Comparison of the effects of remimazolam tosylate and propofol on immune function and hemodynamics in patients undergoing laparoscopic partial hepatectomy: a randomized controlled trial.

BACKGROUND: Laparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic side effects. Despite studies showing a negligible impact of remimazolam tosylate on hemodynamics, it has not been reported for partial hepatectomy patients. Its influence on immune function also remains unexplored. This study sought to investigate the differences in immune function and intraoperative hemodynamics between patients who underwent laparoscopic partial hepatectomy with remimazolam tosylate and those who underwent laparoscopic partial hepatectomy with propofol. METHODS: This was a single-center, randomized controlled trial involving 70 patients, who underwent elective laparoscopic partial hepatectomy. The patients were randomly divided into two groups: the remimazolam group (group R) and the propofol group (group P). In this study, the primary outcomes assessed included the patient's immune function and hemodynamic parameters, and the secondary outcomes encompassed the patient's liver function and adverse events. RESULTS: Data from 64 patients (group R, n = 31; group P, n = 33) were analyzed. The differences in the percentages of CD3+, CD4+, CD8+, and NK cells and the CD4+/CD8+ ratio between the two groups were not statistically significant at 1 day or 3 days after surgery. Compared with those in group P, the MAP and HR at T2 and the MAP at T1 in group R were significantly increased(P < 0.05). The differences in HR and MAP at T0, T3, T4, T5, T6, and T7 and HR at T1 between the two groups were not statistically significant. There were no differences in liver function or adverse effects between the two groups, suggesting that remimazolam tosylate is a safe sedative drug(P > 0.05). CONCLUSION: The effects of remimazolam tosylate on the immune function of patients after partial hepatectomy are comparable to those of propofol. Additionally, its minimal effect on hemodynamics significantly decreases the incidence of hypotension during anesthesia induction, thereby enhancing overall perioperative safety. TRIAL REGISTRATION: The trial was registered on May 9, 2022 in the Chinese Clinical Trial Registry, registration number ChiCTR2200059715 (09/05/2022).

The Sustained Antidepressant Effects of Ketamine Are Independent of the Lateral Habenula.

Ketamine is known to have a rapid and lasting antidepressant effect. Recent studies have shown that ketamine exerts it rapid antidepressant effect by blocking burst firing in the lateral habenula (LHb). Whether the sustained antidepressant effect of ketamine occurs through the same mechanism has not been explored. Here, using male rats, we found that local infusion of (R,S)-ketamine into the LHb resulted in a rapid antidepressant-like effect 1 h after infusion, which almost returned to baseline levels after 24 h. Intra-LHb injection of (S)-ketamine also showed a significant antidepressant-like effect 1 h after injection, which recovered at 24 h. No significant antidepressant-like effect was found at 1 or 24 h after the administration of (R)-ketamine into the LHb. Injection of (2R,6R)-hydroxynorketamine, a ketamine metabolite, into the LHb did not result in any obvious antidepressant-like effect 1 or 24 h after injection. Systemic administration of (R,S)-ketamine (intraperitoneally) significantly suppressed LHb bursting activity at 1 h, but the inhibitory effect was reversed 24 h after injection. No significant effect of (R,S)-ketamine on miniature excitatory postsynaptic potentials of LHb neurons was found at 1 or 24 h after systemic application. Our study demonstrated that the sustained antidepressant-like effect of ketamine may not depend on burst firing of LHb neurons.SIGNIFICANCE STATEMENT Ketamine exerts it rapid antidepressant effect by blocking burst firing in the lateral habenula (LHb). However, whether the sustained antidepressant effect of ketamine occurs through the same mechanism has not been explored. In the present study, we demonstrated that the sustained antidepressant effect of ketamine may not depend on the burst firing of LHb neurons. This finding may lead to a novel perspective on LHb in the antidepressant effect of ketamine.

METTL3 regulates inflammatory pain by modulating m6A-dependent pri-miR-365-3p processing.

