Transcriptome analysis reveals PRKCA as a potential therapeutic target for overcoming cisplatin resistance in lung cancer through ferroptosis.

Cisplatin-based chemotherapy is the current standard care for lung cancer patients; however, drug resistance frequently develops during treatment, thereby limiting therapeutic efficacy.The molecular mechanisms underlying cisplatin resistance remain elusive. In this study, we conducted an analysis of microarray data from the Gene Expression Omnibus (GEO) database under the accession numbers GSE21656, which encompassed expression profiling of cisplatin-resistant H460 (DDP-H460)and the parental cells (H460). Subsequently, we calculated the differentially expressed genes (DEGs) between DDP-H460 and H460. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs demonstrated significant impact on the Rap1, PI3K/AKT and MAPK signaling pathways. Moreover, protein and protein interaction (PPI) network analysis identified PRKCA, DET1, and UBE2N as hub genes that potentially contribute predominantly to cisplatin resistance. Ultimately, PRKCA was selected for validation due to its significant prognostic effect, which predicts unfavorable overall survival and disease-free survival in patients with lung cancer. Network analysis conducted on The Cancer Genome Atlas (TCGA) database revealed a strong gene-level correlation between PRKCA and TP53, CDKN2A, BYR2, TTN, KRAS, and PIK3CA; whereas at the protein level, it exhibited a high correlation with EGFR, Lck, Bcl2, and Syk. The in vitro experiments revealed that PRKCA was upregulated in the cisplatin-resistant A549 cells (DDP-A549), while knockdown of PRKCA increased DDP-A549 apoptosis upon cisplatin treatment. Moreover, we observed that PRKCA knockdown attenuated DDP-A549 proliferation, migration and invasion ability. Western blot analysis demonstrated that PRKCA knockdown downregulated phosphorylation of PI3K expression while upregulated the genes involved in ferroptosis signaling. In summary, our results elucidate the role of PRKCA in acquiring resistance to cisplatin and underscore its potential as a therapeutic target for cisplatin-resistant lung cancer.

Mitochondrial uptake of aristolactam I plays a critical role in its toxicity.

Aristolochic acid I (AAI), a component of aristolochic acids, can be converted to the toxic metabolite Aristolactam I (ALI) in vivo which forms aristolactam-nitrenium with delocalized positive charges. It is widely accepted that delocalized lipophilic cations can accumulate in mitochondria due to the highly negatively charged microenvironment of the mitochondrial matrix, but the uptake of ALI by mitochondria is not known. In this study, the cell uptake and mitochondrial localization of ALI, and its subsequent impact on mitochondrial function were investigated. Results show that ALI can rapidly penetrate HK-2 cells without relying on organic anion transporters 1/3 (OAT1/3). The cellular distribution of ALI was found to align with the observed distribution of a mitochondria-selective dye in HK-2 cells. Furthermore, the cell uptake and mitochondrial uptake of ALI were both inhibited by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, which induces mitochondrial membrane depolarization. These results suggest that ALI is selectively taken up by mitochondria. Consequently, mitochondrial dysfunction was observed after treatment with ALI. It should be noted that inhibiting OAT1/3 could result in an increased exposure of ALI in vivo and cause more seriously nephrotoxicity. In conclusion, this research reports the mitochondrial uptake of ALI and provides new insight on potential strategies for protection against AAI-induced nephrotoxicity.

Analysis aqueous humor lipid profile of neovascular glaucoma secondary to diabetic retinopathy and lipidomic alteration response to anti-VEGF treatment.

The objective of this study was to examine the lipid spectrum of aqueous humor (AH) in patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy and to investigate the lipid alteration response to anti-vascular endothelial growth factor (anti-VEGF) treatment. Lipidomic analysis using ultra-high performance liquid chromatography-tandem mass spectrometry was conducted to compare the lipid profiles of the AH in NVG patients with those of a control group. Lipid changes in the AH of NVG patients before and after intravitreal conbercept injections were also evaluated. The identification of lipids showing differential expression was accomplished through both multivariate and univariate analyses. This study included 13 NVG patients and 20 control subjects. Based on LipidSearch software, 639 lipid species across 33 lipid classes were detected in the participants' AH. The combination of univariate and multivariate statistical analyses yielded 53 differentially expressed lipids (VIP >1 and P < 0.05). In addition, 9 lipids were found to be differentially expressed before and after the intravitreal conbercept injections in the NVG patients. Significant alterations in the metabolic pathways of glycerophospholipid and glycerolipid exhibited notable changes. Our results highlighted the lipid changes in patients' AH in relation to the progression of NVG, and indicated that the modified lipids could potentially be utilized as therapeutic targets for NVG.

