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The inward rectifying potassium channel, Kir2.1, is selected as cargo at the trans-Golgi network (TGN) for export to the cell surface through a unique signal-dependent interaction with the AP1 clathrin-adaptor, but it is unknown how the channel is targeted at earlier stages in the secretory pathway for traffic to the TGN. Here we explore a mechanism. A systematic screen of Golgi tethers identified Golgin-97 as a Kir2.1 binding partner. In vitro protein-interaction studies revealed the interaction is direct, occurring between the GRIP domain of Golgin-97 and the cytoplasmic domain of Kir2.1. Imaging and interaction studies in COS-7 cells suggest that Golgi-97 binds to the channel en route through the Golgi. RNA interference-mediated knockdown of Golgin-97 prevented exit of Kir2.1 from the Golgi. These observations identify Golgin-97 as a Kir2.1 binding partner that is required for targeting the channel to the TGN. Based on our studies in COS-7 cells, we propose Golgi-97 facilitates formation of AP1-dependent export carriers for Kir2.1 by coupling anterograde delivery of Kir2.1 with retrograde recycling of AP-1 containing endosomes to the TGN.

Megalurothrips usitatus (Bagrall) is an important pest of legumes worldwide, causing great economic loss every year. Beauveria brongniartii and Akanthomyces attenuatus have shown considerable pathogenicity against M. usitatus in our previous studies. The medial lethal concentration (LC50) and the sublethal lethal concentration (LC25) of B. brongniartii isolate SB010 against M. usitatus were 8.38 × 105 and 1.73 × 105 conidia mL−1, respectively, whereas those of A. attenuatus isolate SCAUDCL-53 against M. usitatus were 4.37 × 105 and 2.97 × 104 conidia mL−1, respectively. This study reports the transcriptome-based explanation of the stress responses of M. usitatus following the application of B. brongniartii and A. attenuatus. The analysis of the transcriptomic data revealed the expression of 254, 207, 195, and 234 immunity-related unigenes by M. usitatus in response to B. brongniartii LC50 (SB1), B. brongniartii LC25 (SB2), A. attenuatus LC50 (V1), and A. attenuatus LC25 (V2), respectively. The biological function and metabolic pathway analyses showed that these unigenes were mainly related to pattern recognition receptors, information transduction factors, and reaction factors, such as scavenger receptor, cytochrome b5, cuticle protein, lysozyme, and serine protease.

ObjectivePrevious studies made controversial claims about the alleged effects of Kinesio taping (KT) on pain relief. To date, the mechanism by which KT relieves pain remains unclear. Moreover, pain evaluation lacks objective and quantitative parameters. This study compared the acute effects of different KT interventions on the local thresholds of pressure pain and current perception in healthy adults to determine the potential mechanisms by which KT relieves pain.MethodsThirty healthy female subjects randomly received four KT interventions, namely, no taping (NT), placebo taping (PT), Y strips of KT (KY), and fan strips of KT (KF), on the waist. Current perception threshold (CPT), pressure pain threshold (PPT), soft tissue hardness, and the visual analog scale (VAS) scores of the subjects’ perceived pain were immediately measured after taping. Repeated-measures ANOVA was performed to determine significant differences in these parameters among the four interventions.ResultsSignificant differences in CPT values among the interventions were observed at the frequency of 5 Hz (F = 3.499, p = 0.019, ηp2 = 0.111). Post hoc analysis revealed that CPT was significantly higher for KF than for NT (p = 0.008, 95% CI = 1.390–11.990). Significant differences in PPT values (F = 4.352, p = 0.012, ηp2 = 0.130) and soft tissue hardness (F = 2.957, p = 0.049, ηp2 = 0.093) were observed among the different taping conditions. Post hoc analysis revealed that PPT was significantly higher for KF than for PT (p = 0.011, 95% CI = 0.071–0.749), and soft tissue hardness was significantly higher for KF than for NT (p = 0.010, 95% CI = 0.461–4.586) and KY (p = 0.040, 95% CI = 0.059–3.800). No significant differences in self-perceived pain among the interventions were observed.ConclusionThe healthy adult females had higher PPT values, lower soft tissue hardness, and higher CPT values at 5 Hz under KF intervention applied on the waist than those under the other taping interventions. Moreover, the different taping conditions had no significant differences in terms of VAS of perceived pain. These results provide guidance for the application of KT on pain management.

