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Motivated by the excellent detonation performance of octanitrocubane, prismane is another potential backbone with high strain energy in energetic molecule design. In this work, we aim to screen out candidates of highly energetic molecules from the space of prismane derivatives. The high-throughput computation (HTC) is performed based on 200 molecules derived from the molecule space of 1503 prismane derivatives with four substituents. Based on the calculated results, the machine learning (ML) models of density, detonation velocity, detonation pressure, heat of formation and detonation heat are established, and thereby the performances of the remaining 1303 samples are predicted. It is found that the –NHNO2group increases density, while both –NO2and –C(NO2)3groups promote detonation performances. Based on the detonation velocity and bond dissociation energy as criteria representing energy and molecular stability, four molecules were screened out with good detonation performance and acceptable thermal stability. This work demonstrates the efficiency of HTC and ML combined strategy for screening high-quality energetic molecules.

Organic room temperature phosphorescence (RTP) materials have potential applications in information technology and bioimaging. However, the precise control of the afterglow in reversible manners remains challenging for organic matters. Here, we report a kind of organic RTP material fabricated by simple heating mixtures of tartaric acid (TA) and aromatic acids, which can switch their phosphorescence by laser. Those mixtures show tunable phosphorescence from indigo to orange with phosphorescence efficiency of up to 53.99% due to locking different organic luminogens by the TA-formed matrix through the non-covalent interactions. The afterglow of those materials lasts a few seconds and disappears by water fumigation, which can be repeated in response to wet/heat stimuli. With drop-casting those materials on glass slides, a laser-repatternable phosphorescence is achieved by facile laser direct writing and quenched by water cyclically. Those results open the opportunity for the design of smart stimuli-responsive phosphorescence materials from sustainable natural products.

Glassy polymers are generally stiff and strong yet have limited extensibility1. By swelling with solvent, glassy polymers can become gels that are soft and weak yet have enhanced extensibility1–3. The marked changes in properties arise from the solvent increasing free volume between chains while weakening polymer–polymer interactions. Here we show that solvating polar polymers with ionic liquids (that is, ionogels4,5) at appropriate concentrations can produce a unique class of materials called glassy gels with desirable properties of both glasses and gels. The ionic liquid increases free volume and therefore extensibility despite the absence of conventional solvent (for example, water). Yet, the ionic liquid forms strong and abundant non-covalent crosslinks between polymer chains to render a stiff, tough, glassy, and homogeneous network (that is, no phase separation)6, at room temperature. Despite being more than 54 wt% liquid, the glassy gels exhibit enormous fracture strength (42 MPa), toughness (110 MJ m−3), yield strength (73 MPa) and Young’s modulus (1 GPa). These values are similar to those of thermoplastics such as polyethylene, yet unlike thermoplastics, the glassy gels can be deformed up to 670% strain with full and rapid recovery on heating. These transparent materials form by a one-step polymerization and have impressive adhesive, self-healing and shape-memory properties.

The study of logistics network of Yangtze River Delta city group can enable us to understand the logistics integration status. There are 25 cities in Yangtze River Delta Urban Agglomerations selected as the study object of this paper. The values of logistics links to those cities are calculated on the basis of the gravity model. Then, social network analysis method is used to analyze the logistics network density, centrality, cohesive subgroup and core–periphery structure. The research finds that the logistics connection between those cities is low; a few nodes have high degree of centrality and most of these nodes have little difference; there exists subgroup in the network, and the link density inside and between those subgroup are weak; the network has the core–periphery structure; both links inside the marginal area and links between the core area and the edge area are weak, so the network has vulnerabilities. Therefore, some measures need to be taken in in order to realize coordinative development of logistics in Silk Road Economic belt, including breaking the administrative constraints, taking the lead on the core nodes and strengthening the interaction between the edge region and the core region.

Exosomal microRNA (miRNA) is a potential biomarker for cancer diagnosis, metastasis, and treatment. In situdetection of exosomal miRNA is an attractive option due to its simplicity and high accuracy. However, in situexosomal miRNA detection has encountered challenges because of the low target abundance of targets and limited probe permeability. Herein, a label-free and activatable biosensor was developed for in situexosomal miRNA assays by utilizing hairpin-shaped nucleic acid probes and DNA-hosted silver nanoclusters (DNA-AgNCs). The probe is directly internalized into the exosomes, and then hybridized with the target miRNA-21. Subsequently, the DNA-AgNCs are pulled closer to the G-rich sequence, ultimately leading to in situred fluorescence activation. The biosensor not only can detect exosomal miRNA-21 but also distinguish cancer cells from normal cells. Under optimal reaction conditions, the detection limit (LOD) of exosomal miRNA-21 is 1.53 × 107particles per mL. Furthermore, DNA-AgNCs are used as label-free signal elements for in situdetection of exosomal miRNAs for the first time, expanding the application of nanomaterials in this field. This strategy does not require tedious RNA extraction steps and expensive instruments, and may develop into a non-invasive diagnostic tool for ovarian cancer.

