LncRNA GAS5 restrains ISO-induced cardiac fibrosis by modulating mir-217 regulation of SIRT1.

Considering the effect of SIRT1 on improving myocardial fibrosis and GAS5 inhibiting occurrence and development of myocardial fibrosis at the cellular level, the aim of the present study was to investigate whether LncRNA GAS5 could attenuate cardiac fibrosis through regulating mir-217/SIRT1, and whether the NLRP3 inflammasome activation was involved in this process. Isoprenaline (ISO) was given subcutaneously to the male C57BL/6 mice to induce myocardial fibrosis and the AAV9 vectors were randomly injected into the left ventricle of each mouse to overexpress GAS5. Primary myocardial fibroblasts (MCFs) derived from neonatal C57BL/6 mice and TGF-ß1 were used to induce fibrosis. And the GAS5 overexpressed MCFs were treated with mir-217 mimics and mir-217 inhibitor respectively. Then the assays of expression levels of NLRP3, Caspase-1, IL-1ß and SIRT1 were conducted. The findings indicated that the overexpression of GAS5 reduced the expression levels of collagen, NLRP3, Capase-1, IL-1ß and SIRT1 in ISO treated mice and TGF-ß1 treated MCFs. However, this effect was significantly weakened after mir-217 overexpression, but was further enhanced after knockdown of mir-217. mir-217 down-regulates the expression of SIRT1, leading to increased activation of the NLRP3 inflammasome and subsequent pyroptosis. LncRNA GAS5 alleviates cardiac fibrosis induced via regulating mir-217/SIRT1 pathway.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report.

BACKGROUND: Breast cancer brain metastasis (BCBM) is an advanced breast disease that is difficult to treat and is associated with a high risk of death. Patient prognosis is usually poor, with reduced quality of life. In this context, we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb (inetetamab) combined with a small molecule tyrosine kinase inhibitor (TKI). CASE SUMMARY: The patient was a 58-year-old woman with a 12-year history of type 2 diabetes. She was compliant with regular insulin treatment and had good blood glucose control. The patient was diagnosed with invasive carcinoma of the right breast (T3N1M0 stage IIIa, HER2-positive type) through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019. Immunohistochemistry showed ER (-), PR (-), HER-2 (3+), and Ki-67 (55-60%+). Preoperative neoadjuvant chemotherapy, i.e., the AC-TH regimen (epirubicin, cyclophosphamide, docetaxel-paclitaxel, and trastuzumab), was administered for 8 cycles. She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year. Brain metastasis was found 9 mo after surgery. She underwent brain metastasectomy in August 2020. Immunohistochemistry showed ER (-) and PR. (-), HER-2 (3+), and Ki-67 (10-20%+). In November 2020, the patient experienced headache symptoms. After an examination, tumor recurrence in the original surgical region of the brain was observed, and the patient was treated with inetetamab, pyrotinib, and capecitabine. Whole-brain radiotherapy was recommended. The patient and her family refused radiotherapy for personal reasons. In September 2021, a routine examination revealed that the brain tumor was considerably larger. The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases, followed by regular hospitalization and routine examinations. The patient's condition is generally stable, and she has a relatively high quality of life. This case report demonstrates that in patients with BCBM and resistance to trastuzumab, inetetamab combined with pyrotinib and chemotherapy can prolong survival. CONCLUSION: Inetetamab combined with small molecule TKI drugs, chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Combined proteomics and transcriptomics identifies serpin family C member 1 associated protein as a biomarker of endometriosis.

OBJECTIVE: To explore potential biomarkers indicating endometriosis (EM). MATERIALS AND METHODS: A proteomics method and combined quantitative transcriptomics were adopted to highlight markers in the EM. Venn analysis was used to integrate the ribonucleic acid sequencing (RNA-seq) and protein profiles. Promising candidate markers were tested by enzyme-related immunosorbent assay. RESULTS: A sum of 979 mRNAs and 39 proteins were tested to be significantly differentially expression in the standard cluster compared with the EM cluster. Venn analysis showed a filtered signature of only two down-regulated molecules in the EM group, i.e. fetuin B (FETUB) and serpin family C member 1 (SERPINC1); the latter showed a big variance between the control category and the EM set in the authentication test. CONCLUSION: SERPINC1 may be a useful possible biomarker for the analysis of EM.

