Multifunctional Biodegradable Conductive Hydrogel Regulating Microenvironment for Stem Cell Therapy Enhances the Nerve Tissue Repair.

The nerve guidance conduits incorporated with stem cells, which can differentiate into the Schwann cells (SCs) to facilitate myelination, shows great promise for repairing the severe peripheral nerve injury. The innovation of advanced hydrogel materials encapsulating stem cells, is highly demanded for generating supportive scaffolds and adaptive microenvironment for nerve regeneration. Herein, this work demonstrates a novel strategy in regulating regenerative microenvironment for peripheral nerve repair with a biodegradable conductive hydrogel scaffold, which can offer multifunctional capabilities in immune regulation, enhancing angiogenesis, driving SCs differentiation, and promoting axon regrowth. The biodegradable conductive hydrogel is constructed by incorporation of polydopamine-modified silicon phosphorus (SiP@PDA) nanosheets into a mixture of methacryloyl gelatin and decellularized extracellular matrix (GelMA/ECM). The biomimetic electrical microenvironment performs an efficacious strategy to facilitate macrophage polarization toward a pro-healing phenotype (M2), meanwhile the conductive hydrogel supports vascularization in regenerated tissue through sustained Si element release. Furthermore, the MSCs 3D-cultured in GelMA/ECM-SiP@PDA conductive hydrogel exhibits significantly increased expression of genes associated with SC-like cell differentiation, thus facilitating the myelination and axonal regeneration. Collectively, both the in vitro and in vivo studies demonstrates that the rationally designed biodegradable multifunctional hydrogel significantly enhances nerve tissues repair.

Multi-omics revealed molecular mechanism of biphenyl phytoalexin formation in response to yeast extract-induced oxidative stress in Sorbus aucuparia suspension cells.

KEY MESSAGE: Yeast extract-induced oxidative stress in Sorbus aucuparia suspension cells leads to the biosynthesis of various hormones, which activates specific signaling pathways that augments biphenyl phytoalexin production. Pathogen incursions pose a significant threat to crop yield and can have a pronounced effect on agricultural productivity and food security. Biphenyl phytoalexins are a specialized group of secondary metabolites that are mainly biosynthesized by Pyrinae plants as a defense mechanism against various pathogens. Despite previous research demonstrating that biphenyl phytoalexin production increased dramatically in Sorbus aucuparia suspension cells (SASCs) treated with yeast extract (YE), the underlying mechanisms remain poorly understood. To address this gap, we conducted an in-depth, multi-omics analysis of transcriptome, proteome, and metabolite (including biphenyl phytoalexins and phytohormones) dynamics in SASCs exposed to YE. Our results indicated that exposure to YE-induced oxidative stress in SASCs, leading to the biosynthesis of a range of hormones, including jasmonic acid (JA), jasmonic acid isoleucine (JA-ILE), gibberellin A4 (GA4), indole-3-carboxylic acid (ICA), and indole-3-acetic acid (IAA). These hormones activated specific signaling pathways that promoted phenylpropanoid biosynthesis and augmented biphenyl phytoalexin production. Moreover, reactive oxygen species (ROS) generated during this process also acted as signaling molecules, amplifying the phenylpropanoid biosynthesis cascade through activation of the mitogen-activated protein kinase (MAPK) pathway. Key genes involved in these signaling pathways included SaBIS1, SaBIS2, SaBIS3, SaPAL, SaB4H, SaOMT, SaUGT1, SaLOX2, SaPR1, SaCHIB1, SaCHIB2 and SaCHIB3. Collectively, this study provided intensive insights into biphenyl phytoalexin accumulation in YE-treated SASCs, which would inform the development of more efficient disease-resistance strategies in economically significant cultivars.

Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Melt-electrowriting-enabled anisotropic scaffolds loaded with valve interstitial cells for heart valve tissue Engineering.

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.

Biomimetic bone-periosteum scaffold for spatiotemporal regulated innervated bone regeneration and therapy of osteosarcoma.

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.

Urethral-sparing laparoscopic simple prostatectomy for the treatment of benign prostatic hyperplasia with asymptomatic urethral stricture after urethral stricture surgery.

