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This study presents the fabrication of an all‐solid‐state lithium‐ion battery using lithium manganese oxide (LiMn2O4; LMO) as the cathode, graphite (C), and carbon‐coated magnesium (MgC) as the anode, along with a silicate‐based solid electrolyte. To assess the charge/discharge mechanism, three polymeric membranes with varying weight percentages (5%, 30%, and 50%) of magnesium silicate are produced through battery‐cloth deposition (BCD) for use as the solid electrolyte. The findings reveal that enhancing the magnesium silicate content in the solid electrolyte (particularly at 50%) results in an increased specific capacity of the battery. The MgC anode exhibits a peak capacity of approximately 780 mAh/g during the third cycle, maintaining capacity retention of 100% over 26 cycles, addressing the issues of low specific capacity and self‐discharge in the solid‐state Li‐ion battery. Nevertheless, prolonged charge/discharge testing leads to an escalation in the surface roughness and porosity of the carbon coating on the MgC anode, resulting in a decline in capacity. These results demonstrate that the LMO‐BCD‐MgC battery system proposed in this study is a secure, eco‐friendly, and cost‐effective option with potential applications in energy storage. [ABSTRACT FROM AUTHOR]

Six ionone glycosides (1–3 and 5–7), including three new ones, named capitsesqsides A−C (1–3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8–10) were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS. [ABSTRACT FROM AUTHOR]

Human iPSC-derived airway organoids (iPSC-AOs) exhibit cellular heterogenicity resembling the human native airway. Bioinformatics analysis revealed a robust dysregulation in inflammation, lipid-metabolism pathway, and alternative splicing in SARS-CoV-2 infected airway organoids. Manipulating lipid homeostasis using cholesterol-lowering drugs (e.g. Statins) relocated the viral entry receptor angiotensin-converting enzyme-2 (ACE-2), leading to the reduction of SARS-CoV-2 entry and replication. [Display omitted] • Single-cell RNA sequencing showed that iPSC-AOs exhibition of the genetic profiles highly resembling the genotypes of human airways. • iPSC-AOs are susceptible to SARS-COV-2 infection and the expressions of S and N proteins after viral infection. • Bioinformatics analysis indicated the involvement of aberrant enrichment of lipid transport and lipid pathways in infected iPSC-AOs. • Statin preincubation relocated ACE2, reduced N protein, and limited SARS-CoV-2 infection in iPSC-AOs. • Lipid modifications consistently inhibited viral entry of various SARS-CoV-2 strains (wild-type, alpha, delta, omicron). Modifications of lipid metabolism were closely associated with the manifestations and prognosis of coronavirus disease of 2019 (COVID-19). Pre-existing metabolic conditions exacerbated the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while modulations of aberrant lipid metabolisms alleviated the manifestations. To elucidate the underlying mechanisms, an experimental platform that reproduces human respiratory physiology is required. Here we generated induced pluripotent stem cell-derived airway organoids (iPSC-AOs) that resemble the human native airway. Single-cell sequencing (ScRNAseq) and microscopic examination verified the cellular heterogeneity and microstructures of iPSC-AOs, respectively. We subjected iPSC-AOs to SARS-CoV-2 infection and investigated the treatment effect of lipid modifiers statin drugs on viral pathogenesis, gene expression, and the intracellular trafficking of the SARS-CoV-2 entry receptor angiotensin-converting enzyme-2 (ACE-2). In SARS-CoV-2-infected iPSC-AOs, immunofluorescence staining detected the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins and bioinformatics analysis further showed the aberrant enrichment of lipid-associated pathways. In addition, SARS-CoV-2 hijacked the host RNA replication machinery and generated the new isoforms of a high-density lipoprotein constituent apolipoprotein A1 (APOA1) and the virus-scavenging protein deleted in malignant brain tumors 1 (DMBT1). Manipulating lipid homeostasis using cholesterol-lowering drugs (e.g. Statins) relocated the viral entry receptor angiotensin-converting enzyme-2 (ACE-2) and decreased N protein expression, leading to the reduction of SARS-CoV-2 entry and replication. The same lipid modifications suppressed the entry of luciferase-expressing SARS-CoV-2 pseudoviruses containing the S proteins derived from different SARS-CoV-2 variants, i.e. wild-type, alpha, delta, and omicron. Together, our data demonstrated that modifications of lipid pathways restrict SARS-CoV-2 propagation in the iPSC-AOs, which the inhibition is speculated through the translocation of ACE2 from the cell membrane to the cytosol. Considering the highly frequent mutation and generation of SARS-CoV-2 variants, targeting host metabolisms of cholesterol or other lipids may represent an alternative approach against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most prevalent diseases of wheat worldwide and can lead to severe yield reductions. Identifying genes involved in powdery mildew resistance will be useful for disease resistance breeding and control. Calreticulin (CRT) is a member of multigene family widely found in higher plants and is associated with a variety of plant physiological functions and defense responses. However, the role of CRT in wheat resistance to powdery mildew remains unclear. TaCRT3 was identified from the proteomic sequence of an incompatible interaction between the wheat (Triticum aestivum) cultivar Xingmin 318 and the Bgt isolate E09. Following analysis of transient expression of the GFP-TaCRT3 fusion protein in Nicotiana benthamiana leaves, TaCRT3 was localized in the nucleus, cytoplasm, and cell membrane. Transcript expression levels of TaCRT3 were significantly upregulated in the wheat-Bgt incompatible interaction. More critically, knockdown of TaCRT3 using virus-induced gene silencing resulted in attenuated resistance to Bgt in wheat. Histological analysis showed a significant increase in Bgt development in TaCRT3-silenced plants, whereas the pathogen-related gene was significantly downregulated in TaCRT3-silenced leaves. In addition, overexpression of TaCRT3 in wheat enhanced the resistance to powdery mildew, the growth of Bgt was significantly inhibited, and the area of H2O2 near the infection site and the expression of defense-related genes of the salicylic acid pathway significantly increased. These findings imply that TaCRT3 may act as a disease resistance factor that positively regulates resistance to powdery mildew, during which SA signaling is probably activated. [ABSTRACT FROM AUTHOR]

