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Abstract In this paper, we analyze the symmetry properties of the complete family of type D spacetimes generalized form the Plebański-Demiański solution in four dimensions holographically in terms of a warped CFT. The generalized Plebański-Demiański solutions are black hole-like spacetimes characterized by seven physical parameters. Most of the black holes in four dimensions are included within this family. Generically consider a solution with horizon in this family, we figure out the possible warped conformal symmetry attached to the horizon. The horizon can be either extremal or non-extremal. In the extremal case, the near horizon region can be mapped to an infinite spacetime with geometry given by a warped and twist product of AdS2 and S2. The new boundary conditions for AdS2 as well as their higher dimensional uplifts are applied here to manifest the asymptotic symmetry as the warped conformal symmetry. In the non-extremal case, the global warped conformal symmetry is singled out by analyzing the scalar wave equation with constant frequency. The local warped conformal symmetries are represented by the charge algebra associated to the vector fields which preserve the scalar wave equation as well as its frequency. In defining the variation of the covariant charges, a proper counterterm is introduced for consistency conditions which is supposed to be suitable for all the solutions within the family. As a consistency check, the horizon entropy is reproduced by the entropy formula of the warped CFT by using its modular covariance and the central terms derived in the bulk spacetimes.

In view of the disaster caused by the instability of room-and-pillar goaf, taking the coal pillar left over from a pillar goaf in Yulin as the research background, the roof instability mechanism of room-and-pillar goaf is studied by means of theoretical analysis, physical similarity simulation, numerical analysis and so on. The research results show that the safety factor of the stability of the remaining coal pillar in the mine goaf is 1.54, considering the creep of the coal pillar under the long-term roof load, the large area instability will occur in the end. The influencing factors of the failure and instability of the coal pillar in the room-pillar goaf include five factors, such as physical and mechanical properties of coal, weathering, mining mode, water erosion, creep and so on. The failure law of the catastrophic evolution of roof in room-and-pillar goaf is from point to surface, and the roof from failure to instability is divided into four stages: preliminary failure stage, failure expansion stage, failure aggravation stage and complete instability stage. When the goaf is completely unstable, the peak stress of coal pillar is 15.08 MPa, the stress concentration factor is 3.92, and the roof subsidence displacement is 392.44 mm.

Abstract The warped conformal symmetries have been found in the covariant phase space of a set of non-trivial diffeomorphism near the Kerr black hole horizon. In this paper, we consider the retarded Green’s function and the absorption probability for the scalar and higher spin perturbations on a generic non-extreme Kerr black hole background, and perform their holographic calculations in terms of the warped CFT. This provide further evidence on the conjecture that the warped CFT is relevant to the microstate description of the Kerr black hole.

Abstract Recent studies on the holographic descriptions of Kerr black holes indicate that the conformal or the warped conformal symmetries are responsible for the Kerr black hole physics at both background and perturbation levels. In the present paper, we extend the validity of these studies to the case of accelerating Kerr black hole. By invoking a set of non-trivial diffeomorphisms near the horizon bifurcation surface of the accelerating Kerr black hole, the Dirac brackets among charges of the diffeomorphisms form the symmetry algebra of a warped CFT which consists of one Virasoro and one Kac-Moody algebra with central extensions. This provides the evidence for warped CFTs being possible holographic dual to accelerating Kerr black holes. The thermal entropy formula of the warped CFT fixed by modular parameters and vacuum charges reproduces the entropy of the rotating black hole with acceleration.

BackgroundEmerging evidence demonstrates that the gastrointestinal microbiome has the potential to be a biomarker in neoadjuvant chemoradiotherapy for colorectal cancer (CRC). Yet studies on the impact of the gastric microbiome (GM) on the response to neoadjuvant chemotherapy (NACT) are still scarce.MethodsForty-eight patients with gastric cancer participated in this retrospective study, and 16S rRNA sequencing was performed to evaluate formalin-fixed and paraffin-embedded (FFPE) tissue biospecimens and fresh-frozen tissues.ResultsIn this study, 16 bacterial taxa at different levels, including Bacillus, Anaerococcus, and Chloroflexi, were identified to be enriched before NACT in response (R) patients in group FFPE. In contrast, 6 bacterial taxa, such as Haemophilus, Veillonellaceae (Veillonella), etc. were enriched after NACT, in which we reported for the first time that the phylum Chloroflexi was enriched before NACT in R patients. Thirty-one bacterial taxa of Coriobacteriaceae, Ruminococcaceae, Veillonellaceae, and Lachnospiraceae were identified in group mucosa as being enriched in R patients. In comparison, 4 bacterial taxa dominated by the phylum Proteobacteria were enriched in NR patients. Notably, the family Veillonellaceae was found in both tissue samples, and the metabolic pathways, including the citrate cycle (TCA cycle) and various amino acids, including alanine, were found to be potentially predictive in both sample species.ConclusionThere are differences in the features of the GM for different NACT response results. The causal relationship deserves to be confirmed by further investigations.

Molybdenum (Mo) demonstrates excellent industrial application potentials in micro-nano devices, which are inevitably subjected to shock loads during their application under harsh service environments. This study employs molecular dynamics (MD) simulations to investigate the shock responses of Mo under high-strain loading conditions with respect to the effects of crystal orientations. The findings reveal that monocrystalline Mo, along the shock direction of [111], exhibits inhomogeneous microstructure features characterized by significantly high-density and high-temperature localized regions. Once the rarefaction wave is produced, the physical parameters, including density and lateral pressure, will gradually decrease while normal pressure retains a residual value. The us-up, Pzz-up, and Pzz-V/V0 relations along the shock loading direction of [111] show deviations from those of [001] and [110] directions, with this difference being more pronounced for Pzz-V/V0. The formation of dislocations and the magnitude of shear stress experienced within the post-shock region are strongly dependent on crystal orientations. Specifically, an elevated probability of dislocation formation was observed along the [110] direction. Moreover, the magnitude of shear stress induced by shock loading along the [001] and [110] directions can exceed that of the [111] direction when the shock velocity is 1.5 km/s. The MD simulation results can serve as a valuable supplement to the investigations of mechanical properties pertaining to Mo.