OBJECTIVE: To evaluate the efficacy of urethral-sparing laparoscopic simple prostatectomy (US-LSP) for the treatment of large-volume (>80 ml) benign prostatic hyperplasia (BPH) with asymptomatic urethral stricture (urethral lumen > 16 Fr) after urethral stricture surgery. METHODS: We retrospectively analyzed clinical data of 39 large-volume BPH patients with asymptomatic urethral stricture after urethral stricture surgery who underwent US-LSP from January 2016 to October 2021. Postoperative follow-ups were scheduled at 1, 3, and 6 months. RESULTS: All patients affected by significant BPH-related lower urinary tract symptoms (LUTS) including 22 cases with asymptomatic anterior urethral stricture and 17 cases with asymptomatic posterior urethral stricture. Median operative time was 118 min (interquartile range [IQR]100-145). Median estimated blood loss was 224 ml (IQR: 190-255). 33 patients(84.6%) avoided continuous bladder irrigation. Postoperative complications occurred in 5 patients (12.8%), including 4 cases with Clavien-Dindo grade 1 and grade 2 and 1 case with grade 3a. During follow-up, US-LSP presented statistically significant improvements in LUTS compared to baseline (P < 0.05). A total of 25 patients had normal ejaculation preoperatively and 3 patients (12%) complained retrograde ejaculation postoperatively. Two patients (5.1%) reported stress urinary incontinence (SUI) and no patient reported aggravated urethral stricture during follow-up. CONCLUSIONS: US-LSP was safe and effective in treating large-volume BPH with asymptomatic urethral stricture after urethral stricture surgery. Meanwhile, US-LSP could reduce the risk of SUI in patients with asymptomatic posterior urethral stricture and maintain ejaculatory function in a high percentage of patients.

Customizing biomimetic surface attributes of dendritic lipopeptide nanoplatforms for extended circulation.

The pressing demand for innovative approaches to create delivery systems with heightened drug loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for biomimetic nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % simvastatin loading content and kept stable even after one-month storage at 4 °C. These nanoplatforms demonstrated low cytotoxicity in NIH-3T3 and L02 cells and negligible hemolysis (<5 %). NNPs inhibited protein adhesion (>95 %) from positively and negatively charged sources through surface hydration. In comparison to positively charged CNPs, NNPs demonstrated an 86 % decrease in phagocytic rate by BMDMs, highlighting their efficacy. Importantly, NNPs showed prolonged circulation compared to CNPs and free simvastatin. These findings highlight the potential of this biomimetic nanoplatform for future therapeutic applications with enhanced drug loading and circulation traits.

Lithographic Microneedle-Motors from Multimodal Microfluidics for Cargo Delivery.

Micromotors have led to an unprecedented revolution in the field of cargo delivery. Attempts in this area trend toward enriching their structures and improving their functions to promote their further applications. Herein, novel microneedle-motors (MNMs) for active drug delivery through a flexible multimodal microfluidic lithographic approach are presented. The multimodal microfluidics is composed of a co-flow geometry-derived droplet fluid and an active cargo mixed laminar flow in a triangular microchannel. The MNMs with sharp tips and spherical fuel-loading cavities are obtained continuously from microfluidics with the assistance of flow lithography. The structural parameters of the MNMs could be precisely tailored by simply choosing the flow speed or the shape of the photomask. As the actives are mixed into the phase solution during the generation, the resultant MNMs are loaded with cargoes for direct applications without any extra complex operation. Based on these features, it is demonstrated that with sharp tips and autonomous movement, the MNMs can efficiently penetrate the tissue-like substrates, indicating the potential in overcoming physiological barriers for cargo release. These results indicate that the proposed multimodal microfluidic lithographic MNMs are valuable for practical active cargo delivery in biomedical and other relative areas.

FePSe3 -Nanosheets-Integrated Cryogenic-3D-Printed Multifunctional Calcium Phosphate Scaffolds for Synergistic Therapy of Osteosarcoma.