N6-methyladenosine (m6A) modification in RNA has been implicated in diverse biological processes. However, very little is currently known about its role in nociceptive modulation. Here, we found that the level of spinal m6A modification was significantly increased in a mouse model of Complete Freund's Adjuvant (CFA)-induced chronic inflammatory pain, which was accompanied with the augmentation of methyltransferase-like 3 (METTL3) expression in the spinal cord. Knockdown of spinal METTL3 prevented and reversed CFA-induced pain behaviors and spinal neuronal sensitization. In contrast, overexpression of spinal METTL3 produced pain behaviors and neuronal sensitization in naive mice. Moreover, we found that METTL3 positively modulated the pri-miR-65-3p processing in a microprocessor protein DiGeorge critical region 8-dependent manner. Collectively, our findings reveal an important role of METTL3-mediated m6A modification in nociceptive sensitization and provide a novel perspective on m6A modification in the development of pathological pain.

PiRNA-DQ541777 Contributes to Neuropathic Pain via Targeting Cdk5rap1.

Piwi-Interacting RNA (piRNA) is the largest class of small noncoding RNA and is involved in various physiological and pathological processes. However, whether it has a role in pain modulation remains unknown. In the present study, we found that spinal piRNA-DQ541777 (piR-DQ541777) was significantly increased in the male mouse model of sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain. Knockdown of spinal piR-DQ541777 alleviated CCI-induced thermal hyperalgesia and mechanical allodynia and spinal neuronal sensitization. However, the overexpression of spinal piR-DQ541777 in naive mice produced pain behaviors and increased spinal neuron sensitization. Furthermore, we found that piR-DQ541777 regulates pain behaviors by targeting CDK5 regulatory subunit-associated protein 1 (Cdk5rap1). CCI increased the methylation level of CpG islands in the cdk5rap1 promoter and consequently reduced the expression of Cdk5rap1, which was reversed by the knockdown of piR-DQ541777 and mimicked by the overexpression of piR-DQ541777 in naive mice. Finally, piR-DQ541777 increased the methylation level of CpG islands by recruiting DNA methyltransferase 3A (DNMT3a) to cdk5rap1 promoter. In conclusion, this study represents a novel role of piR-DQ541777 in the regulation of neuropathic pain through the methylation of cdk5rap1SIGNIFICANCE STATEMENT Chronic pain affects ∼20% of the population of the world and is a major global public health problem. Although we have studied the neurobiological mechanism of neuropathic pain for decades, there is still no ideal drug available to treat it. This work indicates that a novel role of Piwi-interacting RNA (piRNA) DQ541777 in the regulation of neuropathic pain through the methylation of cdk5rap1 Our findings provide the first evidence of the regulatory effect of piRNAs on neuropathic pain, which may improve our understanding of pain mechanisms and lead to the discovery of novel drug targets for the prevention and treatment of neuropathic pain.

NF-κB p65-dependent transcriptional regulation of histone deacetylase 2 contributes to the chronic constriction injury-induced neuropathic pain via the microRNA-183/TXNIP/NLRP3 axis.

BACKGROUND: Neuropathic pain is related to the sustained activation of neuroglial cells and the production of proinflammatory cytokines in the spinal dorsal horn. However, the clinical efficacy of currently available treatments is very limited. The transcription factor nuclear factor κB (NF-κB) is a ubiquitously expressed protein family and considered to be crucial in autoimmunity. Thus, our study aimed to examine the influence of NF-κB p65 in chronic constriction injury (CCI)-induced neuropathic pain as well as its underlying mechanism. METHODS: A rat model of neuropathic pain was established by CCI induction followed by isolation of microglial cells. The binding of NF-κB p65 to HDAC2, of miR-183 to TXNIP, and of TXNIP to NLRP3 was investigated. Expression of miR-183, NF-κB p65, HDAC2, TXNIP, and NLRP3 was determined with their functions in CCI rats and microglial cells analyzed by gain- and loss-of-function experiments. RESULTS: NF-κB p65 and HDAC2 were upregulated while miR-183 was downregulated in the dorsal horn of the CCI rat spinal cord. NF-κB p65 was bound to the HDAC2 promoter and then increased its expression. HDAC2 reduced miR-183 expression by deacetylation of histone H4. Additionally, miR-183 negatively regulated TXNIP. Mechanistically, NF-κB p65 downregulated the miR-183 expression via the upregulation of HDAC2 and further induced inflammatory response by activating the TXNIP-NLRP3 inflammasome axis, thus aggravating the neuropathic pain in CCI rats and microglial cells. CONCLUSION: These results revealed a novel transcriptional mechanism of interplay between NF-κB and HDAC2 focusing on neuropathic pain via the miR-183/TXNIP/NLRP3 axis.