BackgroundThere were limited studies on the effect of skin temperature and local blood flow using kinesio tape (KT) adhered to the skin in different taping methods. This study aimed to determine the short-term effect of KT and athletic tape (AT) on skin temperature in the lower back and explore the possible effect of different taping methods (Y-strip and fan-strip taping) on local microcirculation.Materials and MethodsTwenty-six healthy participants completed the test-retest reliability measurement of the infrared thermography (IRT), intraclass correlation coefficient (ICC), and standard error of measurement (SEM) were calculated to evaluate the reliability. Then, 21 healthy participants received different taping condition randomly for 5 times, including Y-strip of kinesio taping (KY), fan-strip of kinesio taping (Kfan), Y-strip of athletic taping (AY), fan-strip of athletic taping (Afan), and no taping (NT). Above taping methods were applied to the participants’ erector spinae muscles on the same side. Skin temperature of range of interest (ROI) was measured in the taping area through IRT at pre taping and 10 min after taping. Additionally, participants completed self-perceived temperature evaluation for different taping methods through visual analog scaling. One-way repeated-measured analysis of variance was used to compare the temperature difference among different taping methods. Bonferroni test was used for post hoc analysis.ResultsThere was a good test-retest reliability (ICC = 0.82, 95% CI = 0.60–0.92; SEM = 0.33; and MD = 0.91) of the IRT. Significant differences were observed in the short-term effect on skin temperature among all different taping methods (p = 0.012, F = 3.435, and ηp2 = 0.147), post hoc test showed a higher significantly skin temperature difference in Kfan taping compared to no taping (p = 0.026, 95% CI = 0.051–1.206); However, no significant differences were observed among self-perceived temperature (p = 0.055, F = 2.428, and ηp2 = 0.108).ConclusionThis study showed that the fan-strip of KT increased significantly the skin temperature of the waist after taping for 10 min. The application of KT may modify the skin temperature of the human body and promote local microcirculation, although it remained unclear for the real application.

AimSigma-1 receptors have been investigated and shown to play a protective role in both depression and cardiovascular disease. SA4503, known as a σ1 receptor agonist, regulates cardiac calcium and potassium channels in rat models of depression. However, it remains unknown whether SA4503 can alleviate myocardial inflammation or conduction junctions in the atrium after exposure to chronic mild stress.Methods and ResultsSprague-Dawley male rats received 28-day treatment with SA4503, simultaneously with chronic mild stress. Behavior measurements were assessed after the daily doses. Additionally, a multielectrode array assessment, electrophysiological study, immunohistochemistry analysis, histological analysis, and Western blot analysis were performed. Depression rats’ hearts showed abnormal electrical activity, including disordered excitation propagation and prolonged total activation time (TAT). In addition, atrial arrhythmias (AAs), induced by burst stimulation, showed higher incidence and longer duration in the depression group compared to the control group. These changes were related to reduced conduction junctions and enhanced spatial heterogeneity. Importantly, depressed rat hearts showed greater expression of inflammatory factors (TGF-α, IL-6, and TGF-β), more collagen distribution in the extracellular matrix, and lower expression of gap junction proteins (CX40 and CX43). Furthermore, SA4503 partially mitigated the above indices in the depression group (P < 0.01 for all groups).ConclusionThese findings show the effects of the σ1R agonist SA4503; it alleviates atrial myocardial inflammation and conduction junctions after chronic mild stress. SA4503 may be the promising pharmacological agent to treat depression-related AAs by increasing conduction function, improving the expression of connexin 40 and 43, and reducing cardiac myocardial inflammation.

