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Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving cognition. In this study, we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01 (a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative) that exhibits both anti-depression effects and improvements in cognition. D01 inhibits serotonin transporters (Ki = 30.1 ± 6.9 nmol/L) and M channels (IC50 = 10.1 ± 2.4 μmol/L). D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on locomotion. Intragastric administrations of D01 (20 and 40 mg/kg) can significantly shorten the immobility time in a mouse model of chronic restraint stress (CRS)-induced depression-like behavior. Additionally, D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice, but not fluoxetine. Furthermore, D01 reverses the long-term potentiation (LTP) inhibition induced by scopolamine. Taken together, our findings demonstrate that D01, a dual-target serotonin reuptake and M channel inhibitor, is highly effective in the treatment-resistant depression and cognitive deficits, thus holding potential for development as therapy of depression with cognitive deficits.

Mixed matrix composite membranes (MMCMs) are considered as one of the potential directions for the development of CO2 capture membranes. Nevertheless, the high cost and the challenging nature of improving separation performance are significant obstacles that prevent MMCMs from being widely applied in practice. In this study, we developed a cost-effective modified pore-optimized MOF-808 (MOF-808@PVAm) and utilized it to fabricate high-performance CO2 capture MMCMs. Specifically, MOF-808 and polyvinylamine (PVAm) were cross-linked by γ-(2,3-epoxypropoxy) propytrimethoxysilane (KH-560), which improved the pore structure characteristics of MOF-808 and led to high-performance MMCMs. For 2 bar feed gas (CO2/N2, 15/85), the MMCM with 33.33 wt.% MOF-808@PVAm loading displayed remarkable CO2 permeance of 2753 GPU and selectivity of 181. The prepared MMCM demonstrated good operational stability in simulated flue gas and exhibited potential for application in various gas purification fields (CO2/CH4, CO2/H2) through gas permeation tests.

Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.

Membrane-based separation technology exhibits significant potential in the fields of CO2 capture and gas purification. Mixed-matrix membranes (MMMs) integrate the easy processing of polymeric materials with excellent transport properties of fillers, and thereby have become a focus for the next-generation gas separation membranes. Herein, we demonstrated a novel mixed-matrix membrane comprising porous organic molecular cages (POCs) and amine-rich polyvinylamine (PVAm) polymer matrix for efficient CO2 separation. Micro-sized CC3 crystals featuring a pore size of ∼4.9 Å, a high micropore volume of 0.16 cm3 g−1 and specific surface area of 326 m2 g−1 were synthesized and immobilized onto the surface of the PVAm thin selective layer to generate rapid CO2-transport channels. The resulting CC3/PVAm/mPSf MMM displayed excellent binary gas mixture (CO2/N2 15/85 vol %) separation performance, with a high CO2 permeance of 1546 GPU, and appreciable CO2/N2 selectivity of 33 at 1.5 bar, which was superior to most reported POCs-based membranes and thin film composite membranes, accompanied with excellent long-term operational stability. The CO2-selective separation facilitated by the incorporation of POCs provided a new inspiration for the development of novel MMMs for efficient CO2 capture.

Objective: To describe our experience of reducing anastomotic leakage, a problem that has not been properly solved. Methods: Starting in January 2020, we began implementing our integrated strategy (application of an esophageal diameter-approximated slender gastric tube, preservation of the fibrous tissue around the residual esophagus and thyroid inferior pole anastomosis) in consecutive patients undergoing esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube. Additionally, the blood supply at the site of the anastomosis was evaluated with a near-infrared fluorescence thoracoscope after the completion of esophagogastric anastomosis in the integrated strategy group. Results: Of 570 patients who were reviewed, 119 (20.9%) underwent the integrated strategy, and 451 (79.1%) underwent the conventional strategy. The rate of anastomotic leakage was 2.5% in the integrated strategy group and 10.2% in the conventional strategy group (p = 0.008). In the integrated strategy group, the site of most of the anastomotic blood supply was the residual esophagus dominant (82.4%), followed by the gastroesophageal dual-dominant (12.6%) and the gastric tube dominant (5.0%). The reconstruction route was more likely to be orthotopic in the integrated strategy group than in the conventional strategy group (89.9% vs. 38.6%, p = 0.004). Gastric dilation was identified in 3.4% of the patients in the integrated strategy group and in 21.1% in the conventional strategy group. Conclusions: Patients who underwent our proposed integrated strategy (Zhengzhou Strategy) during McKeown esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube had a strikingly lower rate of anastomotic leakage and a relatively lower rate of postoperative complications, such as gastric tube dilation and delayed gastric emptying.

