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In vivobioimaging using shortwave infrared (SWIR) (1000–2000 nm) molecular dyes enables deeper penetration and higher contrast compared to visible and near-infrared-I (NIR-I, 700–900 nm) dyes. Developing new SWIR molecules is still quite challenging. This study developed SRHCYs, a panel of fluorescent dyes based on hemicyanine, with adjustable absorbance (830–1144 nm) and emission (886–1217 nm) wavelength. The photophysical attributes of these dyes are precisely tailored by strengthening the donor parts and extending polymethine chains. SRHCY-3, with its clickable azido group, was chosen for high-performance imaging of blood vessels in living mice, enabling the precise detection of brain and lung cancer. The combination of these probes achieved in vivomulticolor imaging with negligible optical crosstalk. This report presents a series of SWIR hemicyanine dyes with promising spectroscopic properties for high-contrast bioimaging and multiplexing detection.

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

ABSTRACTThis study analyzed the application effect of remimazolam besylate combined with sufentanil on percutaneous vertebroplasty (PVP). Forty elderly patients with osteoporotic vertebral compression fractures (OVCF) were randomly divided into sufentanil (A group) and remimazolam besylate + sufentanil groups (B group). A group was given sufentanil anesthesia, B group was given remimazolam besylate combined with sufentanil anesthesia. Heart rate (HR), mean arterial pressure (MAP), saturation of pulse oxygen (SpO2) and Ramsay sedation score were recorded at different time points, including T0 (before administration), T1 (beginning of surgery), T2 (perfusion of bone cement) and T3 (end of surgery). HR, MAP, SpO2 were continuously monitored by electrocardiogram monitor. The visual analogue scale (VAS) pain scores of the two groups were recorded at before anesthesia and immediately after surgery. The adverse reactions (AR) were observed, including respiratory depression, nausea and vomiting, and restlessness during the recovery period. Compared with group A, MAP was increased at T2 and T3 time points in group B. Ramsay sedation scores at T2 time points in group B were higher than that in group A. The VAS score of immediately after operation and incidence of AR of group B was lower than that of group A. In elderly patients undergoing PVP, remimazolam besylate combined with sufentanil has no obvious effect on patients’ respiratory parameters, with clear analgesic and sedative effects and low incidence of AR, which is worthy of promotion.

Recent studies found the intrusion and retention of exogenous fine particles into joints, but epidemiological data for long- and intermediate-term exposure associations are scare. Here, all urban working, retired employee, and rural residents (16.78 million) in Beijing from January 1, 2011 to December 31, 2019 were included to investigate the effects of long- and intermediate-term ambient particulate exposure on development of osteoarthritis. We identified 1,742,067 participants as first-visit patients with osteoarthritis. For each interquartile range increase in annual PM2.5(23.32 μg/m3) and PM10(23.92 μg/m3) exposure concentration, the pooled hazard ratios were respectively 1.238 (95% CI: 1.228, 1.249) and 1.178 (95% CI: 1.168, 1.189) for first osteoarthritis outpatient visits. Moreover, age at first osteoarthritis outpatient visits significantly decreased by 4.52 (95% CI: 3.45 to 5.40) days per μg/m3for annual PM2.5exposure at below 67.85 μg/m3. Finally, among the six constituents analyzed, black carbon appears to be the most important component associated with the association between PM2.5exposure and the three osteoarthritis-related outcomes.

This article proposes a cascaded optical system composed of two identical porous silicon (Psi) microcavity structures and investigates its sensing characteristics for DNA detection. In the cascaded optical system, functionalization treatment is performed on only one of the microcavity structures, and then this microcavity structure is enabled to be in contact with the analyte, while the other microcavity structure is kept not in contact with the analyte, to achieve the purpose of changing the light path, that is, changing the incident angle of light onto the microcavity which is contacted with the analyte. The sensor’s response can be obtained by measuring changes in the defect peak varying with the incident angle. Results of numerical simulations and experiments show that the cascade structure can effectively reduce the full-width at half-maxima (FWHM) of the defect peak. By utilizing the change of angular position of the defect peak, detection on an eight-base pair DNA is achieved with a detection limit of 77 nM.

We present a multidimensional inversion methodology for loop source time-domain electromagnetic data. The developed algorithm is a robust, efficient, and user-oriented tool for the multidimensional inversion of typical loop source time-domain electromagnetic configurations. A time-domain finite volume (FV) method and a direct solver are utilized for solving the 3-D forward problem, while the iterative Gauss–Newton (GN) optimization method is implemented for the inversion kernel. The code is parallelized for calculating multiple sources simultaneously to accelerate the inversion. Based on different exploration tasks, we present three different inversion experiments on typical field scales for commonly used loop source TEM configurations. These examples verify the effectiveness and benchmark the developed 3-D algorithm. Considering that TEM data are often gathered along profiles, we carried out an analysis using the 3-D inversion algorithm for 2-D data by adjusting the model roughness along the different domain directions, which seem to sufficiently constrain but not over-regularize the model along the strike direction to retrieve the true model structure. Besides using the vertical signal component for large-scale moving and fixed loop configurations, the horizontal components are also included in the 3-D inversion. The inversion algorithm is further verified with dense boat-towed central loop TEM data recorded on a volcanic lake in the Azores, Portugal. The reconstructed model is consistent along the profile line and the main features agree with the 1-D stitched models. Moreover, the 3-D model depicts additional reasonable features not visible in the 1-D models.

