Non-cytotoxic nanomolar concentration of arctigenin protects neuronal cells from chemotherapy-induced ferroptosis by regulating SLC7A11-cystine-cysteine axis.

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.

Neuroendoscopy-Assisted Entire-Process Visualization Technique of Ventricular Puncture for External Ventricular Drainage.

OBJECTIVE: This study aimed to investigate the feasibility, safety, and efficacy of the neuroendoscopy-assisted entire-process visualization technique (NEAEVT) of ventricular puncture for external ventricular drainage. METHODS: Eighty-eight patients with cerebral hemorrhage who underwent unilateral ventricular puncture for external ventricular drainage in our hospital from June 2021 to June 2023 were analyzed. Patients were grouped according to puncture technique: NEAEVT (30 patients), freehand (30 patients), and laser-navigation-assisted (28 patients). Operation time, drainage tube placement, and catheter-related hemorrhage incidence were compared between the groups. RESULTS: Mean operation time significantly differed between the freehand, NEAEVT, and laser-assisted groups (17.07, 18.37, and 34.04 min, respectively; P <0.0001). The position of the drainage tube was optimal or adequate in all patients of the NEAEVT group; optimal/adequate positioning was achieved in 80% of the freehand group. No catheter-related hemorrhage occurred in the NEAEVT group. Three freehand group patients and 2 laser-assisted group patients experienced catheter-related hemorrhage. CONCLUSION: The NEAEVT of ventricular puncture is accurate and achieves ventricular drainage without significantly increasing surgical trauma, operation time, or incidence of hemorrhage.

Genome Identification and Expression Profiling of the PIN-Formed Gene Family in Phoebe bournei under Abiotic Stresses.

PIN-formed (PIN) proteins-specific transcription factors that are widely distributed in plants-play a pivotal role in regulating polar auxin transport, thus influencing plant growth, development, and abiotic stress responses. Although the identification and functional validation of PIN genes have been extensively explored in various plant species, their understanding in woody plants-particularly the endangered species Phoebe bournei (Hemsl.) Yang-remains limited. P. bournei is an economically significant tree species that is endemic to southern China. For this study, we employed bioinformatics approaches to screen and identify 13 members of the PIN gene family in P. bournei. Through a phylogenetic analysis, we classified these genes into five sub-families: A, B, C, D, and E. Furthermore, we conducted a comprehensive analysis of the physicochemical properties, three-dimensional structures, conserved motifs, and gene structures of the PbPIN proteins. Our results demonstrate that all PbPIN genes consist of exons and introns, albeit with variations in their number and length, highlighting the conservation and evolutionary changes in PbPIN genes. The results of our collinearity analysis indicate that the expansion of the PbPIN gene family primarily occurred through segmental duplication. Additionally, by predicting cis-acting elements in their promoters, we inferred the potential involvement of PbPIN genes in plant hormone and abiotic stress responses. To investigate their expression patterns, we conducted a comprehensive expression profiling of PbPIN genes in different tissues. Notably, we observed differential expression levels of PbPINs across the various tissues. Moreover, we examined the expression profiles of five representative PbPIN genes under abiotic stress conditions, including heat, cold, salt, and drought stress. These experiments preliminarily verified their responsiveness and functional roles in mediating responses to abiotic stress. In summary, this study systematically analyzes the expression patterns of PIN genes and their response to abiotic stresses in P. bournei using whole-genome data. Our findings provide novel insights and valuable information for stress tolerance regulation in P. bournei. Moreover, the study offers significant contributions towards unraveling the functional characteristics of the PIN gene family.

Multi-layer reconstruction of skull base after endoscopic transnasal surgery for invasive pituitary adenomas.