With the rapid development of the transportation industry, permeable asphalt pavement has become widely used in the construction of expressways and urban roads due to its safety, comfort, and environmental protection characteristics. However, water-temperature coupling can damage the mechanical properties of permeable asphalt mixtures. The use of high-viscosity modified asphalt can improve the water damage resistance of the mixture to a certain extent, resulting in better mechanical properties. This paper focuses on the preparation of PAC-13 mixture specimens using high-viscosity modified asphalt and the study of its noise reduction and anti-skidding properties under water-temperature coupling. SMA-13 and AC-13 are used for comparative research. The influence of water-temperature coupling on the functional characteristics of permeable asphalt mixture is analyzed through standing wave tube test and pendulum test. The results show that PAC-13 exhibits better noise reduction and anti-skidding characteristics than SMA-13 and AC-13. As the temperature increases, the skid resistance of asphalt mixtures weakens, but the noise reduction properties are less affected. Furthermore, the noise reduction and anti-skidding properties of the three mixtures are significantly damaged by the action of water, with PAC-13 being the most affected. Nevertheless, PAC-13 still exhibits the best noise reduction and anti-skidding properties.

Rapid diagnosis of urogenital schistosomiasis caused by Schistosoma haematobium requires an accurate and timely assay, especially for low-intensity S. haematobium infection cases and in non-endemic areas. The mitochondrial cytochrome c oxidase 1 (cox1) gene fragment of S. haematobium was selected as detection target as this short fragment, which can be rapidly sequenced and yet possess good diagnostic resolution. A pair of primers and a fluorescent probe were designed according to the principle of recombinase-aided amplification (RAA), which was subsequently optimized and applied as an S. haematobium-specific RAA assay. Its diagnostic performance was validated for sensitivity and specificity in comparison to microscopy-based egg counting after urine filtration. The RAA assay could detect as little as 10 copies/μL of S. haematobium recombinant plasmid, and no cross-reactions were observed with S. mansoni, S. japonicum, Ancylostoma duodenale, Clonorchis sinensis, Echinococcus granulosus, or Ascaris lumbricoides. This test can be conducted at 39 °C and the whole RAA reaction can be completed within 20 min. The validation of the RAA assay showed that it had 100 % consistency with urine-egg microscopy, as it does not require an elaborate reading tool, is simple to use, and should be useful for field diagnostics and point-of-care applications.

Under a certain temperature, cracks in asphalt mixtures can heal themselves, but water in the cracks will reduce the self-healing performance of the asphalt mixture. In this study, surfactants were added to asphalt mixtures. In the presence of water, the characteristics of amphiphilic surfactants are used to promote the adsorption between asphalt and aggregates; In this paper, the ability of surfactants to promote the formation of adsorption of asphalt on the crystal surface is verified using a combination of molecular simulations and macroscopic experiments. Molecular simulation results show that the adsorption energies of asphalt and surfactants, surfactants and silica, and asphalt and silica are all negative. Adsorption can occur between the three interfaces, and the surfactants effectively pulls the asphalt molecules onto the silica molecules, achieving adsorption similar to that between asphalt organic polymers and crystals. Macroscopic experiments show that in asphalt mixtures with active agents added, the active agent can be adsorbed on the surface of the aggregate, part of the asphalt is adsorbed on the surface of the active agent, and part is directly adsorbed on the gravel. Some asphalt is also adsorbed on the aggregate under the action of pure water, but the total adsorption capacity is lower than that of asphalt mixtures containing surfactants.

Summary: Free-standing metal-organic frameworks (MOFs) with controllable structure and good stability are emerging as promising materials for applications in flexible pressure sensors and energy-storage devices. However, the inherent low electrical conductivity of MOF-based materials requires complex preparation processes that involve high-temperature carbonization. This work presents a simple method to grow conductive nickel MOF nanowire arrays on carbon cloth (Ni-CAT@CC) and use Ni-CAT@CC as the functional electrodes for flexible piezoresistive sensor. The resulting sensor is able to monitor human activity, including elbow bending, knee bending, and wrist bending. Besides, the soft-packaged aqueous Ni-Zn battery is assembled with Ni-CAT@CC, a piece of glass microfiber filters, and Zn foil acting as cathode, separator, and anode, respectively. The Ni-Zn battery can be used as a power source for finger pressure monitoring. This work demonstrates free-standing MOF-based nanowires as bifunctional fabric electrodes for wearable electronics.

