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Background: SZ-685C, an anthracycline compound derived from the mangrove endophytic fungus Halorosellinia sp. (No. 1403) collected from the South China Sea, has shown strong anticancer activities. Non-functioning pituitary adenomas (NFPAs) are a type of tumor that can be challenging to manage clinically and have a significant unmet medical need. Our research has found that SZ-685C showed an inhibitory effect on the viability, migration ability, and proliferation ability of a human non-functioning pituitary tumor-derived folliculostellate (PDFS) cell line. Methods: SZ-685C was prepared and purified from the mangrove endophytic fungus No. 1403. PDFS cells were exposed to SZ-685C, and the effect of SZ-685C on PDFS cells was evaluated. RNA sequencing was used to analyze the miRNA expression profile in PDFS cells of the control group and SZ-685C-treated group. Quantitative polymerase chain reaction (qPCR) was performed to verify the expression of selected miR-340-3p. The effects of SZ-685C on PDFS cells after overexpression of miR-340-3p were evaluated. Dual-luciferase reporter assays showed PPP1CB is a direct target of miR-340-3p. Finally, the action pathway of the selected miR-340-3p was predicted and evaluated through bioinformatics analysis. Results: SZ-685C reduced cell viability in PDFS cells, accompanied by inhibition of migration ability and proliferation ability. The IC50 value for 24 h is 9.144 ± 0.991 μM, and for 48 h is 4.635 ± 0.551 μM. SZ-685C increased the protein levels of Beclin 1, the ratio of LC3-II to LC3-I, and LAMP-1, and down-regulated p62. MiRNA sequencing and further validation showed that miR-340-3p significantly decreased in PDFS cells treated with SZ-685C. After overexpression of miR-340-3p, the inhibition of viability, migration ability, proliferation ability, and autophagy-promoting effect of SZ-685C on PDFS cells were weakened. SZ-685C caused a decrease in PPP1CB expression and activation of the ERK pathway in PDFS cells, and this trend was reversed after overexpression of miR-340-3p. Conclusions: SZ-685C downregulates the expression of miR-340-3p in PDFS cells, thereby reducing the expression of PPP1CB and activating the ERK pathway to promote autophagic cell death, leading to inhibition of PDFS cell growth.

Abstract Germline-somatic mutation interactions are universal and associated with tumorigenesis, but their role in breast cancer, especially in non-Caucasians, remains poorly characterized. We performed large-scale prospective targeted sequencing of matched tumor-blood samples from 4079 Chinese females, coupled with detailed clinical annotation, to map interactions between germline and somatic alterations. We discovered 368 pathogenic germline variants and identified 5 breast cancer DNA repair-associated genes (BCDGs; BRCA1/BRCA2/CHEK2/PALB2/TP53). BCDG mutation carriers, especially those with two-hit inactivation, demonstrated younger onset, higher tumor mutation burden, and greater clinical benefits from platinum drugs, PARP inhibitors, and immune checkpoint inhibitors. Furthermore, we leveraged a multiomics cohort to reveal that clinical benefits derived from two-hit events are associated with increased genome instability and an immune-activated tumor microenvironment. We also established an ethnicity-specific tool to predict BCDG mutation and two-hit status for genetic evaluation and therapeutic decisions. Overall, this study leveraged the large sequencing cohort of Chinese breast cancers, optimizing genomics-guided selection of DNA damaging-targeted therapy and immunotherapy within a broader population.