Densely Populated Bismuth Nanosphere Semi-Embedded Carbon Felt for Ultrahigh-Rate and Stable Vanadium Redox Flow Batteries.

The elaborate spatial arrangement and immobilization of highly active electrocatalysts inside porous substrates are crucial for vanadium redox flow batteries capable of high-rate charging/discharging and stable operation. Herein, a type of bismuth nanosphere/carbon felt is devised and fabricated via the carbothermic reduction of nanostructured bismuth oxides. The bismuth nanospheres with sizes of ≈25 nm are distributed on carbon fiber surfaces in a highly dispersed manner and its density reaches up to ≈500 pcs µm-2 , providing abundant active sites. Besides, a unique bismuth nanosphere semi-embedded carbon fiber structure with strong interfacial BiC chemical bonding is spontaneously formed during carbothermic reactions, offering an excellent mechanical stability under flowing electrolytes. It shows that the bismuth nanosphere semi-embedded carbon felt can effectively promote V(II)/V(III) redox reactions with appreciable catalytic activity. The battery with the present electrode sustains an energy efficiency of 77.1 ± 0.2% and an electrolyte utilization of 57.2 ± 0.2% even when a current density up to 480 mA cm-2 is applied, which are remarkably higher than those of batteries with the bismuth nanoparticle/carbon felt synthesized by the electrodeposition method (62.6 ± 0.1%, 23.6 ± 0.2%). Further, the battery with the present electrode demonstrates a stable energy efficiency retention of 98.2% after 1000 cycles.

MicroRNA-182-5p Regulates Nerve Injury-induced Nociceptive Hypersensitivity by Targeting Ephrin Type-b Receptor 1.

BACKGROUND: The authors and others have previously shown that the up-regulation of spinal ephrin type-b receptor 1 plays an essential role in the pathologic process of nerve injury-induced nociceptive hypersensitivity, but the regulatory mechanism remains unclear. METHODS: Radiant heat and von Frey filaments were applied to assess nociceptive behaviors. Real-time quantitative polymerase chain reaction, Western blotting, fluorescence in situ hybridization, immunofluorescence, immunohistochemistry, dual-luciferase reporter gene assays, recombinant lentivirus, and small interfering RNA were used to characterize the likely mechanisms. RESULTS: Periphery nerve injury induced by chronic constriction injury of the sciatic nerve significantly reduced spinal microRNA-182-5p (miR-182-5p) expression levels, which were inversely correlated with spinal ephrin type-b receptor 1 expression (R = 0.90; P < 0.05; n = 8). The overexpression of miR-182-5p in the spinal cord prevented and reversed the nociceptive behaviors induced by sciatic nerve injury, accompanied by a decreased expression of spinal ephrin type-b receptor 1 (recombinant lentiviruses containing pre-microRNA-182: 1.91 ± 0.34 vs. 1.24 ± 0.31, n = 4; miR-182-5p mimic: 2.90 ± 0.48 vs. 1.51 ± 0.25, n = 4). In contrast, the down-regulation of spinal miR-182-5p facilitated the nociceptive behaviors induced by sciatic nerve injury and increased the expression of spinal ephrin type-b receptor 1 (1.0 ± 0.26 vs. 1.74 ± 0.31, n = 4). Moreover, the down-regulation of miR-182-5p and up-regulation of ephrin type-b receptor 1 caused by sciatic nerve injury were mediated by the N-methyl-D-aspartate receptor. CONCLUSIONS: Collectively, our findings reveal that the spinal ephrin type-b receptor 1 is regulated by miR-182-5p in nerve injury-induced nociceptive hypersensitivity.

Preoperative Acute Normovolemic Hemodilution for Minimizing Allogeneic Blood Transfusion: A Meta-Analysis.