Water causes the asphalt to readily slip off the surface of the acid aggregate, causing fissures and compromising the structural stability of the asphalt pavement. In addition, fissures between asphalt and acid materials are difficult to cure in the presence of water. As a result, research into the healing of asphalt-acid aggregate fractures in the presence of water is necessary. This article incorporates a surfactant into the asphalt mixture. The application of surfactant “amphiphilic” properties to improve interfacial adhesion and healing between asphalt and acidic particles in moist environments. The molecular simulation approach was used in this study to create a microcrack model of asphalt-surfactant solution-acid aggregate to simulate crack healing at different temperatures. Prepare six sets of water containers for macro tests at the same time. The microscopic model's running results reveal that there is adsorption between asphalt and surfactant, surfactant and silica, and asphalt and silica surfaces, as well as changes in adsorption energy at different temperatures. Macroscopic investigations reveal that the addition of surfactants may improve asphalt adsorption on the surface of acidic aggregates in a wet environment, and the healing effect varies depending on the temperature, and the best healing temperature is 45 °C.

In order to evaluate the high and low temperature rheological properties of different modified asphalt, this paper prepared different types of modifiers and short-term aging modified asphalt (RTFOT), using dynamic shear rheometer (DSR) and bending beam rheological test (BBR) to compare and analyze the deformation resistance and stress sensitivity of different types (organic and inorganic) modified asphalt, determine its PG classification, and evaluate its fitting parameters with the help of Burgers model. The low-temperature mechanical properties of the fitting parameters were evaluated by the Burgers model; the chemical composition of different modified asphalts was analyzed by Fourier transform infrared spectroscopy (FTIR), and the microscopic state of the modified asphalts was observed by fluorescence microscopy. The results show that: with the increase of temperature, the high temperature deformation resistance of organic modified asphalt is better than that of inorganic modified asphalt, and PE modified asphalt is the best, and the low temperature performance of inorganic modified asphalt is poor, and the addition of SBS It will improve the low temperature crack resistance of asphalt. The road performance of different modified asphalts from strong to weak are PE modified asphalt, SBS modified asphalt, diatomite modified asphalt, montmorillonite modified asphalt. The research results have certain reference value for further research on different types (organic and inorganic) of modified asphalt.

Traditional asphalt pavement is prone to rutting, looseness, and other issues during usage resulting in overall poor durability. The service life of asphalt pavement may be improved, however, by targeted modifications. The modification mechanism and strengthening effect of polyester fiber and straw fiber on asphalt were investigated in this study in an effort to optimize the anti-aging and anti-fatigue performance of asphalt pavement. Molecular dynamics simulation, basic performance testing, dynamic shear rheological testing, and bending beam rheological testing were conducted on fiber-modified asphalt to observe the interaction modes between the asphalt components and its applicable conditions. Fiber appears to have some compatibility with asphalt, which can improve its performance; straw fiber’s ability to modify asphalt at high temperatures is less effective than that of polyester fiber, but it is stronger at low temperatures. Under high-temperature conditions, the optimal dosages of polyester fiber and straw fiber are 3.00 % and 3.00 %, respectively, while at low temperatures, they are 2.00 % and 3.00 %.

Exergoenvironmental analysis is used to assess system performance from an environmental point of view. The analyses' guiding principles are formed based on evaluations of the thermodynamic and ambient conditions. The ground source heat pump is one of the most suitable technologies for renewable energy due to its high-performance factor and low-temperature heat energy. In this research, EES software simulated a heat pump with an intermediate economizer and the ground source energy drive. Then the effect of changing different parameters, including the pressure of different parts of the cycle, degree of superheating at the evaporator outlet and degree of subcooling at the condenser outlet, on the environmental parameters (exergoenvironment factor, Exergy stability factor, Environmental damage effectiveness factor, and Exergoenvironmental impact improvement factor), is checked for five working fluids including R134a, R12, R152a, R1234yf and R1234ze(E).

ABSTRACT: The transcription factor csal1 is an important molecule that plays a critical regulatory function in ovarian follicle development, as confirmed by our previous data. However, the candidate genes of csal1 and its regulatory mechanism remain poorly understood in the granulosa cells (GCs) of chicken prehierarchical follicles (PFs). Six transcriptomes of csal1 and empty vector were analyzed in Chinese Dagu hens by RNA sequencing. Six cDNA libraries were constructed, with more than 42 million clean reads and 16,779 unigenes. Of these 16,779 unigenes, 2,762 differentially expressed genes (DEGs) were found in GCs, including 1,605 upregulated and 1,157 downregulated unigenes. Fourteen genes, including BMP5, TACR2, AMH, PLAG1, MYOD1, BOP1, SIPA1, NOTCH1, BCL2L1, SOX9, ADGRA2, WNT5A, SLC7A11, and GATAD2B, were related to GC proliferation and differentiation, hormone production, ovarian follicular development, regulation of reproductive processes, and signaling pathways in the PFs. Further analysis demonstrated the DEGs in GCs of ovarian follicles were enriched in neuroactive ligand–receptor interaction, cell adhesion molecules, and pathways related to cytochrome P450, indicating a critical function for csal1 in the generation of egg-laying features by controlling ovarian follicle development. For the first time, the current study represents the transcriptome analysis with ectopic csal1 expression. These findings provide significant evidence for investigating the molecular mechanism by which csal1 controls PF development in the hen ovary.