OBJECTIVE: To explore the efficacy of multi-layer skull base reconstruction after endoscopic transnasal surgery for invasive pituitary adenomas (IPAs). CLINICAL RATIONALE FOR THE STUDY: Skull base reconstruction for IPAs. MATERIAL AND METHODS: This retrospective analysis involved 160 patients with IPAs who underwent operations from October 2018 to October 2020. All patients were diagnosed with IPAs by pituitary enhanced magnetic resonance imaging, and all tumours were confirmed to be Knosp grades 3a, 3b, or 4. The experimental group and the control group comprised 80 patients in each, and we used different methods to reconstruct the skull base in each group. The comparison indicators included cerebrospinal fluid leakage, sellar floor bone flap (or middle turbinate) shifting, delayed healing of the skull base reconstructed tissue, nasal discomfort, and epistaxis. We used the chi-square test, and p < 0.05 was considered statistically significant. RESULTS: In the experimental group, cerebrospinal fluid leakage occurred intraoperatively in 73 patients, two of whom had cerebrospinal fluid leakage postoperatively. Brain CT 12 months postoperatively showed no sellar floor bone flap (or middle turbinate) shifting. Endoscopic transnasal checks performed seven days after surgery showed that the skull base reconstructed tissue had healed in 74 patients and had failed to heal in six. However, endoscopic transnasal checks showed that all six of these patients' pedicled nasoseptal flaps had healed well by 14 days after surgery. Other sequelae comprised nasal discomfort in four patients, and epistaxis in four. In the control group, cerebrospinal fluid leakage occurred intraoperatively in 71 patients, 14 of whom had cerebrospinal fluid leakage postoperatively. Brain CT 12 months postoperatively showed floor bone flap (or middle turbinate) shifting in 12 patients. Endoscopic transnasal checks performed seven days after surgery showed that the skull base reconstructed tissue had healed in 65 patients. In 12 patients, pedicled nasoseptal flaps had healed well by 14 days after surgery, while the remaining three patients required reoperation. Other sequelae comprised nasal discomfort in five patients, and epistaxis in six. CONCLUSIONS: This new method of multi-layer skull base reconstruction could play an important role in endoscopic transnasal IPA surgery.

Prognostic value and predictive biomarkers of phenotypes of tumour-associated macrophages in colorectal cancer.

BACKGROUND: The roles of different subtypes of tumour-associated macrophages (TAMs) in predicting the prognosis of colorectal cancer (CRC) remain controversial. In this study, different subtypes of TAMs were investigated as prognostic and predictive biomarkers for CRC. METHODS: Expressions of CD68, CD86 and CD163 were investigated by immunohistochemistry (IHC) and immunofluorescence (IF), and the correlation between the expression of CD86 and CD163 was calculated in colorectal cancer tissues from 64 CRC patients. RESULTS: The results showed that high expressions of CD86+ and CD68+ CD86+ TAMs as well as low expression of CD163+ and CD68+ CD163+ TAMs were significantly associated with favourable overall survival (OS). The level of CD86 protein expression showed a negative correlation with CD163 protein expression. In addition, CD86 protein expression remarkably negatively correlated with tumour differentiation and tumour node metastasis (TNM) stage, while CD163 protein expression significantly positively correlated with tumour differentiation and tumour size. As an independent risk factor, high expression of CD86 TAMs had prominently favourable prognostic efficacy, while high expression of CD68+ CD163+ TAMs had significantly poor prognostic efficacy. CONCLUSIONS: These results indicate that CD86+ and CD68+ CD163+ TAMs as prognostic and predictive biomarkers for CRC.

Effect of Solvents on the Color Recovery Responses of Swollen Structural-Color Epoxy Films Based on Inverse Opal Photonic Crystals.

Photonic crystal (PC) films have been widely applied in color displays and the anticounterfeiting field due to their facile fabrication process and easily tunable properties. However, the method for improving the reusability of the color-changed swollen PC films is still a challenge. In this paper, we report the color recovery behavior of epoxy resin inverse opal photonic crystal (EP-IOPC) films, which show different responses after being infiltrated with ethanol, acetone, and dimethyl sulfoxide (DMSO) based on the swelling and deswelling process. DMSO achieved the best effect on the color recovery of the swollen EP-IOPC films compared to ethanol and acetone, and the reflection spectrum blue-shifted in a small range and finally stabilized at a 60 nm deviation from the original spectrum after 10 times recovery. This strategy of color recovery not only solved the problem that the swollen EP-IOPC film's color changes to a certain extent but also showed promising potential in the color display and anticounterfeiting field.

Insights into Thiourea-Based Bifunctional Catalysts for Efficient Conversion of CO2 to Cyclic Carbonates.

