An antioxidant feedforward cycle coordinated by linker histone variant H1.2 and NRF2 that drives nonsmall cell lung cancer progression.

Nonsmall cell lung cancer (NSCLC) is highly malignant with limited treatment options, platinum-based chemotherapy is a standard treatment for NSCLC with resistance commonly seen. NSCLC cells exploit enhanced antioxidant defense system to counteract excessive reactive oxygen species (ROS), which contributes largely to tumor progression and resistance to chemotherapy, yet the mechanisms are not fully understood. Recent studies have suggested the involvement of histones in tumor progression and cellular antioxidant response; however, whether a major histone variant H1.2 (H1C) plays roles in the development of NSCLC remains unclear. Herein, we demonstrated that H1.2 was increasingly expressed in NSCLC tumors, and its expression was correlated with worse survival. When crossing the H1c knockout allele with a mouse NSCLC model (KrasLSL-G12D/+), H1.2 deletion suppressed NSCLC progression and enhanced oxidative stress and significantly decreased the levels of key antioxidant glutathione (GSH) and GCLC, the catalytic subunit of rate-limiting enzyme for GSH synthesis. Moreover, high H1.2 was correlated with the IC50 of multiple chemotherapeutic drugs and with worse prognosis in NSCLC patients receiving chemotherapy; H1.2-deficient NSCLC cells presented reduced survival and increased ROS levels upon cisplatin treatment, while ROS scavenger eliminated the survival inhibition. Mechanistically, H1.2 interacted with NRF2, a master regulator of antioxidative response; H1.2 enhanced the nuclear level and stability of NRF2 and, thus, promoted NRF2 binding to GCLC promoter and the consequent transcription; while NRF2 also transcriptionally up-regulated H1.2. Collectively, these results uncovered a tumor-driving role of H1.2 in NSCLC and indicate an "H1.2-NRF2" antioxidant feedforward cycle that promotes tumor progression and chemoresistance.

FPGA implementation of power-lite Volterra-inspired neural network equalizer in 180-Gb/s net bitrate IMDD short-reach optical system.

A white-box power-lite Volterra-inspired neural network (VINN) equalizer is proposed to solve the problem of complexity discontinuity in a Volterra nonlinear equalizer (VNLE). By adjusting the granularity of the solution space, it conserves computational resources while maintaining nonlinear compensation capability. The performance of VINN is verified on a field-programmable gate array (FPGA) in a short-reach intensity modulation and direct detection (IMDD) system, and a 240-Gb/s real-time signal processing rate is achieved. Under the 25% overhead soft-decision forward error correction (SD-FEC) bit error rate (BER) threshold, we realize a record net rate of up to 180 Gb/s based on the FPGA.

Signal-to-noise ratio degradation analysis for optoelectronic feedback-based chaotic optical communication systems.

Chaotic optical communication encrypts transmitted signals through physical noise; this ensures high security while causing a certain decrease in the signal-to-noise ratio (SNR). Thus, it is necessary to analyze the SNR degradation of decrypted signals after chaotic encryption and the minimum requirements for the SNR of the fiber channel to meet the required bit error rate (BER) performance. Accordingly, an SNR model of decrypted signals for optoelectronic feedback-based chaotic optical communication systems is proposed. Under different channel SNRs, the SNR degradation of 40 Gbit/s phase chaos and intensity chaos models is investigated by simulation and experiment, respectively, with a 15 GHz wideband chaotic carrier. Comparing decrypted signals with original signals, the simulation results show that there is a 2.9 dB SNR degradation for both intensity chaos and phase chaos. Further, in experiments, SNR degradation from 4.5 dB to 5.6 dB, with various channel SNRs for intensity chaos, is analyzed, while there is an SNR degradation from 7.1 dB to 8.3 dB for phase chaos. The simulation and experimental results provide guidance for long-distance transmission chaotic optical communication systems.