Anoctamin 1 (ANO1) is a kind of calcium-activated chloride channel involved in nerve depolarization. ANO1 inhibitors display significant analgesic activity by the local peripheral and intrathecal administration. In this study, several thiophenecarboxylic acid and benzoic acid derivatives were identified as novel ANO1 inhibitors through the shape-based virtual screening, among which the 4-arylthiophene-3-carboxylic acid analogues with the best ANO1 inhibitory activity were designed, synthesized and compound 42 (IC50 = 0.79 μmol/L) was finally obtained. Compound 42 selectively inhibited ANO1 without affecting ANO2 and intracellular Ca2+ concentration. Subsequently, the analgesic effect was investigated by intragastric administration in pain models. Compound 42 significantly attenuated allodynia which was induced by formalin and chronic constriction injury. Through homology modeling and molecular dynamics, the binding site was predicted to be located near the calcium-binding region between α6 and α8. Our study validates ANO1 inhibitors having a significant analgesic effect by intragastric administration and also provides selective molecular tools for ANO1-related research.

Obstructive sleep apnea-hypopnea (OSAH) is correlated with an increased incidence of lung cancer. In our study, we explored the functional roles of microRNAs (miRNAs) in lung cancer patients that were complicated with OSAH involving the deubiquitination enzyme. The miR-320b expression pattern in lung cancer tissues and cells was determined. The interactions between ubiquitin-specific peptidase 37 (USP37) and miR-320b were evaluated by a dual-luciferase reporter gene assay, whereas USP37 and Cdc10-dependent transcript 1 (CDT1) was assessed by co-immunoprecipitation and immunofluorescence. After the induction of intermittent hypoxia (IH), a gain-of function approach was performed to investigate roles of miR-320b, USP37, and CDT1 in lung cancer cell proliferation and invasion. In addition, nude mouse xenograft models were used to study their effects on tumor growth in vivo. miR-320b was poorly expressed in lung cancer patients with OSAH. IH treatment downregulated the expression of miR-320b but promoted the proliferation and invasion capabilities of lung cancer cells, both of which were suppressed by the overexpression of miR-320b through decreasing USP37. USP37 interacted with and deubiquitinated CDT1 to protect it from proteasomal degradation. Our study uncovered that IH-induced downregulation of miR-320b promoted the tumorigenesis of lung cancer by the USP37-mediated deubiquitination of CDT1.

Lead (Pb) is a naturally occurring heavy metal, which can damage the brain and affect learning and memory. Sodium para-aminosalicylic acid (PAS-Na), a non-steroidal anti-inflammatory drug, can readily cross the blood-brain barrier. Our previous studies have found that PAS-Na alleviated Pb-induced hippocampal ultrastructural damage and neurodegeneration, but the mechanism has yet to be defined. Here, we investigated the molecular mechanisms that mediate Pb-induced apoptosis in hippocampal neurons, and the efficacy of PAS-Na in alleviating its effects. This work showed that juvenile developmental Pb exposure impaired rats cognitive ability by inducing apoptotic cell death in hippocampal neurons. Pb-induced neuronal apoptosis was accompanied by increased inositol 1,4,5-trisphosphate receptor (IP3R) expression and enhanced intracellular calcium [Ca2+]i levels, which resulted in increased phosphorylation of neuronal apoptosis signal-regulating kinase 1 (ASK1) and p38. Activation of ASK1 and p38 was blocked by IP3R inhibitor and a Ca2+ chelator. Importantly, PAS-Na treatment improved the Pb-induced effects on cognitive deficits in rats, concomitant with rescued neuronal apoptosis. In addition, PAS-Na reduced the expression of IP3R and the ensuing increase in intracellular Ca2+ and decreased the phosphorylation of ASK1 and p38 in Pb-exposed neurons. Taken together, this study demonstrates that the IP3R-Ca2+-ASK1-p38 signaling pathway mediates Pb-induced apoptosis in hippocampal neurons, and that PAS-Na, at a specific dose-range, ameliorates these changes. Collectively, this study sheds novel light on the cellular mechanisms that mediate PAS-Na efficacy, laying the groundwork for future research to examine the treatment potential of PAS-Na upon Pb poisoning.