Potato (Solanum tuberosum L.) is the fourth largest food crop in the world. Low temperatures cause serious damage to potato plants every year, and freezing tolerance has become a hot spot in potato research. Galactinol synthase (GolS) is a key enzyme in the synthesis of raffinose family oligosaccharides (RFOs), and plays an important role in the response of plants to abiotic stress. In this study, the ScGolS1 gene from Solanum commersonii was cloned and introduced into the S. tuberosum cultivars ‘Atlantic’ and ‘Desiree’ via Agrobacterium-mediated transformation. Phenotyping assays showed that overexpression of ScGolS1 could significantly improve freezing tolerance in transgenic potato plants. Further physiological and biochemical experiments showed that the transgenic lines had lower relative conductivity, malondialdehyde content, and 3,3′-diaminobenzidine staining and a higher plant survival rate compared with wild type (WT) under cold stress. Moreover, the C-repeat binding factors (CBF1, CBF2 and CBF3), the downstream cold-responsive genes COR413 and COR47, and the ethylene-responsive factor (ERF) transcription factor genes ERF3, ERF4 and ERF6, which function in the ethylene signaling pathway, were all induced by freezing treatment and expressed at higher levels in the ScGolS1 overexpression lines compared with WT. Besides, the expression of some genes such as MIPS, STS and RS from the RFO metabolic pathway was up-regulated under cold stress, resulting in changes in the content of some soluble sugars. This indicated that ScGolS1 overexpression altered the sugar composition and enhanced freezing tolerance in transgenic potato by inducing the ethylene and CBF signaling pathways. These results provided theoretical support and genetic resources for freezing tolerance breeding in potato.

The timely injection of gangue slurry into the mining space formed after coal mining can scale up the disposal of gangue and control surface deformation. However, the waterproof effect of gangue slurry in the mining space remains unclear, necessitating urgent investigation into the permeability characteristics of compacted backfill bodies of gangue slurry under the action of overburden. In this study, a multi-field coupled seepage test system for backfill materials was developed based on Forchheimer’s nonlinear seepage law, and a laboratory preparation method for compacted backfill body (CBB) of gangue slurry after grouting and backfilling in mining space under pseudo-triaxial conditions was proposed. Additionally, the pressure bleeding characteristics of gangue slurry under the action of overburden were studied, the variation law of permeability of the CBB with the axial pressure, a particle size range, and cement dosage was revealed, and the determination method for the permeability level of the CBB and its optimization method were put forward. The research results indicate that there are obvious staged characteristics in the pressure bleeding changes in gangue slurry. Axial pressure, particle size range, and cement dosage all have a significant impact on the permeability of the CBB. The permeability level of the CBB of gangue slurry is within the range of poor permeability and extremely poor permeability. After backfilling into the mining space, gangue slurry exhibits a significant water-blocking effect.

Bicontinuous nanoporous metallic glasses (BNPMGs) are promising candidates in functional applications such as energy storage, sensors, and fuel cells. The time-dependent deformation strongly affects their long-term in-service performance. This study investigates the tensile creep behavior and its underlying deformation mechanisms of Cu50Zr50 BNPMGs through molecular dynamics simulations. The creep-recovery fatigue behavior is revealed. Our results manifest that both the transient and steady creep strengths increase with the solid fraction. The transient strength is larger for smaller ligament sizes, but the steady creep strength has very mild sensitivity to the ligament size. The generalized Kelvin model, consisting of two Kelvin units and one Maxwell unit connected in series, can accurately predict the creep and recovery curves. The rotation of individual ligaments, rather than atomic diffusion, is the dominant creep mechanism. During creep, the shear transformation zones are mainly developed on the ligament surface, and the strain in the ligament core is relatively smaller. The creep stress exponent has no definite relation with the creep mechanism and decreases with the increasing solid fraction. With the increase in the creep-recovery cycle number, the creep rate decreases, and the recovery procedure makes a milder impact on the creep response.

Abstract Background Studies on robotic total gastrectomy (RTG) are currently limited. This study aimed to compare the intraoperative performance as well as short‐ and long‐term outcomes of RTG and laparoscopic total gastrectomy (LTG). Methods A total of 969 patients underwent robotic (n = 161) or laparoscopic (n = 636) total gastrectomy between October 2014 and October 2021. The two groups of patients were matched 1:3 using the propensity score matching (PSM) method. The intraoperative performance as well as short‐ and long‐term outcomes of the robotic (n = 147) and the laparoscopic (n = 371) groups were compared. Results After matching, the estimated intraoperative blood loss was lower (80.51 ± 68.77 vs. 89.89 ± 66.12, p = 0.008), and the total number of lymph node dissections was higher (34.74 ± 12.44 vs. 29.83 ± 12.22, p

Abstract Objective To evaluate the multiple factors influencing the survival of elderly patients with locally advanced gastric cancer (LAGC) and develop and validate the novel nomograms for predicting the survival. Methods The clinical features of patients treated between 2000 and 2018 were collected and collated from the Surveillance, Epidemiology, and End Results (SEER) database and three medical centres in China, and the patients were randomly divided into a training cohort (3494), internal validation cohort (1497) and external validation cohort (841). Univariate and multivariate analyses of the prognostic values were performed to identify independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS), and two nomogram models were developed. Harrell’s concordance index (C-index) and calibration curves were employed to assess discrimination and calibration. Decision curve analysis (DCA) and receiver-operating characteristic (ROC) curves were utilized to investigate the clinical usefulness. Results In the SEER database, the 5-year OS of the patients was 31.08%, while the 5-year CSS of the patients was 44.09%. Furthermore, in the external validation set, the 5-year OS of the patients was 49.58%, and the 5-year CSS of these patients was 53.51%. After statistical analysis, nine independent prognostic factors of OS and CSS were identified, including age, race, tumour size, differentiation, TNM stage, gastrectomy type, lymph node metastasis (LNM), lymph node ratio (LNR) and chemotherapy. The C‐index (approximately 0.7) and calibration curve (close to the optimal calibration line) indicated satisfactory discrimination and calibration of the nomogram. DCA and ROC curves showed that the developed nomogram was superior to TNM stage. Conclusion The novel validated nomogram could accurately predict the prognosis of individual elderly patients with LAGC and guide the selection of clinical treatment measures.

