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The trafficking of ion channels to/from the plasma membrane is considered an important mechanism for cellular activity and an interesting approach for disease therapies. The transient receptor potential vanilloid 3 (TRPV3) ion channel is widely expressed in skin keratinocytes, and its trafficking mechanism to/from the plasma membrane is unknown. Here, trafficking from the plasma membrane to lysosomes.

Chronic pain with comorbid emotional disorders is a prevalent neurological disease in patients under various pathological conditions, yet patients show considerable difference in their vulnerability to developing chronic pain. Understanding the neurobiological basis underlying this pain vulnerability is essential to develop targeted therapies of higher efficiency in pain treatment of precision medicine. However, this pain vulnerability has not been addressed in preclinical pain research in animals to date. In this study, we investigated individual variance in both sensory and affective/emotional dimensions of pain behaviors in response to chronic neuropathic pain condition in a mouse model of chronic pain. We found that mice displayed considerably diverse sensitivities in the chronic pain-induced anxiety- and depression-like behaviors of affective pain. Importantly, the mouse group that was more vulnerable to developing anxiety was also more vulnerable to developing depressive behavior under the chronic pain condition. In contrast, there was relatively much less variance in individual responses in the sensory dimension of pain sensitization. Molecular analysis revealed that those mice vulnerable to developing the emotional disorders showed a significant reduction in the protein level of DNA methyltransferase 3a in the emotion-processing central nucleus of the amygdala. In addition, social stress also revealed significant individual variance in anxiety behavior in mice. These findings suggest that individual pain vulnerability may be inherent mostly in the emotional/affective component of chronic pain and remain consistent in different aspects of negative emotion, in which adaptive changes in the function of DNA methyltransferase 3a for DNA methylation in central amygdala may play an important role. This may open a new avenue of basic research into the neurobiological mechanisms underlying pain vulnerability.

The transition from the closed to open state greatly alters the intra- and inter-subunit interactions of the P2X receptor (P2XR). The interactions that occur in the transmembrane domain of the P2X2R remain unclear. We used substituted cysteine mutagenesis disulfide mapping to identify pairs of residues that are in close proximity within the transmembrane domain of rP2X2R and compared our results to the predicted positions of these amino acids obtained from a rat P2X2R homology model of the available open and closed zebrafish P2X4R structures. Alternations in channel function were measured as a change in the ATP-gated current before and after exposure to dithiothreitol. Thirty-six pairs of double mutants of rP2X2R expressed in HEK293 cells produced normal functioning channels. Thirty-five pairs of these mutants did not exhibit a functionally detectable disulfide bond. The double mutant H33C/S345C formed redox-dependent cross-links in the absence of ATP. Dithiothreitol ruptured the disulfide bond of H33C/S345C and induced a 2 to 3-fold increase in current. The EC50 for H33C/S345C before dithiothreitol treatment was ∼2-fold higher than that after dithiothreitol treatment. Dithiothreitol reduced the EC50 to wild-type levels. Furthermore, expression of trimeric concatamer receptors with Cys mutations at some but not all six positions showed that the more disulfide bond formation sites within the concatamer, the greater current potentiation after dithiothreitol incubation. Immunoblot analysis of H33C/S345C revealed one monomer band under nonreducing conditions strongly suggesting that disulfide bonds are formed within single subunits (intra-subunit) and not between two subunits (inter-subunit). Taken together, these data indicate that His33 and Ser345 are proximal to each other across an intra-subunit interface. The relative movement between the first transmembrane and the second transmembrane in the intra-subunit is likely important for transmitting the action of ATP binding to the opening of the channel.

Temperature sensing is an important adaptive mechanism for warm‐blooded animals such as humans. ThermoTRP ion channels are activated by distinct but overlapping physiological temperatures. Our previous research demonstrated that sorting nexin 11 (SNX11) regulates lysosomal degradation of plasma membrane TRPV3, one of ThermoTRP ion channel proteins. Here, we found that SNX11, a vesicular trafficking protein, modulates mouse behaviour in response to temperature changes. Snx11‐knockout mice exhibit a stronger preference for mild temperatures along with enhanced sensitivity to harmful heat. Mechanistically, keratinocytes from Snx11‐knockout mice exhibit a larger temperature‐gated TRPV3 membrane current and have enhanced thermoTRPV3 expression in the plasma membrane compared to wild‐type keratinocytes. Additionally, Snx11‐knockout mice show higher endogenous TRPV3 protein levels in skin tissues than wild‐type mice do. Therefore, our results indicate that SNX11 may regulate thermal perception via alteration of functional thermoTRPV3 on the plasma membrane of thermally sensitive cells, which is the first link between vesicular trafficking and thermal transduction.

This study aimed to explore the relationship between caregiver burden and anticipatory grief among caregivers of elderly cancer patients, and to examine the chain mediation effects of family functioning and resilience. A total of 624 valid questionnaires were collected. The Structural Equation Model was established to test the mediating effects of family functioning and resilience. Results showed that caregiver burden has a direct positive effect on anticipatory grief, both family functioning and resilience have negative effects on caregiver burden and anticipatory grief, and that resilience moderates the mediating effect of family functioning. Our findings suggest that reducing the caregiver burden among caregivers of elderly cancer patients, improving family functioning, and enhancing resilience have important effects in alleviating the anticipatory grief of caregivers. Our findings provide some references for further research. Medical staff should better understand the grief experience of caregivers and implement interventions to enable caregivers to better cope with anticipatory grief and psychological stress, so as to promote the quality of care for elderly cancer patients.

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Although the bilateral diplomatic relations between China and Romania have 65 years, the communication and cooperation in the fields of education, science and technology, culture and politics have a long history. And what’s more there is a traditional friendship between the Romanian and Chinese people. When we talk about the first reception of Chinese literature and culture in Romania, we can’t forget one important person-Nicolae Milescu Spatarul and his contribution. In this paper first I will talk about the brief introduction of the relationship between Romania and China, and then I will focus on Nicolae Milescu Spatarul and his famous books Jurnal de călătorie în China, Descrierea Chinei.Jurnal de calatorie in China.