Search

The advancement of electronic technology has led to increasing research on performance and stability. Continuous electrical pulse stimulation can cause crystal structure changes, affecting performance and accelerating aging. Controlled repair of these defects is crucial. In this study, we investigated crystal structure changes in van der Waals (vdW) InSe crystals under continuous electric pulses by using electron beam lithography (EBL) and spherical aberration corrected transmission electron microscopy (Cs-TEM). Results show that electrical pulses induce amorphous regions in the InSe lattice, increasing the device resistance. We used Cs-STEM probe scanning for precise repair, abbreviated SPRT, to optimize device performance. SPRT is related to electric fields induced by the electron beam and can be applied to other 2D materials like α-In 2 Se 3 and CrSe 2 , offering a potential approach to extend device lifespan.

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as potential therapeutic strategies. A systematic review and analysis must be carried out to investigate the effect of mannose modification on the immune response to nanoparticles in regulating the tumor microenvironment, as well as to explore its potential clinical application in tumor therapy. Despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and the overexpression of immunosuppressive factors limit its clinical application. Therefore, our review explored how to intervene in the immunosuppressive mechanism in the tumor microenvironment through the use of mannan-decorated lipid calcium phosphate nanoparticle vaccines to improve the efficacy of immunotherapy in patients with tumors and to provide new ideas and strategies for the field of tumor therapy.

Insulin has been shown to modulate neuronal processes through insulin receptors. The ion channels located on neurons may be important targets for insulin/insulin receptor signaling. Both insulin receptors and acid-sensing ion channels (ASICs) are expressed in dorsal root ganglia (DRG) neurons. However, it is still unclear whether there is an interaction between them. Therefore, the purpose of this investigation was to determine the effects of insulin on the functional activity of ASICs. A 5 min application of insulin rapidly enhanced acid-evoked ASIC currents in rat DRG neurons in a concentration-dependent manner. Insulin shifted the concentration-response plot for ASIC currents upward, with an increase of 46.2 ± 7.6% in the maximal current response. The insulin-induced increase in ASIC currents was eliminated by the insulin receptor antagonist GSK1838705, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol-3 kinase antagonist wortmannin. Moreover, insulin increased the number of acid-triggered action potentials by activating insulin receptors. Finally, local administration of insulin exacerbated the spontaneous nociceptive behaviors induced by intraplantar acid injection and the mechanical hyperalgesia induced by intramuscular acid injections through peripheral insulin receptors. These results suggested that insulin/insulin receptor signaling enhanced the functional activity of ASICs via tyrosine kinase and phosphatidylinositol-3 kinase pathways. Our findings revealed that ASICs were targets in primary sensory neurons for insulin receptor signaling, which may underlie insulin modulation of pain., (© 2024. The Author(s).)

Both CXCL10/CXCR3 and acid-sensing ion channels (ASICs) are expressed in nociceptive sensory neurons and participate in various pain processes, but it is still unclear whether there is a link between them. Herein, we report that CXCL10 enhances the electrophysiological activity of ASICs in rat dorsal root ganglia (DRG) neurons. A brief (10 min) application of CXCL10 increased acid-evoked ASIC currents in a concentration-dependent manner. CXCL10 increased the maximum response of ASICs to acidic stimuli without changing their sensitivity. CXCL10 enhanced ASIC currents in DRG cells through CXCR3, as this enhancement was completely blocked by AMG487, a selective CXCR3 antagonist. CXCL10 also increased ASIC3 currents in CHO cells coexpressing ASIC3 and CXCR3 but not in cells expressing ASIC3 alone. The CXCL10-mediated increase in ASIC currents was prevented by the application of either the G protein inhibitor GDP-β-S or the p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 but not by the ERK inhibitor U0126 or the JNK inhibitor SP600125. Moreover, CXCL10 increased the number of action potentials triggered by acidic stimuli via CXCR3. CXCL10 dose-dependently exacerbated acid-induced nociceptive behavior in rats through peripheral CXCR3. These results indicated that CXCL10/CXCR3 signaling enhanced ASIC-mediated electrophysiological activity in DRG neurons and nociception in rats via a p38 MAPK-dependent pathway, revealing a novel mechanism underlying pain. CXCL10/CXCR3 signaling may be an effective target in the treatment of pain associated with tissue acidification., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The NK cell is an important component of the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC), also plays a significant role in PDAC development. This study aimed to explore the relationship between NK cell marker genes and prognosis, immune response of PDAC patients. By scRNA-seq data, we found the proportion of NK cells were significantly downregulated in PDAC and 373 NK cell marker genes were screened out. By TCGA database, we enrolled 7 NK cell marker genes to construct the signature for predicting prognosis in PDAC patients. Cox analysis identified the signature as an independent factor for pancreatic cancer. Subsequently, the predictive power of signature was validated by 6 GEO datasets and had an excellent evaluation. Our analysis of relationship between the signature and patients' immune status revealed that the signature has a strong correlation with immunocyte infiltration, inflammatory reaction, immune checkpoint inhibitors (ICIs) response. The NK cell marker genes are closely related to the prognosis and immune capacity of PDAC patients, and they have potential value as a therapeutic target., (© 2024. The Author(s).)

Purpose: To examine radiologist experiences and perceptions during a transition from score-based peer review to a peer learning program, and to assess differences in time-cost efficiency between the two models of quality improvement., Methods: Differences in Likert scale survey responses from radiologists (N = 27) in a multispecialty group at a single tertiary academic center before and following intervention were evaluated by Mann-Whitney U test. Multiple variable linear regression analysis assessed independent variables and program preference., Results: All positive impacts rated significantly higher for the peer learning program. Workflow disruption for the peer learning program rated significantly lower. 70.4 % (19 of 27) preferred the new program, and 25.9 % (7 of 27) preferred the old program. Only the "worth investment" questionnaire score demonstrated a significant correlation to program preference and with an effect that was greatest among all variables (Beta = 1.11, p = 0.02). There was a significantly decreased amount of time per month used to complete peer learning exercises (0.76 ± 0.45 h, N = 27) versus peer review exercises (1.71 ± 1.84 h, N = 34, p = 0.011). The result was a difference of 0.95 ± 1.89 h/month (11.4 ± 22.7 h/year), translating to an estimated direct salary time-cost saving of $1653.68/year/radiologists and a direct productivity time-cost saving of $3469.39/year/radiologist when utilizing the peer learning program., Conclusions: There was a strongly positive perception of the new peer learning program. There was a substantial implied direct time-cost saving from the transition to the peer learning program., Precis: The peer learning model emphasizes learning from errors via feedback in a non-punitive environment. This model was positively perceived and demonstrated substantial implied direct time-cost saving., 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. Published by Elsevier Inc.)

Cholecystokinin (CCK) is a peptide that has been implicated in pain modulation. Acid sensitive ion channels (ASICs) also play an important role in pain associated with tissue acidification. However, it is still unclear whether there is an interaction between CCK signaling and ASICs during pain process. Herein, we report that a functional link between them in rat dorsal root ganglion (DRG) neurons. Pretreatment with CCK-8 concentration-dependently increased acid-evoked ASIC currents. CCK-8 increased the maximum response of ASICs to acid, but did not changed their acid sensitivity. Enhancement of ASIC currents by CCK-8 was mediated by the stimulation of CCK2 receptor (CCK2R), rather than CCK1R. The enhancement of ASIC currents by CCK-8 was prevented by application of either G-protein inhibitor GDP-β-S or protein kinase C (PKC) inhibitor GF109203×, but not by protein kinase A (PKA) inhibitor H-89 or JNK inhibitor SP600125. Moreover, CCK-8 increased the number of action potentials triggered by acid stimuli by activating CCK2R. Finally, CCK-8 dose-dependently exacerbated acid-induced nociceptive behavior in rats through local CCK2R. Together, these results indicated that CCK-8/CCK2R activation enhanced ASIC-mediated electrophysiological activity in DRG neurons and nociception in rats. The enhancement effect depended on G-proteins and intracellular PKC signaling rather than PKA and JNK signaling pathway. These findings provided that CCK-8/CCK2R is an important therapeutic target for ASIC-mediated pain., 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 Ltd. All rights reserved.)

