[Expression of CREB in children with recurrent wheezing and its effect on ORMDL3 gene expression].

OBJECTIVE: To study the expression level of cAMP response element-binding protein (CREB) in children with recurrent wheezing under three years of age and its effect on the expression of the serum orosomucoid 1-like protein 3 (ORMDL3) gene. METHODS: Thirty-six children with recurrent wheezing under three years of age who visited the hospital from June 2017 to June 2019 were selected as the recurrent wheezing group. Twenty-four healthy children from physical examination were selected as the control group. The CREB expression level in peripheral blood was measured by quantitative real-time PCR. Human bronchial epithelial cells (BEAS-2B) were cultured, and dual-luciferase reporter assay and quantitative real-time PCR were used to investigate the effects of overexpression and siRNA interference of CREB on the promoter activity and mRNA expression of the ORMDL3 gene in the BEAS-2B cells. RESULTS: The expression level of CREB in the recurrent wheezing group was significantly higher than that in the control group (P<0.001). In BEAS-2B cells, overexpression of CREB significantly up-regulated the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05), while siRNA interference of CREB significantly reduced the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05). CONCLUSIONS: The expression of CREB is increased in children with recurrent wheezing, and CREB may be involved in the pathogenesis of recurrent wheezing by regulating expression of the ORMDL3 gene.

A Migratory Ether Formation Route to Medium-Sized Sugar Mimetics.

Polyol-substituted cyclic ethers are fundamental building blocks of biomolecules. The position and stereochemistry of multiple hydroxy substituents of cyclic ethers play a central role in their biological function. Current methods for the synthesis of such structures are limited to "naked" ring products with no or few substituents. Here we describe a general route to medium-sized polyol cyclic ethers using a migratory ether formation strategy. In contrast to the common pathway of direct opening of epoxides, Me3 Al was found to promote an unprecedented ether addition reaction, opening a neighboring epoxide. The resulting oxonium intermediate triggers a 1,3-methyl shift to yield 2-deoxyribital products. When the hemiacetal auxiliary is a monosaccharide, the sugar ring is expanded by four atoms to give the corresponding 9- to 11-membered analogues. This method provides an entry into the untapped chemical space of medium-sized sugar mimetics.

Surgical treatment of scoliosis associated with syringomyelia with no or minor neurologic symptom.

PURPOSE: Syringomyelia with coexisting intraspinal abnormities is thought to increase the risk of neurologic injury during surgical correction of the scoliosis. However, surgical treatment for intraspinal abnormities carries significant morbidity risks including worsening neurological function and wound complications. The authors' aim in this study was to evaluate one-stage posterior correction of scoliosis in this patient population without prophylactic surgical treatment for neural axis malformations before scoliosis correction. METHODS: A total of 29 patients with syringomyelia and coexisting intraspinal abnormities who underwent scoliosis correction were evaluated. The average age was 15.6 years (range 12-23). All patients were examined for neural axis abnormalities using MRI, including syringomyelia with Chiari I malformation in 18 patients, syringomyelia with tethered cord and/or diastematomyelia in 11. None of patients presented with symptoms suggesting significant neurological dysfunction. The surgical efficacies and complications of correction were reviewed. RESULTS: The preoperative Cobb angle of major coronal curve averaged 65° (range 46°-95°), and it measured 28° (range 22°-43°) at the last follow-up, for a 63 % correction. Maximal kyphosis averaged 52° (range 41°-69°) preoperatively, and improved to 29° (range 22°-43°) at ultimate follow-up, for a 46 % correction. The average follow-up was 6 years (4-8 years). None of the patients experienced deterioration in their neurologic status. CONCLUSION: The study results suggested that prophylactic neurosurgery for intraspinal abnormality may be unnecessary in patients with asymptomatic or minor symptomatic syringomyelia and coexisting intraspinal abnormities. One-stage posterior correction of scoliosis in this patient population does not involve significant complications and seems to be an alternative and safe treatment option.