Background: Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG. Methods: Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots. Results: Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression. Conclusions: Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression. [ABSTRACT FROM AUTHOR]

Al 6082 aluminum alloy has excellent corrosion resistance, strength, and formability. However, owing to the recrystallization effect of a hot working process, coarse grains form easily in this material, which reduces its strength and service life. The novel continuous casting direct rolling (CCDR) method can prevent the deterioration of this material. Thus, we used CCDR Al 6082 aluminum alloy as the research material in this study. By subjecting a CCDR Al 6082 aluminum alloy to heat treatment (T4 and T6) and cold rolling, the influence of recrystallization effect on its mechanical properties and on impact failure resistance were explored. The results demonstrated that the specimen subjected to T4 heat treatment had a higher elongation and that the specimen subjected to T6 heat treatment had a higher strength. After cold rolling, the hardness and strength of the specimens subjected to different heat treatments (coded T4R4 and T6R4) increased because of the work's hardening effect. Moreover, the elongations of both specimens decreased, but they were higher than the industrial standard (>10%). The strength of specimen T6R4 was higher (up to 400 MPa) than specimen T4R4. Moreover, relative to specimen T4R4, specimen T6R4 had greater tensile and Charpy impact failure toughness. [ABSTRACT FROM AUTHOR]

Currently, the primary commercial aluminum alloy fillers used are 4043 and 5356. However, when welded with high-strength work pieces like 6061 and 7075 aluminum alloys, the strength of weld beads significantly lags behind that of the original welded material. Both 4043 and 5356 aluminum alloys cannot be strengthened through heat treatment. The strength difference between the weld bead and base material doubles after heat treatment. In this study, an Al-Si-Cu-Mg alloy (SCM) filler modified using a heat-treatable A319 aluminum alloy was employed to investigate the post-welding microstructural and mechanical properties of specimens under room- and high-temperature conditions and after prolonged exposure in a saltwater environment (3.5 wt.% NaCl). The aim was to demonstrate that commercial aluminum alloy fillers could be substituted with a high-silicon aluminum alloy boasting excellent solidification and mechanical properties. The results revealed that, after heat treatment of the weld bead, dendrites were not eliminated, but the tensile strength increased to 310 MPa, closely matching that of commercial 6061 aluminum alloy. The strength of the weld bead remained higher than 250 MPa in high-temperature (240 °C) and saltwater environments. These findings underscore the potential application of this material. [ABSTRACT FROM AUTHOR]