The MYB4 transcription factor family regulates plant traits. However, their overexpression often results in undesirable side effects like growth reduction. We have reported a green tea (Camellia sinensis) MYB4 transcription factor (CsMYB4) that represses the phenylpropanoid and shikimate pathways and stunts plant growth and development. In the current study, we observed that in CsMYB4atransgenic tobacco (Nicotiana tabacum) plants, primary metabolism was altered, including sugar and amino acid metabolism, which demonstrated a pleiotropic regulation by CsMYB4a. The CsMYB4atransgenic tobacco plants had improved drought tolerance, which correlated to alterations in carbohydrate metabolism and an increase in proline content, as revealed by metabolic profiling and transcriptomic analysis. To mitigate the undesirable repressive side effects on plant traits, including dwarfism, shrunken leaves, and shorter roots of CsMYB4atransgenic plants, we deleted the C4 domain of CsMYB4a to obtain a CsMYB4a-DC4 variant and then overexpressed it in transgenic plants (CsMYB4a-DC4). These CsMYB4a-DC4 plants displayed a normal growth and had improved drought tolerance. Metabolite analysis demonstrated that the contents of carbohydrates and proline were increased in these transgenic plants. Our findings suggest that  an approriate modification of TFs can generate novel crop traits, thus providing potential agricultural benefits and expanding its application to various crops.

Based on the experiment and first-principles calculation methods, the evolution of microstructure, mechanical properties and electrical conductivity of low-carbon steel were investigated at various annealing conditions. The results show that with the increase of annealing temperature, the morphology of ferrite matrix grain undergoes a transformation from narrow and long fibrous to, accompanied by the continuous growth in size. The strength of α-fibre texture is reduced continuously while the strength of γ-fibre texture increases evidently. The tensile and conductivity testing results indicate that with the increase of annealing temperature, both the yield strength and tensile strength of the steel decrease, while the elongation exhibits an opposite tendency due to the continuous growth of ferrite grains and dissolution of tertiary cementites. Additionally, the electrical conductivity increases because the reduction in the number of grain boundaries weakens their scattering ability to electronic waves. The first-principles calculation results indicate that with increasing distance to the interface, the segregation energy of Nb atom in ferrite matrix is reduced, as well as the interfacial energy of the structure is also decreased. The interface segregation preference of Nb atoms induces the transfer of charge, which is beneficial to enhance the conductivity of the ferrite matrix.

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The radial basis function partition of unity (RBF-PU) method is used to solve various types of partial differential equations, since it is based on scattered node sets that can be easily implemented. In this paper, a framework for the RBF-PU method is proposed to solve the convection–diffusion equations on closed surfaces. The surface gradient and Laplace–Beltrami operators are discretized based on the RBF-PU method using the polyharmonic spline radial basis functions augmented with polynomials. Since the RBF-PU method is a local meshless method, an advantage is that the differential matrix obtained by discretizing the surface differential operator is sparse. Additionally, solving convection-dominated problems or transport equations directly using RBF-PU method can produce numerical oscillations. For this reason, we add hyperviscosity term to improve the stability of the RBF-PU method for solving the convection–diffusion equations on surfaces, and numerical experiments show that such a combination has higher-order convergence rates. Finally, we solve the discontinuous source problem on the torus and the Turing system with convection term on different surfaces to demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) overexpressed on prostate cancer (PCa) cells is a satisfactory theranostic target in PCa. To seek novel non-glutamate-urea-based PSMA inhibitors by the strategy of bioisosterism, 10 ligands were designed, synthesized, and characterized. Among them, ligands 17, 18, and 21–24bearing the squaramic acid moiety proved to be potent PSMA inhibitors, with Kivalues ranging from 0.40 to 2.49 nM, which are comparable or higher in inhibitory potency compared to previously reported glutamate-urea-based inhibitors. Docking studies of 15, 17, and 19were carried out to explore their binding mode in the active site of PSMA. Two near-infrared (NIR) probes, 23(λEM= 650 nm) and 24(λEM= 1088 nm), displayed favorable in vivo NIR imaging and successful NIR-II image-guided tumor resection surgery in PSMA-positive tumor-bearing mice, which demonstrated the effectiveness of these new squaramic acid-based inhibitors.

ABSTRACTThis study investigated the effects of ibandronate (IBN) on cardiomyopathy remodeling in diabetic rats. A rat model of diabetic cardiomyopathy (DCM) was established by supplementing them with a high-calorie diet combined with a low dose of streptozotocin (STZ). The diabetic rats received IBN (5 µg/kg per day) or normal saline subcutaneously for 16 weeks. The hematoxylin and eosin (H&E) and Masson’s trichrome staining were performed for evaluating the myocardial morphologies of the rats. Echocardiography and cardiac catheter were performed to assess their cardiac functional parameters. The protein levels of connective tissue growth factor (CTGF), farnesyl pyrophosphate synthase (FPPS), and mitogen-activated protein kinase (MAPK) were determined using Western blot analysis. RhoA activation was detected using a small GTP protease-linked immunosorbent assay (GLISA). The diabetic rats showed the development of moderate hyperglycemia, insulin resistance, hyperlipidemia, myocardial fibrosis, FPPS overexpression, cardiac systolic, and diastolic dysfunction. Inhibiting the FPPS could ameliorate myocardial hypertrophy and fibrosis. These anatomical findings were accompanied by a significant improvement in heart function. Furthermore, the inhibition of FPPS, the increased activation of RhoA, and phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 in DCM decreased significantly with the treatment of IBN. This study for the first time demonstrated that the upregulation of FPPS expression might be involved in diabetic myocardial remodeling in diabetes mellitus (DM). In addition, IBN might exert its inhibitory effects on myocardial tissue remodeling by suppressing the RhoA/ERK1/2 and RhoA/p38 MAPK pathways in DCM.