Resolvin D2 (RvD2), an endogenous lipid mediator derived from docosahexaenoic acid, has been demonstrated to have analgesic effects. However, little is known about the mechanism underlying RvD2 in pain relief. Herein, we demonstrate that RvD2 targeted the P2X3 receptor as an analgesic. The electrophysiological activity of P2X3 receptors was suppressed by RvD2 in rat dorsal root ganglia (DRG) neurons. RvD2 pre-application dose-dependently decreased α,β-methylene-ATP (α,β-meATP)-induced inward currents. RvD2 remarkably decreased the maximum response to α,β-meATP, without influencing the affinity of P2X3 receptors. RvD2 also voltage-independently suppressed ATP currents. An antagonist of the G protein receptor 18 (GPR18), O-1918, prevented the RvD2-induced suppression of ATP currents. Additionally, intracellular dialysis of the Gα i/o -protein antagonist pertussis toxin (PTX), the PKA antagonist H89, or the cAMP analog 8-Br-cAMP also blocked the RvD2-induced suppression. Furthermore, α,β-meATP-triggered depolarization of membrane potential along with the action potential bursts in DRG neurons were inhibited by RvD2. Lastly, RvD2 attenuated spontaneous nociceptive behaviors as well as mechanical allodynia produced by α,β-meATP in rats via the activation of the peripheral GPR18. These findings indicated that RvD2 inhibited P2X3 receptors in rat primary sensory neurons through GPR18, PTX-sensitive Gα i/o -proteins, and intracellular cAMP/PKA signaling, revealing a novel mechanism that underlies its analgesic effects by targeting P2X3 receptors., (© 2023 International Society for Neurochemistry.)

Endowing room-temperature polymorphs with both long-term stability and easy interconvertibility is a big challenge due to the complexity of intermolecular interactions. Herein, we present a chiral hexagonal perovskite (R-3-hydroxy-1-methylpiperidinium)[CdCl 3 ] having two room-temperature crystalline forms featuring obviously distinct second-harmonic-generation (SHG) signals with a high switching contrast of ~18 times. The two room-temperature forms could be long-term stable yet easily interconvertible through an irreversible thermal-induced phase transition and a pressure-driven backward transition, by switching hydrogen bonds via collective reorientation of ordered homochiral cations. Based on the essential role of homochiral organic cations in inducing switchable hydrogen bond linkages, this present instance provides good evidence that relatively irregular organic cations could induce more obvious inorganic chain deformations, thus endowing polymorphs with significantly different SHG signals at room temperature., (© 2023 Wiley-VCH GmbH.)

In the area of manipulating the spatial electromagnetic (EM) waves fields, the metasurfaces have become much more attractive and powerful in recent years. Here, we propose a design to realize the simultaneous control of spatial fundamental and harmonic EM waves applying nonlinear metasurfaces in microwave band. The proposed meta-atom composed of three topological layers which are transmitting antenna, nonlinear wave guiding and receiving antenna respectively. And the critical factor of generating the harmonic is the nonlinear chip which is integrated into the middle layer. The microstrip power divider and phase shifter in each meta-atom are preciously tailored to actualize the spatial control of the fundamental and harmonic transmission beams in the far field. One prototype of the nonlinear metasurfaces is fabricated and corresponding radiation patterns of fundamental and harmonic modes are observed very well in the experience that can verify the validity of our proposed method.

Northern corn leaf blight, caused by the fungal pathogen Exserohilum turcicum, is a major disease of maize. The first major locus conferring resistance to E. turcicum race 0, Ht1, was identified over 50 years ago, but the underlying gene has remained unknown. We employed a map-based cloning strategy to identify the Ht1 causal gene, which was found to be a coiled-coil nucleotide-binding, leucine-rich repeat (NLR) gene, which we named PH4GP-Ht1. Transgenic testing confirmed that introducing the native PH4GP-Ht1 sequence to a susceptible maize variety resulted in resistance to E. turcicum race 0. A survey of the maize nested association mapping genomes revealed that susceptible Ht1 alleles had very low to no expression of the gene. Overexpression of the susceptible B73 allele, however, did not result in resistant plants, indicating that sequence variations may underlie the difference between resistant and susceptible phenotypes. Modelling of the PH4GP-Ht1 protein indicated that it has structural homology to the Arabidopsis NLR resistance gene ZAR1, and probably forms a similar homopentamer structure following activation. RNA sequencing data from an infection time course revealed that 1 week after inoculation there was a threefold reduction in fungal biomass in the PH4GP-Ht1 transgenic plants compared to wild-type plants. Furthermore, PH4GP-Ht1 transgenics had significantly more inoculation-responsive differentially expressed genes than wild-type plants, with enrichment seen in genes associated with both defence and photosynthesis. These results demonstrate that the NLR PH4GP-Ht1 is the causal gene underlying Ht1, which represents a different mode of action compared to the previously reported wall-associated kinase northern corn leaf blight resistance gene Htn1/Ht2/Ht3., (© 2022 PIONEER HI-BRED INTERNATIONAL, INC. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Liver cancer (LC) is a malignant tumour that is associated with high mortality rates worldwide. Cell division cycle 23 (CDC23) acts as an oncogene in papillary thyroid cancer. In addition, epithelial-mesenchymal transition (EMT) is frequently involved in the malignant metastasis of various cancer types. Therefore, we hypothesized that CDC23 may regulate the malignant biological behaviours of LC cells through EMT. Proliferation, colony formation and Transwell assays, western blotting and xenograft experiments were performed. The results of the present study showed that CDC23 was highly expressed in LC cell lines. In addition, it was found via multiple in vitro assays that CDC23 knockdown reduced the proliferation, migration and invasion of LC cell lines. Finally, an in vivo study confirmed that CDC23 knockdown inhibited the growth of xenograft LC in nude mice. More importantly, the changes in the levels of EMT-related marker proteins were analysed in the sh-CDC23 group compared with the sh-NC group of cells and xenografts. E-cadherin was upregulated, and N-cadherin and vimentin were significantly downregulated after CDC23 silencing. Taken together, these results revealed that the knockdown of CDC23 inhibits the progression of LC by regulating EMT and that CDC23 may be a novel therapeutic target for LC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhang et al.)

Introduction: Cancer patients treated with paclitaxel often develop chemotherapy-induced peripheral neuropathy, which has not been effectively treated with drugs. The anti-diabetic drug metformin is effective in the treatment of neuropathic pain. The aim of this study was to elucidate effect of metformin on paclitaxel-induced neuropathic pain and spinal synaptic transmission., Methods: Electrophysiological experiments on rat spinal slices were performed in vitro and mechanical allodynia quantified in vitro ., Results: The present data demonstrated that intraperitoneal injection of paclitaxel produced mechanical allodynia and potentiated spinal synaptic transmission. Intrathecal injection of metformin significantly reversed the established mechanical allodynia induced by paclitaxel in rats. Either spinal or systemic administration of metformin significantly inhibited the increased frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in spinal dorsal horn neurons from paclitaxel-treated rats. We found that 1 h incubation of metformin also reduced the frequency rather than the amplitude of sEPSCs in the spinal slices from paclitaxel-treated rats., Discussion: These results suggested that metformin was able to depress the potentiated spinal synaptic transmission, which may contribute to alleviating the paclitaxel-induced neuropathic pain., 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 © 2023 Liu, Qiu and Hu.)