1,1-dinitro-2,2-diamino ethylene (FOX-7) is typically representative of low sensitivity and high energy compound. In this work, analogues of FOX-7 are screened using a combined method of high-throughput computation (HTC) and machine learning (ML). The molecules are generated with typical unsaturated hydrocarbons backbones and random combination of substituents -H, -NH2and -NO2, then HTC is performed based on 200 sample molecules. ML models are established based on the HTC results, with detonation parameters predicted using the most accurate model of extreme gradient boosting (XGB). Finally, stability of the filtered high energy molecules are confirmed by quantum chemistry calculations, and besides FOX-7, 8 more energetic molecules with high energy as well as high stability (detonation velocity ≥ 8841.1 m/s, detonation pressure ≥ 34.6 GPa and stability parameter bond dissociation energy ≥ 201.7 kJ/mol) are achieved. This work has shown the efficiency of HTC and ML methods in searching new target molecules.

C12H12N2O8Co, orthorhombic, Pbca(no. 61), a= 11.4542(10) Å, b= 9.2421(8) Å, c= 25.501(2) Å, V= 2699.6(4) Å3, Z= 2, Rgt(F) = 0.0342, wRref(F2) = 0.0888, T = 296 K.

Antibiotic resistance caused by biofilm formation is a clinical challenge. Nitric oxide (NO) can effectively disperse a mature biofilm and can also synergistically influence the level of cyclic diguanylate (c-di-GMP), a universal secondary messenger that plays an important role in biofilm formation in bacteria. Based on our previous finding that c-di-GMP G-quadruplex inducers are effective biofilm formation inhibitors, we designed and synthesized a c-di-GMP G-quadruplex inducer-NO donor conjugate (A11@NO) as a bifunctional antibiofilm agent after obtaining the c-di-GMP G-quadruplex inducer (A11), which has an amino group capable of binding to a nitroso group (NO donor). The conjugate A11@NOshowed better biofilm inhibition efficiency than A11, and it can also eradicate mature biofilm. Additionally, it exhibited good antimicrobial synergism against Pseudomonas aeruginosaand helped elevate the bactericidal efficiency of tobramycin against biofilm-formed bacteria. In combination with tobramycin, A11@NOalso improved the survival rate of Caenorhabditis elegansin a hyperbiofilm environment.

Non-alcoholic fatty liver disease (NAFLD) has become a growing public health problem. However, the complicated pathogenesis of NAFLD contributes to the deficiency of effective clinical treatment. Here, we demonstrated that liver-specific loss of Arid2induced hepatic steatosis and this progression could be exacerbated by HFD. Mechanistic study revealed that ARID2 repressed JAK2-STAT5-PPARγ signaling pathway by promoting the ubiquitination of JAK2, which was mediated by NEDD4L, a novel E3 ligase for JAK2. ChIP assay revealed that ARID2 recruited CARM1 to increase H3R17me2a level at the NEDD4L promoter and activated the transcription of NEDD4L. Moreover, inhibition of Jak2 by Fedratinib in liver-specific Arid2knockout mice alleviated HFD-induced hepatic steatosis. Downregulation of ARID2 and the reverse correlation between ARID2 and JAK2 were also observed in clinical samples. Therefore, our study has revealed an important role of ARID2 in the development of NAFLD and provided a potential therapeutic strategy for NAFLD.