In the present study, a finite element impact model was developed and analyzed using commercial FEM code ANSYS® and then validated via a drop-weight impact experiment. Moreover, double-impactor impact models were designed and developed with different impact distribution and locations of two impactors to compare impact properties. A total of 18 impact scenarios comprised of asymmetric and symmetric types were performed. The effect of impact location on the impact resistance force and duration time was investigated: the closer the impact point is to the fabric center, the longer the impact duration time. In addition, the effect of impact location on impactor failure deflection was also investigated and it was concluded that regardless of the symmetric or asymmetric impact scenario, the smaller the average distance between the impact location of the two impactors from the fixed boundary, the smaller the overall average failure deflection that occurs. The relevance of impact location and fabric energy absorption capacity was also identified. Furthermore, the effect of impact location on fabric stress distribution and transverse deformation and of the variation of the impact velocity on fabric impact behaviors were investigated. These findings will provide important guidance for engineering soft body armor and composite materials.

The high accumulation of galloylated flavan-3-ols in Camellia sp. is a noteworthy phenomenon. We identified a flavan-3-ol galloylation-related functional gene cluster in tannin-rich plant Camellia sp., which included UGT84A22and SCPL-ATgene clusters. We investigated the possible correlation between the accumulation of metabolites and the expression of SCPL-ATsand UGT84A22. The results revealed that C. sinensis, C. ptilophylla, and C. oleiferaaccumulated galloylated cis-flavan-3-ols (EGCG), galloylated trans-flavan-3-ols (GCG), and hydrolyzed tannins, respectively; however, C. nitidissimadid not accumulate any galloylated compounds. C. nitidissimaexhibited no expression of SCPL-ATor UGT84A22, whereas the other three species of Camelliaexhibited various expression patterns. This indicated that the functions of the paralogs of SCPL-ATvary. Enzymatic analysis revealed that SCPL5was neofunctionalized as a noncatalytic chaperone paralog, a type of chaerone-like protein, associating with flavan-3-ol galloylation; moreover, CsSCPL4was subfunctionalized in association with the galloylation of cis- and trans-flavan-3-ols. In C. nitidissima, an SCPL4homolog was noted with mutations in two cysteine residues forming a disulfide bond, which suggested that this homolog was defunctionalized. The findings of this study improve our understanding of the functional diversification of SCPLparalogs in Camellia sp.

When clustering gene expression, it is expected that correlation coefficients of genes in the same clusters are high, and that gene ontology (GO) enrichment analysis of most clusters will be significant. However, existing short-term gene expression clustering algorithms have limitations. To address this problem, we proposed a novel clustering process based on angular features for short-term gene expression. Our method (named AngClust) uses angular features to indicate the change of trend in gene expression levels at two neighboring time points. The changes of angles at multiple time points reflects the change of trend of the overall expression levels. Such changes are used to measure whether the expression trends of different genes are similar. To obtain functionally significant clusters from the clustering results, we evaluated numbers of genes in clusters, average correlation coefficient, fluctuation, and their correlation with GO term enrichment. The efficacy of AngClust outperform two other measures, Euclidean distance (ED) and dynamic time warping of correlation (DTW), on a dataset of yeast gene expression. The ratios of GO and pathway term-enriched of clusters of AngClust is higher than or equal to that of STEM and TMixClust on human, mouse, and yeast time series of gene expression.

ABSTRACT Rebar corrosion is a major deterioration mechanism for reinforced concrete and other cementitious materials, which is often resulted from the ingress of chloride ions from deicer applications or marine [...]

ABSTRACT This work aims to validate the design assumptions by the California Department of Transportation in order to better define the strategies used to design concrete structures with adequate corrosion [...]

In this paper, we design a new framework of direct radial basis function partition of unity (D-RBF-PU) method to solve parabolic equation on surface with and without boundary. Resort to the tangent plane approach, the proposed method avoids dealing with complex surface differentiation operators, and only needs to approximate the standard differentiation operators on the two-dimensional tangent space compared with the existing RBF-PU methods on surface. The new meshfree method is called the "D-RBF-PU tangent plane" method. Additionally, for the surface parabolic equation with Neumann boundary condition, the ghost node technique is considered to avoid the concentration of test nodes on one side of the patch near the boundary and improve the computational accuracy. Numerical examples are performed to confirm the convergence and the eigenvalue stability and applications to the Fitzhugh–Nagumo model and Schnakenberg model on different surfaces demonstrate the efficiency of the proposed method. [ABSTRACT FROM AUTHOR]

The development of new polymerization routes to afford N-heterocyclic polymers is of vital importance and highly desired for various practical applications. Herein, a facile and efficient polyannulation reaction of dual-activated alkyne and pyridines was developed to construct novel N-heterocyclic poly(quinolizine)s. This polymerization can proceed smoothly under catalyst-free conditions with 100% atom utilization to furnish poly(quinolizine)s with high molecular weights (up to 34,100) and well-defined structures in acceptable yields. The resulting polymers show good solubility, high thermal stability and strong red emission. Moreover, the prepared poly(quinolizine)s exhibit low cytotoxicity and can selectively label lysosomes in live cells. Considering the remarkable advantages of readily available raw materials, mild polymerization conditions, atom economy, and excellent product performance, this new and efficient polymerization tool will open up enormous opportunities for preparing functional N-heterocyclic polymers.

In practice, the volatile organic compounds (VOCs) pollution can exist when refueling due to the properties of the gasoline, low viscosity and high saturated-vapor pressure. A new gasoline vapor recovery system involving frequency conversion technology and machine learning is developed to cope with this problem. In the proposed system, firstly, the pumping capacity of the vacuum pump is evaluated, and test shows an almost linear relationship between suction volume and frequency. Then, the Multi-Layer Perception (MLP) neural network and the support vector regression (SVR) are employed to predict the gas-liquid ratio, and the numerical examples are presented to prove the high prediction accuracy of the MLP and SVR, respectively, where the MLP neural network has better generalization ability. Finally, compared with the two gasoline vapor recovery systems based on the 1: 1 fixed control model and the PID control model, respectively, the gasoline vapor recovery efficiency is improved significantly by the new gasoline vapor recovery system.

