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Aquatic animals suffer from heat and hypoxia stress more frequently due to global climate change and other anthropogenic activities. Heat and hypoxia stress can significantly affect mitochondrial function and energy metabolism. Here, the response and adaptation characteristics of mitochondria and energy metabolism in the gill of the hard clam Mercenaria mercenaria under heat (35 °C), hypoxia (0.2 mg/L), and heat plus hypoxia stress (35 °C, 0.2 mg/L) after 48 h exposure were investigated. Mitochondrial membrane potentials were depolarized under environmental stress. Mitochondrial fusion, fission and mitophagy played a key role in maintain mitochondrion function. The AMPK subunits showed different expression under environmental stress. Acceleration of enzyme activities (phosphofructokinase, pyruvate kinase and lactic dehydrogenase) and accumulation of anaerobic metabolites in glycolysis and TCA cycle implied that the anaerobic metabolism might play a key role in providing energy. Accumulation of amino acids might help to increase tolerance under heat and heat combined hypoxia stress. In addition, urea cycle played a key role in amino acid metabolism to prevent ammonia/nitrogen toxicity. This study improved our understanding of the mitochondrial and energy metabolism responses of marine bivalves exposed to environmental stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is a lack of studies elaborating the differences in mechanisms of low-frequency ultrasound-enhanced coagulation for algae removal among different ultrasound energy densities, which are essential to optimizing the economy of the ultrasound technology for practical application. The performance and mechanisms of low-frequency ultrasound (29.4 kHz, horn type, maximum output amplitude = 10 μm) -coagulation process in removing a typical species of cyanobacteria, Microcystis aeruginosa, at different ultrasound energy densities were studied based on a set of comprehensive characterization approaches. The turbidity removal ratio of coagulation (with polymeric aluminum salt coagulant at a dosage of 4 mg Al/L) was considerably increased from 44.1% to 59.7%, 67.0%, and 74.9% with 30 s of ultrasonic pretreatment at energy densities of 0.6, 1.11, and 2.22 J/mL, respectively, indicating that low-frequency ultrasound-coagulation is a potential alternative to effectively control unexpected blooms of M. aeruginosa. However, the energy density of ultrasound should be deliberately considered because a high energy density (≥18 J/mL) results in a significant release of algal organic matter, which may threaten water quality security. The specific mechanisms for the enhanced coagulation removal by low-frequency ultrasonic pretreatment under different energy densities can be summarized as the reduction of cell activity (energy density ≥ 0.6 J/mL), the slight release of negatively charged algal organic matter from cells (energy density ≥ 1.11 J/mL), and the aggregation of M. aeruginosa cells (energy density ≥ 1.11 J/mL). This study provides new insights for the ongoing study of ultrasonic pretreatment for the removal of algae via coagulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 suppresses food intake and decreases body weight. However, the mediating site(s) of action of the anorectic effects induced by peripheral administration of GLP-1R agonists are not well known. The present study investigated the effects of bilateral lesions of the central nucleus of the amygdala (CeA) on the suppression of chow and high-sucrose food intake by exendin-4 in rats. Adult male Sprague-Dawley rats with bilateral sham or electrolytic lesions (400 μA; 25 s) of the CeA were used for this experiment. No significant difference was found in the daily chow intake and high-sucrose food intake in rats with CeA lesion compared to sham-operated rats. Bilateral lesions of the CeA significantly attenuated the suppression of high-sucrose food intake by i.p. exendin-4, but not the suppression of chow intake. These results suggest that a mediating role of the CeA on the peripheral effects of exendin-4., (Copyright © 2019. Published by Elsevier Inc.)