The bifunctional thiourea catalyst system with both electrophilic and nucleophilic centers has been certified to be effective for fixing CO2 under mild reaction conditions; however, many questions remain, especially concerning the relationship between structure and performance. Herein, we systematically studied a series of such bifunctional catalysts with different chain lengths, nucleophilic anions, and substituents, which impact obvious influence on the catalytic performance. The activation energies of catalysts with different chain lengths are calculated via in situ IR. On this basis, we disclosed for the first time that the spacer length of tetramethylene -(CH2)6- is the optimal spatial effect for the coupling of epoxides and CO2. Particularly, the single crystal X-ray diffraction analysis of the molecular structures of the bifunctional catalyst C8 indicated the discovery of the existence of interaction force between the sulfur atom on the thiourea group and one hydrogen atom on the benzene ring, as well as the intermolecular hydrogen bonding interaction of the bromide (Br-) and two NH groups on the thiourea group. The catalyst structure performance, direct observation of the crystal structure, the thermodynamic study, and a wide range of substrates (12 examples) should be informative on the optimization of the existing catalysts or the design of new catalysts in the future.

Numerical analysis and animal study of noninvasive handheld electroporation delivery device for skin superficial lesion treatment.

INTRODUCTION: This study aims to investigate the feasibility of a noninvasive handheld electroporation pulses delivery device (EPDD) for electroporation-based treatment (EBT) of skin superficial lesions through numerical analysis and animal study. METHODS: Finite element analysis was performed to investigate the performance of the EPDD. The electric field, temperature, EI and TI were calculated under pulse voltages of 600, 800, and 1000 V. A mouse subcutaneous tumor model was established to evaluate the performance of the EPDD through histopathology and survival analyses. RESULTS: The electrical field strength increased from 151 (600 V) to 252 V/cm (1000 V) in the skin and from 1302 (600 V) to 2171 V/cm (1000 V) in the tumor. The volume of EI grew and reached a plateau at the 165th pulse, whereas the maximum volume of EI increased with higher voltage. The growth tendency of TI differed between groups, and it was higher in the high-voltage group (HVG) than in the low-voltage group. Histopathological analysis showed that the depth and range of the ablation area could be controlled by adjusting pulse voltage. Survival analysis showed that the survival of the HVG was better than that of the low-voltage and the control group (p < 0.01). CONCLUSIONS: The results demonstrate that the EPDD is feasible, safe, and effective for skin EBT. The volume of EP tissue injury can be controlled by adjusting the pulse voltage, pulse number, and other parameters. The proposed noninvasive handheld EPDD can be a potential therapeutic tool for EBT of superficial skin lesions in the future.

Physiological and histopathological effects of electroporation pulse on stomach of rats.

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique with widespread potential, especially for cancer treatment. Although the safety and efficacy of IRE for gastric tissue ablation have been demonstrated, there is a gap of knowledge regarding the effect of electroporation pulse (EP) on the physiology and histopathology of the stomach. This study applied EP to the stomach of healthy rats and investigated the digestive function, serum marker levels, and gastric tissue structure of EP-treated rats. METHODS: Ninety male rats were divided into nine groups and examined up to 28 days post-treatment. A single burst of electroporation pulse (500 V, 99 pluses, 1 Hz, 100 µs) was delivered to the stomachs of rats using a tweezer-style round electrode. Gastric emptying, small intestinal transit, and gastric secretion were measured to evaluate the digestive function. Serum marker levels were determined using ELISA. Haematoxylin-eosin, Masson trichrome, and immunofluorescence were performed for histopathological analysis. RESULTS: No  significant effect on gastric emptying or secretion was found post-EP, whereas the small intestinal transit decreased at 4 h and rapidly recovered to normal on 1-day post-EP. Further, serum TNF-α and IL-1ß levels temporarily changed during the acute phase but returned to baseline within 28 days. Moreover, histopathological analysis revealed that cell death occurred immediately post-EP in the ablation area, whereas the gastric wall scaffold in the ablation region remained intact post-EP. CONCLUSIONS: This study demonstrates the safety and efficacy of EP on the physiology and histopathology of the stomach and lays a foundation for more comprehensive applications of this technique.

Magnetic anchoring and guidance-assisted endoscopic irreversible electroporation for gastric mucosal ablation: a preclinical study in canine model.