Developing new energy, reducing fossil energy consumption, and building a green and low-carbon energy system are important strategies to achieve carbon neutrality. To realize the grid connection of new energy generation, rechargeable potassium-ion batteries (KIBs) are expected to be used in large-scale energy storage, considering sufficient potassium resources and potential high-energy density. Anode, an essential battery component, directly determines the battery safety, cycle life, and energy density. Among various anodes, alloys can provide high theoretical specific capacity based on the multi-electron reaction mechanism, which is promising in terms of improving the energy density of a full battery. Their K-storage voltages also stay away from the deposition/stripping potentials of metallic K, thereby enhancing battery safety. However, the dramatic volume variation upon alloying and dealloying leads to electrode pulverization and capacity fading in traditional carbonate-based electrolytes. An effective method for stabilizing an alloy-based anode structure is the construction of a stable electrode–electrolyte interface by electrolyte optimization, which has the advantages of a simple process and low cost. Accordingly, the utilization of interfacial engineering to achieve stable alloy anodes has been frequently reported in the past few years. This topic includes the following: (1) regulation of the components of solid electrolyte interphase (SEI) layers to improve mechanical strength and ionic conductivity, buffer volume fluctuation, and reduce electrode corrosion; (2) adjustment of the solvated structure of K+ to enhance the diffusion rate and inhibit the electrolyte decomposition; and (3) utilization of solvent molecular chemisorption on the electrode to induce its microstructure change, improve the electrolyte wetting ability, and relieve volume change. The SEI is a passivation film generated on the electrode surface at the initial battery operation stage. Research on its structure, component, and formation mechanism is still basic due to its instability and complexity and limited research methods. Whether the solvated structure of cation and electrolyte adsorption affect the SEI structure and composition remains unclear. How the solvated structure and the electrolyte adsorption improve the electrode stability must also be further studied. This review covers recent research progress on the interfacial interaction between alloy anodes and electrolytes in KIBs, summarizes the electrolyte optimization strategies, analyzes the potassium storage mechanisms and electrochemical performance of alloy anodes, and highlights the interfacial interaction mechanisms. More importantly, this paper provides new insights for the future development of KIB electrolytes.

AbstractBackground Atelectasis affects approximately 90% of anaesthetized patients, with laparoscopic surgery and pneumoperitoneum reported to exacerbate this condition. High-frequency oscillation therapy applies continuous positive pressure pulses to oscillate the airway, creating a pressure difference in small airways obstructed by secretions. This process helps reduce peak airway pressure, open small airways, and decrease atelectasis incidence, while also facilitating respiratory tract clearance. This study examines the efficacy of high-frequency oscillation on reduction of atelectasis in laparoscopic cholecystectomy (LC) patients under general anaesthesia, evaluated using lung ultrasound.Methods Sixty-four patients undergoing laparoscopic cholecystectomy were randomly divided into a control group and a high-frequency oscillation (HFO) group. Both groups underwent total intravenous anaesthesia under invasive arterial monitoring. The HFO group received a 10-minute continuous high-frequency oscillation therapy during surgery, while the control group received no intervention. Lung ultrasound evaluations were performed three times: five minutes post-intubation (T1), at the end of the surgery (T2), and before leaving the Post-Anaesthesia Care Unit (PACU; T3). Blood gas analysis was performed twice: prior to induction with no oxygen supply and before PACU discharge (oxygen supply off).Results The HFO group displayed a significantly lower incidence of atelectasis at T3 (57.5% vs. 90.3%, OR 6.88, 95%CI (1.74 to 27.24)) compared to the control group. Moreover, the HFO group’s PaO2 levels remained consistent with baseline levels before PACU discharge, unlike the control group. Although there was no significant difference in LUS scores between the groups at T1 (8.56 ± 0.15 vs. 8.19 ± 0.18, p = 0.1090), the HFO group had considerably lower scores at T2 (13.41 ± 0.17 vs.7.59 ± 0.17, p

AIM: To assess the relationships of final best-corrected visual acuity (BCVA) and the optic nerve structural loss in varying age-cohorts of optic neuritis (ON) patients. METHODS: This is a retrospective, cross-sectional study. Totally 130 ON subjects (200 eyes) without ON onset within 6mo were included, who underwent BCVA assessment, peripapillary retinal nerve fibre layer (pRNFL) and macular segmented layers evaluation by optical coherence tomography (OCT). RESULTS: For the 0-18y cohort, the final BCVA (logMAR) was significantly better and less frequent recurrences than adult cohorts (P=0.000). The final BCVA (logMAR) in all age-cohorts of the ON patients had negative and linear correlations to the pRNFL thicknesses and macular retinal ganglion cell layer (mRGCL) volumes, when the pRNFL thicknesses were reduced to the thresholds of 57.2-67.5 µm or 0.691-0.737 mm3 in mRGCL volumes, respectively, with the strongest interdependence in the 19-40y cohort. The ON patients from varying age cohorts would be threatened by blindness when their pRNFL thicknesses dropped 36.7-48.3 µm or the mRGCL volumes dropped to 0.495-0.613 mm3. CONCLUSION: The paediatric ON has best prognosis and young adult ON exhibits perfectly linear correlations of final vision and structural loss. The pRNFL and the mRGCL could be potential structural markers to predict the vision prognosis for varying-age ON patients.