Clinical treatment of osteosarcoma encounters great challenges of postsurgical tumor recurrence and extensive bone defect. To develop an advanced artificial bone substitute that can achieve synergistic bone regeneration and tumor therapy for osteosarcoma treatment, a multifunctional calcium phosphate composite enabled by incorporation of bioactive FePSe3 -nanosheets within the cryogenic-3D-printed α-tricalcium phosphate scaffold (TCP-FePSe3 ) is explored. The TCP-FePSe3 scaffold exhibits remarkable tumor ablation ability due to the excellent NIR-II (1064 nm) photothermal property of FePSe3 -nanosheets. Moreover, the biodegradable TCP-FePSe3 scaffold can release selenium element to suppress tumor recurrence by activating of the caspase-dependent apoptosis pathway. In a subcutaneous tumor model, it is demonstrated that tumors can be efficiently eradicated via the combination treatment with local photothermal ablation and the antitumor effect of selenium element. Meanwhile, in a rat calvarial bone defect model, the superior angiogenesis and osteogenesis induced by TCP-FePSe3 scaffold have been observed in vivo. The TCP-FePSe3 scaffold possesses improved capability to promote the repair of bone defects via vascularized bone regeneration, which is induced by the bioactive ions of Fe, Ca, and P released during the biodegradation of the implanted scaffolds. The TCP-FePSe3 composite scaffolds fabricated by cryogenic-3D-printing illustrate a distinctive strategy to construct multifunctional platform for osteosarcoma treatment.

The tendency of anemia of inflammation in periodontal diseases.

Anemia of inflammation (AI) is associated with inflammatory diseases, and inflammation-induced iron metabolism disorder is the major pathogenic factor. Earlier studies have reported a tendency of AI in periodontitis patients, but the explicit relationship and possible pathological mechanisms remain unclear. Here, the analyses of both periodontitis patients and a mouse model of ligature-induced experimental periodontitis showed that periodontitis was associated with lower levels of hemoglobin and hematocrit with evidence of systemic inflammation (increased white blood cell levels) and evidence of iron restriction (low serum iron along with a high serum hepcidin and ferritin levels), in accordance with the current diagnosis criteria for AI. Moreover, periodontal therapy improved the anemia status and iron metabolism disorders. Furthermore, the increased level of hepcidin and significant correlation between hepcidin and key indicators of iron metabolism emphasized the pivotal role of hepcidin in the pathogenesis of periodontitis-related AI. Administration of the signal transducer and activator of transcription 3 (STAT3) inhibitors Stattic suggested that the IL-6-STAT3-hepcidin signaling pathway participated in this regulatory process. Together, these findings demonstrated that periodontitis should be considered an inflammatory disease that contributes to the development of AI; furthermore, IL-6-STAT3-hepcidin signaling pathway plays a key regulatory role in the pathogenesis of periodontitis-related AI. Our study will provide new insights into the systemic effects of periodontitis, while meaningfully expanding the spectrum of inflammatory diseases that contribute to AI.

All-printed multiplexed electrocatalytic biosensors with rationally designed nanoparticle inks.

Inkjet printing, capable of rapid and template-free fabrication with high resolution and low material waste, is a promising method to construct electrochemical biosensor devices. However, the construction of fully inkjet-printed electrochemical biosensor remains a challenge owing to the lack of appropriate inks, especially the sensing inks of bioactive materials. Herein, we demonstrate a fully inkjet-printed, integrated and multiplexed electrochemical biosensor by combining rationally designed nanoparticle Inks. The stable gold (Au) nanoparticles ink with lower sintering temperature is prepared by using L-cysteine as stabilizer, and it is used to print the interconnects, the counter electrodes, and the working electrodes. The SU-8 ink is used to serve as dielectric layer for the biosensor, whereas the silver electrode is printed on the Au electrode by using commercially silver nanoparticles ink before it is chlorinated to prepare Ag/AgCl reference electrode. Moreover, we synthesize an inkjet-printable and electroactive ink, by the 'one-pot method', which is composed of conductive poly 6-aminoindole (PIn-6-NH2) and gold-palladium (Au-Pd) alloy nanoparticle (Au-Pd@PIn-6-NH2) to enhance the sensing performance of gold electrode towards hydrogen peroxide (H2O2). Especially, the amino groups in PIn-6-NH2can be further used to immobilizing glucose oxidase (GOx) and lactic acid oxidase (LOx) by glutaraldehyde to prepare printable sensing ink for the detection of glucose and lactate. The fully inkjet-printed electrochemical biosensor enabled by advanced inks can simultaneously detect glucose and lactate with good sensitivity and selectivity, as well as facile and scalable fabrication, showing great promise for metabolic monitoring.