The effective regulation of heterogeneous N-heterocyclic carbenes: structures, electronic properties and transition metal adsorption.

Heterogeneous N-heterocyclic carbene materials have attracted increasing interest in the fields of materials science and catalysis due to their unique properties and potential applications. However, current heterogeneous systems primarily focus on a single class of carbene. In this work, we simultaneously introduce two classes of typical five-membered carbenes into a graphene lattice, forming a series of novel two-dimensional heterogeneous N-heterocyclic carbene nanomaterials (2D-NCMs) composed of multiple carbenes. First-principles calculations demonstrate the thermodynamic stability of the designed 2D-NCMs, as well as their diverse electronic properties ranging from metallic to semiconducting. The incorporation of carbenes in the 2D-NCMs enables them to adsorb both acidic BCl3 and basic CO molecules, thus exhibiting unique amphoteric properties. Furthermore, the 2D-NCMs exhibit remarkable adsorption capacities for ten transition metals, highlighting their promising potential for future catalytic applications. By adjusting the proportions of the two classes of carbenes, we can effectively regulate the electronic properties and adsorption capacities of small molecules and transition metals in the 2D-NCMs. This study presents a novel strategy for designing and regulating the properties of heterogeneous N-heterocyclic carbenes, offering significant implications in the fields of catalysis and materials science.

Histone H1.2 promotes hepatocarcinogenesis by regulating signal transducer and activator of transcription 3 signaling.

Linker histone H1.2 (H1.2), encoded by HIST1H1C (H1C), is a major H1 variant in somatic cells. Among five histone H1 somatic variants, upregulated H1.2 was found in human hepatocellular carcinoma (HCC) samples and in a diethylnitrosamine (DEN)-induced HCC mouse model. In vitro, H1.2 overexpression accelerated proliferation of HCC cell lines, whereas H1.2 knockdown (KD) had the opposite effect. In vivo, H1.2 insufficiency or deficiency (H1c KD or H1c KO) alleviated inflammatory response and HCC development in DEN-treated mice. Mechanistically, H1.2 regulated the activation of signal transducer and activator of transcription 3 (STAT3), which in turn positively regulated H1.2 expression by binding to its promoter. Moreover, upregulation of the H1.2/STAT3 axis was observed in human HCC samples, and was confirmed in mouse models of methionine-choline-deficient diet induced nonalcoholic steatohepatitis or lipopolysaccharide induced acute inflammatory liver injury. Disrupting this feed-forward loop by KD of STAT3 or treatment with STAT3 inhibitors rescued H1.2 overexpression-induced proliferation. Moreover, STAT3 inhibitor treatment-ameliorated H1.2 overexpression promoted xenograft tumor growth. Therefore, H1.2 plays a novel role in inflammatory response by regulating STAT3 activation in HCC, thus, blockade of the H1.2/STAT3 loop is a potential strategy against HCC.

Histone demethylase UTX aggravates acetaminophen overdose induced hepatotoxicity through dual mechanisms.

Acetaminophen (APAP) overdose is a major cause of acute liver failure, while the underlying mechanisms of APAP hepatotoxicity are not fully understood. Recently, emerging evidence suggests that epigenetic enzymes play roles in APAP-induced liver injury. Here, we found that Utx (ubiquitously transcribed tetratricopeptide repeat, X chromosome, also known as KDM6A), a X-linked histone demethylase which removes the di- and tri-methyl groups from histone H3K27, was markedly induced in the liver of APAP-overdosed female mice. Hepatic deletion of Utx suppressed APAP overdose-induced hepatotoxicity in female but not male mice. RNA-sequencing analysis suggested that Utx deficiency in female mice upregulated antitoxic phase II conjugating enzymes, including sulfotransferase family 2 A member 1 (Sult2a1), thus reduces the amount of toxic APAP metabolites in injured liver; while Utx deficiency also alleviated ER stress through downregulating transcription of ER stress genes including Atf4, Atf3, and Chop. Mechanistically, Utx promoted transcription of ER stress related genes in a demethylase activity-dependent manner, while repressed Sult2a1 expression through mediating H3K27ac levels independent of its demethylase activity. Moreover, overexpression of Sult2a1 in the liver of female mice rescued APAP-overdose induced liver injury. Together, our results indicated a novel UTX-Sult2a1 axis for the prevention or treatment of APAP-induced liver injury.

