Downregulation of nuclear STAT2 protein in the spinal dorsal horn is involved in neuropathic pain following chronic constriction injury of the rat sciatic nerve

Regulation of gene transcription in the spinal dorsal horn (SDH) plays a critical role in the pathophysiology of neuropathic pain. In this study, we investigated whether the transcription factor STAT2 affects neuropathic pain and evaluated its possible mechanisms. A proteomic analysis showed that the nuclear fraction of STAT2 protein in the SDH was downregulated after chronic constriction injury of the rat sciatic nerve, which was associated with the development of neuropathic pain. Similarly, siRNA-induced downregulation of STAT2 in the SDH of naïve rats also resulted in pain hypersensitivity. Using RNA-sequencing analysis, we showed that reduction of nuclear STAT2 after chronic constriction injury was associated with increased expression of microglial activation markers, including the class II transactivator and major histocompatibility complex class II proteins. In addition, siRNA-induced downregulation of STAT2 promoted microglial activation and pro-inflammatory cytokine expression in the SDH. Taken together, these results showed that chronic constriction injury caused downregulation of nuclear STAT2 in the SDH, which may result in microglial activation and development of neuropathic pain. Our findings indicate that restoration of nuclear expression of STAT2 could be a potential pathway for the treatment of neuropathic pain

Greenmatch: Renewable-Aware Workload Scheduling For Massive Storage Systems

As datacenters grow in scale, increasing energy costs and carbon emissions have led data centers to seek renewable energy, such as wind and solar energy. However, tackling the challenges associated with the intermittent nature and variability of renewable energy is substantial. This paper proposes a scheme called GreenMatch, which deploys an SSD-cache to match green energy supplies with a time-shifting workload schedule while maintaining low latency for online data-intensive services. With the SSD-cache, the process for a latency-sensitive request to access a disk is divided into two stages: a low-energy low-latency online stage and a high-energy high-latency off-line stage. As the process in the latter stage is off-line, it offers opportunities for time-shifting workload scheduling in response to variations of green energy supplies. We also allocate an HDD-cache to guarantee data availability when renewable energy is non-adequate. Furthermore, we design a novel replacement policy called Inactive Disk First for the HDD-cache to avoid inactive disk accesses. The experimental results show that GreenMatch can make full use of renewable energy while minimizing the negative impact of intermittency and variability on performance and availability

 Carex malipoensis (Cyperaceae), a new species from southeast Yunnan, China

Carex malipoensis, a new species from southeast Yunnan, China, is here described and illustrated. It is morphologically similar to C. trichophylla in sect. Euprepes, but differs from it by its longer inflorescences and peduncles, pendulous spikes, hispidulous female glumes, densely hispidulous utricles, and longer nutlets

The Genetic Diversity of <i>Bletilla</i> spp. Based on SLAF-seq and Oligo-FISH

Bletilla spp. Rchb. F. is a traditional Chinese medicinal material. In this study, Bletilla striata (Thunb. ex A. Murray) Rchb F, Bletilla formosana (Hayata) Schltr, and Bletilla ochracea Schltr were collected to analyze the genetic diversity of 16 materials using specific site-amplified fragment sequencing (SLAF-seq) and fluorescence in situ hybridization (FISH). The results showed that the phylogenetic tree of the single-nucleotide polymorphism (SNP) data rendering system was correlated with the shape and geographical distribution of the material. The results of the population structural analysis showed that all the materials containing yellow labellum came from the same ancestor. The results of the principal component analysis were able to preliminarily judge the genetic distance and provided a reference for the selection of hybrid parents. The FISH analysis showed that the chromosomes of B. striata were 2n = 32 and the chromosomes of the B. striata (safflower) mutant were 2n = 34 and the chromosomes of B. ochracea and B. formosana were 2n = 34–36. The (AG3T3)3 non-terminal signal was different from the 5S rDNA signal. These results revealed that the 16 materials had rich genetic diversity, which can provide molecular and cytogenetic data for the study of the genus and its relatives and serve as a reference for the breeding of new genus varieties and improve breeding efficiency and cost

A Passive Pressure Sensor Fabricated by Post-Fire Metallization on Zirconia Ceramic for High-Temperature Applications

A high-temperature pressure sensor realized by the post-fire metallization on zirconia ceramic is presented. The pressure signal can be read out wirelessly through the magnetic coupling between the reader antenna and the sensor due to that the sensor is equivalent to an inductive-capacitive (LC) resonance circuit which has a pressure-sensitive resonance frequency. Considering the excellent mechanical properties in high-temperature environment, multilayered zirconia ceramic tapes were used to fabricate the pressure-sensitive structure. Owing to its low resistivity, sliver paste was chosen to form the electrical circuit via post-fire metallization, thereby enhancing the quality factor compared to sensors fabricated by cofiring with a high-melting-point metal such as platinum, tungsten or manganese. The design, fabrication, and experiments are demonstrated and discussed in detail. Experimental results showed that the sensor can operate at 600 °C with quite good coupling. Furthermore, the average sensitivity is as high as 790 kHz/bar within the measurement range between 0 and 1 Bar