Mytilus coruscus is a dominant shellfish in the Yangtze estuary and its adjacent sea area. Food deprivation often occurs during their growth due to fluctuations in algal abundance caused by seasonal freshwater flushing and high-density aquaculture mode. To investigate the coping strategies of M. coruscus to starvation stress, electron microscopy and differential proteomic analysis were performed on the critical feeding organ gill of the mussels after 9 days of starvation. The electron microscopy results showed that the cilia of the mussel gills were dissolved, and the gaps between gill filaments widened under starvation. Differential proteomic analysis revealed that phagocytosis-related proteins such as ATPeV1E, ATPeV1C, LAMP1_2 and CTSL were significantly upregulated, and the phagocytosis pathway was significantly enriched (p < 0.05). In addition, the corin content in gill and myeloperoxidase level as well as the number of dead cells in blood were both significantly increased (p < 0.05). What’s more, proteomic data suggested that immune maintenance, cellular transport and metabolism related pathways were significantly enriched, which illustrated an immune and metabolism responses under starvation. This study reveals for the first time that phagocytosis functions as an essential strategy for M. coruscus to cope with starvation, which provides new scientific knowledge and a theoretical basis for understanding the adaptation mechanisms of mussel to starvation and for rational optimization of mussel culture patterns.

Being an industrially valuable species of bivalve, Mytilus is widespread in the area around the eastern coast of China. Starvation is an environmental stress that mussels often encounter in their growth. However, few report carried out on the physiological and biochemical response and molecular regulation and adaptation mechanism of mussels under starvation. To illustrate the molecular mechanism of hosts of Mytilus to starvation, the gill transcriptome was used for analysis before and after 9 days of starvation in Mytilus using the Illumina/HiSeq-2000 deep sequencing platform, accompanied by the study of differentially expressed genes (DEGs). In total, 42.137 GB of clean data were obtained from six sample libraries, the average amount of clean data of each sample is 7.023 GB, and 58,540 unigenes that average 780 bp in length were assembled. Unigenes were illustrated by commenting them against the NR, Swiss-Prot, Pfam, String, GO and KEGG databases. After 9 days of starvation, 2,188 and 2,672 genes were determined to be significantly up- or down-regulated expression genes, separately. Amongst, 4,860 genes were associated with 260 pathways, contains vital enrichment pathways, such as “Metabolic”, “PI3K-Akt signaling pathway”, “Phagosome”, “Apoptosis” and “Lysosome”. In inclusion, autophagy cells were investigated by an electron microscopy, alongside further observations of the expression of autophagy-related genes in gill tissue before and after starvation. The data indicates that the amount of autophagosomes increased and found that atg2, atg6 and atg13 were significantly up-regulated. These results indicated that Mytilus may use autophagy to cope with their damage after starvation. With our research results, we have contributed to a deeper understanding of the role of the molecular mechanisms of immune defence in Mytilus under environmental stress, which has given insights into mussel breeding and the understanding of the molecular mechanisms of Mytilus immune system.

Background Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a promising alternative method for the diagnosis of LQTS, but without uniform standards. Methods and Results A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library through October 14, 2021. The fixed effects model was used to assess the effect of the provocative testing on QTc interval. A total of 22 studies with 1137 patients with LQTS were included. At baseline, QTc interval was 40 ms longer in patients with LQTS than in controls (mean difference [MD], 40.54 [95% CI, 37.43–43.65]; P