Background: Chemotherapy is the standard of treatment for metastatic gallbladder carcinoma (GBC). It is unclear whether chemotherapy plus surgery improves the survival outcomes of patients with isolated liver metastases from GBC. We aimed to investigate the survival benefits of chemotherapy plus surgery in GBC with isolated liver metastases compared to those of chemotherapy alone., Methods: We identified 406 patients with isolated liver metastases from GBC who underwent chemotherapy alone or chemotherapy plus surgery between 2010 and 2015 from Surveillance, Epidemiology, and End Results. Patients were divided into 3 subgroups: group I, chemotherapy alone (n = 263); group II, chemotherapy combined with cholecystectomy (n = 116); and group III, chemotherapy combined with cholecystectomy plus hepatectomy (n = 27). The cancer-specific survival and overall survival were evaluated., Results: Compared with group I, group II revealed a longer survival time (P < .001). In addition, the survival time of the group III was also prolonged (P < .001). Multivariate cox analysis showed that treatment strategy was an independent prognostic factor., Conclusion: Chemotherapy combined with resection of the primary tumor plus or not plus resection of the metastatic lesions may be beneficial in GBC with isolated liver metastases.

P2X3 receptors and group II metabotropic glutamate receptors (mGluRs) have been found to be expressed in primary sensory neurons. P2X3 receptors participate in a variety of pain processes, while the activation of mGluRs has an analgesic effect. However, it's still unclear whether there is a link between them in pain. Herein, we reported that the group II mGluR activation inhibited the electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) neurons. Group II mGluR agonist LY354740 concentration-dependently decreased P2X3 receptor-mediated and α,β-methylene-ATP (α,β-meATP)-evoked inward currents in DRG neurons. LY354740 significantly suppressed the maximum response of P2X3 receptor to α,β-meATP, but did not change their affinity. Inhibition of ATP currents by LY354740 was blocked by the group II mGluR antagonist LY341495, also prevented by the intracellular dialysis of either the G i/o protein inhibitor pertussis toxin, the cAMP analog 8-Br-cAMP, or the protein kinase A (PKA) inhibitor H-89. Moreover, LY354740 decreased α,β-meATP-induced membrane potential depolarization and action potential bursts in DRG neurons. Finally, intraplantar injection of LY354740 also relieved α,β-meATP-induced spontaneous nociceptive behaviors and mechanical allodynia in rats by activating peripheral group Ⅱ mGluRs. These results indicated that peripheral group II mGluR activation inhibited the functional activity of P2X3 receptors via a G i/o protein and cAMP/PKA signaling pathway in rat DRG neurons, which revealed a novel mechanism underlying analgesic effects of peripheral group II mGluRs. This article is part of the Special Issue on "Purinergic Signaling: 50 years"., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Acid-sensing ion channels (ASICs) play an important role in pain associated with tissue acidification. Peripheral inhibitory group II metabotropic glutamate receptors (mGluRs) have analgesic effects in a variety of pain conditions. Whether there is a link between ASICs and mGluRs in pain processes is still unclear. Herein, we show that the group II mGluR agonist LY354740 inhibited acid-evoked ASIC currents and action potentials in rat dorsal root ganglia neurons. LY354740 reduced the maximum current response to protons, but it did not change the sensitivity of ASICs to protons. LY354740 inhibited ASIC currents by activating group II mGluRs. We found that the inhibitory effect of LY354740 was blocked by intracellular application of the G i/o protein inhibitor pertussis toxin and the cAMP analogue 8-Br-cAMP and mimicked by the protein kinase A (PKA) inhibitor H-89. LY354740 also inhibited ASIC3 currents in CHO cells coexpressing mGluR2 and ASIC3 but not in cells expressing ASIC3 alone. In addition, intraplantar injection of LY354740 dose-dependently alleviated acid-induced nociceptive behavior in rats through local group II mGluRs. Together, these results suggested that activation of peripheral group II mGluRs inhibited the functional activity of ASICs through a mechanism that depended on G i/o proteins and the intracellular cAMP/PKA signaling pathway in rat dorsal root ganglia neurons. We propose that peripheral group II mGluRs are an important therapeutic target for ASIC-mediated pain., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Model-free reinforcement learning algorithms based on entropy regularized have achieved good performance in control tasks. Those algorithms consider using the entropy-regularized term for the policy to learn a stochastic policy. This work provides a new perspective that aims to explicitly learn a representation of intrinsic information in state transition to obtain a multimodal stochastic policy, for dealing with the tradeoff between exploration and exploitation. We study a class of Markov decision processes (MDPs) with divergence maximization, called divergence MDPs. The goal of the divergence MDPs is to find an optimal stochastic policy that maximizes the sum of both the expected discounted total rewards and a divergence term, where the divergence function learns the implicit information of state transition. Thus, it can provide better-off stochastic policies to improve both in robustness and performance in a high-dimension continuous setting. Under this framework, the optimality equations can be obtained, and then a divergence actor-critic algorithm is developed based on the divergence policy iteration method to address large-scale continuous problems. The experimental results, compared to other methods, show that our approach achieved better performance and robustness in the complex environment particularly. The code of DivAC can be found in https://github.com/yzyvl/DivAC.

The main objective of present study was to understand the community succession of microbial populations related to carbon-nitrogen-phosphorus-sulfur (CNPS) biogeochemical cycles during cow-manure-driven composting and their correlation with product maturity. The abundance of microbial populations associated with C degradation, nitrification, cellular-P transport, inorganic-P dissolution, and organic-P mineralization decreased gradually with composting but increased at the maturation phase. The abundance of populations related to N-fixation, nitrate-reduction, and ammonification increased during the mesophilic stage and decreased during the thermophilic and maturation stages. The abundance of populations related to C fixation and denitrification increased with composting; however, the latter tended to decrease at the maturation stage. Populations related to organic-P mineralization were the key manipulators regulating compost maturity, followed by those related to denitrification and nitrification; those populations were mediated by inorganic N and available P content. This study highlighted the consequence of microbe-driven P mineralization in improving composting efficiency and product quality., 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 © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To compare the consistency between the actual diameter of capsulotomy (ADC) and the predicted diameter of capsulotomy (PDC) in femtosecond laser-assisted cataract surgery (FLACS) and analyze the factors that influence the deviation of the diameter of capsulotomy (DDC) between the actual and predicted., Setting: Aier Eye Hospital of Wuhan University, China., Design: Retrospective observational case series., Methods: Patients who underwent FLACS from March 2020 to March 2021 were reviewed. The ADC in FLACS was measured and compared with the PDC. The effects of age, sex, and biometrics on DDC were analyzed., Results: 412 eyes of 336 patients were included. The mean age was 53.0 ± 0.91 years (range 3 to 91 years). When the PDC was set to 4.50 mm, the results showed that the ADC was 5.21 ± 0.21 mm with a significant difference between them ( P &lt; .05). However, when the PDC was set to 5.2 mm, the ADC was 5.10 ± 0.38 mm without a significant difference between them ( P &gt; .05). No correlation ( P &gt; .05) was found between the DDC and the axial length, the DDC and the anterior chamber depth (ACD), and the DDC and the mean keratometry (Km), but a negative correlation was found between the DDC and the lens thickness (LT) ( r = -0.21; P &lt; .05) and the DDC with age ( r = -0.70; P &lt; .05). Using curvilinear regression analysis, a development of an age-depending correction formula was predicted: ADC = PDC + 1.23 - 0.30 ln (x) (x = age ≥3) ( R2 = 0.65; F = 752.39; P = .00)., Conclusions: The consistency of the ADC and PDC was influenced by age and LT. For patients aged 40 years or younger, the younger the patient, the wider the DDC; for patients older than 40 years, the DDC was small. The thicker the LT, the smaller the DDC., (Copyright © 2022 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purinergic signaling is involved in multiple pain processes. P2X3 receptor is a key target in pain therapeutics, while A1 adenosine receptor signaling plays a role in analgesia. However, it remains unclear whether there is a link between them in pain. The present results showed that the A1 adenosine receptor agonist N 6 -cyclopentyladenosine (CPA) concentration dependently suppressed P2X3 receptor-mediated and α,β-methylene-ATP (α,β-meATP)-evoked inward currents in rat dorsal root ganglion (DRG) neurons. CPA significantly decreased the maximal current response to α,β-meATP, as shown a downward shift of the concentration-response curve for α,β-meATP. CPA suppressed ATP currents in a voltage-independent manner. Inhibition of ATP currents by CPA was completely prevented by the A1 adenosine receptor antagonist KW-3902, and disappeared after the intracellular dialysis of either the G i/o protein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, or the cAMP analog 8-Br-cAMP. Moreover, CPA suppressed the membrane potential depolarization and action potential bursts, which were induced by α,β-meATP in DRG neurons. Finally, CPA relieved α,β-meATP-induced nociceptive behaviors in rats by activating peripheral A1 adenosine receptors. These results indicated that CPA inhibited the activity of P2X3 receptors in rat primary sensory neurons by activating A1 adenosine receptors and its downstream cAMP signaling pathway, revealing a novel peripheral mechanism underlying its analgesic effect., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lysophosphatidic acid (LPA) is a phospholipid which has been implicated in pain. Acid-sensing ion channels (ASICs) are important players in pain associated with tissue acidification. However, it is still unclear whether there is a link between LPA signaling and ASICs in pain processes. Herein, we show that a functional interaction between them in rat dorsal root ganglia (DRG) neurons. Pre-application of LPA enhanced ASIC-mediated and acid-evoked inward currents in a concentration-dependent manner. LPA shifted the concentration-response curve for protons upwards, with an increase of 41.79 ± 4.71% in the maximal current response of ASICs to protons in the presence of LPA. Potentiation of ASIC currents by LPA was blocked by the LPA 1 receptor antagonist Ki16198, but not by the LPA 2 receptor antagonist H2L5185303. The LPA-induced potentiation was also prevented by intracellular application of either G protein inhibitor or protein kinase C (PKC) inhibitor, but not by Rho inhibitor. LPA also enhanced ASIC3 currents in CHO cells co-expressing ASIC3 and LPA 1 receptors, but not in cells expressing ASIC3 alone. Moreover, LPA increased the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, LPA exacerbated acid-induced nociceptive behaviors in rats. These results suggested that LPA enhanced ASIC-mediated electrophysiological activity and nociception via a LPA 1 receptor and its downstream PKC rather than Rho signaling pathway, which provided a novel peripheral mechanism underlying the sensitization of pain., (© 2022 International Society for Neurochemistry.)