[Seasonal Variation Characteristics and Pollution Assessment of Heavy Metals in Water and Sediment of Taipu River].

Taipu River is a river spanning two provinces and one city in a demonstration area in the Yangtze River Delta on an ecologically friendly developmentand an important water source in the upper reaches of the Huangpu River in Shanghai. To understand the multi-media distribution characteristics, pollution status, and ecological risk of heavy metals in the Taipu River, the contents of heavy metals (As, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sb, and Zn) in the sediments of Taipu River were analyzed, and the pollution status and potential ecological risk were evaluated using the Nemerow comprehensive pollution index, geo-accumulation index, and potential ecological risk index methods. In addition, the health risk assessment model was used to assess the health risk of heavy metals in surface water of Taipu River. The results showed that the concentrations of Cd, Cr, Mn, and Ni in the surface water of Taipu River exceeded the class Ⅲ water limit at the upstream point in spring; the concentrations of Sb exceeded the class Ⅲ water limit at all points in winter; the average value of As exceeded the class Ⅲ water limit in overlying water during the wet season; and the average values of As and Cd exceeded the class Ⅲ water limit in pore water during the wet season. The health risk assessment of surface water implied that both adults and children had higher health risk in spring and lower health risk in other seasons. The health risk of children was significantly higher than that of adults, and it mainly came from chemical carcinogenic heavy metal elements As, Cd, and Cr. The average contents of Co, Mn, Sb, and Zn in Taipu River sediments in the four seasons all exceeded the Shanghai soil baseline; the average contents of As, Cr, and Cu in summer, autumn, and winter exceeded the Shanghai soil baseline; and the average contents of Cd, Ni, and Pb in summer and winter exceeded the Shanghai soil baseline. The evaluation results of the Nemerow comprehensive pollution index and geo-accumulation index showed that the pollution degree of the middle reaches of Taipu River was higher than that of the upper and lower reaches, and the Sb pollution was more serious. The potential ecological risk index method revealed that the Taipu River sediment was at a low risk. Cd had a high contribution in both the wet and dry seasons and could be regarded as the main heavy metal of potential ecological risk in the Taipu River sediment.

A selective fluorescent probe for hydrogen sulfide from a series of flavone derivatives and intracellular imaging.

In this work, through the orthogonal design of two fluorophores and two recognition groups, a series of fluorescent probes were developed from the flavone derivatives for hydrogen sulfide (H2S). The probe FlaN-DN stood out from the primarily screening on the selectivity and response intensities. It could respond to H2S with both the chromogenic and fluorescent signals. Among the recent reported probes for the H2S detection, FlaN-DN indicated the most highlighted advantages including the rapid response (within 200 s) and the high response multiplication (over 100 folds). FlaN-DN was sensitive to the pH condition, thus could be applied to distinguish the cancer micro-environment. Moreover, FlaN-DN suggested practical capabilities including a wide linear range (0-400 µM), a relatively high sensitivity (limit of detection 0.13 µM), and high selectivity towards H2S. As a low cytotoxic probe, FlaN-DN achieved the imaging in living HeLa cells. FlaN-DN could detect the endogenous generation H2S and visualize the dose-dependent responses to the exogenous H2S level. This work provided a typical case of natural-sourced derivatives as functional implements, which might inspire the future investigations.

Seasonal heavy metal speciation in sediment and source tracking via Cu isotopic composition in Huangpu River, Shanghai, China.

The present study systematically analyzed and evaluated the variations in chemical speciation, pollution assessment, and source identification of heavy metals in sediments of Huangpu River. The methods employed included heavy metal concentration, chemical speciation and Cu isotopic compositions analysis. Results showed that the chemical speciation of sediment-bound heavy metals, characterized by significant seasonal variation, shifted from non-residual fractions dominating in spring and summer to residual fractions dominating in autumn and winter. Precipitation was identified as an important factor influencing the chemical speciation of sediment-bound heavy metals. Furthermore, ratio of the secondary phase to the primary phase, RSP (=Cnon-residual/Cresidual) values in Huangpu River sediments were higher than 1 in spring and summer, indicating that sediment-bound heavy metals in Huangpu River were mainly composed of non-residual fractions and could potentially be released into the river water. Principal component analysis (PCA) revealed that navigation, traffic, agricultural, and industrial activities could be the potential sources of heavy metal pollution. Notably, the δ65Cu values in Huangpu River sediments were observed to be isotopically lighter (from -0.37 to +0.18 ‰), suggesting that navigation might be the primary pollution source. These results will not only provide guidance in reducing heavy metal concentrations, but also serve as a crucial basis for policy making regarding heavy metal control.

Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer: a single-center, single-arm, prospective Phase II trial (PKUCH-R02).

Background: Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk, locally advanced rectal cancer. However, the benefit of more intensive total neoadjuvant treatment (TNT) is unknown. This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer. Methods: This was a single-center, single-arm, prospective Phase II trial in Peking University Cancer Hospital (Beijing, China). Patients received three cycles of induction oxaliplatin and capecitabine (CapeOX) followed by chemoradiotherapy and two cycles of consolidation CapeOX. The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate, completion of TNT, and pathological downstaging rate. Results: Between August 2017 and August 2018, 68 rectal cancer patients with at least one high risk factor (cT3c/3d/T4a/T4b, cN2, mesorectal fascia involvement, or extramural venous invasion involvement) were enrolled. The overall compliance of receiving the entire treatment was 88.2% (60/68). All 68 patients received induction chemotherapy, 65 received chemoradiotherapy, and 61 received consolidation chemotherapy. The Grade 3-4 adverse event rate was 30.8% (21/68). Nine patients achieved clinical complete response and then watch and wait. Five patients (7.4%) developed distant metastasis during TNT and received palliative chemotherapy. Fifty patients underwent surgical resection. The complete response rate was 27.9%. After a median follow-up of 49.2 months, the overall 3-year disease-free survival rate was 69.7%. Conclusions: For patients with high-risk rectal cancer, this TNT regimen can achieve favorable survival and complete response rates but with high toxicity. However, it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.

KRAS, NRAS, BRAF signatures, and MMR status in colorectal cancer patients in North China.

We assessed the clinicopathological features and prognostic values of KRAS, NRAS, BRAF, and DNA mismatch repair status in colorectal cancer (CRC) to provide real-world data in developing countries. We enrolled 369 CRC patients and analyzed the correlation between RAS/BRAF mutation, mismatch repair status with clinicopathological features, and their prognostic roles. The mutation frequencies of KRAS, NRAS, and BRAF were 41.7%, 1.6%, and 3.8%, respectively. KRAS mutations and deficient mismatch repair (dMMR) status were associated with right-sided tumors, aggressive biological behaviors, and poor differentiation. BRAF (V600E) mutations are associated with well-differentiated and lymphovascular invasion. The dMMR status predominated in young and middle-aged patients and tumor node metastasis stage II patients. dMMR status predicted longer overall survival in all CRC patients. KRAS mutations indicated inferior overall survival in patients with CRC stage IV. Our study showed that KRAS mutations and dMMR status could be applied to CRC patients with different clinicopathological features.

Epigenetic Regulation of Ferroptosis in Central Nervous System Diseases.

Ferroptosis, a newly identified form of cell death, is characterized by iron overload and accumulation of lipid reactive oxygen species. Inactivation of pathways, such as glutathione/glutathione peroxidase 4, NAD(P)H/ferroptosis suppressor protein 1/ubiquinone, dihydroorotate dehydrogenase/ubiquinol, or guanosine triphosphate cyclohydrolase-1/6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin pathways, have been found to induce ferroptosis. The accumulating data suggest that epigenetic regulation can determine cell sensitivity to ferroptosis at both the transcriptional and translational levels. While many of the effectors that regulate ferroptosis have been mapped, epigenetic regulation in ferroptosis is not yet fully understood. Neuronal ferroptosis is a driver in several central nervous system (CNS) diseases, such as stroke, Parkinson's disease, traumatic brain injury, and spinal cord injury, and thus, research on how to inhibit neuronal ferroptosis is required to develop novel therapies for these diseases. In this review, we have summarized epigenetic regulation of ferroptosis in these CNS diseases, focusing in particular on DNA methylation, non-coding RNA regulation, and histone modification. Understanding epigenetic regulation in ferroptosis will hasten the development of promising therapeutic strategies in CNS diseases associated with ferroptosis.