The prognostic value of 4L lymph node dissection (4L-LND) continues to be controversial. We conducted this systematic review and meta-analysis to evaluate the prognosis of 4L-LND in operable non-small-cell lung cancer (NSCLC) patients. We systematically searched studies from PubMed, Embase, and the Cochrane Library up to May 1, 2023. Studies investigating the prognostic value of 4L-LND and non-4L-LND in NSCLC survival were included. Data for analysis mainly comprised postoperative complications, overall survival (OS), and disease-free survival (DFS). The Q-test and I2-test were used to assess heterogeneity. The stability of pooled hazard ratios (HRs) was examined by sensitivity analysis. Six retrospective studies with a total of 4565 NSCLC patients who received 4L-LND or did not receive 4L-LND were considered. The 4L-LND group had significantly better OS (HR = 0.75, 95% CI 0.61–0.91, P = 0.004) and DFS (HR = 0.76, 95% CI 0.66–0.88, P = 0.0002) than the non-4L-LND group, especially in the subgroup analysis of propensity score matching studies. Although no significant difference in the rate of chest tube drainage for more than 7 days (risk ratio (RR) = 0.98, 95% CI 0.31–3.08, P = 0.97), hoarseness rate (RR = 1.60, 95% CI 0.53–4.87, P = 0.51), and chylothorax rate (RR = 1.28, 95% CI 0.58–2.84, P = 0.54) was observed, those who received 4L-LND had a higher total postoperative complication rate than those who did not (RR = 1.35, 95% CI 1.09–1.67, P = 0.006). No significant heterogeneity existed during our analysis, and no potential publication bias was observed among these studies. Our meta-analysis showed that the 4L-LND group was significantly associated with both survival outcomes and postoperative complications compared with the non-4L-LND group in treating NSCLC patients. However, further prospective clinical trials should be designed to evaluate our conclusion owing to the lack of guideline support.

Wettability of metal surfaces is used to characterise the surface cleanliness of components in the inertial confinement fusion (ICF) facility. In this work, molecular simulations combined with wettability experimentation were performed. The temperature effects of water-metallic interface energies and their influence on the measurements for surface cleanliness were investigated. The simulation results indicated van der Waals forces promoted the attraction between water molecules and metal surfaces. The interaction energies raised with elevated temperatures from 291 K to 303 K. Besides, the wettability experiments showed both the Al and Fe components were hydrophilic, and the contact angle was reduced with elevated temperatures. The correlationship between the energy change and the contact angle at varying temperatures can be found. This research provides a new understanding of the characterisation of metal surface cleanliness.

Single-crystal X-ray diffraction is a powerful characterization technique that enables the determination of atomic arrangements in crystalline materials. Growing or retaining large single crystals amenable to it has, however, remained challenging with covalent organic frameworks (COFs), especially suffering from post-synthetic modifications. Here we show the synthesis of a flexible COF with interpenetrated qtz topology by polymerization of tetra(phenyl)bimesityl-based tetraaldehyde and tetraamine building blocks. The material is shown to be flexible through its large, anisotropic positive thermal expansion along the caxis (αc= +491 × 10–6K–1), as well as through a structural transformation on the removal of solvent molecules from its pores. The as-synthesized and desolvated materials undergo single-crystal-to-single-crystal transformation by reduction and oxidation of its imine linkages to amine and amide ones, respectively. These redox-induced linkage conversions endow the resulting COFs with improved stability towards strong acid; loading of phosphoric acid leads to anhydrous proton conductivity up to ca. 6.0 × 10−2S cm−1.

Mining sufficient discriminative information is vital for effective feature representation in vehicle re-identification. Traditional methods mainly focus on the most salient features and neglect whether the explored information is sufficient. This paper tackles the above limitation by proposing a novel Salience-Navigated Vehicle Re-identification Network (SVRN) which explores diverse salient features at multi-scales. For mining sufficient salient features, we design SVRN from two aspects: 1) network architecture: we propose a novel salience-navigated vehicle re-identification network, which mines diverse features under a cascaded suppress-and-explore mode. 2) feature space: cross-space constraint enables the diversity from feature space, which restrains the cross-space features by vehicle and image identifications (IDs). Extensive experiments demonstrate our method’s effectiveness, and the overall results surpass all previous state-of-the-arts in three widely-used Vehicle ReID benchmarks (VeRi-776, VehicleID, and VERI-WILD), i.e., we achieve an 84.5% mAP on VeRi-776 benchmark that outperforms the second-best method by a large margin (3.5% mAP).

•Gap junction protein alpha 4 (GJA4) on fibroblasts is involved in promoting fibroblast activation in colorectal cancer (CRC).•GJA4 promote epithelial mesenchymal transition (EMT) through a fibroblast-dependent pathway.•GJA4 may act synergistically with M2 macrophages to limit t cell infiltration by stimulating the formation of an immune-excluded desmoplasic barrier.•GJA4 was significantly correlated with pathological stage and D2 dimer.

Lung cancer is the most common malignancy and the leading cause of cancer death worldwide, and lung adenocarcinoma (LUAD) is the most prevalent subtype. Considering the emergence of resistance to therapies, it is urgent to develop more effective therapies to improve the prognosis. Here we reported that pancreatic progenitor cell differentiation and proliferation factor (PPDPF) deficiency inhibited LUAD development both in vitro and in vivo. Mechanistically, PPDPF induces hyperactive STAT3 by interfering STAT3-PTPN1 interaction. Activated STAT3 promoted BMPR2 transcription, which further inhibited apoptosis. Moreover, PPDPF reduced NK cell infiltration and activation to develop an immunosuppressive microenvironment, which was also mediated by STAT3. Furthermore, we identified that the expression of PPDPF was positively correlated with the malignant features of LUAD, as well as BMPR2 and p-STAT3 level in clinical samples. Therefore, our study suggests that PPDPF positively regulates BMPR2 expression and facilitates immune escape via regulating STAT3 activity, providing a potential therapy target for LUAD.