Vertebral column resection for complex congenital kyphoscoliosis and type I split spinal cord malformation.

INTRODUCTION: Congenital progressive kyphoscoliosis associated with split spinal cord malformation (SSCM) is a very rare disease. METHODS AND RESULTS: Here, we present the case of a 23-year-old woman who was found kyphoscoliosis when she was 10 years old and developed rapidly. Thereafter, no management was proposed before her consultation at our center. On examination, numbness was found in the right low limbs, kyphoscoliosis was detected in thoracolumbar, the trunk deviated to the right on standing view and curvature of the thoracolumbar spine was left-sided, the left rib hump was severe and there was little muscle tissue felt under the right side paravertebral area, the pelvis was oblique with the right side higher than the left side, the right arcus costarum was 5 cm below the right iliac crest. One-stage corrective surgery was determined, at first, halo-wheelchair traction gradually with increased traction weights out of hospital for a month; then, after a reasonable correction achieved without any neurological deficits. The one-stage operation was taken through single posterior segmental pedicle screw instrumented fusion with VCR between T12 and L1. Post-operative recovery was uneventful and there were no complications, she was discharged 10 days post operation. At 2 years follow-up, the patient's outcome is excellent with balance and correction of the deformity. CONCLUSION: Based on the Grand Round case and relevant literature, we discuss the different options for the treatment of congenital kyphoscoliosis associated with type I SSCM. In the patient whose kyphoscoliosis is severe and rigid, we recommend an initial release followed by halo-wheelchair traction gradually to correct the deformity, once optimal correction acquires during the traction, the posterior instrumented fusion with VCR upper the bony spur could be done safely without the resection of bony spur.

First isolation, identification, and pathogenicity evaluation of an EV-G6 strain in China.

Enterovirus G (EV-G) belongs to the Picornaviridae family and infects porcine populations worldwide. A total of 20 EV-G genotypes (EV-G1 to EV-G20) have been identified. In this study, we isolated and characterized an EV-G strain, named EV-G/YN29/2022, from the feces of diarrheic pigs. This was the first EV-G6 strain isolated in China. Comparison of the whole genome nucleotide and corresponding amino acid sequences showed that the isolate was more closely related to those of the EV-G6 genotype than other genotypes, with the complete genome sequence similarity ranging from 83.7% (Iba46442) to 84.4% (PEV-B-KOR), and corresponding amino acid homology ranged from 96% (Iba46442) to 96.8% (PEV-B-KOR). Similarly, the VP1 gene and corresponding amino acid sequences of EV-G/YN29/2022 were highly similar to those of the EV-G6 genotype (>82.9% and >94.3%, respectively). Thus, the isolated strain was classified as EV-G6 genotype. This was the first EV-G6 strain isolated in China. Pathogenicity analyses revealed that EV-G/YN29/2022 infection caused mild diarrhea, typical skin lesions, and weight reduction. The strain was mainly distributed to the intestinal tissue but was also found in the brain, mesenteric lymph nodes, spleen, and liver. Our results can be used as a reference to further elucidate the epidemiology, evolution, and pathogenicity of EV-G.

Cytokine release syndrome triggered by programmed death 1 blockade (sintilimab) therapy in a psoriasis patient: A case report.

BACKGROUND: In recent years, immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy across diverse malignancies. Notably, in patients with advanced gastric cancer, the use of programmed death 1 (PD-1) blockade has significantly prolonged overall survival, marking a pivotal advancement comparable to the impact of Herceptin over the past two decades. While the therapeutic benefits of ICIs are evident, the increasing use of immunotherapy has led to an increase in immune-related adverse events. CASE SUMMARY: This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis. Following sintilimab therapy, the patient developed severe rashes accompanied by cytokine release syndrome (CRS). Fortunately, effective management was achieved through the administration of glucocorticoid, tocilizumab, and acitretin, which resulted in favorable outcomes. CONCLUSION: Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

First Identification and Pathogenicity Evaluation of an EV-G17 Strain Carrying a Torovirus Papain-like Cysteine Protease (PLCP) Gene in China.