Sustainable decontamination of heavy metal in wastewater and soil with novel rectangular wave asymmetrical alternative current electrochemistry.

A new concept of removal and recovery of heavy metals and simultaneous regeneration and reuse of ethylenediamine-tetraacetic acid (EDTA) in soil washing effluent containing metal-EDTA complexes is proposed, which is used to remediate heavy metal contaminated soil. To achieve this goal, soil washing approach coupled with rectangular wave asymmetrical alternative current electrochemistry (RW-ACE) equipped with amidoxime-functionalized electrodes (Ami-CF) is employed. With high hydrophilicity and strong binding affinity, Ami-CF could specifically compete for heavy metals over EDTA under electric field. RW-ACE system is found successfully to achieve the non-destructive decomplexation of heavy metal-EDTA, and then regenerate EDTA for highly recycling, which saves as high as 98.9 % EDTA consumption compared with conventional washing method. Moreover, more than 90% of heavy metals are recovered and deposited on the electrode with a majority of them existed as zero-valence state as evidenced by XPS. The RW-ACE method is universal for various heavy metals such as Cu2+, Zn2+, Cd2+, and Pb2+ in an authentic contaminated soil, and the loss of soil nutrient is very limited. Along with long-term assessment and operation cost estimation, the RW-ACE method is a sustainable remediation approach for the heavy metal polluted wastewater and soils, and easily scaled up for field practice.

High efficiency carbon nanotubes-based single-atom catalysts for nitrogen reduction.

Carbon-based single-atom catalysts (SACs) for electrochemical nitrogen reduction reaction (NRR) have received increasing attention due to their sustainable, efficient, and green advantages. However, at present, the research on carbon nanotubes (CNTs)-based NRR catalysts is very limited. In this paper, using FeN3@(n, 0) CNTs (n = 3 ~ 10) as the representative catalysts, we demonstrate that the CNT curvatures will affect the spin polarization of the catalytic active centers, the activation of the adsorbed N2 molecules and the Gibbs free energy barriers for the formation of the critical intermediates in the NRR processes, thus changing the catalytic performance of CNT-based catalysts. Zigzag (8, 0) CNT was taken as the optimal substrate, and twenty transition metal atoms (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Nb, Mo, Tc, Ru, Rh, Pd, W, Re, Ir, and Pt) were embedded into (8, 0) CNT via N3 group to construct the NRR catalysts. Their electrocatalytic performance for NRR were examined using DFT calculations, and TcN3@(8, 0) CNT was screened out as the best candidate with a low onset potential of - 0.53 V via the distal mechanism, which is superior to the molecules- or graphene-support Tc catalysts. Further electronic properties analysis shows that the high NRR performance of TcN3@(8, 0) CNT originates from the strong d-2π* interaction between the N2 molecule and Tc atom. TcN3@(8, 0) CNT also exhibits higher selectivity for NRR than the competing hydrogen evolution reaction (HER) process. The present work not only provides a promising catalyst for NRR, but also open up opportunities for further exploring of low-dimensional carbon-based high efficiency electrochemical NRR catalysts.

A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury.

Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney injury molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, and acts as a biomarker for various renal diseases. However, the exact role and underlying mechanism of KIM1 in the progression of AKI remain elusive. Herein, we report that renal tubular specific knockout of Kim1 attenuates cisplatin- or ischemia/reperfusion-induced AKI in male mice. Mechanistically, transcription factor Yin Yang 1 (YY1), which is downregulated upon AKI, binds to the promoter of KIM1 and represses its expression. Injury-induced KIM1 binds to the ECD domain of death receptor 5 (DR5), which activates DR5 and the following caspase cascade by promoting its multimerization, thus induces renal cell apoptosis and exacerbates AKI. Blocking the KIM1-DR5 interaction with rationally designed peptides exhibit reno-protective effects against AKI. Here, we reveal a YY1-KIM1-DR5 axis in the progression of AKI, which warrants future exploration as therapeutic targets.

Effective regulation of the electronic properties of a biphenylene network by hydrogenation and halogenation.

A biphenylene network, the first synthesized non-graphene planar carbon allotrope composed entirely of sp2-hybridized carbon atoms, has attracted widespread interest due to its unique structure, and electronic and mechanical properties. A pristine biphenylene network is metallic, and the effective regulation of its electronic properties will greatly expand its application in the fields of optoelectronics, nanoelectronic devices and photocatalysis. In this paper, the hydrogenation and halogenation of biphenylene networks were investigated using density functional theory, and their electronic properties were tuned by varying the functionalization concentration. Calculation results show that the maximum functionalization degree is CH1.00, CF1.00, CCl0.67 and CBr0.33, respectively. The band gap could be modulated in the range of 0.00-4.86 eV by hydrogenation, 0.012-4.82 eV by fluorination, 0.090-3.44 eV by chlorination, and 0.017-1.73 eV by bromination. It is also found that CH x (x = 0.92, 1.00), CF x (x = 0.75, 1.00), and CCl x (x = 0.42-0.67) have the potential to photolyse water. Our research indicates that hydrogenation and halogenation can effectively regulate the electronic properties of the biphenylene network by controlling the concentration of functionalization, thus expanding its potential applications in the field of electronic devices and photocatalysis.

Asymmetrical alternating current electrochemically-mediated washing method for sustainable remediation of Cr(VI)-contaminated soil.

The demands for genuine remediation of heavy metal contaminated soil have triggered extensive studies in the soil washing method. However, numerous soil washing methods show poor sustainability for target soil, due to the tremendous cost, hidden secondary pollution and severe soil deterioration. Here, an asymmetrical alternating current electrochemically-mediated remediation platform (ACRP) is developed by fabricating an amidoxime-functionalized electrode (Ami-electrode). The real soil contaminated with 1200 mg/kg Cr(VI) is remediated efficiently to less than safety level (30 mg/kg), meanwhile no exorbitant soil nutrient loss is observed and no secondary pollution occurs. Furthermore, the consumption of washing effluents for the ACRP method is 24 times lower than the traditional washing method. Ami-electrode with asymmetrical alternating current promote the electrocatalytic efficiency by inhibiting the Coulomb repulsion between Cr(VI) species and cathode. With the aid of Ami-electrode and positive bias, Cr(VI) species in effluents are adsorbed on chelating site. By subsequent negative bias, Cr element is reduced and recycled in the less hazardous form of amorphous Cr(III) hydroxide, and effluents are regenerate concurrently in a cyclic system. Durability experiment and cost calculation verify the exceptional sustainability and feasibility for remediation practices. This work provides a sustainable remediation method for Cr(VI)-contaminated soil, and then paves the way to develop electrochemically soil remediation platform for practical applications.

Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver.

Global obesity epidemics impacts human health and causes obesity-related illnesses, including the obesity-related kidney and liver diseases. UTX, a histone H3K27 demethylase, plays important roles in development and differentiation. Here we show that kidney-specific knockout Utx inhibits high-fat diet induced lipid accumulation in the kidney and liver via upregulating circulating serine levels. Mechanistically, UTX recruits E3 ligase RNF114 to ubiquitinate phosphoglycerate dehydrogenase, the rate limiting enzyme for de novo serine synthesis, at Lys310 and Lys330, which leads to its degradation, and thus suppresses renal and circulating serine levels. Consistently, phosphoglycerate dehydrogenase and serine levels are markedly downregulated in human subjects with diabetic kidney disease or obesity-related renal dysfunction. Notably, oral administration of serine ameliorates high-fat diet induced fatty liver and renal dysfunction, suggesting a potential approach against obesity related metabolic disorders. Together, our results reveal a metabolic homeostasis regulation mediated by a renal UTX-PHGDH-serine axis.