BACKGROUND: Previous studies have evaluated the efficacy of preoperative acute normovolemic hemodilution (PANH) in reducing the need for allogeneic blood transfusion. However, the results to date have been controversial. In this study, we sought to reassess the efficacy and safety of PANH based on newly emerging evidence. METHODS: Medline, EMBASE, ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials databases were searched using the key words "hemodilution," "autotransfusion," or "hemorrhage" to retrieve all randomized controlled trials examining the benefits of PANH compared with control patients not undergoing PANH in any type of surgery. RESULTS: Sixty-three studies involving 3819 patients were identified. The risk of requiring an allogeneic blood transfusion and the overall volume of allogeneic red blood cell transfused during the perioperative period were reduced in the PANH group compared with the control group (relative risk, 0.74; 95% confidence interval, 0.63 to 0.88; P = 0.0006; weighted mean difference, -0.94 units; 95% confidence interval, -1.27 to -0.61 units; P < 0.0001). However, there was significant heterogeneity (I2 = 79.6%, χ2 = 151.95, P < 0.0001; I2 = 95.3%, χ2 = 574.28, P < 0.0001) and publication bias (P = 0.001; P = 0.009) for both outcomes, limiting conclusions regarding the efficacy of PANH for reducing allogeneic transfusion. Perioperative blood loss, adverse events, and the length of hospitalization were comparable between these groups. CONCLUSIONS: Although these results suggest that PANH is effective in reducing allogeneic blood transfusion, we identified significant heterogeneity and publication bias, which raises concerns about the true efficacy of PANH.

Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain.

BACKGROUND: The analgesic potency of opioids is reduced in neuropathic pain. However, the molecular mechanism is not well understood. RESULTS: The present study demonstrated that increased methylation of the Mu opioid receptor (MOR) gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and intraplantar (i.pl.), not intracerebroventricular (i.c.v.) injection of morphine, the potency of morphine analgesia was significantly reduced in nerve-injured mice compared with control sham-operated mice. After peripheral nerve injury, we observed a decreased expression of MOR protein and mRNA, accompanied by an increased methylation status of MOR gene PP, in DRG. However, peripheral nerve injury could not induce a decreased expression of MOR mRNA in the spinal cord. Treatment with 5-aza-2'-deoxycytidine (5-aza-dC), inhibited the increased methylation of MOR gene PP and prevented the decreased expression of MOR in DRG, thereby improved systemic, spinal and periphery morphine analgesia. CONCLUSIONS: Altogether, our results demonstrate that increased methylation of the MOR gene PP in DRG is required for the decreased morphine analgesia in neuropathic pain.

Tin Hybrid Flow Batteries with Ultrahigh Areal Capacities Enabled by Double Gradients.

Tin-based hybrid flow batteries have demonstrated dendrite-free morphology and superior performance in terms of cycle life and energy density. However, the quick accumulation of electrodeposits near the electrode/membrane interface blocks the ion transport pathway during the charging of the battery, resulting to a very limited areal capacity (especially at high current density) that significantly hinders its deployment in long-duration storage applications. Herein, a conductivity-activity dual-gradient design is disclosed by electrically passivating the carbon felt near the membrane/electrode interface and chemically activating the carbon felt near the electrode/current collector interface. In consequence, the tin metals are preferentially plated at the region near electrode/current collector, preventing the ion transport pathway from being easily blocked. The resultant gradient electrode demonstrated an unprecedentedly high areal capacity of 268 mAh cm-2 at a current density of as high as 80 mA cm-2 . Numerical modeling and experimental characterizations show that the dual-gradient electrode differs from conventional electrodes with regard to their reaction current density distribution and electrodeposit distribution during charging. This work demonstrates a new design strategy of 3D electrodes for hybrid flow batteries to induce a desirable distribution of electrodeposits and achieve a high areal capacity at commercially relevant current densities.

Single and double developing lines improve ultrasound-guided radial artery catheterization in obese patients: A randomized controlled trial.