Enterovirus G (EV-G) is prevalent in pig populations worldwide, and a total of 20 genotypes (G1 to G20) have been confirmed. Recently, recombinant EV-Gs carrying the papain-like cysteine protease (PLCP) gene of porcine torovirus have been isolated or detected, while their pathogenicity is poorly understood. In this study, an EV-G17-PLCP strain, 'EV-G/YN23/2022', was isolated from the feces of pigs with diarrhea, and the virus replicated robustly in numerous cell lines. The isolate showed the highest complete genome nucleotide (87.5%) and polyprotein amino acid (96.6%) identity in relation to the G17 strain 'IShi-Ya4' (LC549655), and a possible recombination event was detected at the 708 and 3383 positions in the EV-G/YN23/2022 genome. EV-G/YN23/2022 was nonlethal to piglets, but mild diarrhea, transient fever, typical skin lesions, and weight gain deceleration were observed. The virus replicated efficiently in multiple organs, and the pathological lesions were mainly located in the small intestine. All the challenged piglets showed seroconversion for EV-G/YN23/2022 at 6 to 9 days post-inoculation (dpi), and the neutralization antibody peaked at 15 dpi. The mRNA expression levels of IL-6, IL-18, IFN-α, IFN-ß, and ISG-15 in the peripheral blood mononuclear cells (PBMCs) were significantly up-regulated during viral infection. This is the first documentation of the isolation and pathogenicity evaluation of the EV-G17-PLCP strain in China. The results may advance our understanding of the evolution characteristics and pathogenesis of EV-G-PLCP.

Metal Ion Cutting-Assisted Synthesis of Defect-Rich MoS2 Nanosheets for High-Rate and Ultrastable Li2S Catalytic Deposition.

Active metal ions often show a strong cutting effect on the chemical bonds during high-temperature thermal processes. Herein, a one-pot metal ion cutting-assisted method was adopted to design defect-rich MoS2-x nanosheet (NS)/ZnS nanoparticle (NP) heterojunction composites on carbon nanofiber skeletons (CNF@MoS2-x/ZnS) via a simple Ar-ambience annealing. Results show that Zn2+ ions capture S2- ions from MoS2 and form into ZnS NPs, and the MoS2 NSs lose S2- ions and become MoS2-x ones. As sulfur hosts for lithium-sulfur batteries (LSBs), the CNF@MoS2-x/ZnS-S cathodes deliver a high reversible capacity of 1233 mA h g-1 at 0.1 C and keep 944 mA h g-1 at 3 C. Moreover, the cathodes also show an extremely low decay rate of 0.012% for 900 cycles at 2 C. Series of analysis indicate that the MoS2-x NSs significantly improve the chemisorption and catalyze the kinetic process of redox reactions of lithium polysulfides, and the heterojunctions between MoS2-x NSs and ZnS NPs further accelerate the transport of electrons and the diffusion of Li+ ions. Besides, the CNF@MoS2-x/ZnS-S LSBs also show an ultralow self-discharge rate of 1.1% in voltage. This research would give some new insights for the design of defect-rich electrode materials for high-performance energy storage devices.

Construction of all-carbon micro/nanoscale interconnected sulfur host for high-rate and ultra-stable lithium-sulfur batteries: Role of oxygen-containing functional groups.