(Proposed reporting of Tai Chi intervention in clinical trials)

Objective: The objectives of this study are to propose a reporting standard of Tai Chi intervention in clinical studies, based on the organization and experience of STRICTA and CONSORT and its expansion, in order to improve the reporting quality of Tai Chi intervention in clinical trials to facilitate the clinical decision- making and clinical practice. Methods :We developed the proposed reporting standard by summarizing items from the review, consulting experts, organizing group discussions, standard revision and consensus meeting. At last, the reporting items, explanation and examples were determined by the research team. Results: The proposed reporting standard of Tai Chi intervention in clinical trials includes 7 items and 16 sub- items. The 7 items are as follows: Tai Chi rationale, details of learning and practicing, treatment regimen, other components of treatment, instructor background, requirements, and control or comparator interventions. Conclusion: Consensus are needed to be reached by relevant experts and scholars at home and abroad to improve the proposed reporting standard, and its feasibility should be tested in further clinical trials of Tai Chi intervention

Table1_Downregulation of nuclear STAT2 protein in the spinal dorsal horn is involved in neuropathic pain following chronic constriction injury of the rat sciatic nerve.XLSX

Regulation of gene transcription in the spinal dorsal horn (SDH) plays a critical role in the pathophysiology of neuropathic pain. In this study, we investigated whether the transcription factor STAT2 affects neuropathic pain and evaluated its possible mechanisms. A proteomic analysis showed that the nuclear fraction of STAT2 protein in the SDH was downregulated after chronic constriction injury of the rat sciatic nerve, which was associated with the development of neuropathic pain. Similarly, siRNA-induced downregulation of STAT2 in the SDH of naïve rats also resulted in pain hypersensitivity. Using RNA-sequencing analysis, we showed that reduction of nuclear STAT2 after chronic constriction injury was associated with increased expression of microglial activation markers, including the class II transactivator and major histocompatibility complex class II proteins. In addition, siRNA-induced downregulation of STAT2 promoted microglial activation and pro-inflammatory cytokine expression in the SDH. Taken together, these results showed that chronic constriction injury caused downregulation of nuclear STAT2 in the SDH, which may result in microglial activation and development of neuropathic pain. Our findings indicate that restoration of nuclear expression of STAT2 could be a potential pathway for the treatment of neuropathic pain.</p

β-Arrestin2 promotes docetaxel resistance of castration-resistant prostate cancer via promoting hnRNP A1-mediated PKM2 alternative splicing

Abstract Purpose To investigate the influence of β-arrestin2 on the docetaxel resistance in castration-resistant prostate cancer (CRPC) and elucidate the underlying molecular mechanisms. Methods PC3 and DU145 cells with stable β-arrestin2 overexpression and C4-2 cells with stable β-arrestin2 knockdown, were constructed via using lentivirus and puromycin selection. MTT and colony formation assays were carried out to investigate the effect of β-arrestin2 expression on the docetaxel resistance of CRPC cells. Glycolysis analysis was used to assess the glycolytic capacity modulated by β-arrestin2. GO enrichment analysis, gene set enrichment analysis and Spearman correlation test were carried out to explore the potential biological function and mechanism via using public data from GEO and TCGA. The expressions of PKM2, Phospho-PKM2, Phospho-ERK1/2 and hnRNP A1 were detected by western blot. Functional blocking experiments were carried out to confirm the roles of PKM2 and hnRNP A1 in the regulation of β-arrestin2’s biological functions via silencing PKM2 or hnRNP A1 expression in cells with stable β-arrestin2 overexpression. Finally, nude mice xenograft models were established to confirm the experimental results of cell experiments. Results β-Arrestin2 significantly decreased the sensitivity of CRPC cells to docetaxel stimulation, through enhancing the phosphorylation and expression of PKM2. Additionally, β-arrestin2 increased PKM2 phosphorylation via the ERK1/2 signaling pathway and induced PKM2 expression in a post-transcriptional manner through an hnRNP A1-dependent PKM alternative splicing mechanism, rather than by inhibiting its ubiquitination degradation. Conclusion Our findings indicate that the β-arrestin2/hnRNP A1/PKM2 pathway could be a promising target for treating docetaxel-resistant CRPC