Flavonoid glycosides are typical bitter and astringent tasting compounds that contribute to the taste of tea beverages. However, the genes that contribute to the biosynthesis of bitter compounds (e.g., flavanone 7-O-neohesperidoside) in tea plants have yet to be identified. In this study, we identified 194 UDP-glycosyltransferases (UGTs) from the tea transcriptome database. Among them, two genes, CsUGT75L12and CsUGT79B28, encoding flavonoid 7-O-glycosyltransferase and 7-O-glucoside(1→2)rhamnosyltransferase, respectively, were identified from Camellia sinensis. In vitro, the purified recombinant enzyme rCsUGT75L12 specifically transports the glucose unit from UDP-glucose to the 7-OH position of the flavonoid to produce the respective 7-O-glucoside. rCsUGT79B28 regiospecifically transfers a rhamnose unit from UDP-rhamnose to the 2″-OH position of flavonoid 7-O-glucosides to produce flavonoid 7-O-di-glycosides. Additionally, the expression profiles of the two CsUGTswere correlated with the accumulation patterns of 7-O-glucoside and 7-O-neohesperidoside, respectively, in tea plants. These results indicated that the two CsUGTs are involved in the biosynthesis of bitter flavonoid 7-O-neohesperidoside through the sequential glucosylation and rhamnosylation of flavonoids in C. sinensis. Taken together, our findings provided not only molecular insights into flavonoid di-glycoside metabolism in tea plants but also crucial molecular markers for controlling the bitterness and astringent taste of tea.

Beijing Jishuitan Hospital Affiliated to Capital Medical University, known for its leading role in Chinese orthopedics, is the birthplace of orthopedic robotic surgery in China. Over the last two decades, through continuous exploration, Beijing Jishuitan Hospital has gradually matured the robotic and navigation-assisted orthopedic surgery technology, enhancing the precision, intelligence, and safety of orthopedic procedures. This article reviews the development history of orthopedic robots in Beijing Jishuitan Hospital, introduces the application scenarios of orthopedic robots, demonstrates its advantages in clinical work, and looks forward to the future of orthopedic robots.

Context High inputs of plant litters and slow decomposition of soil organic carbon (SOC) influence the biogeochemical cycling of soil carbon in flooded wetlands. Aims To investigate the effects of different quality litter inputs on SOC stability and storage in flooded wetlands. Methods A 180-day microcosmic experiment to investigated the decomposition of litters of two dominant plants (Carex cinerascens Kukenth., CC; Cyperaceae family) and Triarrhena lutarioriparia L. Liu, TL; Poaceae family), in Poyang Lake Wetlands. Key results CC litters (high-quality, low lignin/N mass ratio) reduced gross content of SOC, but increased labile carbon and labile index (LI) of soils. In contrast, inputs of TL litters (low-quality, high lignin/N mass ratio) increased SOC gross content and recalcitrant carbon fractions of soils, but reduced soil labile carbons and LI. Significant effects of litters on SOC were not observed until ∼30days indicating that the effects of litter inputs on soil carbon pools in flooded wetlands need time to be activated. CC and TL litters both increased the soil microbial biomass carbon (MBC) content. Soil MBC in CC treatments was significantly affected by the litter ash-free dry mass, while that in TL treatments was significantly affected by mass loss. Conclusions Litter quality may regulate the growth of soil MBC via different microbial growth strategies. Implications Our results suggest that inputs of high-quality litters can yield a high amount of labile carbon through stimulated microbial decomposition, leading to an overall loss of carbon. In contrast, inputs of low-quality litters can promote the microbial production of more recalcitrant carbons and increase soil carbon stability and carbon sequestration.

Background: HSP90 has been considered an important anticancer target for several decades, but traditional HSP90 N-terminal inhibitors often suffered from organ toxicity and/or drug resistance. Methods: The development of HSP90 C-terminal inhibitors represents a reliable alternative strategy. In view of rare examples of structure-based identification of HSP90 C-terminal inhibitors, we report a virtual screening based strategy for the discovery of HSP90 C-terminal inhibitors as anticancer agents from natural products. Results & Discussion: 13 chemical ingredients from licorice were identified as possible HSP90 inhibitors and 3 of them have been reported as anticancer agents. The binding modes towards HSP90 C-terminus were predicted by molecular docking and refined by molecular dynamics simulation. Conclusion: Further network pharmacological analysis predicted overall possible targets involved in the pathways in cancer and revealed that 8 molecules possibly interact with HSP90. A structure based virtual screening strategy was established for the discovery of HSP90 Cterminal inhibitors.

Flavonoids constitute the main nutraceuticals in the leaves of tea plants (Camellia sinensis). To date, although it is known that drought stress can negatively impact the biosynthesis of flavonoids in tea leaves, the mechanism behind this phenomenon is unclear. Herein, we report a protein phosphorylation mechanism that negatively regulates the biosynthesis of flavonoids in tea leaves in drought conditions. Transcriptional analysis revealed the downregulation of gene expression of flavonoid biosynthesis and the upregulation of CsMPK4aencoding a mitogen-activated protein kinase in leaves. Luciferase complementation and yeast two-hybrid assays disclosed that CsMPK4a interacted with CsWD40. Phosphorylation assay in vitro,specific protein immunity, and analysis of protein mass spectrometry indicated that Ser-216, Thr-221, and Ser-253 of CsWD40 were potential phosphorylation sites of CsMPK4a. Besides, the protein immunity analysis uncovered an increased phosphorylation level of CsWD40 in tea leaves under drought conditions. Mutation of the three phosphorylation sites generated dephosphorylated CsWD403Aand phosphorylated CsWD403Dvariants, which were introduced into the Arabidopsis ttg1mutant. Metabolic analysis showed that the anthocyanin and proanthocyanidin content was lower in ttg1:CsWD403Dtransgenic plants than ttg1::CsWD403Atransgenic and wild type plants. The transient overexpression of CsWD403Ddownregulated the anthocyanidin biosynthesis in tea leaves. The dual-fluorescein protein complementation experiment showed that CsWD403Ddid not interact with CsMYB5a and CsAN2, two key transcription factors of procyanidins and anthocyanidins biosynthesis in tea plant. These findings indicate that the phosphorylation of CsWD40 by CsMPK4a downregulates the flavonoid biosynthesis in tea plants in drought stresses.