A property-oriented adaptive design framework for rapid discovery of energetic molecules based on small-scale labeled datasets.

It remains an important challenge to apply machine learning in material discovery with limited-scale datasets available, in particular for the energetic materials. Motivated by the challenge, we developed a Property-oriented Adaptive Design Framework (PADF) to quickly design new energetic compounds with desired properties. The PADF consists of a search space, machine learning model, optimization algorithm and an evaluator based on quantum mechanical calculations. The effectiveness and generality of the PADF were assessed by two case studies on the heat of formation and heat of explosion as the target properties. 88 compounds were selected as the initial training dataset from the search space containing 84 083 compounds generated. SVR.lin/Trade-off coupled with E-state + SOB and KRR/KG coupled with CDS + E-state + SOB were determined to be the best combination pairs for the heat of formation and the heat of explosion, respectively. Most of the ten compounds selected from the first ten iterations exhibit better properties than the optimal sample in the initial dataset. Besides, the heat of explosion as the target property outperforms the heat of formation in designing energetic compounds with high detonation performance. In particular, a new compound selected at the 3rd iteration exhibits high potential as an explosive. Our strategy could be extended to other domains limited by small-scale datasets labeled.

Paramylon from Euglena gracilis Prevents Lipopolysaccharide-Induced Acute Liver Injury.

Acute liver injury (ALI) is a life-threatening syndrome with high mortality and lacks effective therapies. Rodents under LPS (lipopolysaccharide)/D-Gal (D-galactosamine) stress mimic ALI by presenting dramatically increased inflammation and cell death in the liver. Euglena gracilis, functioning like dietary fiber, is commonly used as a paramylon (Pa)-rich nutritional supplement that has various biological effects such as regulating immune system, anti-obesity, and anti-tumor. Here, we found that Pa or sonicated and alkalized paramylon (SA-Pa) alleviated the LPS/D-Gal-induced hepatic histopathological abnormalities in mice. Compared with Pa, SA-Pa had lower molecular weights/sizes and showed better efficacy in alleviating injury-induced hepatic functions, as well as the transcriptional levels of inflammatory cytokines. Moreover, SA-Pa treatment promoted M2 macrophage activation that enhanced the anti-inflammatory function in the liver, and downregulated STAT3 target genes, such as Fos, Jun, and Socs3 upon the injury. Meanwhile, SA-Pa treatment also alleviated apoptosis and necroptosis caused by the injury. Our results demonstrated that SA-Pa efficiently protected the liver from LPS/D-Gal-induced ALI by alleviating inflammation and cell death.

Clinical lymphocytes construction for light scattering inversion study: a three-dimensional morphology constructed method from defective confocal images.

Constructing models of cells' realistic internal and external morphology is vital for correlation between light scattering and morphology of the scattering structure. The image stack obtained from fluorescent confocal microscopy is at present used to construct the cell's three-dimensional (3-D) morphology. However, due to the poor labeling quality and unavoidable optical noise present in the image stacks, 3-D morphologies are difficult to construct and are an impediment to the statistical analyses of cell structures. We propose a method called the "area and shape constraint method (ASCM)" for constructing 3-D morphology. Blurred 3-D morphologies constructed by common methods from image stacks considered as defective and which are commonly discarded are well restored by the ASCM. Seventy-four clinical blood samples and a series of standard fluorescent spheres are selected to evaluate the validity and precision of our proposed ASCM. Both the qualitative and quantitative results obtained by ASCM indicate the good performance of the method in constructing the cell's 3-D morphology.