Abstract Background 14–3-3 proteins are essential in regulating various biological processes and abiotic stress responses in plants. Although 14–3-3 proteins have been studied in model plants such as Arabidopsis thaliana and Oryza sativa, there is a lack of research on the 14–3-3 gene family in potatoes (Solanum tuberosum L.). Results A total of 18 14–3-3 genes encoding proteins containing a typical conserved PF00244 domain were identified by genome-wide analysis in potatoes. The St14–3-3 gene family members were unevenly distributed across the chromosomes, and gene structure analysis showed that gene length and intron number varied greatly among the members. Phylogenetic analysis of 14–3-3 proteins in potatoes and other plant species showed that they could be divided into two distinct groups (ε and non-ε). Members in the ε group tended to have similar exon-intron structures and conserved motif patterns. Promoter sequence analysis showed that the St14–3-3 gene promoters contained multiple hormone-, stress-, and light-responsive cis-regulatory elements. Synteny analysis suggested that segmental duplication events contributed to the expansion of the St14–3-3 gene family in potatoes. The observed syntenic relationships between some 14–3-3 genes from potato, Arabidopsis, and tomato suggest that they evolved from a common ancestor. RNA-seq data showed that St14–3-3 genes were expressed in all tissues of potatoes but that their expression patterns were different. qRT-PCR assays revealed that the expression levels of nearly all tested St14–3-3 genes were affected by drought, salt, and low-temperature stresses and that different St14–3-3 genes had different responses to these stresses. Conclusions In summary, genome-wide identification, evolutionary, and expression analyses of the 14–3-3 gene family in potato were conducted. These results provide important information for further studies on the function and regulation of St14–3-3 gene family members in potatoes.

High temperatures delay tuberization and decrease potato (Solanum tuberosum L.) yields. However, the molecular mechanisms and regulatory networks underlying tuberization under high temperatures remain largely unknown. Here, we performed the mRNA and miRNA sequencing of leaves and stems to identify genes and regulatory networks involved in tuberization under high temperatures. A total of 2804 and 5001 differentially expressed genes (DEGs) under high-temperature stress were identified in leaves and stems, respectively. These genes were significantly enriched in gene ontology terms regarding meristem development, the sucrose biosynthetic process, and response to heat. Meanwhile, 101 and 75 differentially expressed miRNAs (DEmiRNAs) were identified in leaves and stems, respectively. We constructed an interaction network between DEmiRNAs and DEGs, identifying 118 and 150 DEmiRNA–DEG pairs in leaves and stems, respectively. We found three miRNA–mRNA candidate modules involved in tuberization under high temperatures, including stu-miR8030-5p/StCPY714, stu-miR7981f-p5/StAGL8a, and stu-miR10532A/StAGL8b. Our study constructed an interaction network between miRNAs and target genes and proposes candidate miRNA–gene modules that regulate tuber formation under high temperatures. Our study provides new insights for revealing the regulatory mechanism of the high-temperature inhibition of tuberization and also provides gene resources for improving the heat tolerance in potatoes.

Abstract Background Pulmonary embolism is a common cause of cardiac arrest. Pulmonary embolism-induced cardiac arrest typically suffers from ischemic injuries to various organs, including the central nervous system. However, spinal cord infarction is a rare complication of pulmonary embolism-induced cardiac arrest. At present, there is no case report on the occurrence of spinal cord infarction secondary to pulmonary embolism-induced cardiac arrest without accompanied cerebral complications. Case presentation A 72-year-old woman with dyspnea and chest tightness was admitted to the emergency room. Cardiac arrest occurred within a short period after admission. Subsequent computed tomographic pulmonary angiography revealed multiple pulmonary thromboses, which were highly suspected to be the cause of cardiac arrest. Thrombolytic therapy with alteplase was given after the return of spontaneous circulation. Unfortunately, she was found to be paraplegic in both lower extremities after regaining consciousness. Spinal cord infarction was confirmed by thoracic magnetic resonance imaging. Conclusions Despite receiving high-quality cardiopulmonary resuscitation, patients with cardiac arrest are at high risk of ischemic injury to the central nervous system. After the recovery of consciousness, clinicians should pay more attention to preclude the possibility of spinal cord infarction.

The mining of coal resources is accompanied by a large amount of solid waste such as gangue, which seriously affects the ecological environment. The gangue grouting backfilling technique can achieve the dual goals of gangue disposal and surface deformation control by injecting gangue slurry into the underground. The bearing mechanical characteristics of gangue slurry directly affect the surface deformation control effect of the grouting backfilling technique. In this study, a loading simulation system of grouting backfilling materials was designed, uniaxial confined compression tests were conducted, and the self–bearing mechanism of large particle–sized gangue slurry with different fluidities under instantaneous and creep loading modes was investigated. Additionally, the mechanical characteristics of the compacted body (i.e., the gangue slurry after creep loading) were analyzed. The results indicate that the self–bearing process of gangue slurry can be divided into three stages: the rapid compression and drainage stage, the pore compaction and water bleeding stage, and the particle crushing and elastic–plastic deformation stage. The uniaxial compressive stress–strain curve of a compacted body can be classified into four stages: elastic stage, yield stage, reinforcement stage, and crushing stage, and the strength of the compacted body is affected by the loading time and fluidity of the slurry. When the slurry with a fluidity of 240 mm is subjected to constant pressure for 3 h, the compressive strength of the slurry reaches the maximum value of 4.98 MPa, and 13.1% stress damage occurs when the constant pressure reaches 4 h. This research provides a theoretical basis for the improvement of the proportion and bearing characteristics of gangue grouting materials.