Long non-coding RNAs (lncRNAs) have gathered significant attention due to their pivotal role in plant growth, development, and biotic and abiotic stress resistance. Despite this, there is still little understanding regarding the functions of lncRNA in these domains in the tea plant (Camellia sinensis), mainly attributable to the insufficiencies in gene manipulation techniques for tea plants. In this study, we designed a novel strategy to identify evolutionarily conserved trans-lncRNA (ECT-lncRNA) pairs in plants. We used highly consistent base sequences in the exon-overlapping region between trans-lncRNAs and their target gene transcripts. Based on this method, we successfully screened 24 ECT-lncRNA pairs from at least two or more plant species. In tea, as observed in model plants such as Arabidopsis, alfalfa, potatoes, and rice, there exists a trans-lncRNA capable of forming an ECT-lncRNA pair with transcripts of the 12-oxophytodienoate reductase (OPR) family, denoted as the OPRL/OPRpair. Considering evolutionary perspectives, the OPRLgene cluster in each species likely originates from a replication event of the OPRgene cluster. Gene manipulation and gene expression analysis revealed that CsOPRLinfluences disease resistance by regulating CsOPRexpression in tea plants. Furthermore, the knockout of StOPRL1in Solanum tuberosumled to aberrant growth characteristics and strong resistance to fungal infection. This study provides insights into a strategy for the screening and functional verification of ECT-lncRNA pairs.

Foam concrete or foamcrete is a lightweight, porous material with a wide range of applications in the construction domain. This article focused on reviewing porosity, thermal conductivity, acoustic properties, compressive strength (fc′), elastic modulus (E), flexural strength (fy), stability, resistance to hostile environments, density, and fire resistance of foam concrete. A systematic literature analysis was conducted to identify relevant research trends on foam concrete. The challenges and limitations of foam concrete research were highlighted, including the lack of standardized testing methods and the need for more research on the long-term durability and structural performance of foam concrete. The analysis of the literature data revealed that there had been a growing interest in foamcrete research over the past decade. Foam concrete may be utilized in several construction applications due to its adaptability and wide range of uses. Its potential uses can be increased by developing new manufacturing methods and the inclusion of certain admixtures. The present research has the potential to be advantageous for scholars interested in collaborative advancement and the exchange of novel tactics and concepts, owing to the visual and statistical representation of the regions/countries and researchers that have contributed.

Background: Cerebral ischemia-reperfusion injury is caused by a blood reperfusion injury in the ischemic brain and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury. Objective: Curcumin was reported to exert a good therapeutic effect on neural cells against ischemia- reperfusion injury, However, the mechanism is not clear. Methods: In this study, Oxygen-Glucose Deprivation (OGD) model of fetal rat cerebral cortical neurons and the Middle Cerebral Artery Occlusion (MCAO) model of rats were employed to mimic cerebral ischemia-reperfusion injury in vitro and in vivo, respectively. Results: We confirmed that curcumin has a promotive effect on neuronal proliferation and an inhibitory effect on neuronal pyroptosis. Furthermore, we found that curcumin could improve cerebral infarction. The results of western blotting showed that curcumin down-regulated the expression of nucleotide-binding oligomerization domain-containing protein-, leucine-rich repeats-, and pyrin domain-containing protein 1 (NLRP1), cysteinyl aspartate-specific protease 1 (caspase-1), gasdermin D (GSDMD), IL-1β, IL-6, TNF-α, and iNOS proteins in OGD and MCAO models. NLRP1- dependent neuronal pyroptosis played an important role in cerebral ischemia-reperfusion injury. Conclusion: Curcumin could effectively inhibit NLRP1-dependent neuronal pyroptosis by suppressing the p38 MAPK pathway and therefore exerted neuroprotective effects against cerebral ischemia- reperfusion injury.

Anthocyanins and PAs are the two most common flavonoids, which are widely present among diverse species. Great progress has been made in their synthesis and regulation. In this study, we analyzed the metabolic fluxes from their synthetic precursor leucoanthocyanins, which were obtained by overexpression of dihydroflavonol 4-reductase (DFR) in vitroand in vivo. The unstable product leucocyanidin generated in the CsDFRa enzymatic reaction was easily converted into C-type carbocations under weak acidic conditions, which could be further involved in the synthesis of C-type PAs in vitro. Additionally, the metabolites in tobacco overexpressing CsDFRaand Arabidopsis thalianaDFR and anthocyanidin synthase (ANS) mutants were investigated. In CsDFRatransgenic tobacco, the content of anthocyanins in the petals was greatly increased, but no catechin or PA was detected. In A. thaliana, EC-type carbocation was mainly accumulated in the wild type (WT), and the C-type carbocation was only detected in the ansmutant. In tea plant, the accumulation of C-type PAs is strong positively correlated with the expression of CsDFRa. In summary, leucocyanidin is not only involved in the synthesis of downstream anthocyanin and epicatechin but also can be converted into C-type carbocation to participate in the synthesis of C-type PAs. Hence, from leucocyanidin, three metabolic fluxes were formed toward catechin, cyanidin, and C-type carbocation. These results enriched the metabolic fluxes of leucoanthocyanins and further elaborated the roles of DFR in the process of C-type PA formation.

