Ion cocktail therapy for myocardial infarction by synergistic regulation of both structural and electrical remodeling.

Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI. Here, an "ion cocktail therapy" is proposed to simultaneously reverse cardiac structural and electrical remodeling post-MI in rats and minipigs by applying a unique combination of silicate, strontium (Sr) and copper (Cu) ions due to their specific regulatory effects on the behavior of the key cells involved in MI including angiogenesis of endothelial cells, M2 polarization of macrophages and apoptosis of cardiomyocyte. The results demonstrate that ion cocktail treatment attenuates structural remodeling post-MI by ameliorating infarct size, promoting angiogenesis in both peri-infarct and infarct areas. Meantime, to some extent, ion cocktail treatment reverses the deteriorative electrical remodeling by reducing the incidence rate of early/delayed afterdepolarizations and minimizing the heterogeneity of cardiac electrophysiology. This ion cocktail therapy reveals a new strategy to effectively treat MI with great clinical translation potential due to the high effectiveness and safety of the ion cocktail combination.

Plasmonic Imaging of Multivalent NTD-Nucleic Acid Interactions for Broad-Spectrum Antiviral Drug Analysis.

The discovery and identification of broad-spectrum antiviral drugs are of great significance for blocking the spread of pathogenic viruses and corresponding variants of concern. Herein, we proposed a plasmonic imaging-based strategy for assessing the efficacy of potential broad-spectrum antiviral drugs targeting the N-terminal domain of a nucleocapsid protein (NTD) and nucleic acid (NA) interactions. With NTD and NA conjugated gold nanoparticles as core and satellite nanoprobes, respectively, we found that the multivalent binding interactions could drive the formation of core-satellite nanostructures with enhanced scattering brightness due to the plasmonic coupling effect. The core-satellite assembly can be suppressed in the presence of antiviral drugs targeting the NTD-NA interactions, allowing the drug efficacy analysis by detecting the dose-dependent changes in the scattering brightness by plasmonic imaging. By quantifying the changes in the scattering brightness of plasmonic nanoprobes, we uncovered that the constructed multivalent weak interactions displayed a 500-fold enhancement in affinity as compared with the monovalent NTD-NA interactions. We demonstrated the plasmonic imaging-based strategy for evaluating the efficacy of a potential broad-spectrum drug, PJ34, that can target the NTD-NA interactions, with the IC50 as 24.35 and 14.64 µM for SARS-CoV-2 and SARS-CoV, respectively. Moreover, we discovered that ceftazidime holds the potential as a candidate drug to inhibit the NTD-NA interactions with an IC50 of 22.08 µM from molecular docking and plasmonic imaging-based drug analysis. Finally, we validated that the potential antiviral drug, 5-benzyloxygramine, which can induce the abnormal dimerization of nucleocapsid proteins, is effective for SARS-CoV-2, but not effective against SARS-CoV. All these demonstrations indicated that the plasmonic imaging-based strategy is robust and can be used as a powerful strategy for the discovery and identification of broad-spectrum drugs targeting the evolutionarily conserved viral proteins.

Unveiling the luminescence property of Li2MgGeO4:Mn4+ featuring the tetrahedral crystallographic-site occupancy of Mn4.

Owing to the occupying tendency of Mn4+ at octahedral sites, doping Mn4+ activators in tetrahedral structures poses challenges and hence is seldom reported. In this work, tetrahedrally sited Mn4+ phosphors were studied. By combining X-ray diffraction (XRD) data with Rietveld refinement analysis, the location of Mn4+ was determined. It was found that by adding excessive raw MgO, the phosphor synthesis temperature can be improved, enhancing the crystallinity of the crystal and thus improving the emission performance of the phosphor. In addition, excessive raw MgO forms a second phase in an LMGO matrix, which does not change the doping site for Mn4+. The Tanabe-Sugano diagram of Mn4+ in the tetrahedral field and the energy-level diagram of these phosphors were constructed for the first time, and the excitation and emission mechanisms are discussed in detail. With 1.2-fold excess of raw MgO, the prepared sample (LMGO-Mn-1.2) shows the best luminescence, demonstrating red emissions peaked at 656 nm and affording an emission intensity enhancement of over 50 times compared to a stoichiometric LMGO:Mn4+ system. At 150 °C, LMGO-Mn-1.2 keeps 90% emission intensity compared to that at room temperature. Finally, a high-efficiency warm white light-emitting diode was built. This work provides new insights into the study of Mn4+-activated phosphors in a tetrahedron crystal field.