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.

S-RNase plays vital roles in the process of self-incompatibility (SI) in Rutaceae plants. Data have shown that the rejection phenomenon during self-pollination is due to the degradation of pollen tube RNA by S-RNase. The cytoskeleton microfilaments of pollen tubes are destroyed, and other components cannot extend downwards from the stigma and, ultimately, cannot reach the ovary to complete fertilisation. In this study, four S-RNase gene sequences were identified from the 'XiangShui' lemon genome and ubiquitome. Sequence analysis revealed that the conserved RNase T2 domains within S-RNases in 'XiangShui' lemon are the same as those within other species. Expression pattern analysis revealed that S 3 -RNase and S 4 -RNase are specifically expressed in the pistils, and spatiotemporal expression analysis showed that the S 3 -RNase expression levels in the stigmas, styles and ovaries were significantly higher after self-pollination than after cross-pollination. Subcellular localisation analysis showed that the S 1 -RNase, S 2 -RNase, S 3 -RNase and S 4 -RNase were found to be expressed in the nucleus according to laser confocal microscopy. In addition, yeast two-hybrid (Y2H) assays showed that S 3 -RNase interacted with F-box, Bifunctional fucokinase/fucose pyrophosphorylase (FKGP), aspartic proteinase A1, RRP46, pectinesterase/pectinesterase inhibitor 51 (PME51), phospholipid:diacylglycerol acyltransferase 1 (PDAT1), gibberellin receptor GID1B, GDT1-like protein 4, putative invertase inhibitor, tRNA ligase, PAP15, PAE8, TIM14-2, PGIP1 and p24beta2. Moreover, S 3 -RNase interacted with TOPP4. Therefore, S 3 -RNase may play an important role in the SI of 'XiangShui' lemon.

Resveratrol can relieve pain under various pain conditions. One of the mechanisms of resveratrol analgesia is the regulation of ion channels. Acid-sensing ion channels (ASICs) are expressed predominantly in nociceptive sensory neurons to detect changes in extracellular pH. ASICs are important players in pain associated with tissue acidification. However, it is still unclear whether ASICs are resveratrol targets. Electrophysiological recordings showed that resveratrol decreased acid-induced and ASIC-mediated currents in male rat dorsal root ganglion (DRG) neurons in a concentration-dependent manner. Resveratrol downwardly shifted the concentration-response curve for protons, suggesting that it inhibited ASICs not by changing the pH 0.5 , but by suppressing the proton-induced maximum response. It also suppressed acid-triggered action potentials in the rat DRG neurons. Finally, intraplantar pretreatment with resveratrol relieved acid-induced nociceptive responses in male rats in a dose-dependent manner. These results indicated that resveratrol inhibited ASIC-mediated electrophysiological activity and nociception, suggesting a novel peripheral mechanism underlying its analgesic effect., (© 2022 Wiley Periodicals LLC.)

Immune checkpoint inhibitor (ICI) is one of the most important tumor treatment methods. Although the therapeutic efficiency of immune checkpoint inhibitor mono-therapy is limited, the combination of chemotherapy plus immune checkpoint inhibitors has shown great advantages in cancer treatment. This is mainly due to the fact that tumor reactive T cells could fully provide their anti-tumor function as chemotherapy could not only cause immunogenic cell death to increase antigen presentation, but also improve the immunosuppressive tumor micro-environment to synergize with immune checkpoint inhibitors. However, traditional chemotherapy still has shortcomings such as insufficient drug concentration in tumor region, short drug duration, drug resistance, major adverse events, etc, which might lead to the failure of the therapy. Nano chemotherapeutic drugs, which refer to chemotherapeutic drugs loaded in nano-based drug delivery system, could overcome the above shortcomings of traditional chemotherapeutic drugs to further improve the therapeutic effect of immune checkpoint inhibitors on tumors. Therefore, the scheme of nano chemotherapeutic drugs combined with immune checkpoint inhibitors might lead to improved outcome of cancer patients compared with the scheme of traditional chemotherapy combined with immune checkpoint inhibitors., 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 © 2022 Qian, Hu and Yan.)

Hepatic alveolar echinococcosis (HAE) is a zoonotic parasitic disease caused by the larvae of Echinococcus multilocularis . Because of its characteristics of diffuse infiltration and growth similar to tumors, the disability rate and mortality rate are high among patients. Although surgery (including hepatectomy, liver transplantation, and autologous liver transplantation) is the first choice for the treatment of hepatic alveolar echinococcosis in clinic, drug treatment still plays an important and irreplaceable role in patients with end-stage echinococcosis, including patients with multiple organ metastasis, patients with inferior vena cava invasion, or patients with surgical contraindications, etc. However, Albendazole is the only recommended clinical drug which could exhibit a parasitostatic rather than a parasitocidal effect. Novel drugs are needed but few investment was made in the field because the rarity of the cases. Drug repurposing might be a solution. In this review, FDA-approved drugs that have a potential curative effect on hepatic alveolar echinococcosis in animal models are summarized. Further, nano drug delivery systems boosting the therapeutic effect on hepatic alveolar echinococcosis are also reviewed. Taken together, these might contribute to the development of novel strategy for advanced hepatic alveolar echinococcosis., 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 © 2022 Xu, Qian, Gao, Pang, Zhou, Zhu, Wang, Pang, Wu, Yu, Kong, Shi, Guo, Su, Hu, Yan, Feng and Fan.)