Chromosomal fragile sites (CFSs) contain AT-rich sequences that tend to form hairpins on lagging strands in DNA replication, making them hotspots for chromosomal rearrangements in cancers. Here, we investigate the structural stability of the AT-rich CFS DNA hairpins with a single non-AT base pair using magnetic tweezers. Strikingly, a single G-T mismatched base pair in the short CFS DNA hairpin gives a 38.7% reduction of the unfolding Gibbs free energy and a 100-fold increase of the transition kinetics compared to a single G-C matched base pair, which are deviated from the theoretical simulations. Our study reveals the unique features of CFSs to provide profound insights into chromosomal instability and structure-specific genome targeting therapeutics for genetic disorder-related diseases.

Aluminum (Al) influences crop yield in acidic soil. The tea plant (Camellia sinensis) has high Al tolerance with abundant monomeric catechins in its leaves, especially epigallocatechin gallate (EGCG), and polymeric proanthocyanidins in its roots (rPA). The role of these polyphenols in the Al resistance of tea plants is unclear. In this study, we observed that these polyphenols could form complexes with Al in vitro, and complexation capacity was positively influenced by high solution pH (pH 5.8), polyphenol type (rPA and EGCG), and high Al concentration. In the 27Al nuclear magnetic resonance (NMR) experiment, rPA-Al and EGCG-Al complex signals could be detected both in vitroand in vivo. The rPA-Al and EGCG-Al complexes were detected in roots and old leaves, respectively, of both greenhouse seedlings and tea garden plants. Furthermore, in seedlings, Al accumulated in roots and old leaves and mostly existed in the apoplast in binding form. These results indicate that the formation of complexes with tea polyphenols in vivoplays a vital role in Al resistance in the tea plant.

The present study was performed to evaluate the effects of ormosanine against spinal cord injury (SCI) in rats and to examine the possible molecular mechanism of action. SCI was induced using an impactor device, and rats were treated with ormosanine 10, 50 or 100 mg/kg, p.o., for 10 days after induction of SCI. The effect of ormosanine on SCI was determined by estimating neurological functions and cytokines and parameters of oxidative stress level were estimated in SCI rats. Quantitative reverse transcription polymerase chain reaction, Western blotting analysis and histopathological study were performed on spinal tissue of SCI rats. The data suggested that treatment with ormosanine reversed the alterations of neurological function in SCI rats. Moreover, the levels of cytokines, oxidative stress and reactive oxygen species production were reduced in the ormosanine treatment group compared to the SCI group. The levels of calpain and neuronal nitric oxide synthase activity were significantly reduced in the spinal tissue of the ormosanine treatment group compared to the SCI group. Moreover, ormosanine treatment reduced the percentage of viable neurons in the spinal tissue of SCI rats. In conclusion, the results of this study showed that ormosanine treatment had a protective effect against neuronal injury in spinal cord-injured rats by regulating the peroxynitrite/calpain activity.

Proanthocyanidins (PAs) are mainly composed of epicatechin (EC) or catechin (C) subunits. C-type catechins (C and GC) are generally considered to be catalyzed by leucocyanidin reductase (LAR). In this study, we re-evaluated the function of LAR. LcLAR1was isolated from Lotus corniculatus, which is rich in C-type catechins. Overexpression of LcLAR1in tobacco resulted in a significantly increased content of EC and EC-glucoside. Overexpression of LcLAR1in Arabidopsis thalianapromoted the accumulation of soluble PAs, including EC, PA dimers, and PA trimers. However, in the transgenic ansmutant overexpressing LcLAR1, the contents of C and C-glucoside were increased. In addition, overexpression of LcLAR1in L. corniculatusresulted in a significant increase of C levels. Taken together, the products of LcLAR1 depended on the substrates, which revealed the substrate diversity of LcLAR1. Our study provides new insights into the flavonoid pathway, especially the role of LAR.

Doxorubicin (DOX) ranks among the most effective anticancer agents. Increasing the formation of covalent DOX-DNA interstrand cross-links can improve the anticancer activity of DOX. However, due to the low stability of the DOX-DNA cross-links to heat and alkali, DOX can be extensively lost during isolation procedures of biochemical methods, thus reducing the apparent clinical relevance of this mechanism. Here, we developed a drug label-free, single-molecule magnetic tweezers assay that can detect a single DOX-DNA cross-link on the basis of the significant increase of the unzipping forces of DNA hairpins upon drug binding. Using this assay, we measured the DOX concentration-dependent cross-linking rates at clinically relevant concentrations of DOX. We report an ∼26-fold higher formaldehyde concentration dependence of cross-linking rates than previously reported and 0.9 ± 0.8 cross-links/103bp at the clinically relevant concentrations of 70 nM DOX and 50 μM formaldehyde. Our results suggest a much higher cross-link formation ability than previous bulk measurements have reported and suggest that the cross-linking mechanism has promising therapeutic potential. This general method can be used to detect the formation kinetics of other DNA lesions or DNA adducts that affect DNA duplex stability.

HSP90 is a member of the family of heat shock proteins responsible for folding proteins into mature conformations and thus maintaining their biological function in cells. Since it is involved in all hallmarks of cancer, HSP90 has been considered as a promising drug target for cancer therapy. Eighteen HSP90 inhibitors have entered clinical trials, however, none has been approved by the FDA. There is still a great need for novel HSP90 inhibitors with strong anticancer activity and good safety profile. In the past several years, many new molecules were identified as HSP90 inhibitors and some of them have shown promising pharmacological profiles in preclinical evaluations. In this review, HSP90 inhibitors identified from 2014 to date are summarized and their design strategies, chemical structures, and biological activities are reviewed. The inhibitors are categorized by their different target domains and selectivity as N-terminal, C-terminal, and isoform-selective HSP90 inhibitors.