Neural progenitor cells derived from fibroblasts induced by small molecule compounds under hypoxia for treatment of Parkinson's disease in rats.

Neural progenitor cells (NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox (VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR (0.5 mM valproic acid, 3 µM CHIR99021, and 1 µM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition (5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6 (Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs (ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson's disease.

[VCR, a Small Molecule Compound, Induces Reprogramming of Rat Fibroblasts into Neural Progenitor Cells under Hypoxic Condition].

Objective: To explore for a protocol for reprogramming rat embryonic fibroblasts (REFs) under hypoxic conditions (5% O 2) to form chemically induced rat neural progenitor cells (ciRNPCs). Methods: The reprogramming of REFs into ciNPCs was done in two stages. The first stage involved chemical induction to generate intermediate cells. The REFs were cultured in KSR medium containing valproic acid, CHIR99021, and RepSox (VCR) and 10000 U/mL leukemia inhibitory factor (LIF) for 15 days, under a physiological hypoxic condition. The formation of dense cell colonies, i.e., intermediate cells, were observed. The second stage involved the specific induction of ciRNPCs. The induced intermediate cells were digested with trypsin, seeded on a low adhesion plate, and cultured under normoxic condition to form ciRNPCs neurospheres. Then, after CM-DiI cell-labeling, the ciRNPCs were stereotactically transplanted into the substantia nigra (SN) of rats. The survival, migration, and differentiation of ciRNPCs in the host brain were examined with immunofluorescence assays. Results: After induction under hypoxic condition for 5 to 10 days, a clear trend of cell aggregation was observed. Compact cell colonies were observed in REFs treated with VCR for 15 days under a hypoxic condition. Approximately 30 colonies emerged from 1×10 5 cells, and most colonies were positive for AP staining. Moreover, when these cells were cultured further in suspension, free-floating neurospheres formed and stained positive for neural progenitor cell (NPC) markers, including Nestin, Sox2 and Pax6. These ciRNPCs could differentiate into glial cells and neurons, and express neurite marker Tuj1 and astrocyte marker GFAP. Eight weeks after transplantation, the cells could differentiate into GFAP+ and Tuj1+ cells in the rat brain. Conclusion: Our study demonstrates that VCR, a small molecule compound, can directly induce, under a hypoxic condition, the reprogramming of REFs to form ciRNPCs with the potential to be induced for differentiation into glial cells and neurons in vivo and in vitro, laying the foundation for transplanting ciRNPCs to treat neurodegenerative diseases.

Regulatory effect of long-stranded non-coding RNA-CRNDE on neurodegeneration during retinal ischemia-reperfusion.

Ischemia/reperfusion (I/R) injury is a common pathological mechanism involved in many ocular diseases. I/R is characterized by microvascular dysfunction and neurodegeneration. However, the mechanisms of neurodegeneration induced by I/R remain largely unknown. This study showed that the expression of long non-coding RNA-CRNDE was significantly upregulated after retinal ischemia-reperfusion (RIR). LncRNA-CRNDE knockdown alleviated retinal neurodegeneration induced by RIR injury, as shown by decreased reactive gliosis and reduced retinal cells loss. Furthermore, lncRNA-CRNDE knockdown directly regulated Müller cell function and indirectly affected RGC function in vitro. In addition, lncRNA-CRNDE knockdown led to a significant reduction in the release of several cytokines after RIR. This study suggests that lncRNA-CRNDE is a promising therapeutic target for RIR.

PagWOX11/12a positively regulates the PagSAUR36 gene that enhances adventitious root development in poplar.