Optimization of offshore wind farm inspection paths based on K-means-GA.

As global demand for offshore wind energy continues to rise, the imperative to enhance the profitability of wind power projects and reduce their operational costs becomes increasingly urgent. This study proposes an innovative approach to optimize the inspection routes of offshore wind farms, which integrates the K-means clustering algorithm and genetic algorithm (GA). In this paper, the inspection route planning problem is formulated as a multiple traveling salesman problem (mTSP), and the advantages of the K-means clustering algorithm in distance similarity are utilized to effectively group the positions of wind turbines, thereby optimizing the inspection schedule for vessels. Subsequently, by harnessing the powerful optimization capability and robustness of genetic algorithms, further refinement is conducted to search for the optimal inspection routes, aiming to achieve cost reduction objectives. The results of simulation experiments demonstrate the effectiveness of this integrated approach. Compared to traditional genetic algorithms, the inspection route length has been significantly reduced, from 93 kilometers to 79.36 kilometers. Simultaneously, operational costs have also experienced a notable decrease, dropping from 141,500 Chinese Yuan to 125,600 Chinese Yuan.

ZBTB16 inhibits DNA replication and induces cell cycle arrest by targeting WDHD1 transcription in lung adenocarcinoma.

Lung adenocarcinoma is a malignant tumor with high morbidity and mortality. ZBTB16 plays a double role in various tumors; however, the potential mechanism of ZBTB16 in the pathophysiology of lung adenocarcinoma has yet to be elucidated. We herein observed a decreased expression of ZBTB16 mRNA and protein in lung adenocarcinoma and a significantly increased DNA methylation level of ZBTB16 in patients with lung adenocarcinoma. Analysis of public databases and patients' clinical data indicated a close association between ZBTB16 and patient survival. Ectopic expression of ZBTB16 in lung adenocarcinoma cells significantly inhibited cell proliferation, invasion, and migration. It also induced cell cycle arrest in the S phase. Meanwhile, mitotic catastrophe was induced, and DNA damage and apoptosis occurred. In line with these findings, the overexpression of ZBTB16 in xenograft mice resulted in the inhibition of tumor growth. Comprehensive analysis showed that WDHD1 was a potential target for ZBTB16. The overexpression of both isoforms of WDHD1 significantly reversed the ZBTB16-mediated inhibition of lung adenocarcinoma proliferation and cell cycle. These studies suggest that ZBTB16 impedes the progression of lung adenocarcinoma by interfering with WDHD1 transcription, making it a potential novel therapeutic target in the management of lung adenocarcinoma.

Modulation of supramolecular structure by stepwise removal of tert-butyl groups from tetraazaperopyrene derivatives on Ag(111).

Tert-butyl functional groups can modulate the self-assembly behavior of organic molecules on surfaces. However, the precise construction of supramolecular architectures through their controlled thermal removal remains a challenge. Herein, we precisely controlled the removal amount of tert-butyl groups in tetraazaperopyrene derivatives by stepwise annealing on Ag(111). The evolution of 4tBu-TAPP supramolecular self-assembly from the grid-like structure composed of 3tBu-TAPP through the honeycomb network formed by 2tBu-TAPP to the one-dimensional chain co-assembled by tBu-TAPP and TAPP was successfully realized. This series of supramolecular nanostructures were directly visualized by high resolution scanning tunneling microscopy. Tip manipulation and density functional theory calculations show that the formation of honeycomb network structure can be attributed to the van der Waals interactions, N-Ag-N coordination bonds, and weak C-H⋯N hydrogen bonds. Further addition of two tert-butyl groups (6tBu-TAPP) leads to a completely different assembly evolution, due to the fact that the additional tert-butyl groups affect the molecular adsorption behavior and ultimately induce desorption. This work can possibly be exploited in constructing stable and long-range ordered nanostructures in surface-assisted systems, which can also promote the development of nanostructures in functional molecular devices.