Carbon nanotubes (CNTs) are often used to settle down the sluggish reaction kinetics in lithium-sulfur batteries (LSBs). However, the self-aggregation of CNTs often makes them fail to effectively inhibit the shuttling effect of soluble lithium polysulfide (LiPS) intermediates. Herein, a type of ultra-stable carbon micro/nano-scale interconnected "carbon cages" has been designed by incorporating polar acid-treated carbon fibers (ACF) into three-dimensional (3D) CNT frameworks during vacuum filtration processes. Results show that the ACF-CNT composite frameworks possess a reinforced-concrete-like structure, in which the ACFs can well work as the main mechanical supporting frames for the composite electrodes, and the oxygen-containing functional groups (OFGs) formed on them as cross linker between ACFs and CNTs. Benefitted from this design, the ACF-CNT/S cathodes deliver an excellent rate capability (retain 72.6% at 4C). More impressively, the ACF-CNT/S cathodes also show an ultrahigh cycling stability (capacity decay rate of 0.001% per cycle over 350 cycles at 2C). And further optimization suggests that the suitable treatment on CFs could balance the chemical adsorption (OFGs) and physical confinement (carbon cages), leading to fast and durable electrochemical reaction dynamics. In addition, the assembled soft-pack LSBs further show a high dynamic bending stability.

Activation of hypoxia-inducible factor-1 ameliorates postischemic renal injury via inducible nitric oxide synthase.

Hypoxia-inducible factor-1 (HIF-1) could ameliorate renal ischemia reperfusion injury (IRI), but the underlying mechanism remains elusive. In the current study, we aim to investigate the possible role of prolyl hydroxylases inhibitor dimethyloxalylglycine (DMOG) in inducing delayed preconditioning-like effects against IRI. Mice were divided into four groups (n = 6): sham group; IRI group; DMOG group: pretreated with DMOG 24 h before IRI; and GW274150 + DMOG group: pretreated with DMOG followed by iNOS inhibitor GW274150 treatment 24 h before IRI. The results showed that the protein level of HIF-1a and the expression of its targets inducible nitric oxide synthase (iNOS), erythropoietin, and heme oxygenase-1 were obviously increased after administration of DMOG. Histological analysis of renal function showed improvement in tubulointerstitial injury due to ischemia by delayed preconditioning with DMOG. GW274150 antagonized the delayed renal protection afforded by DMOG as reflected by deteriorated renal dysfunction, aggravated histological injury, increased renal cell apoptosis, and increased vimentin expression in the kidney. In conclusion, our data demonstrate that DMOG pretreatment induces delayed renal protection against IRI in mice and the beneficial effects are mitigated by pharmacological inhibition of iNOS, suggesting that the protective effects derived from HIF-1 activation via DMOG in the kidney are partially mediated by iNOS.

IL-33 as a Novel Serum Prognostic Marker of Intracerebral Hemorrhage.

OBJECTIVE: Interleukin 33 (IL-33) is a key cytokine involved in inflammation and oxidative stress. The significance of serum IL-33 levels on the prognosis of patients with intracerebral hemorrhage (ICH) has not been well studied. The purpose of this study is to determine whether there is a relationship between the serum IL-33 level and the prognosis of patients with ICH upon admission. METHODS: A total of 402 patients with confirmed ICH were included in this study. Their demographic data, medical history, laboratory data, imaging data, and clinical scores on admission were collected. At the same time, enzyme-linked immunoassay (ELISA) was used to detect the serum IL-33 levels of patients. The prognosis of patients was evaluated by mRS scale after 3 months, and mRS > 2 was defined as poor prognosis. RESULTS: Among 402 patients with ICH, the number of patients with good prognosis and poor prognosis after 3 months was 148 and 254, respectively. Compared with the ICH group with poor prognosis, the ICH group with good prognosis had lower baseline NHISS scores (p = 0.039) and hematoma volume (p = 0.025) and higher GCS scores (p < 0.001) and serum IL-33 levels (p < 0.001). The results of linear correlation analysis showed that serum IL-33 levels were significantly negatively correlated with baseline NHISS scores (r = -0.224, p = 0.033) and hematoma volume (r = -0.253, p = 0.046) but were significantly positively correlated with baseline GCS scores (r = 0.296, p = 0.020). The receiver operating characteristic curve (ROC) analysis showed that the sensitivity and specificity of serum IL-33 level in evaluating the prognosis of ICH were 72.1% and 74.3%, respectively. A cut-off value of serum IL-33 level < 109.3 pg/mL may indicate a poor prognosis for ICH. CONCLUSIONS: Serum IL-33 level on admission may be a prognostic indicator of ICH, and its underlying mechanism needs further study.