Microalgae are the primary source of food and energy for marine bivalves, and hence play a vital role in their development and growth. To characterize the microalgal feeding preference and the effects of fatty acid composition and digestive gland microorganisms on Mytilus, four microalgal species (Chlorella vulgaris, Chaetoceros muelleri, Isochrysis zhanjiangensis and Platymonas helgolandica) were used in a mix and single feeding experiments. The feeding preference in the mix feeding was determined using quantitative PCR analysis of water samples obtained at various time periods from biodeposits. The results demonstrated that C. muelleri and I. zhanjiangensis were selectively filtered by M. coruscus, while C. vulgaris and P. helgolandica were preferentially rejected. Individuals of M. coruscus fed with C. muelleri and I. zhanjiangensis had higher levels of fatty acids contents, particularly some unsaturated fatty acids like eicosapentaenoic acid (EPA), which rose by 63.6% after 28 days feeding with C. muelleri. In the digestive glands of M. coruscus fed these two microalgae diets, the relative abundance of digestion-related bacteria such as Polaribacter was also dramatically enhanced, indicating that they had a greater ability to degrade and metabolize microalgal polysaccharides. The metabolic pathway may also play a dominant role as a feedback reaction to microalgal diet feeding, according to potential function prediction. In comparison to C. vulgaris and P. helgolandica, our findings showed that C. muelleri and I. zhanjiangensis had a better nutritional value and could be utilized more efficiently by M. coruscus, implying that C. muelleri and I. zhanjiangensis may be employed to boost M. coruscus growth and output.

Objectives Occipitocervical fusion (OCF) is an effective treatment for instability of occipitocervical junction (OCJ). The occipital condyle screw serves as a novel surgical technique for occipitocervical fixation. However, the intraoperative procedures for the occipital condyle screw technique have relied on surgeons’ experience, so the pool of surgeons who are able to perform this surgery safely is limited. The present study aims to evaluate the feasibility and safety of the occipital condyle screw technique using human cadavers and to provide image anatomy for clinical application basis. Methods The scientific study comprised 10 fresh‐frozen cadaveric specimens from the anatomy department of Qingdao University. Placement of the occipital condyle screws (3.5 mm diameter and 20.0 mm length) was performed in the 10 fresh‐frozen cadaveric specimens with intact occipitocervical junctions, respectively. Occipitocervical CT was performed for all specimens and the DICOM data was obtained. Occipitocervical CT three‐dimensional (3D) reconstruction was performed for the cadavers. Morphometric analysis was performed on the bilateral occipitocervical junction of 10 cadaveric specimens based on the 3D reconstruction CT images. Detailed morphometric measurements of the 20 occipital condyles screws were conducted including the average length of the screw trajectory, inside and upper tilting angles of screws, distance to the hypoglossal canal, and to the medial wall of occipital condyle. Results Placement of the occipital condyle screws into the 20 occipital condyles of the 10 cadaveric specimens was performed successfully and the trajectory of implantation was satisfactory according to 3D CT reconstruction images, respectively. There was no obvious injury to the spinal cord, nerve root, and vertebral artery. The length of the bilateral screw trajectory was, respectively, 20.96 ± 0.91 mm (left) and 20.59 ± 0.77 mm (right) (t = 1.306, P > 0.05). The upper tilting angle of bilateral screws was, respectively, 11.24° ± 0.74° (left) and 11.11° ± 0.64° (right) (t = 0.681, P > 0.05). The inside tilting angle of bilateral screws was, respectively, 31.00° ± 1.32° (left) and 30.85° ± 1.27° (right) (t = 0.307, P > 0.05). The screw's distance to the bilateral hypoglossal canal was, respectively, 4.84 ± 0.54 mm (left) and 4.70 ± 0.54 mm (right) (t = 0.685, P > 0.05). The screw's distance to the medial wall of the bilateral occipital condyle was, respectively, 5.13 ± 0.77 mm (left) and 5.04 ± 0.71 mm (right) (t = 0.384, P > 0.05). Conclusion The occipital condyle screw technique can serve as a feasible and safe treatment for instability of the occipitocervical junction with meticulous preoperative planning of the screw entry point and direction based on individual differences. Morphometric trajectory analysis is also an effective way to evaluate the surgical procedure.