Early tuberization, a short period from stolon occurrence to tuber formation, is one of the major characteristics of a good early-maturing potato cultivar, while the regulatory mechanism of tuberization time (TT) is still unclear. In this study, two tetraploid cultivars, Zhongshu 3 (Z3) and Zhongshu 18 (Z18), with short and long TT respectively, were examined to reveal regulatory genes related to TT using RNA sequencing of tissue samples taken during stolon occurrence, stolon swelling and tuber formation. Cluster analysis showed that the gene expression patterns at the stolon swelling and tuber formation stages were significantly different from those at stolon occurrence in both Z3 and Z18. Therefore, we screened the differentially expressed genes (DEGs) at stolon swelling and tuber formation and compared them to those at stolon occurrence. A total of 3 085 DEGs were specifically identified and analyzed according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment, and DEGs involved in starch and sucrose metabolism, plant hormone signal transduction and plant circadian clock were significantly enriched. The circadian clock genes were significantly differentially expressed between Z3 and Z18, revealing an important role for the plant circadian pathway in regulating TT. Furthermore, three candidate genes, StGI, StPRR and StEFM involved in circadian regulation and significantly differentially expressed between Z3 and Z18, were discovered and confirmed by qRT-PCR. The results provide valuable information for understanding the regulatory mechanisms of potato TT and represent a step toward breeding early-maturing potato cultivars.

Abstract Background The respiratory rate-oxygenation (ROX) index has been increasingly applied to predict the outcome of high-flow nasal cannula (HFNC) in pneumonia patients with acute hypoxemic respiratory failure (AHRF). However, its diagnostic accuracy for the HFNC outcome has not yet been systematically assessed. This meta-analysis sought to evaluate the predictive performance of the ROC index for the successful weaning from HFNC in pneumonia patients with AHRF. Methods A literature search was conducted on electronic databases through February 12, 2022, to retrieve studies that investigated the diagnostic accuracy of the ROC index for the outcome of HFNC application in pneumonia patients with AHRF. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy due to the varied cutoff values of the index. We observed the distribution of the cutoff values and estimated the optimal threshold with corresponding 95% confidential interval (CI). Results Thirteen observational studies comprising 1751 patients were included, of whom 1003 (57.3%) successfully weaned from HFNC. The ROC index exhibits good performance for predicting the successful weaning from HFNC in pneumonia patients with AHRF, with an AUHSROC of 0.81 (95% CI 0.77–0.84), a pooled sensitivity of 0.71 (95% CI 0.64–0.78), and a pooled specificity of 0.78 (95% CI 0.70–0.84). The cutoff values of the ROX index were nearly conically symmetrically distributed; most data were centered between 4.5 and 6.0, and the mean and median values were 4.8 (95% CI 4.2–5.4) and 5.3 (95% CI 4.2–5.5), respectively. Moreover, the AUHSROC in the subgroup of measurement within 6 h after commencing HFNC was comparable to that in the subgroup of measurement during 6–12 h. The stratified analyses also suggested that the ROC index was a reliable predictor of HFNC success in pneumonia patients with coronavirus disease 2019. Conclusions In pneumonia patients with AHRF, the ROX index measured within 12 h after HFNC initiation is a good predictor of successful weaning from HFNC. The range of 4.2–5.4 may represent the optimal confidence interval for the prediction of HFNC outcome.

Androgenetic alopecia is an androgen-dependent skin disorder that commonly affects hair follicle growth and hair loss. Gene therapy that can promote the proliferation and survival of hair follicle cells can be a potential choice for its cure. While transdermal application of therapeutic functional nucleic acids across the stratum corneum is quite difficult. Here, we first develop a transdermal agent for functional nucleic acid delivery using Triton X-100-modified low molecular weight polyethyleneimine (PEI-Triton-N, N ​= ​6 or 8). In vitro cell experiments demonstrate that the PEI-Triton-N conjugates can stably encapsulate and efficiently deliver plasmid DNA to hard-to-transfect keratinocyte HaCaT cells. Further mouse model studies show that PEI-Triton-6 can encapsulate and deliver growth arrest-specific protein 6 (Gas6) plasmid through transdermal administration. The transfected Gas6 prolongs the anagen status, inhibits the apoptosis of hair follicle cells, and further promotes the proliferation and differentiation of hair follicle cells. The PEI-Triton-6/pDNAGas6 complexes can obviously alleviate hair loss in androgenetic alopecia mice and provides a promising strategy for gene therapy via transdermal administration.

Phenotypic evaluation and molecular biotechnology are both important in the identification and utilization of crop germplasm resources. In this study, the phenotypic variation and genetic diversity of 149 main potato cultivars in China were investigated with 12 phenotypic traits and 24 SSR markers. The coefficient of variation of 12 phenotypic traits ranged from 12.11% to 156.93%. The results of SSR markers exhibited a relatively high level of genetic variation (Na =5.458 ± 1.499, Ne =3.300 ± 1.087, I =1.397 ± 0.298, Ho =0.797 ± 0.178, He = 0.660 ± 0.117, and PIC=0.702 ± 0.087). Population structure and phylogenetic tree analysis divided the varieties into three subgroups. The results indicated that ninety percent of the molecular variance was attributed to within-group differences, and the remaining 10% was attributed to variation among groups. Consistent with previous report, alleles of the STI032 marker were significantly associated with tuber starch content and growth period traits in the population. The results of this study could facilitate the utilization of potato germplasm resources, molecular genetic breeding and improvement.