Adventitious root (AR) development is an extremely complex biological process that is affected by many intrinsic factors and extrinsic stimuli. Some WUSCHEL-related homeobox (WOX) transcription factors have been reported to play important roles in AR development, but their functional relationships with auxin signaling are poorly understood, especially the developmental plasticity of roots in response to adversity stress. Here, we identified that the WOX11/12a-SMALL AUXIN UP RNA36 (SAUR36) module mediates AR development through the auxin pathway in poplar, as well as under salt stress. PagWOX11/12a displayed inducible expression during AR development, and overexpression of PagWOX11/12a significantly promoted AR development and increased salt tolerance in poplar, whereas dominant repression of PagWOX11/12a produced the opposite phenotype. PagWOX11/12a proteins directly bind to the SAUR36 promoter to regulate SAUR36 transcription, and this binding was enhanced during salt stress. Genetic modification of PagWOX11/12a-PagSAUR36 expression revealed that the PagWOX11/12a-PagSAUR36 module is crucial for controlling AR development via the auxin pathway. Overall, our results indicate that a novel WOX11-SAUR-auxin signaling regulatory module is required for AR development in poplar. These findings provide key insights and a better understanding of the involvement of WOX11 in root developmental plasticity in saline environments.

Perianesthesia emergency repair of a cut endotracheal tube's inflatable tube: A case report.

BACKGROUND: During the perianesthesia period, emergency situations threatening the life and safety of patients can occur at any time. When dealing with some emergencies, occasional confusion is inevitable. CASE SUMMARY: This case report describes the rare situation wherein a surgeon inadvertently detached the inflatable tube of an endotracheal tube during a tonsillectomy, and positive pressure ventilation could not be provided. While reintubation may increase the risk of respiratory tract infection and aspiration, patients with a difficult airway might die due to apnea. The best treatment method is to optimize the damaged tracheal tube junction to avoid secondary intubation and ensure patient safety. An intravenous needle and cannula were used to repair the damaged gap in the current case. Following the repair, the anesthesia machine showed no indication of low tidal volume, and there was no deflation of the endotracheal tube cuff. Subsequently, the patient was transferred to the post-anesthesia recovery room, and the tracheal tube was removed with satisfactory results. CONCLUSION: Using an intravenous needle to repair a break in the inflatable tube surrounding an endotracheal tube is safe and reliable.

Vibrationally excited intermolecular potential energy surfaces and the predicted near infrared overtone (vOH = 2 ← 0) spectra of a H2O-Ne complex.

The ab initio intra- and inter-molecular potential energy surfaces (PESs) for the H2O-Ne system that explicitly incorporate the intramolecular overtone state (vOH = 2) of H2O are presented. The electronic structure computations have been carried out at the explicitly correlated coupled cluster theory [CCSD(T)-F12] level with an augmented correlation-consistent triple zeta basis set and an additional bond function. The vibrationally averaged three-dimensional intermolecular potentials for |00+〉, |02+〉, |02-〉 and |11+〉 are obtained analytically by fitting to the multi-dimensional Morse/Long-range potential function form. These fits to 46 980 points have a root-mean-square (RMS) discrepancy of 0.12 cm-1 for interaction energies less than 1000.0 cm-1. With the vibrationally averaged PESs for the H2O-Ne, we employed the combined radial discrete variable representation/angular finite basis representation method and Lanczos algorithm to calculate rovibrational energy levels (J = 0-10, ns ≤ 2). The predicted infrared transitions and intensities of the para- and ortho-H2O-Ne complex are in good agreement with the available experimental data for |02-〉 ← |00+〉, |02+〉 ← |00+〉 transitions. In particular, the RMS discrepancy for |02-〉∑e(000,0) ← |00+〉∑e(101,0), including P and R branch patterns, is only 0.045 cm-1, which is comparable with the experimental values. These results will provide reliable theoretical guidance for the future infrared overtone spectroscopy of clusters.

Effects of paired associative magnetic stimulation between nerve root and cortex on motor function of lower limbs after spinal cord injury: study protocol for a randomized controlled trial.