Excess intracellular reactive oxygen species (ROS) production is a significant causative factor of many diseases, exemplified by vascular diseases. Mitochondria are a major source of endogenous ROS, which simultaneously induce mitochondrial dysfunction. Nuclear factor-erythroid 2-related factor 2 (Nrf2) represents an important intracellular defense system that protects cells against oxidative insults caused by ROS. Therefore, molecules with the capacities of inducing Nrf2, and preventing mitochondrial dysfunction can inhibit cell apoptosis, and thus are potential drug candidates for the therapy of ROS-mediated vascular diseases. Homoeriodictyol (HE), previously isolated from Viscum articulatum Burm, has been found to be an Nrf2 inducer. In the present study, we investigated its protection on ROS-induced endothelial cell injury using a H 2 O 2 -induced human umbilical vein EA.hy926 cell oxidative insult model. Our results indicated that HE activated Nrf2 signaling pathway and protected cells against H 2 O 2 -induced cell damage. HE alleviated H 2 O 2 -induced loss of mitochondrial membrane potential (MMP), blocked the releases of cytochrome C and apoptosis inducing factor (AIF) from mitochondria, and thus inhibited mitochondria-mediated cell apoptosis. Furthermore, HE inhibited H 2 O 2 -induced changes of apoptosis-related proteins, such as Bcl-2, Bcl-xL, caspases -3, -9 and PARP. Further study demonstrated that the protection of HE against H 2 O 2 -induced endothelial cell damage was Nrf2-dependent. Collectively, our observations suggest that HE is capable of counteracting oxidative insults in endothelial cells, and has a potential to be a therapeutic agent against ROS-mediated vascular diseases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Natural product-inspired discovery of new drug leads plays a key role in drug development. Recently, small-molecule JAK inhibitors have been pursued for the development of anticancer therapeutics. However, most of these inhibitors reported up to now are multi-nitrogen polycyclic aromatic heterocycles. Undoubtedly, the discovery of new types of promising JAK-inhibitory leads is pivotal for JAK inhibitor-based anticancer drug development. Herein we report an unprecedented sesquiterpenoid-alkaloid named thespesilactam, containing a benzo[cd]indole scaffold, from the heartwood of the Portia tree, Thespesia populnea. Its 3-O-Me product, i.e. 8-hydroxy-5-isopropyl-3-methoxy-7-methylbenzo[cd]indol-2(1H)-one, named 3-O-methylthespesilactam, of which the structure was identified by NMR investigations and single-crystal X-ray diffraction analysis, was discovered as a new type of small-molecule anticancer pan-JAK inhibitor against A2058 human melanoma cells, and selective and potent inhibitor of JAK1 and TYK2., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To determine the spinal innervation and neuronal connections is important for studying renal metabolic responses., Materials and Methods: In this study, the spinal cords of 10 adult male C57BL/6J strain mice were mapped retrograde using injections of pseudorabies virus (PRV)-614. The virus, injected into the kidney, was specifically transported to the spinal cord., Results: At 5 days after injection of the PRV-614, PRV-614-positive cells were found in the intermediolateral cell column, the intercalates nucleus, or the central autonomic nucleus of spinal cord segments T4-L1, and most PRV-614-labeled cells were found in the T9 segment., Conclusion: Our results revealed neuroanatomical circuits between kidney and the spinal intermediolateral cell column neurons., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To present our surgical techniques and experience with retroperitoneal laparoscopic upper pole nephroureterectomy for a duplex kidney in adult patients without vesicoureteral reflux., Methods: A total of 32 adult patients with a duplex kidney underwent laparoscopic upper pole nephroureterectomy. A 3-port, finger- and balloon-dissecting, retroperitoneal approach was used. The upper pole renal parenchyma was divided circumferentially between the upper and lower poles using a harmonic scalpel, maintaining a margin around the upper pole parenchyma to avoid any possible injury to the lower pole functioning moiety. The urothelium of the remnant upper pole parenchyma was stripped off, and the edges of the remnant upper pole parenchyma were approximated with figure-of-8 stitches. The distal upper pole ureter was mobilized and transected at the point at which the ureter crossed anterior to the iliac vessels. Intravenous urography and renal ultrasonography were performed at 3 and 6 months postoperatively., Results: All laparoscopic operations were performed successfully without conversion to open surgery. The mean operative time was 83 minutes. The mean blood loss was 18 mL. The mean postoperative hospital stay was 7 days. No intraoperative or major postoperative complications occurred. The intravenous urography and renal ultrasound findings 3 and 6 months postoperatively demonstrated normal pyelography findings