Identification of key immune cells infiltrated in lung adenocarcinoma microenvironment and their related long noncoding RNA.

LncRNA associated with immune cell infiltration in tumor microenvironment (TME) may be a potential therapeutic target for lung adenocarcinoma. We established a machine learning (ML) model based on 3896 samples characterized by the degree of immune cell infiltration, and further screened the key lncRNA. In vitro experiments were applied to validate the prediction. Treg is the key immune cell in the TME of lung adenocarcinoma, and the degree of infiltration is negatively correlated with the prognosis. PCBP1-AS1 may affect the infiltration of Tregs by regulating the TGF-ß pathway, which is a potential predictor of clinical response to immunotherapy. PCBP1-AS1 regulates cell proliferation, cell cycle, invasion, migration, and apoptosis in lung adenocarcinoma. The results of clinical sample staining and in vitro experiments showed that PCBP1-AS1 was negatively correlated with Treg infiltration and TGF-ß expression. Tregs and related lncRNA PCBP1-AS1 can be used as targets for the diagnosis and treatment of lung adenocarcinoma.

Large-scale array for radio astronomy on the farside (LARAF).

At the Royal Society meeting in 2023, we have mainly presented our lunar orbit array concept called DSL, and also briefly introduced a concept of a lunar surface array, LARAF. As the DSL concept had been presented before, in this article, we introduce the LARAF. We propose to build an array in the far side of the Moon, with a master station which handles the data collection and processing, and 20 stations with maximum baseline of 10 km. Each station consists of 12 membrane antenna units, and the stations are connected to the master station by power line and optical fibre. The array will make interferometric observation in the 0.1-50 MHz band during the lunar night, powered by regenerated fuel cells. The whole array can be carried to the lunar surface with a heavy rocket mission, and deployed with a rover in eight months. Such an array would be an important step in the long-term development of lunar-based ultralong wavelength radio astronomy. It has a sufficiently high sensitivity to observe many radio sources in the sky, though still short of the dark age fluctuations. We discuss the possible options in the power supply, data communication, deployment etc. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

On-surface synthesis of two types of cyano-substituted polyfluorene derivatives via Ullmann coupling on Au(111).

Using 4-(3,6-dibromo-9H-carbazol-9-yl)benzonitrile (DBCB) precursors, we successfully constructed two types of cyano-substituted polymers on Au(111) by the molecular beam epitaxy method. According to the geometry, the two polymers are referred to as w-type polymers composed of cis-dimers and z-type polymers composed of trans-dimers. The intermediate dimers and final polymers were well characterized by high-resolution scanning tunneling microscopy (HR-STM). Moreover, the productivities of these two polymers can be controlled by adjusting the heating rate and different treatment methods. High heating rates and hot deposition can provide more ample space and time for molecular diffusion, which is conducive to the formation of w-type polymers with relatively low density. In addition, by combining scanning tunneling spectroscopy (STS) and density functional theory (DFT) calculations, we have shown that the addition of CN groups reduces the band gap of the two polymers. Our investigation thus shows the controllable construction of nanostructures through efficient surface synthesis parameters and reveals the potential of using functional groups as tools to modify the electronic properties of polymers.

Identification of the key DNA damage response genes for predicting immunotherapy and chemotherapy efficacy in lung adenocarcinoma based on bulk, single-cell RNA sequencing, and spatial transcriptomics.