Classic paired associative stimulation can improve synaptic plasticity, as demonstrated by animal experiments and human clinical trials in spinal cord injury patients. Paired associative magnetic stimulation (dual-target peripheral and central magnetic stimulation) has been shown to promote neurologic recovery after stroke. However, it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury. We hypothesize that the current caused by central and peripheral magnetic stimulation will converge at the synapse, which will promote synapse function and improve the motor function of the relevant muscles. Therefore, this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials, motor and sensory function of the lower limbs, functional health and activities of daily living, and depression in patients with spinal cord injury. We will recruit 110 thoracic spinal trauma patients treated in the Department of Spinal Cord Injury, China Rehabilitation Hospital and randomly assign them to experimental and control groups in a 1:1 ratio. The trial group (n = 55) will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment. The control group (n = 55) will be treated with sham stimulation and conventional rehabilitation treatment. Outcomes will be measured at four time points: baseline and 4, 12, and 24 weeks after the start of intervention (active or sham paired associative magnetic stimulation). The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up. Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function score, motor evoked potentials, sensory evoked potentials, modified Ashworth scale score, Maslach Burnout Inventory score, and Hamilton Depression Scale score over time. Motor evoked potential latency reflects corticospinal tract transmission time, while amplitude reflects recruitment ability; both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency. Adverse events will be recorded. Findings from this trial will help to indicate whether paired associative magnetic stimulation (1) promotes recovery of lower limb sensory and motor function, reduces spasticity, and improves quality of life; (2) promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity; and (3) improves rehabilitation outcome in patients with spinal cord injury. Recruitment for this trial began in April 2021 and is currently ongoing. It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University, China (approval No. YZ2020-018) on May 18, 2020. The study protocol was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2100044794) on March 27, 2021 (protocol version 1.0). This trial will be completed in April 2022.

Protective effects of Radix Isatidis polysaccharide ameliorates obesity via promotion AMPK pathway in high-fat-diet-induced obese rats and 3T3-L1 adipocyte cells.

OBJECTIVES: The purpose of this paper is to ascertain the effect and mechanism of Radix Isatidis polysaccharide (RIP) on obesity. METHODS: High fat diet (HFD)-induced obese rats and the MDI-induced 3T3-L1 adipocyte cells were established to evaluate the ameliorated obesity effect and mechanism from RIP. KEY FINDINGS: Experiments in vivo show that oral administration of RIP has significant preventive effects on HFD-induced obesity and metabolic disorders in rats. With treatment of RIP (20, 40 and 80 mg/kg BW), the body weight, fat accumulation, adipocyte cell size, serum lipid levels and antioxidant enzyme activity were progressively improved. On the other hand, the treatment of 3T3-L1 cells with RIP (25, 50 and 100 mg/L) led to a decrease in lipid accumulation and glucose consumption. In addition, during adipogenesis in 3T3-L1 cells, RIP remarkably down-regulated mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein-α (C/EBPα), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase and glycerol-3-phosphate dehydrogenase. Furthermore, after RIP treatment, the protein expression of PPARγ, C/EBPα, FAS, HMG-CoA reductase and acetyl-CoA synthetase-1 (AceCS1) were significantly decreased and the expression of p-AMPK was increased. CONCLUSION: These results highlight the potential of RIP for obesity interventions and suggest that RIP inhibited adipocyte differentiation and lipid synthesis by activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signalling pathway and down-regulating the expression of major adipogenic transcription factors, PPARγ, C/EBPα, etc.

Adsorptive behavior of thallium using Fe3O4-kaolin composite synthesized by a room temperature ferrite process.

Thallium (Tl) contaminants pose serious threats to the ecological environment and human health due to its acute/chronic poisoning on the health of most organisms even at low concentrations. To find a rapid and efficient technology in removing Tl from waters thus becomes a crucial issue. A magnetic Fe3O4-kaolin composite (denoted by FKC) with high specific surface area (133.7 m2/g) was successfully synthesized via a simple and low-cost technique for Tl(I) removing from various water media. The HRTEM images confirmed the existence of lattice fingers Fe3O4 and displayed that a large number of Fe3O4 nanoparticles dispersed on the surface of kaolin sheets. Compared with kaolin or Fe3O4 alone, FKC enhanced obviously the adsorption rate and capacity of Tl(I) over a wide pH range (4.5-9.0). The maximum adsorption capacity of FKC for Tl(I) was 19,347 mg/kg (calculated by Langmuir model), which was almost one hundred times and two times higher than those of kaolin and Fe3O4, respectively. Importantly, FKC was observed to have a great potential in removing Tl(I) from surface water, groundwater, and tap water in more alkaline conditions. By applying the external magnetic field, FKC could be recovered efficiently (99%) and rapidly (20 s). Moreover, Tl L3-edge XANES spectra revealed that Tl(I) was adsorbed on the FKC and would not be converted to more toxic Tl(III). The cations (CaCl2, NaCl, and KCl) and the ionic strength with concentrations of 0.001-1.0 mol/L showed a great influence on the adsorption of Tl(I) by FKC, implying that this adsorption was dominated by outer-sphere surface complexation at investigated pH values. The information provided is essential for designing a rapid and effective scavenger for removing Tl in various natural waters.