Background: Salidroside (SDS) is the main effective ingredient of Rhodiola rosea L with a variety of pharmacologic properties. We aim to investigate the effects of SDS on ventilation induced lung injury (VILI) and explore the possible underlying molecular mechanism. Methods: Lung injury was induced in male ICR mice via mechanical ventilation (30 ml/kg) for 4h. The mice were divided in four groups:(1) Control group; (2) Ventilation group; (3) SDS group; (4) Ventilation with SDS group. SDS (50 mg/kg) was injected intraperitoneally 1h before operation. Mouse lung vascular endothelial cells (MLVECs) were subjected to cyclic stretch for 4h. Results: It was found that SDS attenuated VILI as shown in HE staining, cell count and protein content levels in BAL fluid, W/D and Evans blue dye leakage into the lung tissue. SDS treatment inhibited the activation of NLRP3 inflammasome and subsequent caspase-1 cleavage as well as interleukin (IL)-1β secretion both in vivo and in vitro. Moreover, SDS administration up-regulated SIRT1 expression. Importantly, knockdown of SIRT1 reversed the inhibitory effect of SDS on NLRP3 inflammasome activation. Conclusions: Taken together, these findings indicate that SDS may confer protection against ventilation induced lung injury via SIRT1-de-pendent inhibition of NLRP3 inflammasome activation.

Objective: To study the effects of dexmedetomidine on cerebral injury, inflammation, oxidative stress and renal function of patients with diabetes mellitus type 2 complicated with acute cerebral hemorrhage. Methods: A total of 98 cases who had been diagnosed with diabetes mellitus type 2 complicated with acute cerebral hemorrhage and treated with interventional therapy in Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from September 2014 January 2016 were chosen to be our study subjects. Among them, 50 cases given dexmedetomidine treatment in the process of anesthesia were included in the dexmedetomidine group (Group A), while the other 48 cases treated with equal amount of normal saline were considered as the negative control group. The postoperative cerebral injury indexes and the serum biochemical indexes were detected after 24 h. Results: The contents of serum S100b [(2.1 ± 0.2) mg/L] and neuron-specific enolase (NSE) [(14.2 ± 1.3) mg/mL] in Group A were all significantly lower than serum S100b [(2.9 ± 0.3) mg/L] and NSE [(16.6 ± 1.7) mg/mL] of patients in negative control group. The contents of cerebrospinal fluid S100b [(0.9 ± 0.1) mg/L] and NSE [(10.7 ± 1.3) mg/ mL] in Group A were all significantly lower than cerebrospinal fluid S100b [(1.3 ± 0.2) mg/L] and NSE [(15.3 ± 1.7) mg/mL] of patients in negative control group. The contents of erythrocyte sedimentation rate [(11.7 ± 2.5) mm/h], c-reactive protein [(2.3 ± 0.4) mg/L], urea nitrogen [(10.7 ± 1.2) mmol/L] and serum creatinine [(151.6 ± 14.9)] mmol/L in Group A were all significantly lower than erythrocyte sedimentation rate [(23.6 ± 3.8) mm/h], c-reactive protein [(6.9 ± 1.1) mg/L], urea nitrogen [(16.7 ± 1.7) mmol/L] and serum creatinine [(192.5 ± 18.3)] mmol/L of patients in negative control group. Conclusions: The application of dexmedetomidine in the interventional therapy of diabetes mellitus type 2 complicated with acute cerebral hemorrhage could protect brain and renal functions and reduce systemic inflammatory responses.

To examine the associations of near work related parameters with spherical equivalent refraction and axial length in Chinese children.A total of 1770 grade 7 students with mean age of 12.7 years were examined with cycloplegic autorefraction and axial length. Questions were asked regarding time spent in near work and outdoors per day, and near work related parameters.Multivariate models revealed the following associations with greater odds of myopia: continuous reading (> 45min), odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8; close television viewing distance (≤ 3m), OR, 1.7; 95% CI, 1.2-2.3; head tilt when writing, OR, 1.3; 95% CI, 1.1-1.7, and desk lighting using fluorescent vs. incandescent lamp, OR, 1.5; 95% CI, 1.2-2.0. These factors, together with close reading distance and close nib-to-fingertip distance were significantly associated with greater myopia (P