Temporal patterns and driving factors of sediment carbon, nitrogen, and phosphorus stoichiometry in a eutrophication plateau lake.

Stoichiometry determines the key characteristics of organisms and ecosystems on a global scale and provides strong instructions on the fate of sediment carbon, nitrogen, and phosphorus (C-N-P) during the sedimentation process, contributing to the Earth's C-N-P balance. However, the mechanisms underlying C-N-P stoichiometry in response to intensive human activity and organic matter sources remain underexplored, especially in freshwater ecosystems. This study identifies the temporal patterns of C-N-P stoichiometry, reveals the inner driving factors, and clarifies its impact path, especially in eutrophication (the late 1970s). The results revealed that sediment RCP and RNP increased significantly and were controlled by TCAR and TNAR, respectively, indicating the direct impact of burial rate on C-N-P stoichiometry. Based on redundancy analysis and the STM model, autochthonous origin, GDP, and population had positive effects on sediment TCAR, TNAR, and TPAR, which, in turn, affected RCN, RCP, and RNP. Organic matter sources and human activities have a significant influence on RCN, RCP, and RNP, possibly regulated by the variation of TCAR and TNAR. Autochthonous origin had an indirect positive impact on RCN and RCP through the mediating effect of TCAR. Similarly, through the mediating effect of TNAR, it had an indirect negative impact on RCN and an indirect positive impact on RNP. This study showed that TCAR, TNAR, TPAR, GDP, autochthonous, allochthonous and population better explained the changes in RCN, RCP, and RNP over a-hundred-year deposition, highlighting an in-depth understanding of the dynamic change mechanism of sediment C-N-P stoichiometry during the lake deposition process.

Comprehensive Comparison of MOCVD- and LPCVD-SiNx Surface Passivation for AlGaN/GaN HEMTs for 5G RF Applications.

Passivation is commonly used to suppress current collapse in AlGaN/GaN HEMTs. However, the conventional PECV-fabricated SiNx passivation layer is incompatible with the latest process, like the "passivation-prior-to-ohmic" method. Research attention has therefore turned to high-temperature passivation schemes. In this paper, we systematically investigated the differences between the SiNx/GaN interface of two high-temperature passivation schemes, MOCVD-SiNx and LPCVD-SiNx, and investigated their effects on the ohmic contact mechanism. By characterizing the device interface using TEM, we reveal that during the process of MOCVD-SiNx, etching damage and Si diffuses into the semiconductor to form a leakage path and reduce the breakdown voltage of the AlGaN/GaN HEMTs. Moreover, N enrichment at the edge of the ohmic region of the LPCVD-SiNx device indicates that the device is more favorable for TiN formation, thus reducing the ohmic contact resistance, which is beneficial to improving the PAE of the device. Through the CW load-pull test with drain voltage VDS = 20V, LPCVD-SiNx devices obtain a high PAE of 66.35%, which is about 6% higher than MOCVD-SiNx devices. This excellent result indicates that the prospect of LPCVD-SiNx passivation devices used in 5G small terminals will be attractive.

Simulation of Single-Event Transient Effect for GaN High-Electron-Mobility Transistor.

A GaN high-electron-mobility transistor (HEMT) was simulated using the semiconductor simulation software Silvaco TCAD in this paper. By constructing a two-dimensional structure of GaN HEMT, combined with key models such as carrier mobility, the effects of a different state, different incidence position, different drain voltage, different LET values, and a different incidence angle on the single-event transient effect of GaN HEMT are simulated. LET stands for the linear energy transfer capacity of a particle, which refers to the amount of energy transferred by the particle to the irradiated substance on the unit path. The simulation results show that for GaN HEMTs, the single-event transient effect is more obvious when the device is in off-state than in on-state. The most sensitive location of GaN HEMTs to the single-event effect is in the region near the drain. The peak transient current increases with the increase in the drain bias and incident ion LET values. The drain charge collection time increases with the angle of incidence of heavy ion.