To improve lubricating effect and reduce cutting fluid, a new lubricating method was proposed and a new cutting tool was fabricated. A micro-channel connected tool rake face with hydraulic pressure system was fabricated to continuously supply cutting fluid to tool-chip interface. Cutting tests on cast iron were carried out with the new cutting tool and conventional tools. Results show that the cutting forces, the friction coefficient at the tool–chip interface, chip size, the wear area and the adhesive effect of the new tool were significantly reduced compared with those of the conventional tool. EDS analysis results and SEM micrograph of worn surface verified that more cutting fluid can enter into the inner of interface between chip and tool through the micro-channel than flood lubricating. So more area can form liquid film that can reduce cutting force and friction and promote anti-wear. This is the main mechanisms responsible. Although adhesion is reduced, adhesive wear is the main wear mechanism for the new cutting tool as same as conventional tool.

We uncover that O3-induced ageing dynamically alters the surface O-functionalities of carbon black (CB) nanoparticles, a model of airborne particles. The consequent distinct bioreactivity and toxicity towards susceptible cells under low-dose exposure are largely attributed to the variant species of O-functionalities, thereby signifying the importance of the environmental ageing process in changing CB toxicity features.

Janus nanoparticles with an anisotropic feature concentrated multiple properties on a single carrier, providing synergistic effects. In this study, dual-functionalized Janus nanoparticles (HA-JMSN/DOX-DMMA) were constructed with a tumor-targeting ligand (hyaluronic acid, HA) modified on the one side and a charge reversal group (2,3-dimethylmaleic anhydride, DMMA) on the other side. The drug release of HA-JMSN/DOX-DMMA was positively correlated with the acidity of the environment. The cytotoxicity and cell uptake of HA-JMSN/DOX-DMMA were superior to the isotropous nanoparticles. The endocytosis pathway of HA-JMSN/DOX-DMMA involved the clathrin-mediated endocytosis (HA) and the micropinocytosis (DMMA) at the same time, which indicated that they both participated in the interaction between nanoparticles and tumor cells. After being injected intravenously in mice, the distribution of HA-JMSN/DOX-DMMA in tumor was enhanced significantly. The antitumor therapy study in vivo showed that HA-JMSN/DOX-DMMA inhibited tumor growth and improved the survival rate of tumor-bearing mice effectively. In general, HA-JMSN/DOX-DMMA could take the synergistic effect of active targeting and charge reversal to deliver drug in tumor cells and kill them efficiently, which was a promising antitumor nanodrug.

ABSTRACTThere is growing evidence of the position of microRNAs (miRs) in Alzheimer’s disease (AD), thus our objective was to discuss the impact of miR-129-5p regulating nerve injury and inflammatory response in AD rats by modulating SOX6 expression. The AD rat model was established by injecting Aβ25-35into the brain. The pathological changes, ultrastructure, number of neurons, cell degeneration and apoptosis of hippocampal tissue were observed in vivo. MiR-129-5p, SOX6, IL-1β, TNF-α, Bcl-2 and Bax expression in serum and hippocampal tissues were detected by ELISA, RT-qPCR or western blot analysis. The successfully modeled hippocampal neuronal cells of AD were transfected with miR-129-5p mimic, SOX6-siRNA or their controls to figure out their roles in proliferation, apoptosis and inflammatory reaction in vitro. Low expression of SOX6 and high expression of miR-129-5p in vivoof rats would shorten the escape latent period and increase the times of crossing platforms, alleviate the pathological injury, inhibit neuronal apoptosis and reduce the inflammatory reaction. Up-regulation of miR-129-5p and down-regulation of SOX6 promoted proliferation, suppressed apoptosis and degraded the inflammatory reaction of neuronal cells in vitro. Up-regulation of SOX6 reversed the expression of miR-129-5p to reduce the damage and inflammatory response of the cell model of AD. Our study presents that up-regulation of miR-129-5p or down-regulation of SOX6 can reduce nerve injury and inflammatory response in rats with AD. Thus, miR-129-5p may be a potential candidate for the treatment of AD.

Current understanding of the health risks and adverse effects upon exposure to fine particles is premised on the direct association of particles with target organs, particularly the lung; however, fine-particle exposure has also been found to have detrimental effects on sealed cavities distant to the portal-of-entry, such as joints. Moreover, the fundamental toxicological issues have been ascribed to the direct toxic mechanisms, in particular, oxidative stress and proinflammatory responses, without exploring the indirect mechanisms, such as compensated, adaptive, and secondary effects. In this Review, we recapitulate the current findings regarding the detrimental effects of fine-particle exposure on joints, the surrounding cells, and microenvironment, as well as their deteriorating impact on the progression of arthritis. We also elaborate the likely molecular mechanisms underlying the particle-induced detrimental influence on joints, not limited to direct toxicity, but also considering the other indirect mechanisms. Because of the similarities between fine air particles and engineered nanomaterials, we compare the toxicities of engineered nanomaterials to those of fine air particles. Arthritis and joint injuries are prevalent, particularly in the elderly population. Considering the severity of global exposure to fine particles and limited studies assessing the detrimental effects of fine-particle exposure on joints and arthritis, this Review aims to appeal to a broad interest and to promote more research efforts in this field.

Osteoarthritis (OA) is a chronic joint disease highly associated with an imbalance in the network of inflammatory factors and typically characterized by oxidative stress and cartilage damage. Moreover, the specificity of the joint structure makes it difficult for drugs to achieve good penetration and effective enrichment in the joint cavity. Therefore, therapeutic strategies that increase the specific targeting of drugs to inflammatory joint and incorporate antioxidative stress effects are important to improve the efficacy of OA. Here, we developed a folic acid-modified liposomal nanoparticle (AST@Lip-FA) loaded with the antioxidant astaxanthin (AST) to enhance the water solubility and stability of AST and to target the delivery of AST to the site of OA, leading to a significant improvement in therapeutic efficacy. In vitro experiments demonstrated that, due to the recognition by FA of the receptor folate receptor β on the surface of activated macrophages, the cellular uptake efficiency of AST@Lip-FA was increased. Meanwhile, intracellularly overexpressed inflammatory mediators such as reactive oxygen species and nitric oxide were efficiently removed by AST@Lip-FA. In addition, in the ACLT-induced OA mouse model, AST@Lip-FA was precisely enriched in the inflamed joints and achieved long-term retention, fully utilizing the anti-inflammatory, antioxidant, and cartilage-protecting effects of AST to effectively alleviate the progression of OA. In summary, AST@Lip-FA has an important prospect as a potential and effective therapeutic strategy for OA.