To evaluate the efficacy of Chinese eye exercises on reducing accommodative lag in children by a randomized, double-blinded controlled trial.A total of 190 children aged 10 to 14 years with emmetropia to moderate myopia were included. They were randomly allocated to three groups: standard Chinese eye exercises group (trained for eye exercises by doctors of traditional Chinese medicine); sham point eye exercises group (instructed to massage on non-acupoints); and eyes closed group (asked to close their eyes without massage). Primary outcome was change in accommodative lag immediately after intervention. Secondary outcomes included changes in corrected near and distant visual acuity, and visual discomfort score.Children in the standard Chinese eye exercises group had significantly greater alleviation of accommodative lag (-0.10 D) than those in sham point eye exercises group (-0.03 D) and eyes closed group (0.07 D) (P = 0.04). The proportion of children with alleviation of accommodative lag was significantly higher in the standard Chinese eye exercises group (54.0%) than in the sham point eye exercises group (32.8%) and the eyes closed group (34.9%) (P = 0.03). No significant differences were found in secondary outcomes.Chinese eye exercises as performed daily in primary and middle schools in China have statistically but probably clinically insignificant effect in reducing accommodative lag of school-aged children in the short-term. Considering the higher amounts of near work load of Chinese children, the efficacy of eye exercises may be insufficient in preventing myopia progression in the long-term.ClinicalTrials.gov NCT01756287.

Several large high-grade iron skarn deposits in the Laiwu district of Shandong Province (North China Craton) are developed along the contact zone between the Early Cretaceous Kuangshan diorite pluton and Middle Ordovician dolomitic limestone. In sharp contrast, no iron skarn mineralization has been recognized in association with other contemporaneous dioritic intrusions (Jiaoyu, Jinniushan, Tietonggou) in this district. The reason for this contrast remains elusive. Here we present a comparative study of the orerelated Kuangshan pluton and its barren equivalents using whole-rock and mineral (zircon, apatite) geochemistry combined with existing Sr-Nd isotope data to provide new insights into the critical controls on iron skarn mineralization and shed light on future mineral exploration. Geochemical and Sr-Nd isotope data suggest that both the ore-related and barren intrusions were derived from a common enriched lithospheric mantle source following variable degrees of fractional crystallization and crustal assimilation. Modeling based on whole-rock Sr-Nd isotopes implies that the magmas responsible for the Kuangshan and Jinniushan diorite plutons assimilated significant quantities of the Ordovician evaporite-bearing carbonates. Both the fertile and barren diorites show high wholerock Sr/Y ratios, high zircon Eu/Eu* and Eu/Eu*/Y ratios, and low zircon Dy/Yb ratios. These data, combined with high magmatic water contents (4.4-8.0 wt%) calculated from amphibole compositions, indicate that those four plutons crystallized from hydrous magmas. High whole-rock Fe2O3/FeO, and high ΔFMQ values (mostly >1; fayalitemagnetite-quartz oxygen buffers) estimated from zircon, apatite, and amphibole suggest that the magmas from which the diorite intrusions crystallized were all oxidized. Using available partitioning coefficients for Cl between apatite and magma, the parental melts of the Kuangshan and Jinniushan diorite are estimated to have had higher Cl contents (0.15-0.77 wt%) than the Jiaoyu and Tietonggou diorites (0.06-0.34 wt%). Two types of apatite from the intrusions studied are recognized based on their paragenetic relations: Type 1 apatite (Ap1) is an early-formed phase enclosed in euhedral amphibole, plagioclase, and biotite, whereas type 2 (Ap2) is a late-formed variety hosted in, or intergrown with, anhedral K-feldspar (± anhedral amphibole ± subhedral to anhedral quartz). In the fertile Kuangshan diorite, Cl and OH contents of apatite decrease, but Sr contents increase from Ap1 to Ap2. However, those parameters show reverse trends or remain constant from Ap1 to Ap2 in barren diorites. Such distinctive apatite geochemical signatures are best interpreted as reflecting more efficient fluid exsolution from the parental magma of the Kuangshan diorite than from the barren intrusions. This view is supported by the presence of abundant fluid inclusions in apatite and quartz exclusively from the mineralized intrusion, indicating its crystallization from volatile oversaturated melts. The results presented here indicate that elevated magma Cl contents and efficient separation of magmatic hydrothermal fluid from cooling magmas have been the critical factors controlling iron skarn mineralization in the Laiwu district. Mass balance constraints on Cl budget indicate that a minimum of 44-60 km3 of magma was required to form the Fe deposits associated with the Kuangshan pluton. Our preliminary results suggest that decreasing OH and Cl contents from early to late apatite in intermediate rocks can be used as an indicator for efficient fluid exsolution and consequently metal fertility of those rocks. [ABSTRACT FROM AUTHOR]