Individualized treatment for gastric cancer with rib metastasis: A case report.

BACKGROUND: Gastric cancer (GC) with bone metastasis is rare, and rib metastasis is even less common. The clinical prognosis of GC with bone metastasis is poor given the lack of an effective treatment. CASE SUMMARY: A 70 year old man was referred to Shaoxing People's Hospital with left chest pain and slight dyspnea. Chest computed tomography (CT) revealed a metastatic lesion in the left 3rd rib. Esophagogastroduodenoscopy revealed several ulcers in the angle and antrum of the stomach, and tumor biomarkers including CEA and CA-199 were clearly increased. In addition, lymph node metastasis in the lesser curvature of the stomach was identified by positron emission tomography/CT scanning. Further pathological examination confirmed metastatic adenocarcinoma in the rib and medium-low differentiated adenocarcinoma in the gastric space. The patient had GC with rib metastasis, and was clinically staged as T3NxM1 (IVB). Based on multidisciplinary team opinions, the patient received five courses of chemotherapy (CAPOX plus aptinib), and then underwent rib resection and laparoscopic radical distal gastrectomy. The patient started four courses of chemotherapy after surgery, and then capecitabine and aptinib were administered orally for 3 mo. Follow-up was performed on an outpatient basis using abdominal/chest CT and tumor biomarkers. The patient exhibited an overall survival greater than 2 years, and the disease-free survival was approximately 18 mo. His adverse events were tolerable. CONCLUSION: The incidence of GC with rib metastases is extremely low, and patients can obtain more benefits from individualized treatment formulated by multidisciplinary team. Chemotherapy plus surgery might represent an alternative option for GC with rib metastasis.

Can Posterior Ligament Structure Be Functionally Healed After Anterior Reduction and Fusion Surgery in Patients with Traumatic Subaxial Cervical Fracture-Dislocations?

BACKGROUND: Selection of approach for subaxial cervical fracture-dislocation (SCFD) is controversial. The questions of whether a posterior ligamentous structure (PLS) can be functionally healed in patients with SCFD and how long this healing process takes are critical in these patients. METHODS: This study retrospectively enrolled 394 patients with SCFD who underwent anterior decompression, reduction, and fusion between January 2002 and December 2017. The definition of functional healing of PLS was based on evaluations of clinical function and radiographic stability of PLS. RESULTS: Follow-up was available for 354 patients (89.8%). The PLS of 339 cases was functionally healed at the first follow-up interval without any posterior surgical intervention. No hardware failure or progressive cervical kyphosis was observed at further follow-up. At 12 months postoperatively, interbody fusion was satisfactory. However, the other 15 patients experienced nonhealing PLS at 8 weeks postoperatively and developed cervical deformity at further follow-up. Five patients refused revision surgery; the other 10 patients obtained solid fusion after revision surgeries. CONCLUSIONS: Among 354 patients with SCFD and treated by single anterior reduction and fixation, simple PLS injury without any bony instability at the posterior column of the cervical spine can be functionally healed in 95.8% of patients by external fixation for 8 weeks. Whether this finding is applicable to various types of SCFD should be verified in further prospective studies with larger samples.

Brand new 1D branched CuO nanowire arrays for efficient photoelectrochemical water reduction.