This study conducts low-vacuum sulfidation to form a sulfidation layer on the serpentinite-derived magnesium iron silicate, thereby enhancing its electrochemical properties. Results show (Mg,Fe)2SiO4 calcined at 900 °C has the best crystallinity, and the cubic FeS2 is synthesized on the surface of the orthorhombic magnesium iron silicate (MFS). Two distinct charge plateaus can be distinguished during the first charge process, and the discharge capacities increased significantly. This study confirms that the surface FeS2 layer provides extra ion pathways, allowing more lithium/magnesium ions to be extracted and inserted in the serpentinite-derived magnesium iron silicate. Accordingly, the serpentinite electrode boasts straightforward exploitation with low-cost advantages and potential. [ABSTRACT FROM AUTHOR]

In this paper, we are devoted to the study of a problem proposed in Aujol and Dossal (SIAM J Optim 29:3131–3153, 2019), which concerns the optimal convergence rates for damped inertial gradient dynamics with flat geometries. Fortunately, we find a solution to the problem. More specifically, we obtain an optimal decay rate for the system energy of the second-order differential equation with time-dependent damping in a Hilbert space H x ¨ (t) + γ (t) x ˙ (t) + ∇ F (x (t)) = 0 , where F : H → R is a differentiable convex function possessing at least one minimizer and γ (t) = α / t with α > 0. It is known that this system, with the time-dependent damping coefficient γ (t) , models a nonlinear oscillator with viscous damping, and is associated with the Nesterov acceleration scheme, FISTA, or the accelerated gradient method in the area of numerical optimization. [ABSTRACT FROM AUTHOR]

Heterosis and polyploidy have an overwhelming influence on plant evolution. Recently, polyploid rice hybrids have been used to breed new rice varieties because they combine the advantages of both heterosis and polyploidy. In this study, we generated six rice lines: autotetraploid rice hybrids and their autotetraploid parents, diploid donors, and hybrids of the diploid donors. To investigate the molecular mechanism controlling the effects of both hybridization and polyploidization, we performed bisulfite and RNA sequencing on young panicles at the pollen meiosis stage to compare the DNA metabolomes and transcriptomes among the six rice lines. The hybrids lines were hypermethylated compared to their corresponding parents and the autotetraploid lines showed globally increased DNA methylation of their transposable elements compared to the diploid donors. The alteration in DNA methylation level corresponded to the differential gene expressions among the rice genotypes, suggesting that methylation changes induced by polyploidization and hybridization may affect gene expression. Groups of gene candidates were identified that may be associated with heterosis and polyploidy. Our results provide DNA information that can be used to investigate epigenetic modification during heterosis and polyploidy in rice. [ABSTRACT FROM AUTHOR]

Chloride ions contained in the sealing compound currently used in the electronic packaging industry not only interact with intermetallic compounds but also have a serious impact on silver alloy wires. A 15 μm ultrafine quaternary silver-palladium-gold-platinum alloy wire was used in this study. The wire and its bonding were immersed in a 60 °C saturated sodium chloride solution (chlorination experiment), and the strength and elongation before and after chlorination were measured. Finally, the fracture surface and cross-section characteristics were observed using a scanning electron microscope and focused ion microscope. The results revealed that chloride ions invade the wire along the grain boundary, and chlorides have been generated inside the cracks to weaken the strength and elongation of the wire. In addition, chloride ions invade the interface of the wire bonding to erode the aluminum substrate after immersing it for enough long time, causing galvanic corrosion, which in turn causes the bonding joint to separate from the aluminum substrate. [ABSTRACT FROM AUTHOR]