Introduction: Anatomical liver resection is the optimal treatment for patients with resectable hepatocellular carcinoma (HCC). Laparoscopic Couinaud liver segment resection could be performed easily as liver segments could be stained by ultrasound-guided indocyanine green (ICG) injection into the corresponding segment portal vein. Several smaller liver anatomical units (liver watersheds) have been identified (such as S8v, S8d, S4a, and S4b). However, since portal veins of liver watersheds are too thin to be identified under ultrasound, the boundaries of these liver watersheds could not be stained intraoperatively, making laparoscopic resection of these liver watersheds demanding. Digital subtraction angiography (DSA) could identify arteries of liver watersheds with a diameter of less than 2 mm. Yet, its usage for liver watershed staining has not been explored so far., Purpose: The aim of this study is to explore the possibility of positive liver watershed staining via trans-arterial ICG injection under DSA examination for navigating laparoscopic watershed-oriented hepatic resection., Methods: We describe, in a step-by-step approach, the application of trans-arterial ICG injection to stain aimed liver watershed during laparoscopic anatomical hepatectomy. The efficiency and safety of the technique are illustrated and discussed in comparison with the laparoscopic anatomical liver resection via ultrasound-guided liver segment staining., Results: Eight of 10 HCC patients received successful trans-arterial liver watershed staining. The success rate of the trans-artery staining approach was 80%, higher than that of the ultrasound-guided portal vein staining approach (60%). Longer surgical duration was found in patients who underwent the trans-artery staining approach (305.3 ± 23.2 min vs. 268.4 ± 34.7 min in patients who underwent the ultrasound-guided portal vein staining approach, p = 0.004). No significant difference was found in major morbidity, reoperation rate, hospital stay duration, and 30-day and 90-day mortality between the 2 groups., Conclusions: Trans-arterial ICG staining is safe and feasible for staining the aimed liver watershed, navigating watershed-oriented hepatic resection under fluorescence laparoscopy for surgeons., Competing Interests: Author BW was employed by Beijing Jingzhen Medical Technology Ltd. The remaining 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 © 2022 Qian, Hu, Gao, Xu, Wang, Song, Yang, Lu, Zhang, Yan and Dong.)

Biochar is a promising novel material for mitigating phosphorus (P) loss and enhancing P retention in chemical-amended agricultural soils. However, the optimal application rate for aforesaid effectiveness and potential drivers of the process are not well understood. Herein, a column-based pot experiment was carried out to investigate how and to what extent reed-biochar is effective in positively triggering P loss and availability in paddy soils treated by chemical fertilizer. Compared with chemical-only treatment, the accumulated leakage of total P, dissoluble P, and particulate P in chemical fertilizer coupled with 1-4% reed-biochar treatment decreased by 5.3-13.3%, 8.3-10.4%, and 3.0-15.4%, respectively. The accumulated leakage of total P and dissoluble P in 6-8% rate treatments was increased by 5.6-7.5% and 18.3-32.9%, respectively. Increasing reed-biochar rate from 1% to 8% caused an enhancement in soil total P and available P content and P activation coefficient, and the 4% rate achieved a similar effectiveness to the higher rate. Reed-biochar application increased the abundance and diversty of soil phoD-harboring microbes (P < 0.05), while the increment had little to do with the application rate. Soil phoD-harboring community composition and total C content were the main predictors of the P leaching losses, and meanwhile, the total C content was the dominated predictor of soil P retention and availability. These results suggest that adding 1-4% reed-biochar was more beneficial to mitigate paddy P loss and to enhance soil P availability. This study highlights the importance of understanding how microbial populations mediate P transformation to decipher the biochar-driven improvement of soil P utilization., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The application of straw biochar in farmland in Dongting Lake area can realize the resource utilization of straw and reduce environmental risk. In 2020, a rice pot experiment was conducted to investigate the effects of different biochar application levels on ammonia volatilization rate, cumulative ammonia volatilization, pH value, and NH 4 + -N concentration in surface water. Six levels of reed ( Miscanthus lutarioriparius ) biochar amount, i.e. , 0%, 1%, 2%, 4%, 6% and 8% of soil weight of the 0-20 cm column, were applied in two typical paddy soils in sou-thern China, i.e ., reddish clayey soil derived from quaternary red soil and granitic sandy soil derived from granite. Compound fertilizer was applied at a rate of 200 kg N·hm -2 . The results showed that biochar application resulted in significant differences in the rate and cumulative amount of ammonia volatilization between the two soils and among different biochar treatments. For the granitic sandy soil, peak ammonia volatilization under different biochar treatments appeared at the second day after fertilization, which was decreased by 23.6%-53.4%. For the reddish clayey soil, peak ammonia volatilization appeared between the 7th to 13th day after fertilization, which increased with biochar addition level. The rate of ammonia volatilization from the granitic sandy soil was generally higher than that from the reddish clayey soil. For the granitic sandy soil, addition of <4% biochar could inhibit the ammonia volatilization and cumulative volatilization amount, with the greatest reduction (46.9%) at the treatment with 2% biochar addition. The addition of biochar did not affect the pH value of surface water at the early stage of rice growth. For the reddish clayey soil, the pH value and NH 4 + -N concentration in the surface water increased with biochar addition level, resulting in the increases of ammonia volatilization rate and cumulative volatilization amount by 1.3-10.5 times. Biochar addition level was the key factor affecting ammonia volatilization from the two soils. Elovich equation could well fit the variation trend of cumulative ammonia volatilization with time for the two soils, with the correlation reaching extremely significant level for each treatment. Overall, the application of reed biochar could suppress ammonia volatilization from the granitic sandy soil which was nearly neutral in acidity, while would promote ammonia volatilization via increasing pH value and NH 4 + -N concentration of surface water for the acidic reddish clayey soil. Therefore, appropriate dosages of reed biochar should be selected for different types of soil in order to reduce nitrogen loss.

Lysophosphatidic acid (LPA), a lipid metabolite, plays a role in both neuropathic and inflammatory pain through LPA 1 receptors. P2X3 receptor has also been shown to participate in these pathological processes. However, it is still unclear whether there is a link between LPA signaling and P2X3 receptors in pain. Herein, we show that a functional interaction between them in rat dorsal root ganglia (DRG) neurons. Pretreatment of LPA concentration-dependently enhanced α,β-methylene-ATP (α,β-meATP)-induced inward currents mediated by P2X3 receptors. LPA significantly increased the maximal current response of α,β-meATP, showing an upward shift of the concentration-response curve for α,β-meATP. The LPA enhancement was independent on the clamping-voltage. Enhancement of P2X3 receptor-mediated currents by LPA was prevented by the LPA 1 receptor antagonist Ki16198, but not by the LPA 2 receptor antagonist H2L5185303. The LPA-induced potentiation was also attenuated by intracellular dialysis of either G-protein inhibitor or protein kinase C (PKC) inhibitor, but not by Rho inhibitor. Moreover, LPA significantly changed the membrane potential depolarization and action potential burst induced by α,β-meATP in DRG neurons. Finally, LPA exacerbated α,β-meATP- induced nociceptive behaviors in rats. These results suggested that LPA potentiated the functional activity of P2X3 receptors in rat primary sensory neurons through activation of the LPA 1 receptor and its downstream PKC rather than Rho signaling pathway, indicating a novel peripheral mechanism underlying the sensitization of pain., 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 © 2022 Qiao, Li, Hao, Wei, Li, Liu, Qiu and Hu.)

