Erythromycin could be used to treat various bacterial infection, but it was harmful to the colonic microflora. Therefore, it is highly desirable to develop a fluorescence probe that could selectively and sensitively detect Erythromycin in pure water. In this work, a fluorescent probe named EHMC, which exhibited aggregation-induced emission (AIE) characteristic in solid state and water/EtOH binary solvent was developed for "turn on" sensing Erythromycin in pure water with high selectivity and sensitivity (detection limit: 1.78 × 10-8 M). Also, there are fewer interference from other antibiotics in the detection process of probe EHMC for Erythromycin. Moreover, probe EHMC could as a portable test strips for highly selective detection of Erythromycin and identification of different concentrations of Erythromycin. In addition, living cells imaging experiments displayed that probe EHMC could detect Erythromycin in A549 cells and BEAS-2B cells successfully. Combined with the theoretical calculation results The sensing mechanisms that the CO in Erythromycin and OH in EHMC formed intermolecular hydrogen bond and further formed new aggregates were confirmed by job' plot, 1H NMR, FT-IR, ESI-MS, DLS and TEM and DFT calculation.

Circularly polarized luminescence enlargement from crystals to oriented films of enantiopure 2D hybrid perovskites.

Chiral 2D organic-inorganic hybrid perovskites (C-2D-OIHPs) with circularly polarized luminescence (CPL) have important promising applications in optical, electronic, and chiroptoelectronic devices. Herein, we report enantiomeric crystals of R/S-FMBA)2PbBr4. (FMBA = 4-fluorophenethylamine), which demonstrated bright room-temperature CPL emission. For the first time, the oriented films along the c-axis of this pair of C-2D-OIHPs exhibited a 16-fold increase in the asymmetry factors of absorbance (gCD) and a 5-fold rise in the asymmetry factors of CPL (glum), reaching up to ± 1 × 10-2.

Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.

The ankle-link complex (ALC) consists of USH2A, WHRN, PDZD7, and ADGRV1 and plays an important role in hair cell development. At present, its architectural organization and signaling role remain unclear. By establishing Adgrv1 Y6236fsX1 mutant mice as a model of the deafness-associated human Y6244fsX1 mutation, the authors show here that the Y6236fsX1 mutation disrupts the interaction between adhesion G protein-coupled receptor V subfamily member 1 (ADGRV1) and other ALC components, resulting in stereocilia disorganization and mechanoelectrical transduction (MET) deficits. Importantly, ADGRV1 inhibits WHRN phosphorylation through regional cAMP-PKA signaling, which in turn regulates the ubiquitination and stability of USH2A via local signaling compartmentalization, whereas ADGRV1 Y6236fsX1 does not. Yeast two-hybrid screening identified the E3 ligase WDSUB1 that binds to WHRN and regulates the ubiquitination of USH2A in a WHRN phosphorylation-dependent manner. Further FlAsH-BRET assay, NMR spectrometry, and mutagenesis analysis provided insights into the architectural organization of ALC and interaction motifs at single-residue resolution. In conclusion, the present data suggest that ALC organization and accompanying local signal transduction play important roles in regulating the stability of the ALC.

Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease.

Extracellular amyloid beta (Aß) plaques are main pathological feature of Alzheimer's disease. However, the specific type of neurons that produce Aß peptides in the initial stage of Alzheimer's disease are unknown. In this study, we found that 5-hydroxytryptamin receptor 3A subunit (HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice (an Alzheimer's disease model) and patients with Alzheimer's disease. To investigate whether HTR3A-positive interneurons are associated with the production of Aß plaques, we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aß plaques in the mouse model. Some amyloid precursor protein-positive or ß-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aß plaques were co-localized with HTR3A interneurons. These results suggest that HTR3A -positive interneurons may partially contribute to the generation of Aß peptides. We treated 5.0-5.5-month-old model mice with tropisetron, a HTR3 antagonist, for 8 consecutive weeks. We found that the cognitive deficit of mice was partially reversed, Aß plaques and neuroinflammation were remarkably reduced, the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice. These findings suggest that HTR3A interneurons partly contribute to generation of Aß peptide at the initial stage of Alzheimer's disease and inhibiting HTR3 partly reverses the pathological changes of Alzheimer's disease.

Lymphocyte-C-reactive protein ratio can differentiate disease severity of COVID-19 patients and serve as an assistant screening tool for hospital and ICU admission.