BACKGROUND: Immune checkpoint inhibitors (ICI) plus chemotherapy is the preferred first-line treatment for advanced driver-negative lung adenocarcinoma (LUAD). The DNA damage response (DDR) is the main mechanism underlying chemotherapy resistance, and EGLN3 is a key DDR component. METHOD: We conducted an analysis utilizing TCGA and GEO databases employing multiple labels-WGCNA, DEGs, and prognostic assessments. Using bulk RNA-seq and scRNA-seq data, we isolated EGLN3 as the single crucial DDR gene. Spatial transcriptome analysis revealed the spatial differential distribution of EGLN3. TIDE/IPS scores and pRRophetic/oncoPredict R packages were used to predict resistance to ICI and chemotherapy drugs, respectively. RESULTS: EGLN3 was overexpressed in LUAD tissues (p < 0.001), with the high EGLN3 expression group exhibiting a poor prognosis (p = 0.00086, HR: 1.126 [1.039-1.22]). Spatial transcriptome analysis revealed EGLN3 overexpression in cancerous and hypoxic regions, positively correlating with DDR-related and TGF-ß pathways. Drug response predictions indicated EGLN3's resistance to the common chemotherapy drugs, including cisplatin (p = 6.1e-14), docetaxel (p = 1.1e-07), and paclitaxel (p = 4.2e-07). Furthermore, on analyzing the resistance mechanism, we found that EGLN3 regulated DDR-related pathways and induced chemotherapy resistance. Additionally, EGLN3 influenced TGF-ß signaling, Treg cells, and cancer-associated fibroblast cells, culminating in immunotherapy resistance. Moreover, validation using real-world data, such as GSE126044, GSE135222, and, IMvigor210, substantiated the response trends to immunotherapy and chemotherapy. CONCLUSIONS: EGLN3 emerges as a potential biomarker predicting lower response to both immunotherapy and chemotherapy, suggesting its promise as a therapeutic target in advanced LUAD.

Construction of C-S and C-Se Bonds from Unstrained Ketone Precursors under Photoredox Catalysis.

A mild photoredox catalyzed construction of sulfides, disulfides, selenides, sulfoxides and sulfones from unstrained ketone precursors is introduced. Combination of this deacylative process with SN 2 or coupling reactions provides novel and convenient modular strategies toward unsymmetrical or symmetric disulfides. Reactivity studies favor a bromine radical that initiates a HAT (Hydrogen Atom Transfer) from the aminal intermediate resulting in expulsion of a C-centered radical that is intercepted to make C-S and C-Se bonds. Gram scale reactions, broad substrate scope and tolerance towards various functional groups render this method appealing for future applications in the synthesis of organosulfur and selenium complexes.

Polyvinylpyrrolidone-assisted synthesis of ultrathin multi-nanolayered Cu2Nb34O87-x for advanced Li+ storage.

The ultrathin multi-nanolayered structure with ultrathin monolayer thickness (<10 nm) and certain interlayer spacing can significantly shorten Li+ paths and alleviate the volume effect for Li+-storage materials. However, unlike layered materials such as MXene and MoS2, shear ReO3-type niobates have difficulty forming ultrathin multi-nanolayered structures due to their crystal structures, which still remains a challenge. Herein, by a polyvinylpyrrolidone (PVP)-assisted solvothermal method, we first synthesize ultrathin multi-nanolayered Cu2Nb34O87-x with oxygen vacancies composed of ultrathin nanolayers (2-10 nm in thickness) and interlayer spacing (1-5 nm). Oxygen vacancies can radically enhance the inherent electronic/ionic conductivity and Li+ diffusion coefficient of this material. The PVP-induced formation mechanism of this material is expounded in detail. The well-preserved ultrathin multi-nanolayered structure and excellent multi-electron electrochemical reversibility (Nb5+ â†” Nb4+ â†”N b3+ and Cu2+ â†” Cu+) of this material during cycling are fully verified. Based on an ultrathin multi-nanolayered structure and oxygen vacancies, this material as the anode of lithium-ion batteries is highly competitive among reported shear ReO3-type Cu-Nb-O anodes, displaying a high reversible capacity (315.3 mAh g-1 after 300 cycles at 1 C), durable cycling stability (85.7 % capacity retention after 1000 cycles at 10 C), and outstanding rate performance. Moreover, the application of this material to lithium-ion capacitors generates a large energy density (97.9 Wh kg-1 at 87.5 W kg-1) and a high power density (17,500 W kg-1 at 12.6 Wh kg-1), thus further indicating its fast faradaic pseudocapacitive behavior for practical applications. The results of this work indicate a breakthrough in synthesizing ultrathin multi-nanolayered shear ReO3-type niobates.