Thermal barrier coatings (TBCs) play a crucial role in safeguarding aero-engine blades from high-temperature environments and enhancing their performance and durability. Accurate evaluation of TBCs’ porosity is of paramount importance for aerospace material research. However, existing evaluation methods often involve destructive testing or lack precision. In this study, we proposed a novel nondestructive evaluation method for TBCs’ porosity, utilizing terahertz time-domain spectroscopy (THz-TDS) and a machine learning approach. The primary objective was to achieve reliable and precise porosity evaluation without causing damage to the coatings. Multiple feature parameters were extracted from THz-TDS data to characterize porosity variations. Additionally, correlation analysis and p-value testing were employed to assess the significance and correlations among the feature parameters. Subsequently, the dung-beetle-optimizer-algorithm-optimized random forest (DBO-RF) regression model was applied to accurately predict the porosity. Model performance was evaluated using K-fold cross-validation. Experimental results demonstrated the effectiveness of our proposed method, with the DBO-RF model achieving high precision and robustness in porosity prediction. The model evaluation revealed a root-mean-square error of 1.802, mean absolute error of 1.549, mean absolute percentage error of 8.362, and average regression coefficient of 0.912. This study introduces a novel technique that presents a dependable nondestructive testing solution for the evaluation and prediction of TBCs’ porosity, effectively monitoring the service life of TBCs and determining their effectiveness. With its practical applicability in the aerospace industry, this method plays a vital role in the assessment and analysis of TBCs’ performance, driving progress in aerospace material research.

Lin28, a highly conserved carcinogenic protein, plays an important role in the generation of cancer stem cells, contributing to the unfavorable prognosis of cancer patients. This RNA binding protein specifically binds to pri/pre-microRNA (miRNA) lethal-7 (let-7), impeding its miRNA maturation. The reduced expression of tumor suppressor miRNA let-7 fosters development and progression-related traits such as proliferation, invasion, metastasis, and drug resistance. We report a series of miRNA-based Lin28A-miRNA proteolysis-targeting chimeras (Lin28A-miRNA-PROTACs) designed to efficiently degrade Lin28A through a ubiquitin-proteasome-dependent mechanism, resulting in up-regulation of mature let-7 family. The augmented levels of matured let-7 miRNAs further exert inhibitory effects on cancer cell proliferation and migration, and increase its sensitivity to chemotherapy. In a mouse ectopic tumor model, Lin28A-miRNA-PROTAC demonstrates a substantial efficacy in inhibiting tumor growth. When combined with tamoxifen, the tumors exhibit gradual regression. This study displays an effective miRNA-based PROTACs to degrade Lin28A and inhibit tumor growth, providing a promising therapeutic avenue for cancer treatment with miRNA-based therapy. [ABSTRACT FROM AUTHOR]

Background The endothelium is essential for maintaining vascular physiological homeostasis and the endothelial injury leads to the neointimal hyperplasia because of the excessive proliferation of vascular smooth muscle cells. Endothelial Foxp1 (forkhead box P1) has been shown to control endothelial cell (EC) proliferation and migration in vitro. However, whether EC‐Foxp1 participates in neointimal formation in vivo is not clear. Our study aimed to investigate the roles and mechanisms of EC‐Foxp1 in neointimal hyperplasia. Methods and Results The wire injury femoral artery neointimal hyperplasia model was performed in Foxp1 EC‐specific loss‐of‐function and gain‐of‐function mice. EC‐Foxp1 deletion mice displayed the increased neointimal formation through elevation of vascular smooth muscle cell proliferation and migration, and the reduction of EC proliferation hence reendothelialization after injury. In contrast, EC‐Foxp1 overexpression inhibited the neointimal formation. EC‐Foxp1 paracrine regulated vascular smooth muscle cell proliferation and migration via targeting matrix metalloproteinase‐9. Also, EC‐Foxp1 deletion impaired EC repair through reduction of EC proliferation via increasing cyclin dependent kinase inhibitor 1B expression. Delivery of cyclin dependent kinase inhibitor 1B‐siRNA to ECs using RGD (Arg‐Gly‐Asp)‐peptide magnetic nanoparticle normalized the EC‐Foxp1 deletion‐mediated impaired EC repair and attenuated the neointimal formation. EC‐Foxp1 regulates matrix metalloproteinase‐9/cyclin dependent kinase inhibitor 1B signaling pathway to control injury induced neointimal formation. Conclusions Our study reveals that targeting EC‐Foxp1‐matrix metalloproteinase‐9/cyclin dependent kinase inhibitor 1B pathway might provide future novel therapeutic interventions for restenosis.

The unreasonable accumulation of coal gangue in mining areas has caused serious resource waste and environmental pollution. The functional utilization of coal gangue with high added value has become the key to solving the previous problem. Coal gangue has inherent advantages such as large specific surface areas and rich active components, giving rise to an excellent precursor of electrode material in electrochemical energy storage devices. Herein, we, firstly, fabricated an amorphous SiCX/SiOX electrocatalyst with an abundant oxygen vacancy by acid–alkali activation derived from coal gangue for advanced Li-O2 batteries. The in-depth experimental results coupled with an in situ characterization analysis revealed that the amorphous SiCX/SiOX layer with abundant functional groups and oxygen vacancies on the surface of the activated gangue was conducive to promote structural stability and to improve the formation/decomposition efficiency of discharged products (Li2O2). Therefore, the LOBs based on the activated coal gangue electrocatalyst delivered a low overpotential of 1.12 V, high discharge capacity of 9156 mAh g−1, and an improved cyclic stability (more than 350 h). This work can provide a new approach for the development of new functions of coal gangue.