Biochar application to chemical-amended paddy soils has been proposed as a potential strategy to enhance nitrogen (N) retention and nitrogen use efficiency (NUE) by crops. However, optimal concentrations for these enhancements and the potential drivers are not well understood. Herein, a column-based pot experiment was carried out to investigate the impacts of reed-biochar application rate on N losses and dynamics in paddy soils treated by chemical fertilizer, and particularly, to explore the dominant factors of the processes. The addition of 2-4% reed-biochar had the most significant effects on mitigating N loss by leaching. Reed-biochar amendment increased soil total N and mineral N (NH 4 + -N and NO 3 - -N) content, and denitrifying gene abundance, and the increments of those variables were positively related to the application rate. Soil treated with 1-4% reed-biochar at harvest period showed higher gene abundances of ammonia-oxidizing and dissimilatory nitrate reduction to ammonium (DNRA) and higher activity of β-1,4-N-acetyl-glucosaminidase (NAG) and leucine aminopeptidase compared with the 4-8% application rate. The amoA-AOA gene abundance, NAG activity, and total carbon (C) content were the main predictors of total N and mineral N accumulated leakage. Total C content was the main predictor of soil total N and mineral N content, followed by the pH and NAG activity. These results suggest that adding 2-4% reed-biochar was more beneficial to mitigate N loss and thus enhance soil N storage and availability. This study highlights the importance of understanding how microbial populations mediate N transformation to decipher biochar-driven NUE enhancement in paddy soils., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Emerging evidence has demonstrated that RNA-binding protein dysregulation is involved in esophageal squamous cell carcinoma (ESCC) progression. However, the role of poly (A) binding protein cytoplasmic 1 (PABPC1) in ESCC is unclear. We therefore aimed to explore the functions and potential mechanisms of PABPC1 in ESCC progression., Methods: PABPC1 expression was characterized using immunohistochemistry and qRT-PCR in ESCC tissues and cell lines. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to detect histone acetylation in the promoter region of PABPC1. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of PABPC1 in ESCC angiogenesis and malignant procession., Results: PABPC1 expression was upregulated in ESCC tissues compared with in normal esophageal epithelial tissues. Elevated PABPC1 expression was correlated with tumor cell differentiation and poor prognosis in patients. Sp1 and p300 cooperated to increase the level of H2K37ac in the PABPC1 promoter. Functionally, PABPC1 overexpression enhanced esophageal squamous cell proliferation and invasion by activating the IFN/IFI27 signaling pathway. PABPC1 interacted with eIF4G to increase the stability of IFI27 mRNA by competing with RNA exosomes in ESCC. Furthermore, PABPC1/IFI27 could increase miR-21-5p expression to enable exosomal delivery of miR-21-5p to human umbilical vein endothelial cells to increase angiogenesis via inhibiting CXCL10., Conclusion: PABPC1 plays a critical role in ESCC malignant progression by interacting with eIF4G to regulate IFI27 mRNA stability and promote angiogenesis via exosomal miR-21-5p/CXCL10. Taken together, our results suggest that PABPC1 is a promising therapeutic target for ESCC., (© 2022. The Author(s).)

Since uncontrolled lithium (Li) dendrite growth and dendrite-induced dead Li severely limit the development of Li metal batteries, 3D Cu current collectors can effectively alleviate these problems during Li plating/stripping. Herein, one-step galvanostatic electrodeposition method is employed to fabricate a new current collector on Cu foam decorated with large-scale and uniform 3D porous Cu-based nanoflake (NF) structures (abbreviated as 3D Cu NF@Cu foam). This 3D structure with large internal surface areas not only generates lithophilic surface copper oxides and hydroxides as charge centers and nucleation sites for Li insertion/extraction, but also endows abundant space with interlinked NFs for buffering the cell volume expansion and increasing battery performance. As a result, Li-deposited 3D Cu NF@Cu foam current collector can realize stable cycling over 455 cycles with an average Coulombic efficiency of 98.8% at a current density of 1.0 mA cm -2 , as well as a prolonged lifespan of >380 cycles in symmetrical cell without short-circuit, which are superior to those of blank Cu foam current collector. This work realizes Li metal anode stabilization by constructing 3D porous Cu NFs current collectors, which can advance the development of Li metal anode for battery industries., (© 2022 IOP Publishing Ltd.)

Peripheral A1 adenosine receptor signaling has been shown to have analgesic effects in a variety of pain conditions. However, it is not yet fully elucidated for the precise molecular mechanisms. Acid sensing ion channels (ASICs) are expressed predominantly in nociceptive sensory neurons responding to protons. Given that both A1 adenosine receptors and ASICs are present in dorsal root ganglia (DRG) neurons, we therefore investigated whether there was a cross-talk between the two types of receptors. Herein, electrophysiological recordings showed that the A1 adenosine receptor agonist N 6 -cyclopentyladenosine (CPA) suppressed acid-induced currents and action potentials, which were mediated by ASICs, in rat DRG neurons. CPA inhibited the maximum response to protons, as shown a downward shift of concentration-response curve for protons. The CPA-induced suppression of ASIC currents was blocked by the A1 adenosine receptor antagonist KW-3902 and also prevented by intracellular application of the G i/o -protein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, and the cAMP analog 8-Br-cAMP. Finally, intraplantar pretreatment of CPA dose-dependently relieved acid-induced nociceptive responses in rats through peripheral A1 adenosine receptors. These results suggested that CPA suppressed ASICs via A1 adenosine receptors and intracellular G i/o -proteins and cAMP signaling cascades in rat DRG neurons, which was a novel potential mechanism underlying analgesia of peripheral A1 adenosine receptors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: The α 2 -adrenergic receptor (α 2 -AR) agonists have been shown to be effective in the treatment of various pain. For example, dexmedetomidine (DEX), a selective α 2A -AR agonist, can be used for peripheral analgesia. However, it is not yet fully elucidated for the precise molecular mechanisms. P2X3 receptor is a major receptor processing nociceptive information in primary sensory neurons. Herein, we show that a functional interaction of α 2A -ARs and P2X3 receptors in dorsal root ganglia (DRG) neurons could contribute to peripheral analgesia of DEX., Methods: Electrophysiological recordings were carried out on rat DRG neurons, and nociceptive behavior was quantified in rats., Results: The activation of α 2A -ARs by DEX suppressed P2X3 receptor-mediated and α,β-methylene-ATP (α,β-meATP)-evoked inward currents in a concentration-dependent and voltage-independent manner. Pre-application of DEX shifted the α,β-meATP concentration-response curve downwards, with a decrease of 50.43 ± 4.75% in the maximal current response of P2X3 receptors to α,β-meATP in the presence of DEX. Suppression of α,β-meATP-evoked currents by DEX was blocked by the α 2A -AR antagonist BRL44408 and prevented by intracellular application of the G i/o protein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, and the cAMP analog 8-Br-cAMP. DEX also suppressed α,β-meATP-evoked action potentials through α 2A -ARs in rat DRG neurons. Finally, the activation of peripheral α 2A -ARs by DEX had an analgesic effect on the α,β-meATP-induced nociception., Conclusions: These results suggested that activation of α 2A -ARs by DEX suppressed P2X3 receptor-mediated electrophysiological and behavioral activity via a G i/o proteins and cAMP signaling pathway, which was a novel potential mechanism underlying analgesia of peripheral α 2A -AR agonists., (© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