Penfluroidol Attenuates the Imbalance of the Inflammatory Response by Repressing the Activation of the NLRP3 Inflammasome and Reduces Oxidative Stress via the Nrf2/HO-1 Signaling Pathway in LPS-Induced Macrophages.

Objectives: Excessive inflammatory responses and reactive oxygen species (ROS) formation play pivotal roles in the pathogenesis of sepsis. Penfluroidol (PF), an oral long-acting antipsychotic drug, has been suggested to possess diverse biological properties, including antischizophrenia, antitumour effect, and anti-inflammatory activity. The purpose of this research was to explore the anti-inflammatory and antioxidative effects of penfluroidol on lipopolysaccharide (LPS)-related macrophages. Methods: The viability of RAW264.7 and THP-1 cells was measured by Enhanced Cell Counting Kit-8 (CCK-8). The production of nitric oxide was evaluated by the Nitric Oxide Assay Kit. The generation of pro-inflammatory monocytes was detected by qRT-PCR (quantitative real-time PCR) and ELISA (enzyme-linked immunosorbent assay). Oxidative stress was assessed by measuring ROS, malondialdehyde (MDA), and superoxide dismutase (SOD) activity. The protein expression of the Nrf2/HO-1/NLRP3 inflammasome was detected by western blotting. Results: Our results indicated that no cytotoxic effect was observed when RAW264.7 and THP-1 cells were exposed to PF (0-1 µm) and/or LPS (1 µg/ml) for 24 hr. The data showed that LPS, which was repressed by PF, facilitated the generation of the pro-inflammatory molecules TNF-α and IL-6. In addition, LPS contributed to increased production of intracellular ROS compared with the control group, whereas the administration of PF effectively reduced LPS-related levels of ROS. Moreover, LPS induced the generation of MDA and suppressed the activities of SOD. However, PF treatment strongly decreased LPS-induced MDA levels and increased SOD activities in the RAW264.7 and THP-1 cells. Furthermore, our research confirmed that penfluroidol repressed the secretion of pro-inflammatory molecules by limiting the activation of the NLRP3 inflammasome and reducing oxidative effects via the Nrf2/HO-1 signaling pathway. Conclusion: Penfluroidol attenuated the imbalance of the inflammatory response by suppressing the activation of the NLRP3 inflammasome and reduced oxidative stress via the Nrf2/HO-1 signaling pathway in LPS-induced macrophages.

Development of a compensation-aware virtual rehabilitation system for upper extremity rehabilitation in community-dwelling older adults with stroke.

BACKGROUND: Compensatory movements are commonly observed in older adults with stroke during upper extremity (UE) motor rehabilitation, which could limit their motor recovery. AIM: This study aims to develop a compensation-aware virtual rehabilitation system (VRS) that can detect compensatory movements and improve the outcome of UE rehabilitation in community-dwelling older adults with stroke. METHODS: The VRS development includes three main components: (1) the use of thresholds for determining compensatory movements, (2) the algorithm for processing the kinematic data stream from Kinect to detect compensation in real-time, and (3) the audio-visual feedback to assist older adults with stroke to be aware of the compensation. Two studies were conducted following the VRS development, where Study 1 identified the value of thresholds for determining compensatory movements in two planar motor exercises, and Study 2 provided preliminary validation for the developed VRS by comparing two groups undergoing VR training or conventional training (CT) in a community rehabilitation center. RESULTS: The VRS could effectively detect all determined compensatory movements and timely trigger feedback in response to the detected compensatory movements. The VR participants showed significant improvements in Fugl-Meyer Assessment-Upper Extremity (FMA-UE, p = 0.045) and Wolf Motor Function Test (WMFT, p = 0.009). However, the VR and CT groups had no significant differences in outcome measures. CONCLUSION: The VRS demonstrates the ability to detect compensation and the potential of assisting older adults with stroke to improve motor functions. Suggestions are given for further improvements of the VRS to support the older adult with stroke to reduce compensation.