In this study, we aimed to explore whether lymphocyte-C-reactive protein ratio (LCR) can differentiate disease severity of coronavirus disease 2019 (COVID-19) patients and its value as an assistant screening tool for admission to hospital and intensive care unit (ICU). A total of 184 adult COVID-19 patients from the COVID-19 Treatment Center in Heilongjiang Province at the First Affiliated Hospital of Harbin Medical University between January 2020 and March 2021 were included in this study. Patients were divided into asymptomatic infection group, mild group, moderate group, severe group, and critical group according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data including gender, age, comorbidities, severity of COVID-19, white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), red blood cell distribution width (RDW), platelet (PLT), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr), albumin (ALB), total bilirubin (TB), direct bilirubin (DBIL), indirect bilirubin (IBIL), and D-dimer were obtained and collated from medical records at admission, from which sequential organ failure assessment (SOFA) score and LCR were calculated, and all the above indicators were compared among the groups. Multiple clinical parameters, including LYMPH, CRP, and LCR, showed significant differences among the groups. The related factors to classify COVID-19 patients into moderate, severe, and critical groups included age, number of comorbidities, WBC, LCR, and AST. Among these factors, the number of comorbidities showed the greatest effect, and only WBC and LCR were protective factors. The area under the receiver operating characteristic (ROC) curve of LCR to classify COVID-19 patients into moderate, severe, and critical groups was 0.176. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 1,780.7050 and 84.6% and 66.2%, respectively. The related factors to classify COVID-19 patients into severe and critical groups included the number of comorbidities, PLT, LCR, and SOFA score. Among these factors, SOFA score showed the greatest effect, and LCR was the only protective factor. The area under the ROC curve of LCR to classify COVID-19 patients into severe and critical groups was 0.106. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 571.2200 and 81.3% and 90.0%, respectively. In summary, LCR can differentiate disease severity of COVID-19 patients and serve as a simple and objective assistant screening tool for hospital and ICU admission.

Comparison of demographic features and laboratory parameters between COVID-19 deceased patients and surviving severe and critically ill cases.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been far more devastating than expected, showing no signs of slowing down at present. Heilongjiang Province is the most northeastern province of China, and has cold weather for nearly half a year and an annual temperature difference of more than 60ºC, which increases the underlying morbidity associated with pulmonary diseases, and thus leads to lung dysfunction. The demographic features and laboratory parameters of COVID-19 deceased patients in Heilongjiang Province, China with such climatic characteristics are still not clearly illustrated. AIM: To illustrate the demographic features and laboratory parameters of COVID-19 deceased patients in Heilongjiang Province by comparing with those of surviving severe and critically ill cases. METHODS: COVID-19 deceased patients from different hospitals in Heilongjiang Province were included in this retrospective study and compared their characteristics with those of surviving severe and critically ill cases in the COVID-19 treatment center of the First Affiliated Hospital of Harbin Medical University. The surviving patients were divided into severe group and critically ill group according to the Diagnosis and Treatment of New Coronavirus Pneumonia (the seventh edition). Demographic data were collected and recorded upon admission. Laboratory parameters were obtained from the medical records, and then compared among the groups. RESULTS: Twelve COVID-19 deceased patients, 27 severe cases and 26 critically ill cases were enrolled in this retrospective study. No differences in age, gender, and number of comorbidities between groups were found. Neutrophil percentage (NEUT%), platelet (PLT), C-reactive protein (CRP), creatine kinase isoenzyme (CK-MB), serum troponin I (TNI) and brain natriuretic peptides (BNP) showed significant differences among the groups (P = 0.020, P = 0.001, P < 0.001, P = 0.001, P < 0.001, P < 0.001, respectively). The increase of CRP, D-dimer and NEUT% levels, as well as the decrease of lymphocyte count (LYMPH) and PLT counts, showed significant correlation with death of COVID-19 patients (P = 0.023, P = 0.008, P = 0.045, P = 0.020, P = 0.015, respectively). CONCLUSION: Compared with surviving severe and critically ill cases, no special demographic features of COVID-19 deceased patients were observed, while some laboratory parameters including NEUT%, PLT, CRP, CK-MB, TNI and BNP showed significant differences. COVID-19 deceased patients had higher CRP, D-dimer and NEUT% levels and lower LYMPH and PLT counts.