Unusual 3,4-Oxidative Coupling Polymerization on 1,2,5-Trisubstituted Pyrroles for Novel Porous Organic Polymers.

Porous organic polymers (POPs) have demonstrated promising task-specific applications due to their structure designability and thus functionality. Herein, an unusual 3,4-polymerization on 1,2,5-trisubstituted pyrroles has been developed to give linear polypyrrole-3,4 in high efficiency, with Mn of 20000 and PDI of 1.7. This novel polymerization technique was applied to prepare a series of polypyrrole-based POPs (PY-POP-1-4), which exhibited high BET surface areas (up to 762 m2 g-1) with a meso-micro-supermicro hierarchically porous structure. Furthermore, PY-POPs were doped in the mixed matrix membranes based on the polysulfone matrix to enhance the gas permeability and gas pair selectivity, with H2/N2 selectivity up to 84.6 and CO2/CH4 and CO2/N2 selectivity up to 46.8 and 39.6.

Biosensors with Boronic Acid-Based Materials as the Recognition Elements and Signal Labels.

It is of great importance to have sensitive and accurate detection of cis-diol-containing biologically related substances because of their important functions in the research fields of metabolomics, glycomics, and proteomics. Boronic acids can specifically and reversibly interact with 1,2- or 1,3-diols to form five or six cyclic esters. Based on this unique property, boronic acid-based materials have been used as synthetic receptors for the specific recognition and detection of cis-diol-containing species. This review critically summarizes the recent advances with boronic acid-based materials as recognition elements and signal labels for the detection of cis-diol-containing biological species, including ribonucleic acids, glycans, glycoproteins, bacteria, exosomes, and tumor cells. We also address the challenges and future perspectives for developing versatile boronic acid-based materials with various promising applications.

Flow-Through Electrochemical Membrane Reactor with a Self-Supported Carbon Membrane Electrode for Highly Efficient Synthesis of Hydrogen Peroxide.

In situ electroreduction of O2 to H2O2 by using electrons as reagents is known as a green process, which is highly desirable for environmental remediation and chemical industries. However, the development of a cost-effective electrode with superior H2O2 synthesis rate and stability is challenging. A self-supported carbon membrane (CM) was prepared in this study from activated carbon and phenolic resin by carbonization under a H2 atmosphere. It was employed as the cathode to build a flow-through electrochemical membrane reactor (FT-ECMR) for electrosynthesis of H2O2. The results showed that the CM had a small pore size (34 nm), a high porosity (42.3%), and a high surface area (450.7 m2 g-1). In contrast to most of the state-of-the-art self-supported carbon electrode reported in the previous works, the FT-ECMR exhibited a high concentration of continuous and stable H2O2 electrosynthesis (1042 mg L-1) as well as a H2O2 synthesis rate of 5.21 mg h-1 cm-2. It had also demonstrated a high oxygen conversion (0.37%) and current efficiency (88%). The outstanding performance of the FT-ECMR for H2O2 synthesis was attributed to the enhanced mass transfer of the reactor, the existence of a relatively high surface area of CM, and the abundant disordered carbon structures (sp3-C, defects, and edges). In conclusion, our work highlighted using the FT-ECMR with the CM to synthesize H2O2 efficiently and cost-effectively.

Influence of Gate Geometry on the Characteristics of AlGaN/GaN Nanochannel HEMTs for High-Linearity Applications.