Developing high surface area nanostructured electrodes with fast charge separation is one of the main challenges for exploring cupric oxide (CuO)-based photocathodes in solar-driven hydrogen production applications. Herein, brand new 1D branched CuO nanowire arrays have been achieved on fluorine-doped tin oxide-coated glass (FTO) through a two-step wet chemical redox reaction. X-ray diffraction patterns, Raman spectra and X-ray photoelectron spectroscopy confirm the pure phase characteristic of the resulting branched CuO. In addition to the enlarged surface area of this advanced functional structure as compared with that of the 1D wire trunk, the charge injection and separation have been improved by rationally controlling the density of defects and size of branches. As a result, the optimized branched CuO exhibits photocurrent as high as 3.6 mA·cm-2 under AM 1.5G (100 mW·cm-2) illumination and 3.0 mA·cm-2 under visible light (λ > 420 nm) at 0.2 V vs. RHE in 0.5 M Na2SO4, which are 2.8- and 3.0-fold greater than those of 1D wire samples, respectively. In addition, the solution-processed approach established herein seems quite favourable for large-scale and low-cost manufacturing.

Foraminoplasty at the Tip or Base of the Superior Articular Process for Lateral Recess Stenosis in Percutaneous Endoscopic Lumbar Discectomy: A Multicenter, Retrospective, Controlled Study with 2-Year Follow-Up.

OBJECTIVE: To compare the clinical efficacy and complications which obtained foraminoplasty at the tip or base of the superior articular process (SAP) for the patients with lateral recess stenosis treated by percutaneous endoscopic lumbar discectomy (PELD). METHODS: Between January 2015 and January 2016, 156 patients of lumbar disc herniation accompanying with lateral recess stenosis were treated with PELD in five tertiary hospitals and fulfilled the 2-year follow-up. Among them, 78 patients obtained a foraminoplasty at the tip of SAP (group A), and foraminoplasty at the base of SAP was performed in the other 78 cases (group B). Clinical efficacy was evaluated using the visual analog scale (VAS) score for back and leg pain, Oswestry Disability Index (ODI), and 36-item Short-Form Health Survey (SF-36) score. The intervals of follow-up were scheduled at 1 month, 3 months, 6 months, 1 year, and 2 years after surgery. RESULTS: Mean operative duration is shorter in group B (55 versus 61 min, P = 0.047). Only one case belonged to group A could not tolerate the neural irritation and required conversion to an open procedure. During the surgery, no dura tears, cauda equina syndrome, or infections were observed. 5 patients experienced transient dysesthesia located at the exiting nerve in group A, while no cases complained dysesthesia in group B. 2 cases who suffered temporary motor weakness all belonged to group A. A total of 5 cases obtained a revision surgery after recurrence in the follow-up, in which 3 patients belonged to group A. Compared to the preoperative data, significant improvements in VAS scores of low back pain and sciatica, ODI, and SF-36 PCS and MC were observed in the follow-up, respectively (P < 0.05, respectively). However, no statistical difference was observed at all time-points after surgery between these two groups (P > 0.05, respectively). CONCLUSIONS: For the patients of LDH accompanying with lateral recess stenosis, compared with the routine foraminoplasty at the tip of SAP, our modified foraminoplastic technique does not only change place of foraminoplasty to the base of SAP but also simplified puncture process in transforaminal PELD. Although there was no significant difference in symptom relief, the modified foraminoplasty showed the advantages in decreasing the incidence of postoperative neural dysfunction and reducing operation time.

[Treatment of stroke in rats with bone marrow mesenchymal stem cells].