Bacteriocyte development is sexually differentiated in Bemesia tabaci.

Some symbiotic microbes are restricted to specialized host cells called bacteriocytes. However, the molecular and cellular mechanisms underlying the development of bacteriocytes are largely obscure. We find that maternally inherited bacteriocytes proliferate in adult females but degenerate in adult males of the whitefly Bemisia tabaci. Single-cell transcriptomics and immunohistochemistry reveal that cell division only occurs in the bacteriocytes of adult females, whereas autophagy and apoptosis are induced in the bacteriocytes of adult males. A transcription factor, Adf-1, enriched in bacteriocytes, is highly expressed in female bacteriocytes relative to male bacteriocytes. Silencing Adf-1 reduces the bacteriocyte number and Portiera titer and activates autophagy and apoptosis in females. The differential dynamics of both cell division and death in bacteriocytes and distinct expression of Adf-1 in bacteriocytes between whitefly sexes underlie the sexual differentiation of bacteriocyte development. Our study reveals that insect sex affects the development of bacteriocytes by cellular and molecular remodeling.

Laparotomy-Induced Peripheral Inflammation Activates NR2B Receptors on the Brain Mast Cells and Results in Neuroinflammation in a Vagus Nerve-Dependent Manner.

Background: The pathophysiological mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear over the years. Neuroinflammation caused by surgery has been recognized as an important element in the development of POCD. Many studies also suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. Previously, we have demonstrated that brain mast cells (BMCs), as the "first responders", play a vital role in neuroinflammation and POCD. However, how the vagus nerve communicates with BMCs in POCD has not yet been clarified. Methods: In the current study, we highlighted the role of the vagus nerve as a conduction highway in surgery-induced neuroinflammation for the first time. In our model, we tested if mice underwent unilateral cervical vagotomy (VGX) had less neuroinflammation compared to the shams after laparotomy (LP) at an early stage. To further investigate the roles of mast cells and glutamate in the process, we employed KitW-sh mice and primary bone marrow-derived MCs to verify the glutamate-NR2B axis on MCs once again. Results: Our results demonstrated that there were higher levels of glutamate and BMCs activation as early as 4 h after LP. Meanwhile, vagotomy could partially block the increases and reduce neuroinflammation caused by peripheral inflammation during the acute phase. Excitingly, inhibition of NR2B receptor and knockout of mast cells can attenuateneuroinflammation induced by glutamate. Conclusion: Taken together, our findings indicate that the vagus is a high-speed pathway in the transmission of peripheral inflammation to the CNS. Activation of BMCs triggered a neuroinflammatory cascade. Inhibition of NR2B receptor on BMCs can reduce glutamate-induced BMCs activation, neuroinflammation, and memory impairment, suggesting a novel treatment strategy for POCD.

Effects of acute kidney injury on acute pancreatitis patients' survival rate in intensive care unit: A retrospective study.

BACKGROUND: Acute kidney injury (AKI) is one of the most common acute pancreatitis (AP)-associated complications that has a significant effect on AP, but the factors affecting the AP patients' survival rate remains unclear. AIM: To assess the influences of AKI on the survival rate in AP patients. METHODS: A total of 139 AP patients were included in this retrospective study. Patients were divided into AKI group (n = 72) and non-AKI group (n = 67) according to the occurrence of AKI. Data were collected from medical records of hospitalized patients. Then, these data were compared between the two groups and further analysis was performed. RESULTS: AKI is more likely to occur in male AP patients (P = 0.009). AP patients in AKI group exhibited a significantly higher acute physiologic assessment and chronic health evaluation II score, higher Sequential Organ Failure Assessment score, lower Glasgow Coma Scale score, and higher demand for mechanical ventilation, infusion of vasopressors, and renal replacement therapy than AP patients in non-AKI group (P < 0.01, P < 0.01, P = 0.01, P = 0.001, P < 0.01, P < 0.01, respectively). Significant differences were noted in dose of norepinephrine and adrenaline, duration of mechanical ventilation, maximum and mean values of intra-peritoneal pressure (IPP), maximum and mean values of procalcitonin, maximum and mean serum levels of creatinine, minimum platelet count, and length of hospitalization. Among AP patients with AKI, the survival rate of surgical intensive care unit and in-hospital were only 23% and 21% of the corresponding rates in AP patients without AKI, respectively. The factors that influenced the AP patients' survival rate included body mass index (BMI), mean values of IPP, minimum platelet count, and hospital day, of which mean values of IPP showed the greatest impact. CONCLUSION: AP patients with AKI had a lower survival rate and worse relevant clinical outcomes than AP patients without AKI, which necessitates further attention to AP patients with AKI in surgical intensive care unit.