In this study, AlGaN/GaN nanochannel high-electron-mobility transistors (HEMTs) with tri-gate (TGN-devices) and dual-gate (DGN-devices) structures were fabricated and investigated. It was found that the peak value of the transconductance (Gm), current gain cut-off frequency (fT) and power gain cut-off frequency (fmax) of the TGN-devices were larger than that of the DGN-devices because of the enhanced gate control from the top gate. Although the TGN-devices and DGN-devices demonstrated flattened transconductance, fT and fmax profiles, the first and second transconductance derivatives of the DGN-devices were lower than those of the TGN-devices, implying an improvement in linearity. With the nanochannel width decreased, the peak value of the transconductance and the first and second transconductance derivatives increased, implying the predominant influence of sidewall gate capacitance on the transconductance and linearity. The comparison of gate capacitance for the TGN-devices and DGN-devices revealed that the gate capacitance of the tri-gate structure was not simply a linear superposition of the top planar gate capacitance and sidewall gate capacitance of the dual-gate structure, which could be attributed to the difference in the depletion region shape for tri-gate and dual-gate structures.

Effect of P-Type GaN Buried Layer on the Temperature of AlGaN/GaN HEMTs.

In this paper, a P-type GaN buried layer is introduced into the buffer layer of AlGaN/GaN HEMTs, and the effect of the P-type GaN buried layer on the device's temperature characteristics is studied using Silvaco TCAD software. The results show that, compared to the conventional device structure, the introduction of a P-type GaN buried layer greatly weakens the peak of the channel electric field between the gate and drain of the device. This leads to a more uniform electric field distribution, a substantial reduction in the lattice temperature of the device, and a more uniform temperature distribution. Therefore, the phenomenon of negative resistance caused by self-heating effect is significantly mitigated, while the breakdown performance of the device is also notably enhanced.

Biosensors with Metal Ion-Phosphate Chelation Interaction for Molecular Recognition.

Biosensors show promising prospects in the assays of various targets due to their advantages of high sensitivity, good selectivity and rapid response. Molecular recognition is a key event of biosensors, which usually involves the interaction of antigen-antibody, aptamer-target, lectin-sugar, boronic acid-diol, metal chelation and DNA hybridization. Metal ions or complexes can specifically recognize phosphate groups in peptides or proteins, obviating the use of biorecognition elements. In this review, we summarized the design and applications of biosensors with metal ion-phosphate chelation interaction for molecular recognition. The sensing techniques include electrochemistry, fluorescence, colorimetry and so on.

Vertically molybdenum disulfide nanosheets on carbon cloth using CVD by controlling growth atmosphere for electrocatalysis.

Molybdenum disulfide (MoS2) has been deemed as one of the promising noble-metal-free electrocatalysts for hydrogen evolution reaction (HER), but it suffers from the inert basal plane and low electronic conductivity. Regulating the morphology of MoS2during the synthesis on conductive substrates is a synergistic strategy for enhancing the HER performance. In this work, vertical MoS2nanosheets were fabricated on carbon cloth (CC) using an atmospheric pressure chemical vapor deposition method. The growth process could be effectively tuned through introducing hydrogen gas during vapor deposition process, resulting in nanosheets with increased edge density. The mechanism for edge-enriching through controlling the growth atmosphere is systematically studied. The as-prepared MoS2exhibits excellent HER activity due to the combination of optimized microstructures and coupling with CC. Our findings provide new insights to design advanced MoS2-based electrocatalysts for HER.

Multi-functional MXene quantum dots enhance the quality of perovskite polycrystalline films and charge transport for solar cells.