Cardiac magnetic resonance (CMR) is the gold standard for evaluating myocardial fibrosis. Few studies have explored the association between ventricular arrhythmias (VAs) and fibrosis in apparently normal hearts. We aimed to investigate the association between the occurrence and morphology of VAs and left ventricular late gadolinium enhancement (LV-LGE) in patients without known structural heart diseases. This study enrolled 78 patients with apparently normal hearts who underwent 24-h ambulatory Holter electrocardiogram (ECG) and CMR examinations simultaneously. The presence and extent of LGE was determined using CMR imaging and compared based on occurrence and morphology of VAs. The clinical characteristics were also recorded and calculated. LV-LGE was observed in 19 (37.3%) and 4 (14.8%) patients with and without VAs, respectively (P = 0.039). It was more frequently observed in patients with polymorphic VAs (P = 0.024). The polymorphic VAs had a higher tendency of LGE extent than monomorphic VAs, while the difference did not reach statistical significance (P = 0.055). In multivariable analyses, the presence of polymorphic VAs [hazard ratio (HR) 11.19, 95% CI 1.64–76.53, P = 0.014] and hypertension (HR 4.64, 95% CI 1.08–19.99, P = 0.039) were associated with greater prevalence of LV-LGE. In patients without structural heart diseases, besides hypertension, multiple VA morphologies on Holter ambulatory ECG measurements is another important marker of increased incidence of myocardial fibrosis.

PLK1 and Smad4 are two important factors in prostate cancer initiation and progression. They have been reported to play the opposite role in Pten-deleted mice, one is an oncogene, the other is a tumor suppressor. Moreover, they could reversely regulate the PI3K/AKT/mTOR pathway and the activation of MYC. However, the connections between PLK1 and Smad4 have never been studied. Here, we showed that PLK1 could interact with Smad4 and promote the ubiquitination and degradation of Smad4 in PCa cells. PLK1 and PELO could bind to different domains of Smad4 and formed a protein complex. PELO facilitated the degradation of Smad4 through cooperating with PLK1, thereby resulting in proliferation and metastasis of prostate cancer cell. Changes in protein levels of Smad4 led to the alteration of biological function that caused by PLK1 in prostate cancer cells. Further studies showed that PELO upregulation was positively associated with high grade PCa and knockdown of PELO expression significantly decreased PCa cell proliferation and metastasis in vitro and vivo. PELO knockdown in PCa cells could enhance the tumor suppressive role of PLK1 inhibitor. In addition, blocking the interaction between PELO and Smad4 by using specific peptide could effectively inhibit PCa cell metastasis ability in vitro and vivo. Overall, these findings identified a novel regulatory relationship among PLK1, Smad4 and PELO, and provided a potential therapeutic strategy for advanced PCa therapy by co-targeting PLK1 and PELO.

Background: Kaposiform hemangioendothelioma (KHE) is a rare neoplasm of vascular origin. It may involve skin, bone, connective tissue, and parenchymal organs, and it is difficult to make a definite diagnosis in the early stage because Kasabach-Merritt phenomenon may occur in some cases. Case presentation: On June 12, 2022, a 19-month boy was admitted to our department with the chief complaint of flexion of the right hip joint for over 1 year. An exploratory laparotomy and pelvic lesion resection were conducted and the resection of the iliopsoas muscle mass was performed. The intraoperative resection of the neoplasm confirmed the pathological diagnosis of kaposiform hemangioendothelioma. The vital signs of the child were stable and recovered well after surgery, and the platelet and coagulation indices were normal. Conclusion: KHE is a rare disease in clinics, the number of confirmed cases in the world is still relatively few, and the etiology and mechanism of the disease are still unknown, which could result in misdiagnose and delayed treatment in the disease early stages. It is necessary to continue to collect relevant cases, to unify the standard treatment guidelines as soon as possible, to reduce the mortality rate, and to improve the quality of life of the cases.