BACKGROUND: Arterial catheterization is challenging in obese patients. The present study tested the hypothesis that ultrasound guidance with acoustic shadowing improves the success rate of radial artery catheterization in obese patients. METHODS: 240 obese patients were enrolled and were randomly assigned to three groups: control group, single developing line group, or double developing lines group. Patients underwent radial artery catheterization guided by acoustic shadowing ultrasound with none, single or double developing lines. The primary outcome was the first-attempt success rate. The secondary outcomes included the procedure time and complication rate. RESULTS: In the single or double developing lines group, the success rate of radial artery catheterization at the first attempt was higher than in the control group (control vs. single vs. double, 71% vs. 90% vs. 91%, P = 0.001). Besides, the single and double developing lines groups had a shorter procedure time to success at the first attempt and a lower overall complication (vasospasm and hematoma) rate than the control group (procedure time: control vs. single vs. double, 63 s vs. 54 s vs. 40 s, P < 0.001; overall complication rate: control vs. single vs. double, 29% vs. 10% vs. 9%, P = 0.001). There was no significant difference in the first-attempt success rate, the procedure time to success within the first attempt, or overall complications' rate between the single and double developing lines groups. CONCLUSION: Single and double developing lines improve first-attempt success rate and reduced the overall complications' rate of ultrasound-guided radial artery catheterization in obese patients.

Asymmetric Chemical Potential Activated Nanointerfacial Electric Field for Efficient Vanadium Redox Flow Batteries.

Constructing active sites with enhanced intrinsic activity and accessibility in a confined microenvironment is critical for simultaneously upgrading the round-trip efficiency and lifespan of all-vanadium redox flow battery (VRFB) yet remains under-explored. Here, we present nanointerfacial electric fields (E-fields) featuring outstanding intrinsic activity embodied by binary Mo2C-Mo2N sublattice. The asymmetric chemical potential on both sides of the reconstructed heterogeneous interface imposes the charge movement and accumulation near the atomic-scale N-Mo-C binding region, eliciting the configuration of an accelerator-like E-field from Mo2N to Mo2C sublattice. Supported with theoretical calculations and intrinsic activity tests, the improved vanadium ion adsorption behavior and charge-transfer process at the nanointerfacial sites were further substantiated, hence expediting the electrochemical kinetics. Accordingly, the pronounced promotion is achieved in the resultant flow battery, yielding an energy efficiency of 77.7% and an extended lifespan of 1000 cycles at 300 mA cm-2, outperforming flow cells with conventional single catalysts in most previous reports.

Effect of Acute Brief Social Isolation on Visceral Pain.

Objective: The sensitivity of somatic pain could be affected by social isolation; however, few studies have examined the impact of social isolation on visceral pain. In the present study, the effect of acute brief social isolation on visceral pain response was investigated. Methods: Adult male rats were either reared individually or grouped for 2 hours or 24 hours. Colorectal distention (CRD)-induced abdominal withdrawal reflex (AWR) score and pain threshold were used to assess visceral pain sensitivity. The amount of fecal bolus was used to determine the stress level. Results: Acute brief isolation rearing for 2 hours significantly increased AWR score and reduced visceral pain threshold in rats when compared to group rearing. Similarly, acute isolation for 24 hours resulted in visceral hypersensitivity, as indicated by an increase in the AWR score and a decrease in the visceral pain threshold. Furthermore, the amount of fecal bolus in acute isolation rearing (2 or 24 hours) rats was considerably higher than in the control group rearing rats. Conclusion: Acute short-term social isolation enhances visceral pain sensitivity, which could be related to an increase in stress levels.

Long-term social isolation increases visceral pain in rats.

Long-term social isolation can alter the sensitivity to somatic pain, however, its impact on visceral pain sensitivity remains unknown. The purpose of this study is to investigate the effect of long-term social isolation on visceral pain sensitivity in rats. 4-week social isolation rearing significantly increased CRD-induced AWR score and decreased pain threshold as compared to group rearing. There was no significant difference in the number of spontaneous visceral pain behaviors between group and isolation rearing rats. The number of fecal bolus produced by isolation rearing rats was comparable to that produced by group rearing rats. Consistent with 4-week isolation, CRD-induced AWR score in 8-week isolation rearing rats was higher than that in group rearing rats. While, pain threshold was lower in 8-week isolation rearing rats than in group rearing rats. There was no significant difference in the number of spontaneous visceral pain behaviors and fecal bolus between 8-week isolation and group rearing rats. There results indicated that long-term social isolation induces visceral hypersensitivity in rats, but this effect is unrelated to an increase in stress levels.