Recently, two-dimensional (2D) transition metal carbides/nitrides (MXenes) find applications in perovskite solar cells (PSCs), due to their high conductivity, tunable electronic structures, and rich surface chemistry, etc. However, the integration of 2D MXenes into PSCs is limited by their large lateral sizes and relatively-small surface volume ratios, and the roles of MXenes in PSCs are still ambiguous. In this paper, zero-dimensional (0D) MXene quantum dots (MQDs) with an average size of 2.7 nm are obtained through clipping step by step combining a chemical etching and a hydrothermal reaction, which display rich terminals (i.e., -F, -OH, -O) and unique optical properties. The 0D MQDs incorporated into SnO2 electron transport layers (ETLs) of PSCs exhibit multifunction: 1) increasing the electrical conductivity of SnO2, 2) promoting better alignments of energy band positions at the perovskite/ETL interface, 3) improving the film quality of atop polycrystalline perovskite. Particularly, the MQDs not only tightly bond with the Sn atom for decreasing the defects of SnO2, but also interact with the Pb2+ of perovskite. As a result, the defect density of PSCs is significantly decreased from 5.21 × 1021 to 6.4 × 1020 cm-3, leading to enhanced charge transport and reduced nonradiative recombination. Furthermore, the power conversion efficiency (PCE) of PSCs is substantially improved from 17.44% to 21.63% using the MQDs-SnO2 hybrid ETL compared with the SnO2 ETL. Besides, the stability of the MQDs-SnO2-based PSC is greatly enhanced, with only ～4% degradation of the initial PCE after storage in ambient condition (25 °C, RH: 30-40%) for 1128 h, as compared to that of the reference device with a rapid degradation of ～60% of initial PCE after 460 h. And MQDs-SnO2-based PSC also presents higher thermal stability than SnO2-based device with continuous heating for 248 h at 85 °C. The unique MQDs exhibited in this work might also find other exciting applications such as light-emitting diodes, photodetectors, and fluorescent probes.

Case report: A longitudinal study of an unusual rapidly progressive dementia case.

It is daunting to determine the etiology of rapidly progressive dementia (RPD), which includes metabolic, neoplastic, infectious, autoimmune, neurodegenerative and other conditions. Herein, we illustrate an unusual case of a patient primarily exhibiting RPD, overlapping sleep dysfunction, psychosis and abnormal movement, which was finally defined as anti-IgLON5 disease, a novel and rare autoimmune encephalopathy. Furthermore, we longitudinally described his cognitive and psychological performance in detail, and determined that early initiation of immunotherapy in this patient did not result in a good outcome. These data highlight anti-IgLON5 disease as a possible differential diagnosis in patients with RPD.

Switch-on Fluorescence Analysis of Protease Activity with the Assistance of a Nickel Ion-Nitrilotriacetic Acid-Conjugated Magnetic Nanoparticle.

Heterogeneous protease biosensors show high sensitivity and selectivity but usually require the immobilization of peptide substrates on a solid interface. Such methods exhibit the disadvantages of complex immobilization steps and low enzymatic efficiency induced by steric hindrance. In this work, we proposed an immobilization-free strategy for protease detection with high simplicity, sensitivity and selectivity. Specifically, a single-labeled peptide with oligohistidine-tag (His-tag) was designed as the protease substrate, which can be captured by a nickel ion-nitrilotriacetic acid (Ni-NTA)-conjugated magnetic nanoparticle (MNP) through the coordination interaction between His-tag and Ni-NTA. When the peptide was digested by protease in a homogeneous solution, the signal-labeled segment was released from the substrate. The unreacted peptide substrates could be removed by Ni-NTA-MNP, and the released segments remained in solution to emit strong fluorescence. The method was used to determine protease of caspase-3 with a low detection limit (4 pg/mL). By changing the peptide sequence and signal reporters, the proposal could be used to develop novel homogeneous biosensors for the detection of other proteases.

Memristor-Based Signal Processing for Compressed Sensing.

With the rapid progress of artificial intelligence, various perception networks were constructed to enable Internet of Things (IoT) applications, thereby imposing formidable challenges to communication bandwidth and information security. Memristors, which exhibit powerful analog computing capabilities, emerged as a promising solution expected to address these challenges by enabling the development of the next-generation high-speed digital compressed sensing (CS) technologies for edge computing. However, the mechanisms and fundamental properties of memristors for achieving CS remain unclear, and the underlying principles for selecting different implementation methods based on various application scenarios have yet to be elucidated. A comprehensive overview of memristor-based CS techniques is currently lacking. In this article, we systematically presented CS requirements on device performance and hardware implementation. The relevant models were analyzed and discussed from the mechanism level to elaborate the memristor CS system scientifically. In addition, the method of deploying CS hardware using the powerful signal processing capabilities and unique performance of memristors was further reviewed. Subsequently, the potential of memristors in all-in-one compression and encryption was anticipated. Finally, existing challenges and future outlooks for memristor-based CS systems were discussed.

Efficacy and safety of adjuvant chemotherapy for locally advanced cervical cancer: A systematic review and meta-analysis.