Dysfunctional gene expression in nociceptive pathways plays a critical role in the development and maintenance of neuropathic pain. Super enhancers (SEs), composed of a large cluster of transcriptional enhancers, are emerging as new players in the regulation of gene expression. However, whether SEs participate in nociceptive responses remains unknown. Here, we report a spinal-specific SE (SS-SE) that regulates chronic constriction injury (CCI)-induced neuropathic pain by driving Ntmt1 and Prrx2 transcription in dorsal horn neurons. Peripheral nerve injury significantly enhanced the activity of SS-SE and increased the expression of NTMT1 and PRRX2 in the dorsal horn of male mice in a bromodomain-containing protein 4 (BRD4)-dependent manner. Both intrathecal administration of a pharmacological BRD4 inhibitor JQ1 and CRISPR-Cas9-mediated SE deletion abolished the increased NTMT1 and PRRX2 in CCI mice and attenuated their nociceptive hypersensitivities. Furthermore, knocking down Ntmt1 or Prrx2 with siRNA suppressed the injury-induced elevation of phosphorylated extracellular-signal-regulated kinase (p-ERK) and glial fibrillary acidic protein (GFAP) expression in the dorsal horn and alleviated neuropathic pain behaviors. Mimicking the increase in spinal Ntmt1 or Prrx2 in naive mice increased p-ERK and GFAP expression and led to the genesis of neuropathic pain-like behavior. These results redefine our understanding of the regulation of pain-related genes and demonstrate that BRD4-driven increases in SS-SE activity is responsible for the genesis of neuropathic pain through the governance of NTMT1 and PRRX2 expression in dorsal horn neurons. Our findings highlight the therapeutic potential of BRD4 inhibitors for the treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

In this paper, a kind of superconductor ceramics metastructure-photonic crystals (SCMPC) is proposed to investigate the absorption and transmission properties of electromagnetic waves (EW) by combining a metastructure with multiple degrees of freedom regulation and strong energy localization characteristics of photonic crystals. Firstly, for the periodically aligned SCMPC, EW mainly realizes absorption in forward propagation and transmission in backward case. The relative bandwidth (RB) for both forward absorptivity and backward transmittance greater than 0.9 is 2.7 %, and the operating bandwidth (OB) is 696 ∼ 715 terahertz (THz), which is an asymmetric absorption-transmission (AAT) characteristics. Importantly, the periodically aligned SCMPC can realize the double-band rasorber phenomenon, and the forward EW exhibits an absorption-transmission-absorption phenomenon with OBs of 644.2 ∼ 671.1 THz, 700.9 ∼ 742.1 THz, and 766.8 ∼ 784.2 THz. RBs with absorption and transmissivity greater than 0.8 are 4.1 %, 5.7 %, and 2.2 %, respectively, and the backward EW one is mainly transmitted. To optimize AAT, a quasi-periodic Octonacci sequence-aligned SCMPC is introduced. The results show that the maximum OB of forward absorption and backward transmission is 428.3 ∼ 670.5 THz and RB is 44.1 %, achieving favorable broadband AAT. In addition, the effects of temperatures, dielectric thicknesses, and stacking numbers on AAT are also investigated in detail. In conclusion, AAT has promising applications in unidirectional optical transmission, photodiodes, optical isolators, etc.

Highlights A strategy based on metal-organic decomposition is proposed to enhance the tube-tube interactions of carbon nanotubes (CNTs). The robust tube-tube interactions of CNTs enhance both EMI shielding performance and mechanical properties of CNT film. This innovative approach provides an effective way to obtain high-performance CNT film.