Al–Mg–Sc–Zr alloy fabricated through selective laser melting (SLM) is an additive manufacturing alloy with promising industrial potential. In this study, as-printed specimens were subjected to either single-stage or two-stage heat treatment processes to investigate the effect of temperature from room temperature to high temperature on the specimens' tensile and fatigue properties to establish a reliable reference for aerospace applications. The tensile test results indicated that the heat treatment contributed to determine the properties of the nanoprecipitate Al3(Sc, Zr) with a strengthening phase, improving tensile strength. Moreover, the dynamics strain aging (DSA) effect vanished as temperature increased. It is noteworthy that the nanoprecipitation was distributed at the boundary of the melting pool after single-stage heat treatment with the highest tensile properties in all tests. In addition, the microstructure observed after the two-stage heat treatment indicated a melting pool interface decomposition, and the nanoprecipitation was homogeneously scattered over the Al matrix, increasing strength and further delaying fatigue crack transmission. Those features build a high-fatigue-resistance foundation. TEM analysis also confirmed the promotion of Sc thermal diffusion and an Al3(Sc, Zr) precipitation transformation mechanism under two-stage heat treatment, corresponding to aforementioned inferences. The SLM Al–Mg–Sc–Zr alloy with two-stage heat treatment brings about balance between tensile properties and fatigue resistance, providing new insight into additive manufacturing with Al alloys. [ABSTRACT FROM AUTHOR]

Rhein, one of the main active components of rhubarb (Dahuang) and Polygonum multiflorum (Heshouwu), has a wide range of effective pharmacological effects. Recently, increasing studies have focused on its potential hepatorenal toxicity, but the cardiotoxicity is unknown. In this study, we found that the IC 50 of rhein to H9c2 cells at 24 h and 48 h were 94.5 and 45.9μmol/L, respectively, with positive correlation of dose-toxicity and time-toxicity. After the treatment of rhein (106, 124 and 132μmol/L), the number of H9c2 cells decreased significantly, and the morphology of H9c2 cells showed atrophy, round shape and wall detachment. Moreover, the proportion of apoptotic cells in H9c2 cells treated with rhein was significantly increased in a dose-dependent manner. And rhein induced S phase arrest of H9c2 cells and inhibited cell proliferation. Rhein up-regulated ROS, LDH levels and low MMP but down-regulated SOD content in H9c2 cells. Additionally, the results showed that the cardiac function LVEF and LVFS of rhein high-medium-low dose groups (350, 175, 87.5 mg/kg) were significantly reduced. And the contents of Ca2+, cTnT, CK and LDH in serum of KM mice were significantly up-regulated by rhein. Furthermore, western blot results suggested that rhein the above effects via promoting Fas-induced apoptosis pathway in vitro and in vivo. In general, rhein may cause cardiotoxicity via Fas-induced apoptosis pathway in vivo and in vitro , which provides reference for the safe use of medicinal plant containing rhein and its preparations. [Display omitted] • The cardiotoxicity of rhein was identified and verified in vivo and in vitro for the first time. • It was proved that rhein could induce the membrane potential and microscopic changes of mitochondria in H9c2 cardiomyocytes. • The cardiotoxic mechanism of rhein was investigated: FAS - induced apoptosis pathway. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the underlying mechanisms of the relationship between stress response and behavioral response and to develop a moderated mediation model with stress management and risk cognition. Methods: We developed 4 novel questionnaires, namely, stress response questionnaire, behavioral response questionnaire, stress management questionnaire, and risk cognition questionnaire. A total of 5896 university students in China were investigated during the peak period of the coronavirus disease 2019. Results: The results showed that stress response had a significant negative predictive effect on behavioral response (r = -0.489, P < .001). Moreover, stress management had a partial mediating effect between stress response and behavioral response. Risk cognition plays a moderating effect on the mediation model (β = -0.109, P = .030), and the effect of high-risk cognition is more significant. Conclusion: During the coronavirus disease 2019 period, improving the risk awareness of university students will help to enhance the buffering effect of stress management on behavioral response and indirectly reduce their behavioral response. [ABSTRACT FROM AUTHOR]

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to the rapidly increased prevalence of overweight and obesity. To this point, epidemiological, clinical, and experimental evidence supports the existence of a unique disease entity termed “obesity cardiomyopathy,” which develops independent of hypertension, coronary heart disease, and other heart diseases. Our contemporary review evaluates the evidence for this pathological condition, examines putative responsible mechanisms, and discusses therapeutic options for this disorder. Clinical findings have consolidated the presence of left ventricular dysfunction in obesity. Experimental investigations have uncovered pathophysiological changes in myocardial structure and function in genetically predisposed and diet-induced obesity. Indeed, contemporary evidence consolidates a wide array of cellular and molecular mechanisms underlying the etiology of obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover of free fatty acids, lipotoxicity, and amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, myocardial fibrosis, dampened coronary flow reserve, coronary microvascular disease (microangiopathy), and endothelial impairment. Given the important role of obesity in the increased risk of heart failure, especially that with preserved systolic function and the recent rises in COVID-19-associated cardiovascular mortality, this review should provide compelling evidence for the presence of obesity cardiomyopathy, independent of various comorbid conditions, underlying mechanisms, and offer new insights into potential therapeutic approaches (pharmacological and lifestyle modification) for the clinical management of obesity cardiomyopathy [ABSTRACT FROM AUTHOR]