and renal function of the preserved lower pole in all patients., Conclusions: Retroperitoneal laparoscopic upper pole nephroureterectomy is a safe and effective procedure and an excellent minimally invasive treatment option for the adult patient with a duplex kidney., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To present our surgical techniques and experience with retroperitoneal laparoscopic ureteroureterostomy in 10 patients with retrocaval ureter and review the data on the laparoscopic management of retrocaval ureter published in English., Methods: A total of 10 patients with retrocaval ureter underwent laparoscopic ureteroureterostomy. A 3-port, finger and balloon-dissecting, retroperitoneal approach was used. The retrocaval segment of ureter was mobilized and transposed anterior to the inferior vena cava. The ureteroureteral anastomosis was completed with the intracorporal freehand suturing and in situ knot tying techniques. Intravenous pyelography was performed 3 and 6 months, postoperatively. Thereafter, intravenous pyelography follow-up was then continued at 12-month intervals for 3 years, and yearly renal ultrasonography follow-up was continued for at least 2 years. A comprehensive electronic English-language literature search of PUBMED was conducted., Results: All operations were completed laparoscopically without conversion to open surgery. The mean operative time was 82 minutes (range, 60-110 minutes). The blood loss was minimal (< 10 mL). No perioperative complication occurred. All patients achieved an uneventful recovery. At a mean follow-up of 52 months, remarkable improvement in the ureteral obstruction was observed. Data of 19 patients in 12 published English-language literatures were reviewed., Conclusions: Our results indicate that retroperitoneal laparoscopic ureteroureterostomy is a safe and effective procedure, and an excellent minimally invasive treatment option for retrocaval ureter. Moreover, a thorough review of published data supports our viewpoint that laparoscopic surgery should probably be the first-line treatment for retrocaval ureter., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Fulminant hepatic failure (FHF) remains an extremely poor prognosis and high mortality; better treatments are urgently needed. Tetrandrine (TET), a traditional anti-inflammatory drug, has been reported to exhibit hepatoprotective activities in several liver injury models. We now investigated the effects and underlying mechanisms of TET on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced FHF in mice. TET (50, 100, and 200 mg/kg) was given intraperitoneally 1h before LPS/D-GalN injection in mice. The mortality and liver injury was evaluated subsequently. The results showed that administering TET to mice reduced mortality and improved liver injury induced by LPS/D-GalN in a dose-dependent manner. In addition, TET dose-dependently inhibited LPS/D-GalN-induced NF-kappaB activation, serum and hepatic tissues tumor necrosis factor-alpha (TNF-alpha) production, caspase-3 activation and hepatocellular apoptosis, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ECAM-1) expression. Our experimental data indicated that TET might alleviate the FHF induced by LPS/D-GalN through inhibiting NF-kappaB activation to reduce TNF-alpha production., (Copyright 2009 Elsevier B.V. All rights reserved.)

Baicalin, a traditional anti-inflammatory drug, has been found to protect against liver injury in several experimental animal hepatitis models; however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In the present study,we investigated the effects of baicalin on the acute liver injury in mice induced by Lipopolysaccharide/D-galactosamine (LPS/D-GalN). Baicalin (50, 150, and 300 mg/kg) was pretreated intraperitoneally (i.p.) at 2, 24, and 48 h respectively before LPS/D-GalN injected in mice. The mortality, hepatic tissue histology, hepatic tissue Tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO), plasma levels of TNF-alpha and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Besides, western blotting analyses of nuclear factor kappa B (NF-kappaB) translocation and Heme oxygenase-1(HO-1) protein expression, as well as HO-1 activity were determined. The results showed that baicalin protected against LPS/D-GalN-induced liver injury, including dose-dependent alleviation of mortality and hepatic pathological damage, decrease of ALT/AST release and the rise of MPO. Baicalin reduced nuclear translocation of NF-kappa B, TNF-alpha mRNA and protein levels in hepatic tissues and plasma levels of TNF-alpha induced by LPS/D-GalN. Moreover, baicalin dose-dependently increased HO-1 protein expression and activity. Further, inhibition of HO-1 activity significantly reversed the protective effect of baicalin against LPS/D-GalN-induced liver injury. These results suggest that baicalin can effectively prevent LPS/D-GalN-induced liver injury by inhibition of NF-kappa B activity to reduce TNF-alpha production and the underlying mechanism may be related to up-regulation of HO-1 protein and activity.