Low progesterone level is always linked with pre-term birth. Therefore, maintaining of progesterone level is vital during pregnancy. Aldo-keto reductase family one member C1 (AKR1C1) catalyzes the reduction of progesterone to its inactive form of 20-alpha-hydroxy-progesterone and thus limits the biological effect of progesterone. In our effort to identify the natural compound that would specifically inhibit AKR1C1, liquiritin was found to be a selective and potent inhibitor of AKR1C1. Kinetic analyses in the S-(+)-1,2,3,4-tetrahydro-1-naphthol (s-tetralol) catalyzed by AKR1C1 in the presence of the inhibitors suggest that liquiritin is a competitive inhibitor by targeting the residues Ala-27, Val-29, Ala-25, and Asn-56 of AKR1C1. In HEC-1-B cells, treatment with liquiritin results in 85.00% of reduction in progesterone metabolism, which is mediated by AKR1C1 enzymatic activity. Overall, our study not only identify liquiritin as an inhibitor against AKR1C1, but also reveal that liquiritin may be served as a potential intervention strategy for preventing pre-term birth caused by low progesterone level.

To facilitate transplanting razor clam (Sinonovacula constricta) populations to inland saline-alkaline waters (ISWs), we evaluated the tolerance of juvenile S. constricta (JSC) to Ca2+ and Mg2+ concentrations, and determined the effects of these ions on JSC growth and physiological parameters. After 30 days stress, the tolerable ranges of JSC to Ca2+ and Mg2+ were determined to be 0.19 mmol⋅L-1–19.46 mmol⋅L-1 and 0 mmol⋅L-1–29.54 mmol⋅L-1, respectively. The concentrations of Ca2+ (less than 0.65 mmol⋅L-1 or more than 3.24 mmol⋅L-1) and Mg2+ (less than 0.37 mmol⋅L-1 or more than 14.17 mmol⋅L-1) significantly inhibit JSC growth. Physiological enzyme activity no significant response when the concentrations range of Ca2+ and Mg2+ are 0.93 mmol⋅L-1–6.49 mmol⋅L-1 and 0.37 mmol⋅L-1–14.77 mmol⋅L-1, respectively. For transplantation practice, these data indicate that only high concentrations of Ca2+ (3.24–6.825 mmol⋅L-1) and Mg2+ (14.77–33.69 mmol⋅L-1) in target inland saline-alkaline water had significantly impact on growth and physiological response. In addition, present study suggests that the increase in Ca2+ and Mg2+ ion concentrations caused by ocean acidification will not affect the survival, growth and physiology of S. constricta. Current research suggests that S. constricta can adapt to extreme changes in the marine environment (Ca2+ and Mg2+) and may be an excellent candidate for inland saline-alkaline water transplantation practice.

The purpose of this study was to better understand changes in motor unit electrophysiological properties in people with chronic stroke based on concentric needle electromyography (EMG) and single fiber EMG recordings. The first dorsal interosseous (FDI) muscle was studied bilaterally in eleven hemiparetic stroke subjects. A significant increase in mean fiber density (FD) was found in the paretic muscle compared with the contralateral side based on single fiber EMG (1.6 ± 0.2 vs. 1.3 ± 0.1, respectively, P = 0.003). There was no statistically significant difference between the paretic and contralateral sides in most concentric needle motor unit action potential (MUAP) parameters, such as amplitude (768.7 ± 441.7 vs. 855.0 ± 289.9 μV), duration (8.9 ± 1.8 vs. 8.68 ± 0.9 ms) and size index (1.2 ± 0.5 vs. 1.1 ± 0.3) (P > 0.18), nor was there a significant difference in single fiber EMG recorded jitter (37.0 ± 9.6 vs. 39.9 ± 10.6 μs, P = 0.45). The increase in FD suggests motor units of the paretic FDI have enlarged due to collateral reinnervation. However, sprouting might be insufficient to result in a statistically significant change in the concentric needle MUAP parameters. Single fiber EMG appears more sensitive than concentric needle EMG to reflect electrophysiological changes in motor units after stroke. Both single fiber and concentric needle EMG recordings may be necessary to better understand muscle changes after stroke, which is important for development of appropriate rehabilitation strategies. The results provide further evidence that motor units are remodeled after stroke, possibly in response to a loss of motoneurons.