OBJECTIVE: To investigate the effects of treatment of stroke in rats with bone marrow mesenchymal stem cells (BMSCs) and mechanism thereof. METHODS: Bone marrow of a healthy volunteer was collected and the BMSCs were separated with density gradient centrifugation. The hBMSC were cultivated and harvested until the third passage. A number of adult male Sprague-Dawley rats received corresponding behavioral training before surgery and underwent transient middle cerebral arterial occlusion (MCAO) for 2 hours. Sixty of them showing the scores of 6 approximately 12 according to the modified neurological severity score system were randomly divided into 2 groups: treatment group (n = 48, injected into the cortex around the ischemic areas with hBMSCs 3x10(5)/15 microl) and control group (n = 12, injected with D-Hanks solution 15 microl 24 hours after the establishment of MCAO models. Morris water maze test, Rotarod test and adhesive-removal test were performed since the 4th day to the 32 day after transplantation once every 3 days. 1, 2, 3, and 4 weeks after the transplantation 12 rats from each group were killed randomly to take out their brains. Immunofluorescence was used to identify the migration, survival and differentiation of the hBMSC. RESULTS: A large number of hBMSC could be seen within 2 weeks after transplantation. The number of hBMSC decreased since the 21st day after transplantation and few cells could be found at the end of 1 month after. No definite evidence supported the differentiation of neural cells derived from the hBMSCs during the whole process. Morris water maze test showed that the mean escape time 1 week after transplantation of the treatment group was (69 +/- 10) s, significantly shorter than that of the control group [(120 +/- 0) s, P < 0.05] The significant difference persisted until the 4(th) week (P > 0.05). Rotarod test with the speed of 10 r/min showed that the mean latency period 10 days after transplantation of the treatment group was (167 +/- 18) s, significantly longer than that of the control group [(37 +/- 19) s, P < 0.05]. The significant difference persisted until the experimental terminal. The adhesive-removal test showed that the mean latency period 13 days after transplantation of the treatment group was (33 +/- 8) s, significant shorter than that of the control group [(84 +/- 13) s, P < 0.05]. The significant difference persisted until the experimental terminal. CONCLUSION: Injection of hBMSCs into brain cortex improves neurological functional recovery after stroke. The transplanted cells can migrate and survive for a certain period, but no hBMSC express proteins phenotype of neural cells.

Expression of Cyt-c-Mediated Mitochondrial Apoptosis-Related Proteins in Rat Renal Proximal Tubules during Development.

BACKGROUND: Apoptosis regulates embryogenesis, organ metamorphosis and tissue homeostasis. Mitochondrial signaling is an apoptotic pathway, in which Cyt-c and Apaf-1 are transformed into an apoptosome, which activates procaspase-9 and triggers apoptosis. This study evaluated Cyt-c, Apaf-1 and caspase-9 expression during renal development. METHODS: Kidneys from embryonic (E) 16-, 18-, and 20-day-old fetuses and postnatal (P) 1-, 3-, 5-, 7-, 14-, and 21-day-old pups were obtained. Immunohistochemical analysis, dual-labeled immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique assay and Western blot were performed in addition to histological analysis. RESULTS: Immunohistochemistry showed that Cyt-c was strongly expressed in proximal and distal tubules (DTs) at all time points. Caspase-9 and Apaf-1 were strongly expressed in proximal tubules (PTs) but only weakly expressed in DTs. Dual-labeled immunofluorescence showed that most tubules expressed both Cyt-c and Apaf-1, except for some tubules that only expressed Cyt-c. The TUNEL assay showed a greater percentage of apoptotic cells in PTs compared to DTs. Apaf-1 and cleaved caspase-9 protein expression gradually increased during the embryonic period and peaked during the early postnatal period but apparently declined from P7. Cyt-c protein expression was weak during the embryonic period but obviously increased after P1. CONCLUSION: This study showed that PTs are more sensitive to apoptosis than DTs during rat renal development, even though both tubule segments contain a large number of mitochondria. Furthermore, Cyt-c-mediated mitochondrial apoptosis-related proteins play an important role in PTs during the early postnatal kidney development.

[Relationship between leaf litter decomposition and colonization of benthic macroinvertebrates during early frost period in a headwater stream in the Changbai Mountains, Northeast China]. / é•¿ç™½å±±åœ°åŒºæºªæµå†»ç»“åˆæœŸå‡‹è½å¶åˆ†è§£ä¸Žåº•æ –åŠ¨ç‰©å®šæ®–çš„å ³ç³».