Background: Multiple sclerosis (MS) is a chronic disease characterized by loss of myelin. However, data indicate that autoimmune cells could directly impair neuronal cell bodies and myelin sheath is lacking. The aim of the present study was to determine morphological evidence of the direct impairment of neurons by autoreactive lymphocytes and to further identify the subtypes of these lymphocytes., Methods: Lymphocytes activated by myelin basic protein (MBP) 83-99 and neurons of human brain were co-cultured for 24 h., Results: Observations through scanning electron microscope showed that MBP-specific lymphocytes (CD4+, CD8+ cells, and NK cells) aggregated in the vicinity of the neuronal cell bodies and the myelin sheaths and attacked them directly, resulting in the degeneration of both neurons., Conclusions: Our studies provide morphological evidences of the direct impairment of neuronal cell bodies and myelin sheaths by MBP-specific lymphocytes. Our studies also suggest that MBP-specific CD4+, CD8+, and NK cells might be involved in this process. These processes may play a role in the direct impairment of neurons and myelin sheaths in early stages of MS and provide evidences for the application of immunosuppressant therapy of MS.

Previous studies have revealed a direct histaminergic projection from the tuberomamillary nucleus of hypothalamus to the cerebellum and a postsynaptic excitatory effect of histamine on the cerebellar interpositus nucleus neurons via histamine H(2) receptors in vitro, indicating that the histaminergic afferent inputs of cerebellar nuclei may be involved in the cerebellar function of motor control. To test this hypothesis, in this study histaminergic agents were bilaterally microinjected into the cerebellar interpositus nucleus of intact adult male rats, and their effects on motor balance and coordination of the animals performing accelerating rota-rod treadmill and balance beam tasks were observed. The results showed that microinjection of histamine into the cerebellar interpositus nucleus remarkably increased the time that animals balanced steadily on the rota-rod and markedly shortened the duration of passage through the balance beam, whereas GABA significantly depressed motor performances of animals on the rota-rod and beam, and normal saline influenced neither. In addition, administration of selective histamine H(2) receptor antagonist ranitidine considerably decreased the animals' endurance time on rota-rod and noticeably increased the passing time on beam, but selective histamine H(1) receptor antagonist triprolidine showed no effect. Furthermore, microinjection of histamine reversed the inhibitory effects of ranitidine on rota-rod and beam performance. These results demonstrate that histamine enhances rat motor balance and coordination through activation of histamine H(2) receptors in the cerebellar interpositus nucleus and suggest that the hypothalamocerebellar histaminergic projections may play a modulatory role on the cerebellar circuitry to ensure that movements are accurately executed.

Previous studies suggested that the postsynaptic GABA(B) receptors of deep cerebellar nuclear neurons of adult rats were not activated by selective GABA(B) receptor agonist baclofen or endogenous GABA released by cerebellar cortical Purkinje cells, although the receptors have been demonstrated to exist in the deep cerebellar nuclei. In this study, cerebellar slices of adult rats were prepared for testing effects of GABA, baclofen and muscimol (selective GABA(A) receptor agonist) on cerebellar interpositus nucleus (IN) neurons. Perfusing slices with GABA (10-1000 microM), baclofen (1-30 microM) and muscimol (1-100 microM) respectively produced a dose-dependent inhibitory response on the IN neurons (n = 39, 62 and 50), which was not blocked by low-Ca(2+)/high-Mg(2+) medium (n = 5, 6 and 6), supporting a direct postsynaptic action of these GABAergic agonists. Moreover, both selective GABA(B) receptor antagonist CGP35348 and selective GABA(A) receptor antagonist bicuculline were capable of partially blocking the inhibitory response of IN neurons to GABA (n = 14 and 11), suggesting that the GABA-induced inhibition may contain two components, a GABA(B) receptors-mediated component and a GABA(A) receptors-mediated one. Further experiments revealed that not only muscimol (n = 50) but also baclofen (n = 62) suppressed IN cells' activity. The baclofen-induced inhibition was selectively blocked by CGP35348 (n = 12) but not by bicuculline (n = 8), whereas the muscimol-induced inhibition was selectively antagonized by bicuculline (n = 8) instead of CGP35348 (n = 9). These results indicate that GABA(B) receptors in the IN neurons can be activated not only by GABA but also by baclofen, suggesting that besides GABA(A) receptors, GABA(B) receptors may also be involved in mediating the inhibitory effect of GABA on cerebellar IN neurons of adult rats.