Ensembles from silver clusters and cucurbit[6]uril-containing linkers.

In this work, organic supramolecular linkers involving cucubit[6]urils CB[6] and N,N'-hexamethylene-bis(pyrazinyl hexafluorophosphate) (BPHF@CB[6]) were utilized to assemble dodenuclear silver chalcogenolate clusters into three one-dimensional (1D) materials under different synthesis conditions. These three crystal structures of CB[6]-based sliver cluster-organic rotaxane frameworks were well resolved, and their emission properties were investigated systematically. This construction strategy involving organic supramolecular linkers gives a new methodology for cluster-assembled materials with intriguing structural and functional properties.

[Using the Matter-Element Extension Model to Assess Heavy Metal Pollution in Topsoil in Parks in the Main District Park of Lanzhou City].

The UNMIX model was used to analyze the source of heavy metals found to be present in the topsoil of parks in the main district of Lanzhou City. The Hakanson toxicity response coefficient was used concurrently to modify the traditional weights in the model, and the matter-element extension model was used to evaluate heavy metal pollution. The results of the evaluation were compared with the comprehensive pollution index (PN) and potential ecological risk index (RI). The results were as follows. ①The average heavy metal content in the topsoil at each sampling point was higher than that of the background value of soil in Lanzhou, with the proportion of Ni, Cu, and Co being 100% while the proportion of Cr, V, Pb, and As contents were 58.82%, 14.71%, 20.59%, and 2.94%, respectively. ② The results of source analysis showed that there were three major sources of heavy metal pollution in the topsoil of the parks in the study area. Source 1 is construction pollution, which contributes 56% of the Co present. Source 2 is traffic pollution, which contributes 44% and 52% of Cu and Pb, respectively. Source 3 is natural, and contributes 62%, 60%, 56%, and 56% of V, Cr, Ni, and As, respectively. Thus, this research showed that natural sources are predominant. ③ The weight correction effect for each heavy metal was significant; there was an approximately 44% reduction in both Cr and V, while the corrected weights of Ni, Cu, Pb, As, and Co increased in the order Co < Pb < Cu < Ni < As compared with the conventional weights. The most obvious change in weight was that of As, which increased by approximately 188%. ④ The results of the evaluation using the matter-element model showed that the state of 46% of the topsoil in the parks in the study area was grade Ⅴ (severely polluted), while 41% was grade Ⅳ (moderately polluted) and 3% was grade Ⅲ (lightly polluted); Co was the main pollutant. The results of the model evaluation were roughly the same as of from the PN and RI, indicating that the matter-element extension model can be used to evaluate heavy metal pollution in soil and the evaluation results are accurate and objective.

Ultrasound Combined With Microbubbles Loading BDNF Retrovirus to Open BloodBrain Barrier for Treatment of Alzheimer's Disease.

Background: Brain-derived nerve growth factor (BDNF) is a promising effective target for the treatment of Alzheimer's disease (AD). BDNF, which has a high molecular weight, has difficulty in crossing the blood-brain barrier (BBB). The study aimed to prepare microbubbles loading brain-derived nerve growth factor (BDNF) retrovirus (MpLXSN-BDNF), to verify the characteristics of the microbubbles, and to study the therapeutic effect of the microbubbles combined with ultrasound on the opening of the blood-brain barrier in an AD rat model. Methods: 32 adult male SD rats were randomly divided into four groups: control group, ultrasound + pLXSN-EGFP microbubble group (U + MpLXSN-BDNF), ultrasound + pLXSN-BDNF microbubble group, and ultrasound + microbubble + pLXSN-BDNF virus group (U + MpLXSN-BDNF), with eight rats in each group. At the same time, the left hippocampus of rats was irradiated with low-frequency focused ultrasound guided by MRI to open the blood-brain barrier (BBB). The effects of BDNF overexpression on AD rats were evaluated behaviorally before and 1 month after the treatment. The number of acetylcholinesterase (ChAT)-positive cells and the content of acetylcholine (ACh) in brain tissues were determined by immunohistochemistry and high-performance liquid chromatography (HPLC), respectively. IF staining of synaptic spines and Western blot of synaptophysin presented herein detected synaptic density recovery. Results: Signal intensity enhancement at the BBB disruption sites could be observed on the MR images. The behavioral evaluation showed that the times of crossing the original platform in the U + MpLXSN-BDNF group increased significantly after treatment. Immunohistochemistry and HPLC revealed that the number of ChAT-positive neurons and the contents of ACh in the brain were significantly decreased in the treated groups compared with the controls. IF staining of synaptic spines and Western blot data of synaptophysin showed that the U + MpLXSN-BDNF group can recover the synaptic loss better by BDNF supplementation than the other treatment groups. Conclusion: Ultrasound combined with viral microbubbles carrying BDNF can increase the transfection efficiency of brain neurons, promote the high expression of exogenous gene BDNF, and play a therapeutic role in the AD model rats.