Effect of low-dose lidocaine on MEPs in patients undergoing intracranial tumor resection with propofol anesthesia: A randomized controlled trial.

OBJECTIVE: To investigate the effect of low-dose lidocaine on motor evoked potentials (MEPs) in patients undergoing intracranial tumor resection with propofol anesthesia. METHODS: Forty patients who underwent intracranial tumor resection and required MEP monitoring were selected. They were randomly divided into the lidocaine group (group L, n = 20) and the control group (group C, n = 20) by computer-generated randomization. All patients were given propofol anesthesia under the guidance of the bispectral index. In group L, 1 mg/kg of lidocaine was injected intravenously during anesthesia induction. Then, lidocaine was continuously pumped at a speed of 1 mg/kg/h until the operation started. Group C was given an equal volume of normal saline. Heart rate (HR), mean artery pressure (MAP), and bispectral index were recorded before anesthesia induction (T0), 2 minutes after tracheal intubation (T1), and 35 minutes (T2), and 50 minutes (T3) after anesthesia induction. The amplitude and latency of MEP at T2 and T3, the total dosage of propofol after anesthesia induction, and adverse events before T3 were recorded. RESULTS: Compared with those in group C, HR and MAP were significantly decreased at T1 in group L. No significant differences were observed in HR and MAP at T0, T2, and T3 between group L and group C. The total dosage of propofol and the incidence of adverse events were significantly lower in group L than in group C before T3. There were no significant differences in the amplitude and latency of MEP between the 2 groups at each time point. CONCLUSIONS: Low-dose lidocaine has no obvious effect on MEP in patients undergoing intracranial tumor resection. However, it increased hemodynamic stability, reduced propofol use, and decreased the incidence of adverse events.

Flexible Carbon Sponge Electrodes for All Vanadium Redox Flow Batteries.

In the present work, a flexible carbon sponge is experimentally characterized and proposed as an alternative electrode for advanced vanadium redox flow batteries. Such an electrode is prepared via directly carbonizing the commercially-available and inexpensive melamine formaldehyde resin sponge in argon, to inherit the well-defined and three-dimensional bi-continuous architecture of the melamine sponge with 99.6% porosity and 40 µm average pore size. By applying the carbon sponges as the electrodes, it is demonstrated that the vanadium flow battery at 200 mA cm-2 can yield an energy efficiency of 77.9%, significantly higher than that with commonly-used graphite felt electrodes (72.9%). After a thermal treatment in air, the energy efficiency of carbon sponge can further be improved to 81.2% at mA cm-2 due to introduction of favorable oxygen containing functionalities. The operating stability with the carbon sponge is proven by a 200 cycling test with minor efficiency decay.

Astrocyte-neuron lactate transport in the ACC contributes to the occurrence of long-lasting inflammatory pain in male mice.

Lactate transport is an important means of communication between astrocytes and neurons and is implicated in a variety of neurobiological processes. However, the connection between astrocyte-neuron lactate transport and nociceptive modulation has not been well established. Here, we found that Complete Freund's adjuvant (CFA)-induced inflammation pain leads to a significant increase in extracellular lactate levels in the anterior cingulate cortex (ACC). Inhibition of glycogenolysis and lactate release in the ACC disrupted the persistent, but not acute, inflammation pain induced by CFA, and this effect was reversed by exogenous L-lactate administration. Knocking down the expression of lactate transporters (MCT1, MCT4, or MCT2) also disrupted the long lasting inflammation pain induced by CFA. Moreover, glycogenolysis in the ACC is critical for the induction of molecular changes related to neuronal plasticity, including the induction of phospho- (p-) ERK, p-CREB, and Fos. Taken together, our findings indicate that astrocyte-neuron lactate transport in the ACC is critical for the occurrence of persistent inflammation pain, suggesting a novel mechanism underlying chronic pain.

Promoting Pore-Level Mass Transport/Reaction in Flow Batteries: Bi Nanodot/Vertically Standing Carbon Nanosheet Composites on Carbon Fibers.