Esophageal cancer (EC) is a highly aggressive disease, and its progression involves a complex gene regulation network. Transcription factor SOX2 is amplified in various cancers including EC. A pathway involving SOX2 regulation of microRNAs (miRNAs) and their target genes has been previously revealed. This study aims to delineate the ability of SOX2 to influence the EC progression, with the involvement of miR-30e/USP4/SMAD4/CK2 axis. SOX2 expression was first examined in the clinical tissue samples from 30 EC patients. Effects of SOX2 on proliferation, migration, and invasion alongside tumorigenicity of transfected cells were examined by means of gain- and loss-of-function experiments. EC tissues and cells exhibited high expression of SOX2, miR-30e, and CK2 and poor expression of USP4 and SMAD4. Mechanistically, SOX2 was positively correlated with miR-30e and upregulated the expression of miR-30e. miR-30e specifically targeted USP4, which induced deubiquitination of SMAD4 and promoted its expression. Meanwhile, SMAD4 was enriched in the CK2 promoter region and thus inhibited its expression. SOX2 stimulated EC cell proliferative, invasive, and migratory capacities in vitro and tumor growth in vivo by regulating the miR-30e/USP4/SMAD4/CK2 axis. Collectively, our work reveals a novel SOX2-mediated regulatory network in EC that may be a viable target for EC treatment.

Summary: Background: Breathomics testing has been considered a promising method for detection and screening for lung cancer. This study aimed to identify breath biomarkers of lung cancer through perioperative dynamic breathomics testing. Methods: The discovery study was prospectively conducted between Sept 1, 2020 and Dec 31, 2020 in Peking University People's Hospital in China. High-pressure photon ionisation time-of-flight mass spectrometry was used for breathomics testing before surgery and 4 weeks after surgery. 28 volatile organic compounds (VOCs) were selected as candidates based on a literature review. VOCs that changed significantly postoperatively in patients with lung cancer were selected as potential breath biomarkers. An external validation was conducted to evaluate the performance of these VOCs for lung cancer diagnosis. Multivariable logistic regression was used to establish diagnostic models based on selected VOCs. Findings: In the discovery study of 84 patients with lung cancer, perioperative breathomics demonstrated 16 VOCs as lung cancer breath biomarkers. They were classified as aldehydes, hydrocarbons, ketones, carboxylic acids, and furan. In the external validation study including 157 patients with lung cancer and 368 healthy individuals, patients with lung cancer showed elevated spectrum peak intensity of the 16 VOCs after adjusting for age, sex, smoking, and comorbidities. The diagnostic model including 16 VOCs achieved an area under the curve (AUC) of 0.952, sensitivity of 89.2%, specificity of 89.1%, and accuracy of 89.1% in lung cancer diagnosis. The diagnostic model including the top eight VOCs achieved an AUC of 0.931, sensitivity of 86.0%, specificity of 87.2%, and accuracy of 86.9%. Interpretation: Perioperative dynamic breathomics is an effective approach for identifying lung cancer breath biomarkers. 16 lung cancer-related breath VOCs (aldehydes, hydrocarbons, ketones, carboxylic acids, and furan) were identified and validated. Further studies are warranted to investigate the underlying mechanisms of identified VOCs. Funding: National Natural Science Foundation of China (82173386) and Peking University People's Hospital Scientific Research Development Founds (RDH2021–07).

Recent studies have suggested that microRNA let-7i is a tumor suppressor in human cancers, including esophageal cancer, but its underlying mechanism is not yet fully understood. We investigated the role and mechanisms of let-7i in the progression of esophageal cancer. We first showed that let-7i was downregulated in esophageal cancer tissues and cells and then linked its low expression to cancer progression. Bioinformatic analysis predicted KDM5B as a target gene of let-7i, which was confirmed by a dual-luciferase reporter assay. Loss- and gain-of function approaches were adopted to examine the interactions of let-7i, KDM5B, SOX17, and GREB1 in vitro and in vivo. Overexpression of let-7i suppressed esophageal cancer cell proliferation and invasion and promoted apoptosis. Mechanistic investigation showed that let-7i targeted and inhibited KDM5B expression, whereas KDM5B enhanced H3K4me3 at the SOX17 promoter region. Overexpression of let-7i suppressed the expression of GREB1 in esophageal cancer cells by regulating the KDM5B/SOX17 axis in vivo and in vitro. Taken together, our findings reveal the tumor-suppressive properties of let-7i in esophageal cancer in association with an apparent KDM5B-dependent SOX17/GREB1 axis. This study offers a potential prognostic marker and therapeutic target for esophageal cancer.