In this paper, we consider AdS3 with Compère-Song-Strominger (CSS) boundary conditions, under which the dual field theory is warped conformal field theory (WCFT), featuring a Virasoro-Kac-Moody algebra. We provide a holographic dual picture of the single interval entanglement entropy in WCFT in the bulk AdS3. We explicitly show that the bulk object captures the entanglement entropy in WCFT is a massive spinning particle's worldline that anchored on the boundary of the interval. Given the mass and spin of the particle as functions of quantum numbers of the twist operator in WCFT, the on-shell worldline action will match the entanglement entropy in WCFT.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and excessive accumulation of dysfunctional PVAT are hallmarks of pathogenesis after angioplasty. Recent genome-wide association studies reveal that single-nucleotide polymorphism (SNP) in MIA3 is associated with atherosclerosis-relevant VSMC phenotypes. However, the role of MIA3 in the vascular remodeling response to injury remains unknown. Here, we found that expression of MIA3 is increased in proliferative VSMCs and knockdown of MIA3 reduces VSMCs proliferation, migration, and inflammation, whereas MIA3 overexpression promoted VSMC migration and proliferation. Moreover, knockdown of MIA3 ameliorates femoral artery wire injury-induced neointimal hyperplasia and increases brown-like perivascular adipocytes. Collectively, the data suggest that MIA3 deficiency prevents neointimal formation by decreasing VSMC proliferation, migration, and inflammation and maintaining BAT-like perivascular adipocytes in PVAT during injury-induced vascular remodeling, which provide a potential therapeutic target for preventing neointimal hyperplasia in proliferative vascular diseases.

Discovering novel biomarkers that easily accessed is a key step towards the personalized medicine approach for gastric cancer patients. Integrin-β6 (ITGB6) is a subtype of integrin that is exclusively expressed on the surface of epithelial cells and is up-regulated in various tumors. In the present study, a retrospective cohort with 135 gastric cancer patients and a prospective cohort with 34 gastric cancer patients were constructed, ITGB6 expression were detected in both the serum specimens and the tissue specimens. Detailed clinicopathological parameters as well as patients’ survival were recorded. A nomogram including ITGB6 expression was also constructed and validated to predict the prognosis of gastric cancer patients. Results showed that serum ITGB6 expression was obviously increased and associated with tumor stage in gastric cancer patients, serum ITGB6 expression was relatively high in patients with liver metastasis. High ITGB6 expression indicated a poor prognosis, and nomogram including serum ITGB6 expression could predict the prognosis of gastric cancer patients effectively. Moreover, serum ITGB6 expression was associated with ITGB6 expression in tumor tissues. Furthermore, combined serum ITGB6 and CEA levels contributed to the risk stratification and prognostic prediction for gastric cancer patients. In addition, the serum expression of ITGB6 decreased significantly after radical surgery, and a new rise in serum ITGB6 expression indicated tumor recurrence or progression. The present study identified a novel serum biomarker for the risk stratification, prognostic prediction and surveillance of gastric cancer patients.

Late blight, caused by the oomycete Phytophthora infestans, is the most devastating disease in potato-producing regions of the world. Cultivation of resistant varieties is the most effective and environmentally friendly way to control potato late blight disease, and identification of germplasms with late blight resistance and clarification their genetic relationship would promote the development of the resistant varieties. In this study, a diverse population of 189 genotypes with potential late blight resistance, consisting of 20 wild species and cultivated Solanum tuberosum Andigenum group and Chilotanum group, was screened for the presence of late blight resistance by performing challenge inoculation with four Phytophthora infestans isolates including one 13_A2 isolate, CN152. Ten elite resources with broad-spectrum resistance and 127 with isolate-specific resistance against P. infestans were identified. To improve the available gene pool for future potato breeding programs, the population was genotyped using 30 simple sequence repeat (SSR) markers covering the entire potato genome. A total of 173 alleles were detected with an average of 5.77 alleles per locus. Structure analysis discriminated the 189 potato genotypes into five populations based on taxonomic classification and genetic origin with some deviations. There was no obvious clustering by country of origin, ploidy level, EBN (endosperm balance number) value, or nuclear clade. Analysis of molecular variance showed 10.08% genetic variation existed among populations. The genetic differentiation (Fst) ranged from 0.0937 to 0.1764, and the nucleotide diversity (π) was 0.2269 across populations with the range from 0.1942 to 0.2489. Further genotyping of 20K SNP array confirmed the classification of SSRs and could uncover the genetic relationships of Solanum germplasms. Our results indicate that there exits abundant genetic variation in wild and cultivated potato germplasms, while the cultivated S. tuberosum Chilotanum group has lower genetic diversity. The phenotypic and genetic information obtained in this study provide a useful guide for hybrid combination and resistance introgression from wild gene pool into cultivated species for cultivar improvement, as well as for germplasm conservation efforts and resistance gene mining.

Late blight, caused by Phytophthora infestans (P. infestans), is a devastating disease in potato worldwide. Our previous study revealed that the Solanum andigena genotype 03112-233 is resistant to P. infestans isolate 90128, but susceptible to the super race isolate, CN152. In this study, we confirmed by diagnostic resistance gene enrichment sequencing (dRenSeq) that the resistance of 03112-233 toward 90128 is most likely based on a distinct new R gene(s). To gain an insight into the mechanism that governs resistance or susceptibility in 03112-223, comparative transcriptomic profiling analysis based on RNAseq was initiated. Changes in transcription at two time points (24 h and 72 h) after inoculation with isolates 90128 or CN152 were analyzed. A total of 8,881 and 7,209 genes were differentially expressed in response to 90128 and CN152, respectively, and 1,083 differentially expressed genes (DEGs) were common to both time points and isolates. A substantial number of genes were differentially expressed in an isolate-specific manner with 3,837 genes showing induction or suppression following infection with 90128 and 2,165 genes induced or suppressed after colonization by CN152. Hierarchical clustering analysis suggested that isolates with different virulence profiles can induce different defense responses at different time points. Further analysis revealed that the compatible interaction caused higher induction of susceptibility genes such as SWEET compared with the incompatible interaction. The salicylic acid, jasmonic acid, and abscisic acid mediated signaling pathways were involved in the response against both isolates, while ethylene and brassinosteroids mediated defense pathways were suppressed. Our results provide a valuable resource for understanding the interactions between P. infestans and potato.