BACKGROUND: The aim of this study was to evaluate the feasibility, safety, and efficacy of magnetic anchoring and guidance-assisted endoscopic irreversible electroporation (MAG-IRE) for gastric mucosal ablation. METHODS: A catheter-based, donut-like, and MAG-assisted electrode was developed. MAG-IRE for gastric mucosal ablation was performed in eight beagle canines. The parameters of one set of IRE was 500 V voltage, 100 µs pulse duration, and 99 pulses. The MAG time, operation time, success rate, and adverse events were measured. Endoscopic examination was performed from 30 min to 28 days post-IRE. Full-thickness gastric tissue was harvested by wedge biopsy for histopathological analysis. RESULTS: 30 (93.75%) of the 32 lesions were successfully ablated by MAG-IRE. The median MAG time was 300 s (IQR 120-422.5 s), and the median operation time was 491.5 s (IQR 358.3-632.5 s). No adverse events occurred. Ulceration was observed, starting from 3 days post-IRE. The mucosa healed 14 to 28 days post-IRE. Hematoxylin-Eosin (H&E) staining showed inflammatory infiltration, edema, and congestion in the ablated mucosa. Masson's Trichrome staining showed that the gastric wall and blood vessels in the ablation area were intact. TUNEL assay showed diffuse positive cells in ablated mucosa as early as 30 min post-IRE. CONCLUSIONS: MAG-IRE for gastric mucosal ablation is feasible, safe, and effective. It can be a potential therapeutic option for minimally invasive treatment of gastric neoplasm.

Preparation of N-MG-modified PVDF-CTFE substrate composite nanofiltration membrane and its selective separation of salt and dye.

Poly(vinylidene fluoride-co-chlorotrifluoroethylene) (PVDF-CTFE) is considered an ideal membrane material for the treatment of complex environmental water due to its exceptional thermal stability and chemical resistance. Thus, to expand its application in the field of nanofiltration (NF) membranes, in this study, N-methylglucamine (N-MG) was used to hydrophilically modify PVDF-CTFE, overcoming the inherent hydrophobicity of PVDF-CTFE as a porous substrate membrane, which leads to difficulties in controlling the interfacial polymerization (IP) reaction and instability of the separation layer structure. The -OH present in N-MG could replace the C-Cl bond in the CTFE chain segment, thus enabling the hydrophilic graft modification of PVDF-CTFE. The influence of the addition of N-MG on the surface and pore structure, wettability, permeability, ultrafiltration separation, and mechanical properties of the PVDF-CTFE substrate membrane was studied. According to the comparison of the comprehensive capabilities of the prepared porous membranes, the M4 membrane with the addition of 1.5 wt% N-MG exhibited the best hydrophilicity and permeability, indicating that it is a desirable modified membrane for use as an NF substrate membrane. The experiments showed that the rejection of Na2SO4 by the NF membrane was 96.5% and greater than 94.0% for various dyes. In the test using dye/salt mixed solution, this membrane exhibited a good separation selectivity (CR/NaCl = 177.8) and long-term operational stability.

MET fusions and splicing variants is a strong adverse prognostic factor in astrocytoma, isocitrate dehydrogenase mutant.

Liu et al. describe the adverse prognostic role of MET fusions and splicing variants in astrocytoma, isocitrate dehydrogenase mutant. On this basis, MET fusions and splicing variants was suggested to be a biomarker for the diagnosis of high-grade astrocytoma, isocitrate dehydrogenase mutant.

Stability of Multivalent Ruthenium on CoWO4 Nanosheets for Improved Electrochemical Water Splitting with Alkaline Electrolyte.

Engineering low-cost electrocatalysts with desired features is vital to decrease the energy consumption but challenging for superior water splitting. Herein, we development a facile strategy by the addition of multivalence ruthenium (Ru) into the CoWO4/CC system. During the synthesis process, the most of Ru3+ ions were insinuated into the lattice of CoWO4, while the residual Ru3+ ions were reduced to metallic Ru and further attached to the interface between carbon cloth and CoWO4 sheets. The optimal Ru2(M)-CoWO4/CC exhibited superior performance for the HER with an overpotential of 85 mV@10 mA cm-2, which was much better than most of reported electrocatalysts, regarding OER, a low overpotential of 240 mV@10 mA cm-2 was sufficient. In comparison to Ru2(0)-CoWO4/CC with the same Ru mass loading, multivalence Ru2(M)-CoWO4/CC required a lower overpotential for OER and HER, respectively. The Ru2(M)-CoWO4/CC couple showed excellent overall water splitting performance at a cell voltage of 1.48 V@10 mA cm-2 for used as both anodic and cathodic electrocatalysts. Results of the study showed that the electrocatalytic activity of Ru2(M)-CoWO4/CC was attributed to the in-situ transformation of Ru/Co sites, the multivalent Ru ions and the synergistic effect of different metal species stimulated the intrinsic activity of CoWO4/CC.