Application of 3D digital smile design based on virtual articulation analysis in esthetic dentistry: A technique.

A technique for the application of a virtual articulation system in 3-dimensional digital smile design (DSD) during esthetic restoration is described. To acquire stable occlusion and a smooth jaw movement pattern without premature contacts or interference, a digital facebow and a virtual articulator were used to collect and analyze a patient's occlusal data and jaw movement information. The original pattern of occlusal contacts and jaw movements were diagnosed as stable and copied to the digital design of the new prostheses. Preparation of the abutments, crown lengthening surgery, and definitive crown fabrication and cementation were performed according to the design. After 9 months, the occlusion remained stable, and the patient was satisfied with the outcome.

Multifunctional fish gelatin hydrogel inverse opal films for wound healing.

BACKGROUND: Wound healing has become a worldwide healthcare issue. Attempts in the area focus on developing patches with the capabilities of avoiding wound infection, promoting tissue remolding, and reporting treatment status that are of great value for wound treatment. RESULTS: In this paper, we present a novel inverse opal film (IOF) patch based on a photo-crosslinking fish gelatin hydrogel with the desired features for wound healing and dynamic monitoring. The film with vibrant structure colors was constructed by using the mixture of fish gelatin methacryloyl, chitosan, and polyacrylic acid (PAA) to replicate colloidal crystal templates. As the structures of these natural biomolecules are well-retained during the fabrication, the resultant IOF was with brilliant biocompatibility, low immunogenicity, antibacterial property, as well as with the functions of promoting tissue growth and wound healing. In addition, the IOF presented interconnected nanopores and high specific surface areas for vascular endothelial growth factor loading, which could further improve its angiogenesis capability. More attractively, as the pH-responsive PAA was incorporated, the IOF patch could report the wound healing status through its real-time structural colors or reflectance spectra. CONCLUSIONS: These features implied the practical value of the multifunctional fish gelatin hydrogel IOFs in clinical wound management.

Extracorporeal membrane oxygenation for near fatal asthma with sudden cardiac arrest.

INTRODUCTION: Near fatal asthma is a life-threatening disorder that requires mechanical ventilation. Near fatal asthma and COPD with sudden cardiac arrest can worsen the outcomes. Previous studies demonstrated that ECMO is a live-saving measure for near fatal asthma that does not respond to traditional treatment. CASE STUDY: A patient with near fatal asthma (NFA) and COPD presented with high airway resistance, life-threatening acidemia and severe hypoxemia that failed to respond to conventional therapy. His hospital course was complicated by sudden cardiac arrest when preparing to initiate V-V mode extracorporeal membrane oxygenation (ECMO). The mode immediately changed from V-V to V-A, then to V-AV and finally to V-V mode in order to improve cardiac function and promote recovery of lung function. RESULTS: On the sixth day, ECMO was removed and on the ninth day, he was extubated and transferred to the ward. Finally, the patient was discharged home on the nineteenth day after admission to be followed up in the pulmonary clinic. CONCLUSIONS: The early application of ECMO and mode changing plausibly resulted in dramatic improvement in gas exchange and restoration of cardiac function. This case illustrates the critical role of ECMO mode changing as salvage therapy in NFA and COPD with sudden cardiac arrest.

Examining geographical disparities in the incubation period of the COVID-19 infected cases in Shenzhen and Hefei, China.