Elaborate nanoarchitectured solid/liquid interface design of felt electrodes is arguably the most effective pathway to promote the pore-level transport-reaction processes of redox flow batteries. Herein, we conceive a new type of nanocatalytic-layer-architectured graphite felt via introducing the vertically standing carbon nanosheet-confined Bi nanodots onto carbon fiber surfaces. The vertically standing carbon nanosheets construct a nanoporous layer with straight channels for vanadium ion shuttling, where highly dispersed Bi nanodots are stiffly confined to afford abundant active sites. The vanadium redox flow battery utilizing the rationally designed electrodes achieves an energy efficiency of 89% at 150 mA cm-2, which is substantially higher than those of raw felt (61%) and oxidized felt (77%). Also, the battery with the present electrode maintains an energy efficiency of over 73% even at 400 mA cm-2, showing the excellent capability of withstanding fast charging and discharging. The multiphysics simulation shows that the vertically standing architecture optimizes the vanadium ion accessibility to the solid/liquid interfaces and thus maximizes the catalytic activity. Moreover, the battery can sustain more than 1000 cycles without obvious efficiency decay, confirming the superb stability of the present electrode. These encouraging results indicate that engineering vertically standing structures with tailored compositions may open up new avenues for advancing the flow battery technology.

Circular RNA hsa_circ_0006401 promotes proliferation and metastasis in colorectal carcinoma.

Dysregulation of circular RNA (circRNA) expression is involved in the progression of cancer. Here, we aimed to study the potential function of hsa_circ_0006401 in colorectal cancer (CRC). CircRNA hsa_circ_0006401 expression levels in CRC and adjacent nontumor tissues were analyzed by real-time quantitative PCR (qRT-PCR) and circRNA in situ hybridization (RNA-ISH). Then, CRC cell proliferation was assessed by cell counting. Wound-healing and transwell assays were utilized to detect the effect of hsa_circ_0006401 on CRC migration. A circRNA-ORF construct was created, and a specific antibody against the splice junction of hsa_circ_0006401 was prepared. Finally, the proteins directly binding to hsa_circ_0006401 peptides were identified by immunoprecipitation combined with mass spectrometry. In our study, we found hsa_circ_0006401 was closely related to CRC metastasis and exhibited upregulated expression in metastatic CRC tissue samples. Proliferation and migration were inhibited in vitro when hsa_circ_0006401 expression was silenced. Downregulation of hsa_circ_0006401 expression decreased CRC proliferation and liver metastasis in vivo. A 198-aa peptide was encoded by sequences of the splice junction absent from col6a3. Hsa_circ_0006401 promoted CRC proliferation and migration by encoding the hsa_circ_0006401 peptide. Hsa_circ_0006401 peptides decreased the mRNA and protein level of the host gene col6a3 by promoting col6a3 mRNA stabilation. In conclusion, our study revealed that circRNAs generated from col6a3 that contain an open-reading frame (ORF) encode a novel 198-aa functional peptide and hsa_circ_0006401 peptides promote stability of the host gene col6a3 mRNA to promote CRC proliferation and metastasis.

Transcribed ultraconserved noncoding RNA uc.153 is a new player in neuropathic pain.

Transcribed ultraconserved regions are a novel class of long noncoding RNAs and are completely conserved in humans, rats, and mice. Transcribed ultraconserved regions have been implicated in diverse biological processes; however, very little is currently known about their role in pain modulation. Here, we found that the level of the spinal transcribed ultraconserved region uc.153 was significantly increased in a mouse model of sciatic nerve chronic constriction injury (CCI)-induced chronic neuropathic pain. The knockdown of spinal uc.153 prevented and reversed chronic constriction injury-induced pain behaviours and spinal neuronal sensitization. By contrast, the overexpression of spinal uc.153 produced pain behaviours and neuronal sensitization in naive mice. Moreover, we found that uc.153 participates in the regulation of neuropathic pain by negatively modulating the processing of pre-miR-182-5p. Collectively, our findings reveal an important role for uc.153 in pain modulation and provide a novel drug target for neuropathic pain therapy.