Characteristics of quiescent adult neural stem cells induced by the bFGF/BMP4 combination or BMP4 alone in vitro.

Bone morphogenetic protein-4 (BMP4) is involved in regulation of neural stem cells (NSCs) proliferation, differentiation, migration and survival. It was previously thought that the treatment of NSCs with BMP4 alone induces astrocytes, whereas the treatment of NSCs with the bFGF/BMP4 combination induces quiescent neural stem cells (qNSCs). In this study, we performed bulk RNA sequencing (RNA-Seq) to compare the transcriptome profiles of BMP4-treated NSCs and bFGF/BMP4-treated NSCs, and found that both NSCs treated by these two methods were Sox2 positive qNSCs which were able to generate neurospheres. However, NSCs treated by those two methods exhibited different characteristics in state and the potential for neuronal differentiation based on transcriptome analysis and experimental results. We found that BMP4-treated NSCs tended to be in a deeper quiescent state than bFGF/BMP4-treated NSCs as the percentage of ki67-positive cells were lower in BMP4-treated NSCs. And after exposure to differentiated environment, bFGF/BMP4-treated NSCs generated more DCX-positive immature neurons and MAP2-positive neurons than BMP4-treated NSCs. Our study characterized qNSCs treated with BMP4 alone and bFGF/BMP4 combination, providing a reference for the scientific use of BMP4 and bFGF/BMP4-induced qNSCs models.

The Effectiveness of Traditional Chinese Medicine in Treating Malignancies via Regulatory Cell Death Pathways and the Tumor Immune Microenvironment: A Review of Recent Advances.

Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.

A reversible implantable memristor for health monitoring applications.

Conventional implantable electronics based on von Neumann architectures encounter significant limitations in computing and processing vast biological information due to computational bottlenecks. The memristor with integrated memory-computing and low power consumption offer a promising solution to overcome the computational bottleneck and Moore's law limitations of traditional silicon-based implantable devices, making them the most promising candidates for next-generation implantable devices. In this work, a highly stable memristor with an Ag/BaTiO3/MnO2/FTO structure was fabricated, demonstrating retention characteristics exceeding 1200 cycles and endurance above 1000 s. The device successfully exhibited three-stage responses to biological signals after implantation in SD (Sprague-Dawley) rats. Importantly, the memristor perform remarkable reversibility, maintaining over 100 cycles of stable repetition even after extraction from the rat. This study provides a new perspective on the biomedical application of memristors, expanding the potential of implantable memristive devices in intelligent medical fields such as health monitoring and auxiliary diagnostics.

Clinical feasibility of laparoscopic left lateral segment liver resection with magnetic anchor technique: The first clinical study from China.

BACKGROUND: Magnetic anchor technique (MAT) has been applied in laparoscopic cholecystectomy and laparoscopic appendectomy, but has not been reported in laparoscopic partial hepatectomy. AIM: To evaluate the feasibility of the MAT in laparoscopic left lateral segment liver resection. METHODS: Retrospective analysis was conducted on the clinical data of eight patients who underwent laparoscopic left lateral segment liver resection assisted by MAT in our department from July 2020 to November 2021. The Y-Z magnetic anchor devices (Y-Z MADs) was independently designed and developed by the author of this paper, which consists of the anchor magnet and magnetic grasping apparatus. Surgical time, intraoperative blood loss, intraoperative accidents, operator experience, postoperative incision pain score, postoperative complications, and other indicators were evaluated and analyzed. RESULTS: All eight patients underwent a MAT-assisted laparoscopic left lateral segment liver resection, including three patients undertaking conventional 5-port and five patients having a transumbilical single-port operation. The mean operation time was 138 ± 34.32 min (range 95-185 min) and the mean intraoperative blood loss was 123 ± 88.60 mL (range 20-300 mL). No adverse events occurred during the operation. The Y-Z MADs showed good workability and maneuverability in both tissue and organ exposure. In particular, the operators did not experience either a "chopstick" or "sword-fight" effect in the single-port laparoscopic operation. CONCLUSION: The results show that the MAT is safe and feasible for laparoscopic left lateral segment liver resection, especially, exhibits its unique abettance for transumbilical single-port laparoscopic left lateral segment liver resection.

Dioscin induces M1 macrophage polarization through Connexin-43 Channels in Tumor-associated-macrophages-mediated melanoma metastasis.