Autophagy serves as a stress response and may contribute to the pathogenesis of avascular necrosis of the femoral head induced by steroids. Statins promote angiogenesis and ameliorate endothelial functions through apoptosis inhibition and necrosis of endothelial progenitor cells, however the process used by statins to modulate autophagy in avascular necrosis of the femoral head remains unclear. This manuscript determines whether pravastatin protects against dexamethasone-induced avascular necrosis of the femoral head by activating endothelial progenitor cell autophagy. Pravastatin was observed to enhance the autophagy activity in endothelial progenitor cells, specifically by upregulating LC3-II/Beclin-1 (autophagy related proteins), and autophagosome formation in vivo and in vitro. An autophagy inhibitor, 3-MA, reduced pravastatin protection in endothelial progenitor cells exposed to dexamethasone by attenuating pravastatin-induced autophagy. Adenosine monophosphate-activated protein kinase (AMPK) is a key autophagy regulator by sensing cellular energy changes, and indirectly suppressing activation of the mammalian target of rapamycin (mTOR). We found that phosphorylation of AMPK was upregulated however phosphorylation of mTOR was downregulated in pravastatin-treated endothelial progenitor cells, which was attenuated by AMPK inhibitor compound C. Furthermore, liver kinase B1 (a phosphorylase of AMPK) knockdown eliminated pravastatin regulated autophagy protein LC3-II in endothelial progenitor cells in vitro. We therefore demonstrated pravastatin rescued endothelial progenitor cells from dexamethasone-induced autophagy dysfunction through the AMPK-mTOR signaling pathway in a liver kinase B1-dependent manner. Our results provide useful information for the development of novel therapeutics for management of glucocorticoids-induced avascular necrosis of the femoral head.

Bicuspid aortic valve (BAV) can be both sporadic and hereditary, is phenotypically variable, and genetically heterogeneous. The clinical presentation of BAV is diverse and commonly associated with a high prevalence of valvular dysfunction producing altered hemodynamics and aortic abnormalities (e.g., aneurysm and dissection). The thoracic aortic aneurysm (TAA) in BAV frequently involves the proximal aorta, including the aortic root, ascending aorta, and aortic arch, but spares the aorta distal to the aortic arch. While the ascending aortic aneurysm might be affected by both aortopathy and hemodynamics, the aortic root aneurysm is considered to be more of a consequence of aortopathy rather than hemodynamics, especially in younger patients. The management of aortic aneurysm in BAV has been very controversial because the molecular mechanism is unknown. Increasing evidence points toward the BAV root phenotype [aortic root dilation with aortic insufficiency (AI)] as having a higher risk of catastrophic aortic complications. We propose more aggressive surgical approaches toward the BAV with root phenotype.

Epithelial chloride channels provide the pathways for fluid secretion in the intestine. Cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCCs) are the main chloride channels in the luminal membrane of enterocytes. These transmembrane proteins play important roles in many physiological processes. In this study, we have identified a flavonoid quercetin as a modulator of CaCC chloride channel activity. Fluorescence quenching assay showed that quercetin activated Clˉ transport in a dose-dependent manner, with EC50 ~37 µM. Short-circuit current analysis confirmed that quercetin activated CaCC-mediated Clˉ currents in HT-29 cells that can be abolished by CaCCinh-A01. Ex-vivo studies indicated that application of quercetin to mouse ileum and colon on serosal side resulted in activation of CFTR and CaCC-mediated Clˉ currents. Notably, we found that quercetin exhibited inhibitory effect against ANO1 chloride channel activity in ANO1-expressing FRT cells and decreased mouse intestinal motility. Quercetin-stimulated short-circuit currents in mouse ileum was multi-component, which included elevation of Ca2+ concentration through L-type calcium channel and activation of basolateral NKCC, Na+/K+-ATPase and K+ channels. In vivo studies further revealed that quercetin promoted fluid secretion in mouse ileum. The modulatory effect of quercetin on CaCC chloirde channels may therefore represent a potential therapeutic strategy for treating CaCC-related diseases like constipation, secretory diarrhea and hypertension. The inverse effects of quercetin on CaCCs provided evidence that ANO1 and intestinal epithelial CaCCs are different calcium-activated chloride channels.