Ionogels are compelling materials for technological devices due to their excellent ionic conductivity, thermal and electrochemical stability, and non-volatility. However, most existing ionogels suffer from low strength and toughness. Here, we report a simple one-step method to achieve ultra-tough and stretchable ionogels by randomly copolymerizing two common monomers with distinct solubility of the corresponding polymers in an ionic liquid. Copolymerization of acrylamide and acrylic acid in 1-ethyl-3-methylimidazolium ethyl sulfate results in a macroscopically homogeneous covalent network with in situ phase separation: a polymer-rich phase with hydrogen bonds that dissipate energy and toughen the ionogel; and an elastic solvent-rich phase that enables for large strain. These ionogels have high fracture strength (12.6 MPa), fracture energy (~24 kJ m−2) and Young’s modulus (46.5 MPa), while being highly stretchable (~600% strain) and having self-healing and shape-memory properties. This concept can be applied to other monomers and ionic liquids, offering a promising way to tune ionogel microstructure and properties in situ during one-step polymerization.

Targeting poly(ADP-ribose) polymerase1/2 (PARP1/2) is a promising strategy for the treatment of pancreatic cancer with breast cancer susceptibility gene (BRCA) mutation. Inducing the deficiency of homologous recombination (HR) repair is an effective way to broaden the indication of PARP1/2 inhibitor for more patients with pancreatic cancer. Bromodomain-containing protein 4 (BRD4) repression has been reported to elevate HR deficiency. Therefore, we designed, synthetized, and optimized a dual PARP/BRD4 inhibitor III-16, with a completely new structure and high selectivity against PARP1/2 and BRD4. III-16showed favorable synergistic antitumor efficacy in pancreatic cancer cells and xenografts by arresting cell cycle progression, inhibiting DNA damage repair, and promoting autophagy-associated cell death. Moreover, III-16reversed Olaparib-induced acceleration of cell cycle progression and recovery of DNA repair. The advantages of III-16over Olaparib suggest that dual PARP/BRD4 inhibitors are novel and promising agents for the treatment of advanced pancreatic cancer.

The formation of biofilms by clinical pathogens typically leads to chronic and recurring antibiotic-resistant infections. High cellular levels of cyclic diguanylate (c-di-GMP), a ubiquitous secondary messenger of bacteria, have been proven to be associated with a sessile biofilm lifestyle of pathogens. A promising antibiofilm strategy involving the induction of c-di-GMP to form dysfunctional G-quadruplexes, thereby blocking the c-di-GMP-mediated biofilm regulatory pathway, was proposed in this study. In this new strategy, a series of novel c-di-GMP G-quadruplex inducers were designed and synthesized for development of therapeutic biofilm inhibitors. Compound 5hexhibited favorable c-di-GMP G-quadruplex-inducing activity and 62.18 ± 6.76% biofilm inhibitory activity at 1.25 μM without any DNA intercalation effect. Moreover, the favorable performance of 5hin interfering with c-di-GMP-related biological functions, including bacterial motility and bacterial extracellular polysaccharide secretion, combined with the reporter strain and transcriptome analysis results confirmed the c-di-GMP signaling-related action mechanism of 5h.

The phonon is one of the most important elementary excitation in solid system, as a gene related to the thermal properties and chemical stability of energetic materials. This paper reviews the molecular modeling methods and theoretical applications of phonon spectra for energetic crystals, and details the phonon-based investigations of lattice stability, thermal properties, vibrational spectra, and initiation mechanism. Besides, it presents a perspective on coupling mechanics, phonons, and chemical reactions, aiming to achieve deep understanding of the ignition mechanism of energetic crystals.

The potential practical applications of high-energy 1,3,5,7-tetranittro-1,3,5,7-tetrazocane (HMX) are hindered by their unfavorable safety behavior and sluggish thermal decomposition. This paper proposes dye-assisted assembly of HMX crystals with crystal violet (CV) as soft templates (denoted as CV-HMX). As revealed by the XPS and molecular-dynamics simulations, preferred electrical interactions between HMX and conjugation electrons in planar CV molecular ensure that the resultant CV-HMX has a two-dimensional (2D) microstructure. The BAM impact sensitivity of CV-HMX is 12.5 ​J, higher than that of raw-HMX (5 ​J) and HMX recrystallized from pure water (PW-HMX; 4.5 ​J). Meanwhile, the BAM friction sensitivity of CV-HMX is 320 ​N, also much higher than that of PW-HMX (96 ​N) and raw-HMX (88 ​N). In addition, the decomposition kinetics of CV-HMX is improved due to its large specific surface area and high pore volume. Such dye-template assembly can be applied to a large number of systems, indicating that the method proposed in this work is universal. This work provides synergistic template regulation on morphology and pore structure using general dye-assisted assembly, holding great promises in developing practically viable high energy materials with favorable sensitivity and improved energy release performance.