Rhein, belonging to anthraquinone compounds, is one of the main active components of rhubarb and Polygonum multiflorum. Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF-κB, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on. However, to some extent, its clinical application is limited by its poor water solubility and low bioavailability. Even more, rhein has potential liver and kidney toxicity. Therefore, in this paper, the pharmacological effects of rhein and its mechanism, pharmacokinetics, and safety studies were reviewed, in order to provide reference for the development and application of rhein. [ABSTRACT FROM AUTHOR]

[Display omitted] • This study used the evaporated Zn-Ga and graphite film as the electrodes. • Mg-based silicate powders as the solid electrolyte formed a Zn solid-state battery. • Zn and small amount of Na and Mg ions can perform electrochemical reactions. • The maximum capacity of Zn solid-state battery is 83 mAh/g. Zinc is abundant in the Earth's crust, which contributes to its relatively low price. Magnesium-based silicate, as a solid electrolyte material, is environmentally friendly due to its enhanced thermal stability compared to liquid electrolytes. Introducing a graphite film can reduce both the manufacturing process and the cost of zinc-ion solid-state batteries. This study fabricated an all solid-state zinc-graphite battery using an evaporated zinc-gallium (Zn-Ga) alloy film as the negative electrode, pressed magnesium-based silicate powder as the solid electrolyte, and graphite film as the positive electrode. The experimental results revealed the microstructure characteristics of the positive electrode, electrolyte, and negative electrode materials, while the charging-discharging mechanism and practical performance evaluation confirmed the high-efficiency energy storage capabilities of the all-solid-state zinc-graphite battery. [ABSTRACT FROM AUTHOR]

Low-carbon city pilot (LCCP) policy is a progressive pollution regulation policy. Besides its role in carbon emission reduction, it has a profound impact on green growth performance and green innovation efficiency. Based on the data of 12 pilot cities and 14 non-pilot cities in the Yangtze River Delta (YRD), this study applies the PSM-DID and spatial mediating model to investigate the multi-dimensional policy effects of LCCP policy on green growth performance and green innovation efficiency. First, the direct effect of LCCP policy on green growth performance has reached 1.46%, ever since its implementation in 2017. Second, considering the intercity innovation cooperation in YRD, LCCP policy has influenced green innovation efficiency by an increase of 12.6%. Furthermore, the time-spatial DID model and multiple mediating effect model identify that LCCP policies have significantly improved green innovation cooperation. Such policies act on the industrial structure upgrading path to achieve the ultimate objective of carbon emission reduction and green growth performance. Third, the green innovation cooperation and substantial transformation of industrial structure upgrading played an important role in realizing the LCCP policy's effect, with its mediating effect reaching 33.63%. [ABSTRACT FROM AUTHOR]

This study focuses on the additive manufacturing technique of selective laser melting (SLM) to produce Ti-6Al-4V-Zn titanium alloy. The addition of zinc at 0.3 wt.% was investigated to improve the strength and ductility of SLM Ti-6Al-4V alloys. The microstructure and mechanical properties were analyzed using different vacuum heat treatment processes, with the 800-4-FC specimen exhibiting the most favorable overall mechanical properties. Additionally, zinc serves as a stabilizing element for the β phase, enhancing the resistance to particle erosion and corrosion impedance of Ti-6Al-4V-Zn alloy. Furthermore, the incorporation of trace amounts of Zn imparts improved impact toughness and stabilized high-temperature tensile mechanical properties to SLM Ti-6Al-4V-Zn alloy. The data obtained serve as valuable references for the application of SLM-64Ti. [ABSTRACT FROM AUTHOR]