Temperature changes had a huge impact on the growth of aquaculture organisms, which mainly involved two parameters: the changing amplitude and the changing speed. Wide-adaptability and narrow-adaptability were divided by the amplitude, while fast-adaptability and slow-adaptability proposed in this article were divided based on the speed. Investigating the impact of the changing speed on artificial farming was vital. In this study, two fish species of wide-adaptability, Hippocampus kuda and Oryzias melatigma , were selected as research objects, explored the effects of temperature changing speeds on them under 2 changing amplitudes of 2°C and 4°C. The similarities and differences in their responses to temperature changes were analyzed and compared from the aspects of feeding, metabolism, physiology, immunity, and growth. The results showed that all 3 changing speeds (0.5°C/h, 1°C/h, and direct input) had no effect on the growth of O . melatigma under the 2°C amplitude, while there were significant differences in various aspects of H. kuda in the treatments with the speeds between 0.5°C/h and direct input, such as a significant difference in growth, in food intake, and in response speeds and response levels of several enzymes and related genes. Under 4°C amplitude, the impact of all 4 changing speeds (0.5°C/h, 1°C/h, 2°C/h and direct input) on both fish was more pronounced. H. kuda showed a significant difference of growth among 3 groups, and the critical safe speed was about 0.5°C/h in its heating treatments. And the growth decrease only occured the heating treatment of direct input in O . melatigma . Furthermore, some genes responded quickly and efficiently to the low-speed changes of temperature in H. kuda , but were inhibited in the treatments with high-speed changes. However, they can still express rapidly and efficiently in the high-speed treatments of O . melatigma , included several stress-related genes, lipid metabolic-related genes, and immune-related genes. Seen from these differences, the energy source used in H. kuda to resist stress was single and short-lived. So, under a long-term stress, H. kuda gradually transformed from normal physiological stress into pathological stress, leading to the outbreak of diseases. Therefore, for precise aquaculture of H. kuda , stricter and more precise control of environmental temperature is necessary to prevent rapid and big temperature changes from affecting the growth and survival of the seahorse., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Lin, Zhang, Pan, Lu and Bo.)

In order to clarify the possibility of rearing razor clams ( Sinonovacula constricta ) in inland saline water (ISW) and to facilitate their breeding under these stressful conditions, we performed semi-static acute and chronic toxicity tests to determine the effects of carbonate alkalinity (CA) and pH on the survival and growth rate, and critical metabolic enzyme activity in juvenile of S. constricta (JSC). (1) Acute toxicity test. As the water C A increased from 1.22 to 45.00 mmol L -1 , the survival rate decreased significantly, which was exacerbated by the increase in the pH. When the water C A was set at 2.5 mmol L -1 , the 48 h lethal concentration 50% (LC 50 ) for JSCs with respect to pH was 9.86. When the water pH was 9.0, 9.5, and 10.0, the 48 h LC 50 values for JSCs with respect to C A were 10.38, 8.79, and 3.11 mmol L -1 , respectively. (2) Chronic toxicity test. Four experimental groups comprising the control, CAS, pHS, and CA-pHS were designated according to the target ISW data. After 3 months of stress, the JSC survival rate in each group exceeded 85%, but survival was significantly lower in the CA-pHS group than the control group ( p < 0.05) in the first month. For the JSCs in various groups, the shell length growth rate (SGR) and weight gain (WG) rate were significantly lower in the CA-pHS group than the other groups ( p < 0.05 for SGR; p < 0.001 for WG) in the first month. However, the difference in the growth rate among groups decreased in the next 2 months. For the JSCs in the CA-pHS group, the oxygen consumption, ammonia-N excretion, Na + /K + -ATPase, aspartate aminotransferase, and superoxide dismutase levels were significantly higher than those in the other groups during the first month, but there were no significant differences between the groups subsequently. The acetylcholinesterase and lysozyme levels did not differ significantly among groups during stress for 3 months. The integrated biomarker response index showed that stressors comprising high pH and C A could be tolerated well by JSCs over long periods of stress. These results indicate that water C A and pH together affect the survival, growth, and physiological activity of JSCs. S. constricta is suitable for culture in ISW.