"Invisible" pulsation and period-doubling bifurcation of harmonic mode locking in a bidirectional fiber laser.

The harmonic mode-locking (HML) "invisible" pulsation (IP) is reported, here, in a bidirectional passively mode-locked fiber laser (BPMLFL). With the help of dispersive Fourier transform (DFT) technology, it is found that due to the alike nonlinear effects experienced by two pulse trains in HML, their evolution is consistent during the IP. Further, as the increase of pump power, period-doubling bifurcations (PDBs) can be observed based on the IP phenomenon in the HML regime, the PDB path experienced by the HML from steady to chaotic is statistically obtained. Finally, the IP and PDB in the bidirectional laser are reproduced and studied through numerical simulations. The effect of IP on the coherence of solitons is further analyzed. We believe our research results will provide new insights into the study of soliton dynamics in fiber lasers.

Molecular mechanism of the transformation of oxidized lignin to N-substituted aromatics.

The cleavage of C-C bonds in oxidized lignin model compounds is a highly effective methodology for achieving lignin depolymerization, as well the generation of N-substituted aromatics. Here, density functional theory calculations were performed to understand the mechanism of the transformation of an oxidized lignin model compound (ligninox) and hydroxylamine hydrochloride to N-substituted aromatics. The reaction was proposed to proceed via an energetically viable mechanism featuring the initial production of HOAc acting as proton bridge. According to our calculations, Z-type oxime is the major intermediate of the reaction, with an energy barrier of 22.9 kcal mol-1, owing to the weak interactions between methoxy and oximino groups being stronger than that of E-type oxime. Additionally, the hydroxy addition is the rate-determining step, with an energy barrier of 27.0 kcal mol-1. Moreover, the huge net energy change of Beckmann and abnormal Beckmann rearrangements is the main overall thermodynamic driving force for producing N-substituted aromatics from oximes. The theoretical results have provided a clear picture of how ligninox transforms into N-substituted aromatics and are expected to provide valuable theoretical guidance for lignin depolymerization.

On-surface synthesis of Au-C4 and Au-O4 alternately arranged organometallic coordination networks via selective aromatic C-H bond activation.

Selective activation of the C-H bond of aromatic hydrocarbons is significant in synthetic chemistry. However, achieving oriented C-H activation remains challenging due to the poor selectivity of aromatic C-H bonds. Herein, we successfully constructed alternately arranged Au-C4 and Au-O4 organometallic coordination networks through selective aromatic C-H bond activation on Au(111) substrate. The stepwise reaction process of the 5, 12-dibromopyrene 3,4,9, 10-tetracarboxylic dianhydride precursor is monitored by high-resolution scanning tunneling microscopy. Our results show that the gold atoms in C-Au-C organometallic chains play a crucial role in promoting the selective ortho C-H bonds activation and forming Au-C4 coordination structure, which is further demonstrated by a comparative experiment of PTCDA precursor on Au(111). Furthermore, our experiment of 2Br-PTCDA precursor on Cu(111) substrate confirms that copper atoms in C-Cu-C organometallic chains can also assist the formation of Cu-C4 coordination structure. Our results reveal the vital effect of organometallic coordination on selective C-H bond activation of reactants, which holds promising implications for controllable on-surface synthesis.

Multimode optical switch based on cascaded Mach-Zehnder interferometer waveguides.

We present a 1 × 1 multimode optical switch for E11, E21, E12, and E22 modes based on cascaded Mach-Zehnder interferometer (MZI) waveguides, where the primary MZI is used to split E11, E21, E12, and E22 modes into E11 or E12 mode and then couple back to the original mode at the output, and the secondary MZIs are the modulation arms of the primary MZI. In addition, the secondary MZIs are designed to be mode-insensitive for switching E11 and E12 modes simultaneously. As a proof of concept, we fabricate the device with polymer material to achieve thermo-optic switching for the four modes. Our experimental device exhibits the extinction ratios of larger than 10.2 dB with a power consumption of 5.5 mW and response times of less than 1.28 ms for each mode. The presented device can be widely applied in mode-division multiplexing (MDM) systems where multimode switching is needed.