Objectives: To report our techniques and experience with retroperitoneal laparoscopic dismembered pyeloplasty for ureteropelvic junction (UPJ) obstruction., Methods: From May 2000 to September 2004, 50 patients with UPJ obstruction underwent laparoscopic dismembered pyeloplasty. A three-port, balloon-dissecting, retroperitoneal approach was used. All anastomoses were completed with free-hand intracorporeal suture techniques. Follow-up studies were performed with intravenous urography and renal ultrasonography., Results: All operations were completed laparoscopically, and no open conversions were required. The mean operating time was 81.6 minutes (range 55 to 180). The mean blood loss was 12 mL (range 5 to 50), and the mean postoperative hospitalization stay was 7.6 days (range 6 to 12). No intraoperative complications occurred. Aberrant artery vessel and primary stricture as the cause of UPJ obstruction was noted in 6 and 44 patients, respectively. Anastomotic leakage occurred in 2 patients, 1 of whom later underwent open surgery for recurrent UPJ obstruction. Radiographic assessment by intravenous urography showed good results in 49 patients at a mean follow-up of 22 months., Conclusions: Our experience with retroperitoneal laparoscopic dismembered pyeloplasty has demonstrated that this technique is an effective treatment for UPJ obstruction and can be accomplished reasonably quickly.

We provide a battery of screens that reflect the social and sexual behavior displayed by both captive and feral mice. Some screens focus on measuring aspects of chemical communication, providing information about whether or not mice will interact and if they do so, predict the nature of the interaction. Other screens measure direct interactions between target mice and same- and opposite-sex conspecifics, providing an indication of the social status and sexual responsiveness, respectively, of target mice. The battery of screens yields a high-throughput bioassay of a mouse's relative social status, competitive ability, social discrimination, and sexuality. These traits are essential elements of the socio-sexual behavior of mice as well as humans. Thus, by identifying phenotypic deviants for complex behaviors we will allow geneticists to map behavioral abnormalities onto specific chromosomes and increase the efficacy of genetically altered mice as models for human behavioral disorders.

Objectives: To evaluate the feasibility and clinical efficacy of retroperitoneal laparoscopic nephron-sparing surgery for renal tumors., Methods: Between June 2002 and February 2004, 11 cases of renal benign tumor and 21 cases of renal malignant tumor underwent enucleation of the tumor and wedge resection of the tumor through retroperitoneal laparoscopy, respectively. Tumor resection and hemostasis were mainly achieved by harmonic scalpel. Follow-up studies were performed with an evaluation using renal spiral computed tomography., Results: All procedures were technically successful. The mean operating time was 70 minutes for enucleation and 96 minutes for wedge resection. The mean estimated blood loss was 35 mL for enucleation and 65.5 mL for wedge resection. The mean hospital stay after surgery was 6.5 days. No intraoperative complications occurred. The pathologic examination confirmed renal cell carcinoma in 21 patients and angiomyolipoma in 11. The pathologic stage was pT1a in the 21 patients with renal cell carcinoma. All resected tumor specimens had negative surgical margins for cancer. No local recurrence or trocar site metastasis was observed during a mean follow-up period of 13 months., Conclusions: Our results indicate that retroperitoneal laparoscopic nephron-sparing surgery represents a feasible option for patients with localized renal tumors. This procedure could offer precise and complete tumor excision while minimizing morbidity, improving cosmesis, and shortening convalescence.