Abstract Background Proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) have been widely used as stress ulcer prophylaxis (SUP) in critically ill patients, however, its efficacy and safety remain unclear. This study aimed to assess the effect of SUP on clinical outcomes in critically ill adults. Methods Literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane database of clinical trials for randomized controlled trials (RCTs) that investigated SUP, with PPI or H2RA, versus placebo or no prophylaxis in critically ill patients from database inception through 1 June 2019. Study selection, data extraction and quality assessment were performed in duplicate. The primary outcomes were clinically important gastrointestinal (GI) bleeding and overt GI bleeding. Conventional meta-analysis with random-effects model and trial sequential analysis (TSA) were performed. Results Twenty-nine RCTs were identified, of which four RCTs were judged as low risk of bias. Overall, SUP could reduce the incident of clinically important GI bleeding [relative risk (RR) = 0.58; 95% confidence intervals (CI): 0.42–0.81] and overt GI bleeding (RR = 0.48; 95% CI: 0.36–0.63), these results were confirmed by the sub-analysis of trials with low risk of bias, TSA indicated a firm evidence on its beneficial effects on the overt GI bleeding (TSA-adjusted CI: 0.31–0.75), but lack of sufficient evidence on the clinically important GI bleeding (TSA-adjusted CI: 0.23–1.51). Among patients who received enteral nutrition (EN), SUP was associated with a decreased risk of clinically important GI bleeding (RR = 0.61; 95% CI: 0.44–0.85; TSA-adjusted CI: 0.16–2.38) and overt GI bleeding (RR = 0.64; 95% CI: 0.42–0.96; TSA-adjusted CI: 0.12–3.35), but these benefits disappeared after adjustment with TSA. Among patients who did not receive EN, SUP had only benefits in reducing the risk of overt GI bleeding (RR = 0.37; 95% CI: 0.25–0.55; TSA-adjusted CI: 0.22–0.63), but not the clinically important GI bleeding (RR = 0.27; 95% CI: 0.04–2.09). Conclusions SUP has benefits on the overt GI bleeding in critically ill patients who did not receive EN, however, its benefits on clinically important GI bleeding still needs more evidence to confirm.

Abstract We derive a universal formula for the asymptotic growth of the mean value of three-point coefficient for Warped Conformal Field Theories (WCFTs), and provide a holographic calculation in BTZ black holes. WCFTs are two dimensional quantum field theories featuring a chiral Virasoro and U(1) Kac-Moody algebra, and are conjectured to be holographically dual to quantum gravity on asymptotically AdS3 spacetime with Compère- Song-Strominger boundary conditions. The WCFT calculation amounts to the calculation of one-point functions on torus, whose high temperature limit can be approximated by using modular covariance of WCFT, similar to the derivation of Cardy formula. The bulk process is given by a tadpole diagram, with a massive spinning particle propagates from the infinity to the horizon, and splits into particle and antiparticle which annihilate after going around the horizon of BTZ black holes. The agreement between the bulk and WCFT calculations indicates that the black hole geometries in asymptotically AdS3 spacetimes can emerge upon coarse-graining over microstates in WCFTs, similar to the results of Kraus and Maloney in the context of AdS/CFT [1].

Abstract Various aspects of warped conformal field theories (WCFTs) are studied including entanglement entropy on excited states, the Rényi entropy after a local quench, and out-of-time-order four-point functions. Assuming a large central charge and dominance of the vacuum block in the conformal block expansion, (i) we calculate the single-interval entanglement entropy on an excited state, matching previous finite temperature results by changing the ensemble; and (ii) we show that WCFTs are maximally chaotic, a result that is compatible with the existence of black holes in the holographic duals. Finally, we relax the aforementioned assumptions and study the time evolution of the Rényi entropy after a local quench. We find that the change in the Rényi entropy is topological, vanishing at early and late times, and nonvanishing in between only for charged states in spectrally-flowed WCFTs.

Nanog is a homeodomain-containing transcription factor, and it plays a vital role in maintaining the pluripotency of embryonic stem cells. Nanog’s function has been well studied in many species. However, there is lack of reporting on the Nanog gene in reptile. Here, we identified a 1032 bp cDNA sequence of a Nanog gene in Pelidiscus sinensis, known as PsNanog. PsNanog has a highly conserved HD domain and shares a high identity with that of Chelonia mydas and the lowest identity with Oryzias latipes. Similarly, PsNanog presented a tight cluster with C. mydas Nanog, but was far from those of teleosts. Additionally, we cloned a length of 1870 bp PsNanog promoter. Dual luciferase assay showed that the DNA fragment of −1560 to +1 exhibited a high promoter activity. The RT-PCR and RT-qPCR results showed that PsNanog was predominantly expressed in ovary, and then in testis. The in situ hybridization and immunohistochemical analysis showed that PsNanog was expressed in the early primary oocytes and the cytoplasm of the cortical region of stage VIII oocytes in ovary, and distributed in most stages of germ cells in testis. Collectively, the results imply that PsNanog probably has the conserved function in regulating germ cell development across phyla and is also a pluripotent cell gene and expressed in germ cells, which is similar to that in teleosts and mammals.

The temporal activation of siRNA provides a valuable strategy for the regulation of siRNA activity and conditional gene silencing. The bioorthogonal bond-cleavage reaction of benzonorbonadiene and tetrazine is a promising trigger in siRNA temporal activation. Here, we developed a new method for the bio-orthogonal chemical activation of siRNA based on the tetrazine-induced bond-cleavage reaction. Small-molecule activatable caged siRNAs were developed with the 5′-vitamin E-benzonobonadiene-modified antisense strand targeting the green fluorescent protein (GFP) gene and the mitotic kinesin-5 (Eg5) gene. The addition of tetrazine triggered the reaction with benzonobonadiene linker and induced the linker cleavage to release the active siRNA. Additionally, the conditional gene silencing of both exogenous GFP and endogenous Eg5 genes was successfully achieved with 5′-vitamin E-benzonobonadiene-caged siRNAs, which provides a new uncaging strategy with small molecules.