Effect of comprehensive nursing intervention on the outcomes of in vitro fertilization in patients with polycystic ovary syndrome: A randomized controlled study.

OBJECTIVE: To explore the effects of comprehensive nursing intervention on in vitro fertilization (IVF) and pregnancy outcomes in patients with polycystic ovary syndrome (PCOS). METHOD: A total of 130 patients with PCOS admitted to our hospital from April 2021 to March 2023 were selected as the research subjects. They were evenly divided according to a random number table method. The control group received routine care for the patients, while the study group received comprehensive care for the patients. The IVF, pregnancy outcomes, negative emotional changes, serum and follicular fluid (FF) amyloid-related protein and C-reactive protein (CRP) levels of the 2 groups of patients were compared. RESULT: The data on IVF rate and pregnancy rate in the study group were significantly better than those in the control group (P < .05). The SAS and SDS scores of the study group patients after intervention were significantly lower than those of the control group (P < .05). After intervention, the levels of serum and FF amyloid associated protein and CRP in the study group were significantly lower than those in the control group (P < .05). CONCLUSION: Patients with PCOS who receive comprehensive care can increase their probability of IVF, improve their pregnancy outcomes, and have a positive significance in reducing negative emotions.

Examining influencing factors of express delivery stations' spatial distribution using the gradient boosting decision trees: A case study of Nanjing, China.

Online shopping has promoted the development of logistics and express delivery businesses. Express delivery stations are closely related to residents' daily lives, and it is an important topic for the study of urban consumption space and commercial service space. This paper analyzed the factors influencing the spatial distribution of terminal logistics space (express delivery stations) in the process of online shopping. The gradient boosting decision trees (GBDT) was selected for analyzing the factors influencing the distribution of express delivery stations. The results demonstrated that express delivery stations' distribution is mainly influenced by commercial retail and residential neighborhoods, showing a clustering toward consumer spaces and residential areas. This paper studied the association between express delivery stations and other functional spaces in the city, and established an analytical framework for the factors influencing the spatial distribution of express delivery stations. The research results help to improve the rationality and effectiveness of the setting and management of the terminal logistics space in the online shopping process.

Mode-independent thermo-optic switch based on the total-internal-reflection effect.

A broadband mode-independent thermo-optic (TO) switch using the total-internal-reflection (TIR) effect is proposed and experimentally demonstrated on a polymer waveguide platform. By optimizing geometric parameters of the TIR switch, a mode-independent TO switching function with a large bandwidth and extinction ratio can be realized for E11, E12, and E21 modes. The measurement results show an extinction ratio larger than 18.1 dB with a driving power of 160 mW for each mode over the wavelength range of 1500-1620 nm. The designed structure can also be cascaded to form a 1 × N switch network for mode-division multiplexing (MDM) systems, which greatly improves the network flexibility.

Highly Regioselective Cyclodehydrogenation of Diphenylporphyrin on Metal Surfaces.

Exploring the effect of porphin tautomerism on the regioselectivity of its derivatives is a big challenge, which is significant for the development and application of porphyrin drugs. In this work, we demonstrate the regioselectivity of 2H-diphenylporphyrin (H2-DPP) in the planarization reaction on Au(111) and Ag(111) substrates. H2-DPP monomer forms two configurations (anti- and syn-) via a dehydrogenation coupling, between which the yield of the anti-configuration exceeds 90%. Using high-resolution scanning tunneling microscopy, we visualize the reaction processes from the H2-DPP monomer to the final two planar products. Combined with DFT calculations of the potential reaction pathway and comparative experiments on Au(111) and Ag(111) substrates. Using M-DPP (M = Cu and Fe), we confirm that the regioselectivity of H2-DPP is derived from the reaction energy barrier during the cyclodehydrogenation reaction of different tautomers. This work reveals the regioselectivity mechanism of H2-DPP on the atomic scale, which holds great significance for understanding the chemical conversion process of organic macrocyclic molecules.