Background: Total lesion glycolysis has been reported to be a satisfactory predictor of survival in patients with locally advanced esophageal cancer (EC). The aim of the present study is to investigate the function of long intergenic non-protein coding RNA 184 (LINC00184) on the EC cell glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). Methods: The expression of LINC00184 was determined to be highly expressed and PTEN was poorly expressed in EC tissues and cells by RT-qPCR. In order to evaluate the effects of LINC00184 on cellular process in vitro and in vivo, gain- and loss-of-function approaches were performed to alter the expression of LINC00184 and PTEN in EC cells. Results: Silencing of LINC00184 was observed to inhibit the proliferation, migration, invasion, colony formation, and glycolysis of EC cells and tumour growth, while the mitochondrial OXPHOS was restored. By recruiting DNMT1, LINC00184 enhanced the promoter methylation of PTEN. Inhibition of PTEN promoter methylation suppressed EC glycolysis, whereas, improved mitochondrial OXPHOS. Mechanically, LINC00184 modulated glycolysis and mitochondrial OXPHOS in EC cells through induction of the Akt phosphorylation. After blockage of Akt signaling pathway by an Akt inhibitor, LY294002, the regulatory effects of LINC00184 on the glycolysis and mitochondrial OXPHOS of EC cells were reversed. Conclusion: Taken together, the LINC00184/PTEN/Akt axis mediates glycolysis and mitochondrial OXPHOS in EC cells. This study highlighted a potential intervention target for treating EC. Keywords: Esophageal cancer, Long intergenic non-protein coding RNA 184, Phosphatase and tensin homolog, Methylation, Glycolysis, Mitochondrial oxidative phosphorylation

Diabetic peripheral neuropathy (DPN) is the common complication of diabetes mellitus. Histone deacetylase (HDAC) inhibitor trichostatin A (TSA) is reported to ameliorate the peripheral nerves degeneration of DPN. However, the exact mechanism is still not well elucidated. Here, we first revealed that TSA promoted nerve conduction and brain derived neurotrophic factor (BDNF) expression in the sciatic nerves of diabetic mice. In line, TSA also reversed high glucose-reduced mature BDNF expression in vitro cultured rat Schwann cells (RSC96). Then unexpectedly, the downstream targets of TSA HDAC1 and HDAC5 were not involved in TSA-improved BDNF expression. Furthermore, unfolded protein response (UPR) chaperone GRP78 was revealed to be downregulated with high glucose stimulation in RSC96 cells, which was avoided with TSA treatment. Also, GRP78 upregulation mediated TSA-improved mature BDNF expression in high glucose-cultured RSC96 cells by binding with BDNF. As well, TSA treatment enhanced the binding of GRP78 with BDNF in RSC96 cells. Again, UPR-associated transcription factors XBP-1s and ATF6 were involved in TSA-increased GRP78 expression in high glucose-stimulated RSC96 cells. Finally, conditioned medium from high glucose-cultured RSC96 cells delayed neuron SH-SY5Y differentiation and that from TSA-treated high glucose-cultured RSC96 cells promoted SH-SY5Y cell differentiation. Taken together, our findings suggested that TSA increased BDNF expression to ameliorate DPN by improving XBP-1s/ATF6/GRP78 axis in Schwann cells.

Doxorubicin (DOX) as a first-line chemotherapeutic drug has been widely used for therapy of human cancers. However, side effects and chemo-resistance severely blocked its clinic application. Herein, natural borneol (NB) as a novel monoterpenoid chemosensitizer was found to have the potential to increase the blood brain barrier (BBB) permeability and intracellular uptake of DOX in vitro, and synergistically enhanced DOX-induced cytotoxicity in human glioma cells. NB treatment significantly potentiated DOX-induced G2/M cell cycle arrest by triggering reactive oxygen species (ROS)-mediated DNA damage. NB also enhanced DOX-induced dysfunction of MAPKs and PI3 K/AKT pathways. Furthermore, U251 human glioma xenograft growth in vivo was also effectively inhibited by combined treatment of DOX with NB through induction of G2/M-phase arrest and antiangiogenesis. Taken together, our finding validated that NB could act as novel chemosensitizer to enhance DOX-induced anticancer efficacy, and strategy of using NB and DOX could be a high efficient way in therapy of human cancers.