Bioluminescence of bacteria is widely applied in biological imaging, environmental toxicant detection, and many other situations. Understanding the spectral tuning mechanism not only helps explain the diversity of colors observed in nature but also provides principles for bioengineering new color variants for practical applications. In this study, time-dependent density functional theory (TD-DFT) and quantum mechanics and molecular mechanics (QM/MM) calculations have been employed to understand the fluorescence spectral tuning mechanism of bacterial luciferase with a focus on the electrostatic effect. The spectrum can be tuned by both a homogeneous dielectric environment and oriented external electric fields (OEEFs). Increasing the solvent polarity leads to a redshift of the fluorescence emission maximum, λF, accompanied by a substantial increase in density. In contrast, applying an OEEF along the long axis of the isoalloxazine ring (X-axis) leads to a significant red- or blue-shift in λF, depending on the direction of the OEEF, yet with much smaller changes in intensity. The effect of polar solvents is directionless, and the red-shifts can be attributed to the larger dipole moment of the S1state compared with that of the S0state. However, the effect of OEEFs directly correlates with the difference dipole moment between the S1and S0states, which is directional and is determined by the charge redistribution upon deexcitation. Moreover, the electrostatic effect of bacterial luciferase is in line with the presence of an internal electric field (IEF) pointing in the negative Xdirection. Finally, the key residues that contribute to this IEF and strategies for modulating the spectrum through site-directed point mutations are discussed.

The electrooxidation of 5-hydroxymethylfurfural (HMF) into 2,5-furandicarboxylic acid (FDCA) demonstrated its unique superiority, not only in reducing overpotential and improving energy conversion efficiency for green hydrogen production but also in utilizing abundant biomass resources and producing high-value-added chemicals. However, designing highly efficient electrocatalysts for HMF electrooxidation (HMF-EOR) with low cost and high performance for large-scale production remained a huge challenge. Herein, we introduced an easy one-step activation process to produce P-doped porous biochar loaded with multiple crystal surfaces exposed to CoP2O6catalysts (CoP2O6@PC), which exhibited outstanding electrooxidation performance. To achieve a current density of 50 mA cm–2, only a low overpotential of 200 mV was needed for the electrooxidation of HMF in 1.0 M KOH + 10 mM HMF. This performance far surpassed that of other similar materials. CoP2O6@PC exhibited outstanding HMF-EOR performance with high conversion (nearly 100%), selectivity (97.1%), faradaic efficiency (95.3%), and robust stability. This work represents a promising strategy to fabricate macroscale and low-cost HMF-EOR electrocatalysts and achieve potential industrial applications of HMF-EOR.

Repair of large bone defects caused by trauma or disease poses significant clinical challenges. Extensive research has focused on metallic materials for bone repair because of their favorable mechanical properties, biocompatibility, and manufacturing processes. Traditional metallic materials, such as stainless steel and titanium alloys, are widely used in clinics. Biodegradable metallic materials, such as iron, magnesium, and zinc alloys, are promising candidates for bone repair because of their ability to degrade over time. Emerging metallic materials, such as porous tantalum and bismuth alloys, have gained attention as bone implants owing to their bone affinity and multifunctionality. However, these metallic materials encounter many practical difficulties that require urgent improvement. This article systematically reviews and analyzes the metallic materials used for bone repair, providing a comprehensive overview of their morphology, mechanical properties, biocompatibility, and in vivo implantation. Furthermore, the strategies and efforts made to address the short‐comings of metallic materials are summarized. Finally, the perspectives for the development of metallic materials to guide future research and advancements in clinical practice are identified. Metallic materials are widely studied for bone repair due to their biocompatibility and strength. Stainless steel and titanium are commonly used, while biodegradable options like iron, magnesium, and zinc alloys show promise. Porous tantalum and bismuth alloys are gaining attention for their bone‐friendly properties. This article reviews metallic materials for bone repair, covering their properties and addressing deficiencies.

Supercapacitors are a new class of energy storage devices with long cycle life, good reversibility, stability and safety. A (Poly (3,4-propylenedioxythiophene) − OH/CoNi−SeS @Hollow carbon sphere) PProDOT−OH/CoNi−SeS @HCS composite material is synthesized via a sulfurization/selenization ion exchange method and in−situ oxidation, which exhibits excellent electrochemical performance and a heterogeneous structure with multi-phase interfaces. The material's mass specific capacity is as high as 775.1C g−1at 1 A g−1. Even if it is increased to 20 A g−1, it can still maintain 80.4 % of the capacitance. By combining the designed polyvinyl alcohol (PVA)/potassium hydroxide (KOH) hydrogel electrolyte, a conformal interface was formed, which combines both high conductivity and electrochemical stability. After assembling into a quasi-solid-state AC//PVA/KOH//PProDOT−OH/CoNi−SeS@HCS device, when the energy density is as high as 84.8 Wh kg−1, the power density is 8000 W kg−1. The subsequent 20,000 cycle stability test can still prove the excellence of the device, with the Coulombic efficiency as high as 98.81 % and the capacitance retention rate as high as 82.85 %. The better capacitance performance is achieved due to the synergistic effect of the conductive polymer, the hollow structure, the modified electronic structure and the multi-component system.