MicroRNA (miRNA) is vital to the progression of hepatocellular carcinoma (HCC). Thereinto, miR-369-5p could yield assorted effects on various cancers, but there are few reports concerning the effect of miR-369-5p on HCC. Thus this study aimed to investigate the effect and mechanism of miR-369-5p in HCC. The data of miR-369-5p and HOXA13 expressions in liver hepatocellular carcinoma (LIHC) were analyzed by starBase, and then the miR-369-5p expression in HCC tissues and cells was detected by quantitative real-time PCR. Subsequently, miR-369-5p mimic was transfected into HCC cells and then its effects on cell activities were evaluated by cell counting kit-8, colony formation, wound healing, transwell assays, respectively. Expressions of epithelial-mesenchymal transition (EMT)-related genes were determined by western blot. The targeting relationship between miR-369-5p and HOXA13 was predicted by Targetscan and verified by dual-luciferase reporter assay. Pearson correlation test was used to analyze the correlation between HOXA13 and miR-369-5p. The above assays were experimented again to investigate the effects of HOXA13 on biological activity and EMT of HCC cells. MiR-369-5p expression was down-regulated and HOXA13 expression was up-regulated in LIHC. MiR-369-5p targeted HOXA13 and the expression of miR-369-5p was negatively correlated with the HOXA13 expression. MiR-369-5p inhibited the viability, proliferation, migration and invasion of HCC cells, increased E-cadherin level and decreased N-cadherin and Vimentin expressions. Concurrently, HOXA13 overexpression could counteract the effects of miR-369-5p on biological activity and EMT-related biomarkers of HCC cells. To conclude, miR-369-5p inhibits the viability, proliferation, migration and invasion of HCC cells by repressing the expression of HOXA13., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lithium-rich manganese-based layered oxides (LLOs) are considered to be the most promising cathode materials for next-generation lithium-ion batteries (LIBs) for their higher reversible capacity, higher operating voltage, and lower cost compared with those of other commercially available cathode materials. However, irreversible lattice oxygen release and associated severe structural degradation that exacerbate under high temperature and deep delithiation hinder the large-scale application of LLOs. Herein, we propose a strategy to stabilize the layered lattice framework and improve the thermal stability of cobalt-free Li 1.2 Mn 0.53 Ni 0.27 O 2 by doping with 4d transition metal niobium (Nb). Detailed atomic-scale imaging, in situ characterization, and DFT simulations confirm that the induced strong Nb-O bonds stabilize the oxygen lattice framework and restrains the fracture of TM-O bonds, thereby inhibiting the release of lattice oxygen and the continuous migration of TM ions to the lithium layer during the cycle. Furthermore, Nb doping also promotes the surface rearrangement to form a Ni-enrichment layered/rocksalt heterogeneous interface to enhance surface structural stability. As a result, the Nb-doped material delivers a capacity of 181.7 mAh g -1 with retention of 85.5% after 200 cycles at 1C, extraordinary thermal stability with a capacity retention of 80.7% after 200 cycles at 50 °C, and superior rate capability.

Background: In clinical settings, burn wounds are frequently encountered. Since burn wounds are a form of physical injury, they can have long-term adverse effects on the human body. It has been a significant challenge to treat burn wounds completely. Since traditional treatment strategies have been unable to heal burn wounds completely, they lack the efficacy to cure the wounds without long-term effects, such as heavy scarring. Reportedly, platelet-rich plasma (PRP) has shown potential to accelerate wound healing. Yet, there are no conclusive reports on a methodological comparative study of research that has assessed the medical benefits of PRP for treating individuals carrying burn wounds. Thus, the present meta-analysis and systematic study aims to assess the medical benefits of PRP for treating patients carrying burn wounds., Methods: The authors will conduct a comprehensive search for randomized controlled trials that evaluate the safeness and efficiency of PRP to treat burn wounds. The search includes 3 Chinese language databases (WanFang database, Chinese BioMedical Literature database, and China National Knowledge Infrastructure) and 4 English language databases (Cochrane Library, EMBASE, Web of Science, and MEDLINE). These electronic databases will be searched from their establishment till May 2021. A pair of independent authors will be selecting eligible studies for extracting data. The same authors will employ the Cochrane risk of bias tool to evaluate the bias risk. We will make use of RevMan (version: 5.3) software to complete data synthesis., Results: The present protocol will establish practical and targeted results evaluating the efficacy and safeness of using PRP to treat burn wounds. The current study also provides a reference for clinical use of PRP., Conclusion: Stronger evidence about the effectiveness and safety of using PRP to treat and heal burn wounds will be provided for clinicians to refer., Ethics and Dissemination: Ethics approval is unrequired., Registration Number: March 31, 2021.osf.io/whauj. (https://osf.io/whauj/)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

A rational leader selection strategy can enhance a swarm to manage the convergence and diversity during the entire search process. In this article, a novel adaptive multiobjective particle swarm optimization (MOPSO) is proposed on the basis of an evolutionary state estimation mechanism, which is used to detect the evolutionary environment whether in exploitation or exploration state. During the search process, different types of leaders, such as a convergence global best solution (c-gBest) and several diversity global best solutions (d-gBests), are to be selected from the external archive for particles under different evolutionary environments. The c-gBest is selected for improving the convergence when the swarm is in an exploitation state, while the d-gBests are chosen for enhancing the diversity in an exploration state. Furthermore, a modified archive maintenance strategy based on some predefined reference points is adopted to maximize the diversity of the Pareto solutions in the external archive. The experimental results demonstrate that the proposed algorithm performs significantly better than the several state-of-the-art multiobjective PSO algorithms and multiobjective evolutionary algorithms on 31 benchmark functions in terms of convergence and diversity of those obtained approximate Pareto fronts.

Purpose: Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine and involves in a variety of pain conditions. Some findings suggest that TNF-α may act directly on primary afferent neurons to induce acute pain hypersensitivity through non-transcriptional regulation. This study investigated whether TNF-α had an effect on functional activity of P2X3 receptors in primary sensory neurons. Herein, we report that a brief (5 min) application of TNF-α rapidly enhanced the electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) neurons., Methods: Electrophysiological recordings were carried out on rat DRG neurons, and nociceptive behavior was quantified in rats., Results: A brief (5 min) exposure of TNF-α rapidly increased P2X3 receptor-mediated and α,β-methylene-ATP (α,β-meATP)-evoked inward currents in a dose-dependent manner. The potentiation of P2X3 receptor-mediated ATP currents by TNF-α was voltage-independent. TNF-α shifted the concentration-response curve for α,β-meATP upwards, with an increase of 31.57 ± 6.81% in the maximal current response to α,β-meATP. This acute potentiation of ATP currents by TNF-α was blocked by p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not by non-selective cyclooxygenase inhibitor indomethacin, suggesting involvement of p38 MAPK, but not cyclooxygenase. Moreover, intraplantar injection of TNF-α and α,β-meATP produced a synergistic effect on mechanical allodynia in rats. TNF-α-induced mechanical allodynia was also alleviated after local P2X3 receptors were blocked., Conclusion: These results suggested that TNF-α rapidly sensitized P2X3 receptors in primary sensory neurons via a p38 MAPK dependent pathway, which revealed a novel peripheral mechanism underlying acute mechanical hypersensitivity by peripheral administration of TNF-α., Competing Interests: The authors have no conflict of interest to declare., (© 2021 Jin et al.)

An unprecedented A2MIMIIIX6-type double perovskite adopting a fully hexagonal BaNiO3-type structure, (piperidinium)2[KBiCl6], undergoes a 2/mF1[combining macron] ferroelastic phase transition at 285 K with a spontaneous strain of 0.0615, arising from the order-disorder transition of organic cations together with the synchronous displacement of inorganic chains.