Bacillus subtilis strain NCD-2 is an excellent biocontrol agent for plant soil-borne diseases, and the lipopeptide fengycin is one of the active antifungal compounds in strain NCD-2. The regulator PhoP and its sensor kinase PhoR compose a two-component system in B. subtilis. In this study, the phoR- and phoP-knockout mutants were constructed by in-frame deletion and the role of PhoR/PhoP on the production of fengycin was determined. Inactivation of phoR or phoP in B. subtilis decreased its inhibition ability against Botrytis cinerea growth in vitro compared to the strain NCD-2 wild type. The lipopeptides were extracted from strain NCD-2 wild type and its mutant strains by hydrochloric acid precipitate, and the lipopeptides from phoR-null mutant or phoP-null mutant almost lost the inhibition ability against B. cinerea growth compared to the lipopeptides from strain NCD-2 wild type. Fast protein liquid chromatography (FPLC) analysis of the lipopeptides showed that inactivation of phoR or phoP genes reduced the production of fengycin by strain NCD-2. The fengycin production abilities were compared for bacteria under low-phosphate medium (LPM) and high-phosphate medium (HPM), respectively. Results indicated that the regulation of fengycin production by the PhoR/PhoP two-component system occurred in LPM but not in HPM. Reverse transcriptional-PCR confirmed that the fengycin synthetase gene fenC was positively regulated by phoP when cultured in LPM. All of these characteristics could be partially restored by complementation of intact phoR or phoP gene in the mutant. These data indicated that the PhoR/PhoP two-component system greatly regulated fengycin production and antifungal ability in B. subtilis NCD-2 mainly under low-phosphate conditions.

Agricultural soils are deficient of phosphorus (P) worldwide. Phosphatic fertilizers are therefore applied to agricultural soils to improve the fertility and to increase the crop yield. However, the effect of phosphorus application on soil N2O emissions has rarely been studied. Therefore, we conducted a laboratory study to investigate the effects P addition on soil N2O emissions from P deficient alluvial soil under two levels of nitrogen (N) fertilizer and soil moisture. Treatments were arranged as follows: P (0 and 20 mg P kg−1) was applied to soil under two moisture levels of 60 and 90% water filled pore space (WFPS). Each P and moisture treatment was further treated with two levels of N fertilizer (0 and 200 mg N kg−1 as urea). Soil variables including mineral nitrogen (NH4+-N and NO3−-N), available P, dissolved organic carbon (DOC), and soil N2O emissions were measured throughout the study period of 50 days. Results showed that addition of P increased N2O emissions either under 60% WFPS or 90% WFPS conditions. Higher N2O emissions were observed under 90% WFPS when compared to 60% WFPS. Application of N fertilizer also enhanced N2O emissions and the highest emissions were 141 μg N2O kg−1 h−1 in P+N treatment under 90% WFPS. The results of the present study suggest that P application markedly increases soil N2O emissions under both low and high soil moisture levels, and either with or without N fertilizer application.

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been widely used as a first-line agent in EGFR-mutant non-small cell lung cancer (NSCLC). Nevertheless, the development of chemoresistance ultimately limited the curative effect of anti-cancer drugs. The present study aims to investigate the functions of SNHG14 in gefitinib resistance and gain insight into the underlying molecular mechanisms. In the present study, we found that SNHG14 expression was elevated and miR-206-3p expression was decreased in gefitinib-resistant NSCLC tumor tissues and cells. Functionally, SNHG14 overexpression increased gefitinib resistance by promoting cell viability, lowering apoptosis and enhancing colony forming ability, while SNHG14 knockdown reduced gefitinib resistance in NSCLC cells. Mechanistically, SNHG14 induced ABCB1 expression via interaction with miR-206-3p. Moreover, depletion of SNHG14 enhanced the sensitivity of NSCLC cells to gefitinib in vivo. Together, SNHG14 confers gefitinib resistance in NSCLC by regulating miR-206-3p/ABCB1 pathway, contributing to a better understanding of SNHG14 in acquired resistance and elucidating a candidate target to improve treatment response of NSCLC patients.

Long non-coding RNAs (LncRNAs) have been found to be associated with the biological behaviors of human cancers. LINC00152 is reported as an oncogene in many kinds of malignancies. However, the functions and mechanisms of LINC00152 involved in esophageal squamous cell carcinoma (ESCC) remain elusive. Our results revealed that LINC00152 expression was up-regulated in ESCC, and correlated with advanced TNM stage, lymph node metastasis, and poor prognosis of ESCC patients. Functionally, LINC00152 knockdown suppressed proliferation, decreased colony forming ability, and induced apoptosis in ESCC cells. Mechanically, LINC00152 functioned as a competing endogenous RNA (ceRNA) to sponge miR-153-3p, thereby facilitating its downstream target FYN. Moreover, miR-153-3p-mediated tumor-suppressive effects were partly reversed following LINC00152 overexpression. Also, FYN knockdown displayed a similar anti-cancerous role in ESCC cells. Taken together, LINC00152 contributed to ESCC progression by down-regulating miR-153-3p and promoting FYN expression, uncovering a novel LINC00152/miR-153-3p/FYN regulatory pathway in ESCC.