Effects of primary microglia and astrocytes on neural stem cells in in vitro and in vivo models of ischemic stroke.

Transplantation of neural stem cells (NSCs) can protect neurons in animal stroke models; however, their low rates of survival and neuronal differentiation limit their clinical application. Glial niches, an important location of neural stem cells, regulate survival, proliferation and differentiation of neural stem cells. However, the effects of activated glial cells on neural stem cells remain unclear. In the present study, we explored the effects of activated astrocytes and microglia on neural stem cells in vitro stroke models. We also investigated the effects of combined transplantation of neural stem cells and glial cells after stroke in rats. In a Transwell co-culture system, primary cultured astrocytes, microglia or mixed glial cells were exposed to glutamate or H2O2 and then seeded in the upper inserts, while primary neural stem cells were seeded in the lower uncoated wells and cultured for 7 days. Our results showed that microglia were conducive to neurosphere formation and had no effects on apoptosis within neurospheres, while astrocytes and mixed glial cells were conducive to neurosphere differentiation and reduced apoptosis within neurospheres, regardless of their pretreatment. In contrast, microglia and astrocytes induced neuronal differentiation of neural stem cells in differentiation medium, regardless of their pretreatment, with an exception of astrocytes pretreated with H2O2. Rat models of ischemic stroke were established by occlusion of the middle cerebral artery. Three days later, 5 × 105 neural stem cells with microglia or astrocytes were injected into the right lateral ventricle. Neural stem cell/astrocyte-treated rats displayed better improvement of neurological deficits than neural stem cell only-treated rats at 4 days after cell transplantation. Moreover, neural stem cell/microglia-, and neural stem cell/astrocyte-treated rats showed a significant decrease in ischemic volume compared with neural stem cell-treated rats. These findings indicate that microglia and astrocytes exert different effects on neural stem cells, and that co-transplantation of neural stem cells and astrocytes is more conducive to the recovery of neurological impairment in rats with ischemic stroke. The study was approved by the Animal Ethics Committee of Tongji University School of Medicine, China (approval No. 2010-TJAA08220401) in 2010.

Mechanisms of Renal-Splenic Axis Involvement in Acute Kidney Injury Mediated by the α7nAChR-NF-κB Signaling Pathway.

This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.

[Expression of ANO1 during cardiac fibroblasts differentiation and its electrophysiological characteristics as calcium-activated chloride channel protein].

OBJECTIVE: To investigate the expression and electrophysiological characteristics of calcium-activated chlorine channel anoctamin-1 (ANO1) protein during the differentiation of cardiac fibroblasts (CFs) into myofibroblasts (MFs), and to elucidate the role of ANO1 in myocardial fibrosis. METHODS: The primary CFs from neonatal rats were isolated and the cells differentiated into MFs by subculture. The Ca2+-activated Cl- current (ICl(Ca)) in CFs and MFs were measured by whole-cell patch clamp, and the expressions of ANO1, α-smooth muscle actin(α-SMA)and vimentin in CFs and MFs were detected by immunofluorescence assay and Western blot, respectively. RESULTS: The current density in the early adherent CFs was stronger than that in MFs. ANO1 was expressed preferentially within and around the nuclei, and a small amount of ANO1 was expressed on the cell membrane. Moreover, ANO1 expression was weak in the early adherent CFs and displayed stronger expression in the MFs with proliferation tendency. CONCLUSION: The expression of ANO1 is closely related to the differentiation of MFs and it may be involved in modulation myocardial fibrosis.