BACKGROUND: Current studies on the COVID-19 depicted a general incubation period distribution and did not examine whether the incubation period distribution varies across patients living in different geographical locations with varying environmental attributes. Profiling the incubation distributions geographically help to determine the appropriate quarantine duration for different regions. METHODS: This retrospective study mainly applied big data analytics and methodology, using the publicly accessible clinical report for patients (n = 543) confirmed as infected in Shenzhen and Hefei, China. Based on 217 patients on whom the incubation period could be identified by the epidemiological method. Statistical and econometric methods were employed to investigate how the incubation distributions varied between infected cases reported in Shenzhen and Hefei. RESULTS: The median incubation period of the COVID-19 for all the 217 infected patients was 8 days (95% CI 7 to 9), while median values were 9 days in Shenzhen and 4 days in Hefei. The incubation period probably has an inverse U-shaped association with the meteorological temperature. The warmer condition in the winter of Shenzhen, average environmental temperature between 10 °C to 15 °C, may decrease viral virulence and result in more extended incubation periods. CONCLUSION: Case studies of the COVID-19 outbreak in Shenzhen and Hefei indicated that the incubation period of COVID-19 had exhibited evident geographical disparities, although the pathological causality between meteorological conditions and incubation period deserves further investigation. Methodologies based on big data released by local public health authorities are applicable for identifying incubation period and relevant epidemiological research.

LCAL1 enhances lung cancer survival via inhibiting AMPK-related antitumor functions.

Lung cancer is one of the most common cancers and has been the most common cause of cancer deaths for several decades. Recently, lung cancer-associated lncRNA 1 (LCAL1) has been identified to be overexpressed in lung cancer tissues, while inhibiting LCAL1 expression has shown potential to inhibiting lung cancer growth. However, the molecular mechanism between LCAL1 and lung cancer cell survival remains poorly understood. In the present study, we provided the first evidence that LCAL1 may support lung cancer survival via inhibiting the activity of AMP-activated protein kinase (AMPK). According to our results, LCAL1 may physically interact with the catalytic subunit of tumor suppressor AMPK, prevent AMPK activation by upstream kinase (liver kinase B1), and thus inhibit the downstream AMPK signaling network. Our study revealed that overexpressed LCAL1 may induce aerobic glycolysis in lung cancer cells through AMPK/HIF1α axis, enhance protein synthesis through AMPK/mTOR/S6K axis, and suppress autophagic cell death through AMPK/ULK1 pathway. All these alterations supported rapid proliferation of lung cancer cells, while knockdown of LCAL1 expression demonstrated the potential of inhibiting lung cancer growth by reversing the tumorigenic phenotypes triggered by the loss of AMPK activity, and could become a promising therapeutic strategy for lung cancer treatment.

High expression of NFAT2 contributes to carboplatin resistance in lung cancer.

Carboplatin is a platinum-based chemotherapy drug in lung cancer treatment. However, its efficacy is frequently limited by intrinsic and acquired drug resistance. Recently, nucleus factor of activated T cells, cytoplasmic 1 (NFAT2) has been recognized as an oncogene and involved in disease progression and drug resistance in various cancers. In the current study, we found that overexpression of NFAT2 was associated with poor prognosis in lung cancer patients, and is observed in a carboplatin resistant lung cancer cell line, indicative of its role in regulating drug response. We further showed that NFAT2 played a critical role in promoting cell proliferation and overcome carboplatin-induced DNA damage and cell cycle arrest. NFAT2 knockdown or inhibition of its nucleus translation via cyclosporine A largely restored the sensitivity to carboplatin in the resistant line by inducing DNA damage, blocking cell cycle progression and activating apoptotic cell death. We thus suggest that NFAT2 is a putative therapeutic target to overcome carboplatin resistance in lung cancers.

A Microporous Covalent-Organic Framework with Abundant Accessible Carbonyl Groups for Lithium-Ion Batteries.

A key challenge faced by organic electrodes is how to promote the redox reactions of functional groups to achieve high specific capacity and rate performance. Here, we report a two-dimensional (2D) microporous covalent-organic framework (COF), poly(imide-benzoquinone), via in situ polymerization on graphene (PIBN-G) to function as a cathode material for lithium-ion batteries (LIBs). Such a structure favors charge transfer from graphene to PIBN and full access of both electrons and Li+ ions to the abundant redox-active carbonyl groups, which are essential for battery reactions. This enables large reversible specific capacities of 271.0 and 193.1 mAh g-1 at 0.1 and 10 C, respectively, and retention of more than 86 % after 300 cycles. The discharging/charging process successively involves 8 Li+ and 2 Li+ in the carbonyl groups of the respective imide and quinone groups. The structural merits of PIBN-G will trigger more investigations into the designable and versatile COFs for electrochemistry.