Objectives: Brucellar cervical epidural abscess (CEA) is a rare condition with potentially permanent neurological damage if left untreated. This study aims to define the clinical presentation of brucellar CEA and evaluate the outcome of surgical treatment, specifically decompression and fusion surgery. The findings will contribute to understanding whether all patients with brucellar CEA could benefit from this surgical intervention., Methods: A retrospective study on brucellar spondylitis was conducted at the First Hospital of Jilin University from August 2018 to August 2022. During this period, a total of 37 patients were diagnosed with brucellar spondylitis at the hospital. Out of the 37 cases, six patients (16.2%) were confirmed to have CEA through cervical magnetic resonance imaging examination and serology test results.., Results: Six patients were diagnosed with brucellar CEA (16.2%), of whom 5 successfully underwent anterior cervical decompression and fusion surgery. One patient had a large prevertebral abscess that could only be drained. In combination with effective antibiotic therapy, the clinical performance of the 5 patients who underwent surgery improved after the surgery. The remaining one patient required delayed surgery due to instability of the cervical spine. The follow-up period of all the 6 patients was 6 months., Conclusions: Brucellosis should be considered as a potential cause of CEA, especially in endemic areas. Timely detection and effective management of this condition are crucial in order to minimize the associated morbidity and mortality. For patients with detectable brucellar CEA, we recommend decompression and fusion surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Retinal pigment epithelial (RPE) cells contribute to several clinical conditions resulting in retinal fibrotic scars. Myofibroblast trans-differentiation of RPE cells is a critical step in the process of retinal fibrosis. In this study, we investigated the effects of N-oleoyl dopamine (OLDA), a newer endocannabinoid with a structure distinct from classic endocannabinoids, on TGF-β2-induced myofibroblast trans-differentiation of porcine RPE cells. Using an in vitro collagen matrix contraction assay, OLDA was found to inhibit TGF-β2 induced contraction of collagen matrices by porcine RPE cells. This effect was concentration-dependent, with significant inhibition of contraction observed at 3 μM and 10 μM. OLDA did not affect the proliferation of porcine RPE cells. Immunocytochemistry showed that at 3 μM, OLDA decreased incorporation of α-SMA in the stress fibers of TGF-β2-treated RPE cells. In addition, western blot analysis showed that 3 μM OLDA significantly downregulated TGF-β2-induced α-SMA protein expression. Taken together these results demonstrate that OLDA inhibits TGF-β induced myofibroblast trans-differentiation of RPE cells. It has been established that classic endocannabinoid such as anandamide, by activating the CB1 cannabinoid receptor, promote fibrosis in multiple organ systems. In contrast, this study demonstrates that OLDA, an endocannabinoid with a chemical structure distinct from classic endocannabinoids, inhibits myofibroblast trans-differentiation, an important step in fibrosis. Unlike classic endocannabinoids, OLDA has weak affinity for the CB1 receptor. Instead, OLDA acts on non-classic cannabinoid receptors such as GPR119, GPR6, and TRPV1. Therefore, our study indicates that the newer endocannabinoid OLDA and its non-classic cannabinoid receptors could potentially be novel therapeutic targets for treating ocular diseases involving retinal fibrosis and fibrotic pathologies in other organ systems., Competing Interests: Declaration of competing interest All authors: Nothing to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Accurate segmentation of frontal lobe areas on magnetic resonance imaging (MRI) can assist in diagnosing and managing idiopathic normal-pressure hydrocephalus. However, frontal lobe segmentation is challenging due to the complexity of the degree and shape of damage and the ambiguity of the boundaries of frontal lobe sites. Therefore, to extract the rich edge information and feature representation of the frontal lobe, this paper designs an edge guidance (EG) module to enhance the representation of edge features. Accordingly, an edge-guided cascade network framework (EG-Net) is proposed to segment frontal lobe parts automatically. Two-dimensional MRI slice images are fed into the edge generation and segmentation networks. First, the edge generation network extracts the edge information from the input image. Then, the edge information is sent to the EG module to generate an edge attention map for feature representation enhancement. Meanwhile, multi-scale attentional convolution (MSA) is utilized in the feature coding stage of the segmentation network to obtain feature responses from different perceptual fields in the coding stage and enrich the spatial context information. Besides, the feature fusion module is employed to selectively aggregate the multi-scale features in the coding stage with the edge features output by the EG module. Finally, the two components are fused, and a decoder recovers the spatial information to generate the final prediction results. An extensive quantitative comparison is performed on a publicly available brain MRI dataset (MICCAI 2012) to evaluate the effectiveness of the proposed algorithm. The experimental results indicate that the proposed method achieves an average DICE score of 95.77% compared to some advanced methods, which is 4.96% better than the classical U-Net. The results demonstrate the potential of the proposed EG-Net in improving the accuracy of frontal edge pixel classification through edge guidance., 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.)