Expression Analysis of Lanosterol Synthase Gene in Dynamic Accumulation of Triterpenoids in Sanghuangporus baumii.

BACKGROUND: Sanghuangporus baumii is a traditional Chinese medicine with anti- cancer, anti-tumor, and anti-inflammatory effects. Triterpenoids are one of the main medicinal ingredients found in S. baumii. However, the dynamic changes of triterpenoids content and its molecular regulation mechanism are still unclear. OBJECTIVE: Some studies have shown that Lanosterol synthase ( LS) is a key enzyme involved in the mevalonate pathway (MVA pathway) to produce lanosterol, which is a precursor for synthesizing S. baumii triterpenoids. Therefore, the study of LS gene and expression characteristics can provide clues for the further study of triterpenoids synthesis. METHODS: The PCR, RACE PCR, RT-PCR, homologous recombination and prokaryotic expression technology were used to research the gene characteristic and dynamic changes of LS transcription level. RESULTS: The S. baumii LS sequence included a 5'-untranslated region (129 bp), a 3'-untranslated region (87 bp), and an open reading frame (2,229 bp) encoding 734 amino acids. The S. baumii LS protein was expressed in E. coli BL21 (DE3). The transcription start site of the S. baumii LS promoter sequence ranged from 1 740 bp to 1790 bp. The LS promoter contained 12 CAAT-boxes, 5 ABREs, 6 G-Boxes, 6 CGTCA-motifs, and so on. The LS transcription levels were the highest on day 11 in mycelia (1.6-fold), and the triterpenoids content also gradually increased. The transcription levels began to decrease on day 13, but the triterpenoids content still increased. CONCLUSION: The S. baumii LS was cloned and characterized to help to understand the mechanism of triterpenoids synthesis. In addition, we studied the relationship between LS transcription level and triterpenoid dynamic accumulation, and we found that they had a certain correlation.

Clinical Features and Long-Term Outcomes After Laparoscopic Surgery in Patients Co-existing With Endometriosis and Adenomyosis.

Objective: To investigate the difference of clinical features and outcomes between EM patients with and without AM after following up for at least 6 years after surgery. Methods: We retrospectively analyzed 358 EM patients who had a minimum of 6 years follow-up after laparoscopic cystectomy, which was performed by one single doctor at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into AM group and non-AM group and analysis was performed in preoperative characteristics, surgical findings and postoperative outcomes during follow-up. Results: A total of 358 EM patients were recruited, of which 142 (39.7%) were in the AM group and the rest 216 (60.3%) in the non-AM group. Between the two group, the mean age was 34.6 vs. 32.2 years (P < 0.001). The mean operating time in the AM and non-AM group was 73.2 vs. 61.9 min (P < 0.001). According to the revised AFS classification, the mean score of the two group were 60.3 vs. 45.5 (P < 0.001). At the end of the follow-up, though the AM group was with higher rate of disease relapse, yet no significant difference was found between the two groups in statistical comparison (34/142 [23.9%] vs. 34/216 [15.7%], P = 0.053). With a minimum follow-up of 6 years after laparoscopic cystectomy, failed and successful pregnancy were seen in 107/142(75.4%) and 35/142 (24.6%) patients in the AM group vs. 114/216(52.8%) and 102/216 (47.2%) patients in the non-AM group (P < 0.05). As for the successfully pregnant patients, live births, including spontaneous pregnancy and IVF-ET, were seen in 34/35 (97.1) vs. 99/102 (97.1) patients between AM and non-AM groups, while others ended in spontaneous abortion. No significant associations were found between the two groups in infertility, leiomyoma presence, the size of ovarian endometrioma, type of deep infiltrating endometriosis (DIE) or type of recurrence (P > 0.05). Conclusion: Compared with non-AM group, EM patients with concurrent AM may have higher age, longer mean operating time and higher mean AFS score. In terms of fertility outcomes, patients in the AM group were with lower likelihood of pregnancy after surgery during the long-time follow-up.