BACKGROUND: Tumor-associated macrophages (TAMs) are important constituent parts of tumor microenvironment that connected with tumor metastasis in melanoma. Connexin 43 (Cx43) was expressed in all the immune cells which modulated different aspects of immune response. However, the concrete molecular mechanism maintains unclear. PURPOSE: The study aimed to find a natural drug monomer effectively reversed the polarity of tumor-associated macrophages inhibiting melanoma metastasis and improving survival time. METHODS: Flow cytometry was used to determine the effects of dioscin on the macrophage phenotype. Western bolt and ELISA were performed to explore the underlying mechanism of dioscin and a co-culture experiment in vitro was applied to assess the role of dioscin on TAMs-mediated melanoma proliferation, invasion and migration. Moreover, in vivo melanoma metastasis models were established for examining effects of dioscin on TAMs-mediated melanoma metastasis. RESULTS: Dioscin repolarized macrophages from M2 towards M1-like phenotype. Dioscin suppressed M2-like phenotype macrophages through enhanced the expression and transport function of Cx43. Furthermore, the stimulation IFN-γ/STAT1 pathway and suppression IL-4/JAK2/STAT3 pathway were major mechanism of dioscin. Importantly, dioscin suppressed Cx43G21R mutation TAMs induced proliferation, invasion, migration and metastasis of melanoma cells. It worthily noting that dioscin ameliorated tumor-associated-macrophages-mediated melanoma metastasis in vitro and vivo. CONCLUSION: Dioscin re-polarized macrophages from M2 to M1 phenotype through activation of Cx43-gap-junction-intercellular-communications (Cx43-GJs)/IFN-γ/STAT1 pathway and inhibition of Cx43-GJs/IL-4/JAK2/STAT3 suppressing migration, invasion and metastasis of melanoma, which provided a theoretical and experimental basis for treating melanoma metastasis.

Double-Layer ePTFE-Reinforced Membrane Electrode Assemblies Prepared by a Reverse Membrane Deposition Process for High-Performance and Durable Proton Exchange Membrane Fuel Cells.

To promote further commercialization of proton exchange membrane (PEM) fuel cells, developing a novel preparation method for high-performance and durable membrane electrode assemblies (MEAs) is imperative. In this study, we adopt the reverse membrane deposition process and expanded polytetrafluoroethylene (ePTFE) reinforcing technology to optimize the interface combination and durability of MEAs simultaneously for the preparation of novel MEAs with double-layer ePTFE reinforcement skeletons (DR-MEA). With the wet-contact between the liquid ionomer solution and porous catalyst layers (CLs), a tight 3D PEM/CL interface is formed in the DR-MEA. Based on this enhanced PEM/CL interface combination, the DR-MEA exhibits a significantly increased electrochemical surface area, reduced interfacial resistance, and improved power performance compared with a conventional MEA (C-MEA) based on a catalyst-coated membrane method. Furthermore, with the reinforcement of double-layer ePTFE skeletons and the support of rigid electrodes for the membranes, the DR-MEA demonstrates less mechanical degradation than the C-MEA after wet/dry cycle test, reflected in lower increase in hydrogen crossover current, interfacial resistance, and charge-transfer resistance and reduced power performance attenuation. With less mechanical degradation, the DR-MEA therefore shows less chemical degradation than the C-MEA after an open-circuit voltage durability test.

The prognostic impact of tumor-infiltrating B lymphocytes in patients with solid malignancies: A systematic review and meta-analysis.

This study reviewed the prognostic effect of tumor-infiltrating B lymphocytes (TIBLs) on solid malignancies, to determine the potential role of TIBLs in predicting cancer patient's prognosis and their response to immunotherapy. A total of 45 original papers involving 11,099 individual patients were included in this meta-analysis covering 7 kinds of cancer. The pooled results suggested that high levels of TIBLs were correlated with favorable OS in lung, esophageal, gastric, colorectal, liver, and breast cancer; improved RFS in lung cancer; and improved DFS in gastrointestinal neoplasms. Additionally, TIBLs were significantly correlated with negative lymphatic invasion in gastric cancer, small tumor size in hepatocellular carcinoma, and negative distant metastasis in colorectal cancer. Additionally, TIBLs were reported as a discriminative feature of patients treated with immunotherapy with improved survival. We concluded that TIBLs play a favorable prognostic role among the common solid malignancie, providing theoretical evidence for further prognosis prediction for solid tumors.