Maturity is a key trait for breeders to identify potato cultivars suitable to grow in different latitudes. However, the molecular mechanism regulating maturity remains unclear. In this study, we performed a grafting experiment using the early-maturing cultivar Zhongshu 5 (Z5) and the late-maturing cultivar Zhongshu 18 (Z18) and found that abscisic acid (ABA) and salicylic acid (SA) positively regulate the early maturity of potato, while indole-3-acetic acid (IAA) negatively regulated early maturity. A total of 43 long-distance transport mRNAs are observed to be involved in early maturity, and 292 long-distance transport mRNAs involved in late maturity were identified using RNA sequencing. Specifically, StMADS18, StSWEET10C, and StSWEET11 are detected to be candidate genes for their association with potato early maturity. Metabolomic data analysis shows a significant increase in phenolic acid and flavonoid contents increased in the scion of the early-maturing cultivar Z5, but a significant decrease in amino acid, phenolic acid, and alkaloid contents increased in the scion of the late-maturing cultivar Z18. This work reveals a significant association between the maturity of tetraploid cultivated potato and long-distance transport signal molecules and provides useful data for assessing the molecular mechanisms underlying the maturity of potato plants and for breeding early-maturing potato cultivars.

The complexity of the Portevin-Le Chatelier (PLC) effect in an Al alloy at different temperatures was analyzed by modified multiscale entropy. The results show that three evolutions of entropy with scale factor, i.e., near zero, monotonically increasing and peak-shape, were observed corresponding to the smooth curves, type-A serrations and type-B/-C serrations, respectively. The scale factor at the peak was one-third of the average serration period. The sample entropy increased initially and then decreased with temperature, which was opposite to the critical strain. It is also suggested that the type-A serrations corresponded to self-organized criticality and the type-B/-C serrations corresponded to chaos through the evolutions of entropy with scale factor.

China is a major coal producing country, and also one of the countries which has the most serious coal mine accidents around the world. As a result of geological conditions, underground mining is the main way that coal is exploited in China; serious underground disasters and the corresponding fatality rate are much higher than is the case for surface mining. Although safer modern underground mining methods have been introduced across China, accidents still lead to fatalities and the loss of revenue in some mines. It is important to establish a georeferenced coal mine disasters (CMD) database to aid researchers and decision makers in better understanding the spatio-temporal distribution of such accidents across in China. This study has proposed a method to develop a georeferenced spatio-temporal CMD database via a geographic information system (GIS) platform based on statistical data released by the State Administration of Coal Mine Safety (SACMS) for the period between 2000 and 2015. The different levels and spatio-temporal characteristics of coal mining accidents were analyzed, and the space-time scan statistic permutation (STSSP) model was carried out to detect the CMD clusters; and finally, a spatio-temporal cluster analysis of Chinese coal mining accidents in 2000 and 2015 was conducted.

Abstract Warped conformal field theory (WCFT) is a two dimensional quantum field theory whose local symmetry algebra consists of a Virasoro algebra and a U(1) Kac-Moody algebra. In this paper, we study correlation functions for primary operators in WCFT. Similar to conformal symmetry, warped conformal symmetry is very constraining. The form of the two and three point functions are determined by the global warped conformal symmetry while the four point functions can be determined up to an arbitrary function of the cross ratio. The warped conformal bootstrap equation are constructed by formulating the notion of crossing symmetry. In the large central charge limit, four point functions can be decomposed into global warped conformal blocks, which can be solved exactly. Furthermore, we revisit the scattering problem in warped AdS spacetime (WAdS), and give a prescription on how to match the bulk result to a WCFT retarded Green’s function. Our result is consistent with the conjectured holographic dualities between WCFT and WAdS.

Fly ash cement is used to solidify marine clay to prepare marine-clay-based cemented paste backfill (MCCPB) to fill the underground goaf of mines, which not only utilizes solid waste such as fly ash and marine clay, but also controls surface subsidence and protects the environment. To simulate the complex underground mine water environment of the filling body, a dry-wet cycle aquatic environment test under different material ratios and curing ages was designed. The water absorption and unconfined compression strength (UCS) of MCCPB with curing ages of 7 and 28 days under the action of 0, 1, 3, and 7 dry-wet cycles were investigated. The results indicate as the number of dry-wet cycles increases, the surface of MCCPB becomes significantly rougher, and the water content and the solid mass decrease accordingly. Different ratios and curing ages of MCCPB in dry-wet cycles of the UCS tend first to increase, then decrease. Meanwhile, the stress-strain curve of the specimen shows that the trend in the elastic modulus is consistent with that of UCS (first increasing, then decreasing), and that, the minimum UCS value of the specimen still meets the early strength requirements of cemented paste backfill in coal mine geothermal utilization. On the one hand, it proves the feasibility of fly ash cement-solidified marine clay for use as cemented paste backfill in coal mines; on the other hand, it also expands the available range of cemented paste backfill materials in coal mines.

GaoFen-4(GF-4) is the highest spatial resolution Earth observation satellite operating in geosynchronous orbit. Its fixed Earth observation location, rapid responsiveness, and wide observation range make it popular in disaster and emergency monitoring. To evaluate the GF-4 image quality in detail on a long-term basis, this study analyzes the image quality after the commissioning phase by focusing on ground sample distance (GSD) and geometric and radiometric quality. The theoretical calculation, geometric and radiometric measurements, and on-site experiments results show that (1) the GSD of the GF-4 image is ~50 m at the nadir point and increases gradually with the distance away from the nadir point, (2) most external geometric errors are within the design requirements of 4 km despite some exceeding the limit, and the internal geometric errors are tested within 1 pixel, and (3) image sharpness is generally stable but varies with the atmosphere condition and imaging time, and the radiometric response gradually degrades at the rate of less than 5.5% per year.