Dexmedetomidine (DEX), a selective α 2 adrenergic receptor (α 2 -AR) agonist, has been shown to have peripheral analgesic effects in a variety of pain conditions. However, the precise molecular mechanisms have not yet been fully elucidated. Acid sensing ion channels (ASICs) are the major player in pain associated with tissue acidosis. Given that both α 2 -ARs and ASICs exist in dorsal root ganglia (DRG) neurons, we therefore investigated the effects of DEX on the functional activity of ASICs. Herein, whole-cell patch-clamp recordings demonstrated that DEX suppressed ASIC-mediated and acid-evoked currents and action potentials in dissociated rat DRG neurons. DEX shifted downwards concentration-response curve to protons, with a decrease of 35.83 ± 3.91% in the maximal current response to pH 4.5. DEX-induced inhibition of ASIC currents was blocked by the α 2A -AR antagonist BRL44408 in DRG neurons. DEX also inhibited ASIC3 currents in CHO cells co-expressing ASIC3 and α 2A -ARs, but not in ASIC3 transfected CHO cells without α 2A -ARs expression. DEX-induced inhibition of ASIC currents was mimicked by the protein kinase A inhibitor H-89, and blocked by intracellular application of the G i/o protein inhibitor pertussis toxin and the cAMP analog 8-Br-cAMP. In addition, peripherally administration of DEX dose-dependently relieved nociceptive responses to intraplantar injection of acetic acid in rats through local α 2A -ARs. Our results indicated that DEX inhibited the functional activity of ASICs via α 2A -ARs and intracellular G i/o proteins and cAMP/protein kinase A signaling pathway in rat DRG neurons, which was a novel potential mechanism that probably mediated peripheral analgesia of DEX., 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 © 2021 Wei, Qiu, Jin, Liu and Hu.)

Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is a rare subtype in primary liver cancer, which is difficult to diagnose in clinics. In this report, we present a case of a 62-year-old male with abdominal pain and slightly elevated alpha-fetoprotein. The contrast-enhanced computed tomography scans showed a left liver mass, which showed adherence to the imaging characteristics of hepatocellular carcinoma. However, with the treatment of laparoscopic liver resection, the following histological examination displayed two distinct components, which were consistent with the diagnosis of cHCC-CC., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The aim was to compare the outcomes of laparoscopic common bile duct exploration (LCBDE) after failed endoscopic retrograde cholangiopancreatography (group A) versus primary LCBDE (group B) for the management of gallbladder and common bile duct stones., Materials and Methods: A comprehensive and systematic literature search was performed in several databases, including PubMed, Ovid, and Cochrane Library. Meta-analysis of operative outcomes, postoperative outcomes, and gallstone clearance rates was conducted using random-effect models., Results: Six studies including 642 patients (239 in group A and 403 in group B) were included. The operative time was longer in group A (P=0.02). The overall complication, bile leakage, conversion, postoperative hospital stay, and reoperation were comparable in group A and group B. Similarly, no significant difference was present concerning the incidence of stone clearance, residual stone, and recurrent stone (P>0.05)., Conclusion: LCBDE is an alternative acceptable procedure when removal of common bile duct stones by endoscopic therapy fails., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intracerebral hemorrhage (ICH) is the top lethal and disabling form of stroke. The pathophysiology of ICH is not fully understood yet. Metabolites are indicators and regulators of cellular processes. However, the overall brain metabolic pattern and the temporal alterations after ICH remain unknown., Methods: A total of 40 male rats were randomly assigned to sham group and ICH group. ICH was induced by collagenase Ⅶ. Body weight was assessed. Neurological deficits were evaluated by modified neurological severity score. Then, the perihematomal brain tissues were collected for metabolites detection using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). The metabolic profiles were displayed by principal component analysis (PCA), partial least-squares-discriminant analysis (PLS-DA) and cluster analysis. The significant differential metabolites were screened by fold change > 2.0, the false discovery rate (FDR) < 0.05 and Variable Importance of Projection (VIP) > 1. Next, the relevant metabolic pathways were discerned by MetaboAnalyst website. A metabolite-protein interaction network was subsequentially constructed to further annotate the function of differential metabolites., Results: Rats suffered from compromised body weight increasement and impaired neurological function. The metabolomics profiles of brain tissues in the post-ICH rats were markedly different from those in the sham group on days 3 and 14. Thirty-four metabolites (bilirubin, uric acid, 6-Methylnicotinamide et al.) were abnormally upregulated in the acute stage, while 27 metabolites were disturbed in the recovery stage, including bilirubin, uric acid, and histamine et al. Seven and three metabolic pathways altered in the acute and recovery stage, respectively. Metabolite-protein interaction analysis revealed that the disturbed metabolites may participate in ICH pathophysiology by altering amino acid metabolism, peroxisome proliferators-activated receptor signaling pathway, fatty acid metabolism and urea cycle in the acute stage, while influencing amino acid metabolism, urea cycle and peroxisome in the recovery stage., Conclusions: Our study mapped the pathological metabolomics profiles of the post-ICH rat brains in the acute and recovery phases. This work will assist in discovering novel therapeutic targets and treatments for ICH., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Somatostatin (SST) and its analogues like octreotide (OCT) have analgesic effect on a variety of pain through peripheral SST receptors (SSTRs). However, the precise molecular mechanisms have not yet been fully elucidated. This research aimed to identify possible antinociceptive mechanisms, showing functional links of the SSTR2 and acid-sensing ion channels (ASICs). Herein, we reported that OCT inhibited the electrophysiological activity of ASICs in rat dorsal root ganglia (DRG) neurons. OCT concentration-dependently decreased the peak amplitude of acid-evoked inward currents, which were mediated by ASICs. OCT shifted concentration-response curve to protons downwards, with a decrease of 36.53 ± 5.28% in the maximal current response to pH 4.5 in the presence of OCT. OCT inhibited ASIC-mediated currents through SSTR2, since the inhibition was blocked by Cyn 154806, a specific SSTR2 antagonist. The OCT inhibition of ASIC-mediated currents was mimicked by H-89, a membrane-permeable inhibitor of PKA, and reversed by internal treatment of an adenylyl cyclase activator forskolin or 8-Br-cAMP. OCT also decreased the number of action potentials induced by acid stimuli through SSTR2. Finally, peripheral administration of 20 μM OCT, but not 2 μM OCT, significantly relieved nociceptive responses to intraplantar injection of acetic acid in rats. This occurred through local activation of SSTR2 in the injected hindpaw and was reversed following co-application of Cyn 154806. Our results indicate that activation SSTR2 by OCT can inhibit the activity of ASICs via an intracellular cAMP and PKA signaling pathway in rat DRG neurons. These observations demonstrate a cross-talk between ASICs and SSTR2 in peripheral sensory neurons, which was a novel peripheral analgesic mechanism of SST and its analogues.

Background: Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine involved in pain processing and hypersensitivity. It regulates not only the expression of a variety of inflammatory mediators but also the functional activity of some ion channels. Acid-sensing ion channels (ASICs), as key sensors for extracellular protons, are expressed in nociceptive sensory neurons and contribute to pain signaling caused by tissue acidosis. It is still unclear whether TNF-α has an effect on functional activity of ASICs. Herein, we reported that a brief exposure of TNF-α acutely sensitized ASICs in rat dorsal root ganglion (DRG) neurons., Methods: Electrophysiological experiments on rat DRG neurons were performed in vitro and acetic acid induced nociceptive behavior quantified in vitro., Results: A brief (5min) application of TNF-α rapidly enhanced ASIC-mediated currents in rat DRG neurons. TNF-α (0.1-10 ng/ml) dose-dependently increased the proton-evoked ASIC currents with an EC 50 value of 0.12 ± 0.01 nM. TNF-α shifted the concentration-response curve of proton upwards with a maximal current response increase of 42.34 ± 7.89%. In current-clamp recording, an acute application of TNF-α also significantly increased acid-evoked firing in rat DRG neurons. The rapid enhancement of ASIC-mediated electrophysiological activity by TNF-α was prevented by p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not by non-selective cyclooxygenase inhibitor indomethacin, suggesting that p38 MAPK is necessary for this enhancement. Behaviorally, TNF-α exacerbated acid-induced nociceptive behaviors in rats via activation of local p38 MAPK pathway., Conclusions: These results suggest that TNF-α rapidly enhanced ASIC-mediated functional activity via a p38 MAPK pathway, which revealed a novel peripheral mechanism underlying TNF-α involvement in rapid hyperalgesia by sensitizing ASICs in primary sensory neurons.