BACKGROUND: Locally advanced cervical cancer (LACC) is generally treated using concurrent chemo-radiotherapy (CCRT); yet, the effectiveness of adjuvant chemotherapy (ACT) following CCRT remains controversial. METHODS: The databases Embase, Web of Science, and PubMed were analyzed for relevant research. Primary endpoints included overall survival (OS) and progression-free survival (PFS). RESULTS: Fifteen trials with 4041 patients were included. Pooled HRs for PFS and OS were 0.81 (95 % CI: 0.67-0.96) and 0.69 (95 % CI: 0.51-0.93), respectively. However, subgroup analyses indicated that in randomized trials and trials with larger sample sizes (n > 100) as well as ACT cycles ≤ 3, ACT was not linked with improved PFS and OS. Moreover, ACT induced a greater rate of hematologic toxicities (P < 0.05). CONCLUSION: Higher quality of evidence suggests that ACT could not yield additional survival benefits for LACC; however, identifying high-risk patients who may benefit from ACT is required to design further clinical trials and better inform treatment decisions.

Identifying autophagy-related genes as potential targets for immunotherapy in tuberculosis.

PURPOSE: Identifying of host-directed targets and molecular markers of immune response for tuberculosis (TB) immunotherapy is urgent and meaningful. Previous studies have demonstrated an important role of autophagy in the course and pathophysiology of TB and is associated with the efficacy of TB treatment. However, its role in TB immunotherapy is still incomplete. METHODS: The effect of autophagy on intracellular bacteria load was examined in sulforaphane (SFN)-treated THP-1 cells. The immune infiltration was assessed based on public databases. Functional enrichment analysis revealed the pathways involved. LASSO Cox regression analysis was employed to identify hub genes. Moreover, machine learning analysis was used to obtain important targets of TB immunotherapy. Finally, the relationship between hub genes and immune infiltration was assessed, as well as the relevance of chemokines. RESULTS: We found that SFN reduced intracellular bacteria load by enhancing autophagy in THP-1 cells. Thirty-two autophagy-related genes (ARGs) were identified, three types of immune cells (macrophages, neutrophils, and DC cells) were significantly enriched in TB patients, and 6 hub genes (RAB5A, SQSTM1, MYC, MAPK8, MAPK3, and FOXO1) were closely related to TB immune infiltration. The 32 ARGs were mainly involved in autophagy, apoptosis, and tuberculosis pathways. FOXO1, SQSTM1, and RAB5A were identified as important target genes according to the ranking of variable importance, with FOXO1 being a potential autophagy-related target of TB immunotherapy. CONCLUSION: This study highlights the association between autophagy-related genes and immune infiltration in TB. Three key genes, especially FOXO1, regulated by SFN, will provide new insights into diagnostic and immunotherapy strategies for clinical tuberculosis.

Printable Epsilon-Type Structure Transistor Arrays with Highly Reliable Physical Unclonable Functions.

Printed electronics promises to drive the future data-intensive technologies, with its potential to fabricate novel devices over a large area with low cost on nontraditional substrates. In these emerging technologies, there exists a large digital information flow, which requires secure communication and authentication. Physical unclonable functions (PUFs) offer a promising built-in hardware-security system comparable to biometrical data, which can be constructed by device-specific intrinsic variations in the additive manufacturing process of active devices. However, printed PUFs typically exploit the inherent variation in layer thickness and roughness of active devices. The current in devices with enough significant changes to increase the robustness to external environment noise is still a challenge. Here, printable epsilon-type-structure indium tin oxide transistor arrays are demonstrated to construct high-reliability PUFs by modifying the coffee-ring structure. The epsilon-type structure improves the printing scalability, film quality, and device reliability. Furthermore, the print-induced uncertainty along the channel thickness and length can lead to changes in the carrier concentration. Notably, the randomly distributed printing droplets in a small area significantly increase this uncertainty. As a result, the PUFs exhibit near-ideal uniformity, uniqueness, randomness, and reliability. Additionally, the PUFs are resilient against machine-learning-based attacks with a prediction accuracy of only 55% without postprocessing.