Annually, about 70% of the streams in the Changbai Mountains are frosted during November to April, with manifest seasonal freeze-thaw characters. By using monoculture and mixing leaf litters of Tilia amurensis, Acer mono and Quecus mongolica, this research attempted to disentangle the relationship between leaf litter decomposition and colonization of macroinvertebrates in the stream during early frost period. A 35-day investigation was carried out in a headwater stream of the Changbai Mountains. Nylon bags with two hole sizes (5 mm and 0.3 mm) were used to examine decomposition of the litters. The results showed that the mass losses were significantly different among the three kinds of leaf litters in monoculture, whose decomposition rates descended as A. mono, T. amurensis, and Q. mongolica, however, there existed no significant difference among the litter mixing. Mass losses in both mesh bags all showed little difference, except T. amurensis and the mixed litters. Litter mixing effects occurred in the coarse mesh bags with A. mono and Q. mongolica, but no mixture effects for others. Community structures of the macroinvertebrates colonizing in the litter bags differed with each other, but shredders' density had no significant difference among the three litters, and the mixing effects on shredders were poor. Our results implied that microbes play the major decomposers of leaf litters, and macroinvertebrates contribute little to the decomposition in the early frost period. Despite shredder's density is lower, they determine the mixing effects of litters. Macroinvertebrates are selective to food and habitats, however, due to the short term colonizing, and the influence of leaf litters on shredders is still unsure. Our results might contribute to understanding the cold season ecological processes and related management issues of headwater stream ecosystem.

Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy.

BACKGROUND: In vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats. METHODS: Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups: ControlTAK242, IgANTAK242, toll-like receptor 4 inhibitor (TAK242) groups (rats were administrated with TLR4 inhibitor, TAK242) and ControlPio, IgANPio, Pio groups (rats were administrated with PPAR-γ agonist, pioglitazone). Urinary albumin-to-creatinine ratio (ACR), serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin-1 beta (IL-1ß) message ribonucleic acid (mRNA) and protein expression in renal tissues. Results were presented as mean ± standard deviation. Differences between groups were analyzed by one-way analysis of variance. RESULTS: Compared to normal rats, experimental rats showed higher ACR (4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P < 0.05), obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-1ß (48.28 ± 13.49 pg/ml vs. 35.56 ± 7.41pg/ml, P < 0.05), and renal expression of IL-1ß and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-1ß, and serum IL-1ß were decreased in rats treated with TAK242, and the expression of TLR4 mRNA and protein was significantly reduced in Pio group compared to IgANPiogroup (1.22 ± 0.28 vs. 1.72 ± 0.45, P < 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P < 0.01). CONCLUSIONS: Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.

Intra-ventricular infusion of rAAV1-EGFP resulted in transduction in multiple regions of adult rat brain: a comparative study with rAAV2 and rAAV5 vectors.

Most gene transfer studies conducted in the central nervous system (CNS) with recombinant adeno-associated virus (rAAV) vectors have been carried out by direct intra-parenchymal injection. However, this delivery method usually results in transduction of cells in only a limited region and is quite invasive, which may hamper its potential clinical application. Injection of viral vectors into the cerebrospinal fluid (CSF) may provide an alternative strategy for widespread gene delivery to the CNS via the subarachnoid space. In this study we compared the transduction abilities of rAAV types 1, 2, and 5 when infused directly into the right lateral cerebral ventricle of adult rats. Multiple structures in the vicinity of the lateral ventricle were transduced by rAAV1, but not by rAAV2 or rAAV5 vectors. Double immunolabeling showed that the transduced cells included not only neurons, but also glia. Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) experiments demonstrated that rAAV1-mediated EGFP mRNA expression was significantly higher than that induced by either rAAV2 or 5. Our data suggest that intra-ventricular infusion of rAAV1 vectors provides a useful method for broad gene delivery to cells in the adult rat CNS.