We consider a second order non-autonomous evolution equation in a Hilbert space H u ′ ′ (t) + A u (t) + γ (t) u ′ (t) + ∇ F (u (t)) = 0 , where A is a self-adjoint and nonnegative operator on H with a nontrivial kernel, the nonlinear term ∇ F is the gradient of a differentiable function F : D (A 1 / 2) → R , and γ (t) is a damping coefficient, vanishing as t goes to infinity. We focus on a limit case γ (t) = α / t (with some α > 0), which turns out to be quite tricky to deal with. When α exceeds a critical value, we obtain the optimal decay rate of the solution of the equation, in terms of the exponent associated with F. Moreover, we present two examples to illustrate our theoretical results. [ABSTRACT FROM AUTHOR]

The concept of "prevention before disease" in Buddhism has deep roots in traditional Indian medicine and has been integrated into Buddhist philosophy. The Buddhist philosophy of "prevention before disease" is based on the cultivation of mindfulness through the practice of meditation. This philosophy has been integrated into modern medicine through the development of mindfulness-based interventions, which have been found to be effective in reducing symptoms of anxiety, depression, and chronic pain. The article also discusses the spread of Buddhist philosophy and its "prevention before disease" concept in different regions of the world and the potential benefits of integrating this philosophy into patient care. Here, we summarized the concept of "Prevention before Disease" in Buddhism and its specific content in Buddhist teachings and discussed its application & dissemination status in modern medicine. [ABSTRACT FROM AUTHOR]

• The microstructure evolution of heat-treated SLM Al-Ni-Cu-Fe-Zr-Sc specimens was obtained. • The phase transformation of the heat-treated specimen was investigated. • The elemental composition of the bimodal microstructure was obtained. • The nanoprecipitation in the fine-grained region was investigated to clarify the precipitation mechanism. The novel selective laser melting (SLM) Al-Ni-Cu-Fe-Zr-Sc alloy has high temperature stability, but the segregation of the melting pool boundary limits its potential applications. Because conventional heat treatment with a solid solution at 530 °C is inappropriate for the SLM Al-Ni-Cu-Fe-Zr-Sc alloy, this study used hyper-high-temperature solid-solution treatment at three temperatures (560, 570, and 580 °C for 1 h) to investigate the evolution of the melting pool structure. An artificial aging treatment was applied at 175 °C for 6 h to investigate the precipitation mechanism. The results indicated that as-printed presented a bimodal microstructure consisting of a coarse-grained (CG) region and a fine-grained (FG) region. The hyper-high-temperature solid-solution treatment promoted the decomposition of the melting pool boundary and expansion of FG region. The FG region was composed of Ni-, Cu-, and Fe-rich equiaxed grains. After aging treatment, Al 9 Fe(Cu)Ni and Al 3 (Sc, Zr) nano-scale strengthening phases could be found in the FG region. The decomposition of the melting pool boundary, bimodal microstructure, and nano-scale phases can strengthen the matrix and increase hardness. In addition, the mechanism of element diffusion in melting pool was also explored to confirm that heat treatment can reduce material deterioration caused by boundary precipitation. These characteristics mitigate the disadvantages of the SLM Al-Ni-Cu-Fe-Zr-Sc alloy in terms of its strength directionality and establish its potential for use in aerospace applications. [ABSTRACT FROM AUTHOR]

Nerolidol (3,7,11-trimethyl-1,6,10-dodecatrien-3-ol), a sesquiterpene alcohol present in aromatic essential oils of numerous plants, has been reported to possess anticancer activity. The potential therapeutic effect of nerolidol on uterine fibroids (UF), the most common benign tumor of the uterus worldwide, is unknown. In this study, we examined the anti-UF potential of nerolidol in ELT3 cells, a rat leiomyoma cell line widely used as an in vitro model, to identify the potential therapeutic agents for UF. We observed that treatment with cis - or trans -nerolidol inhibited cell proliferation in a dose-dependent manner and induced cell cycle arrest in the G1 phase, which was accompanied by reduction in Akt phosphorylation and downregulation of cyclin D1, cyclin-dependent kinase 4 (CDK4), and CDK6 protein expression. The proliferation-inhibiting activity of nerolidol correlated with the generation of intracellular reactive oxygen species (ROS), which was suppressed by N-acetyl-l-cysteine, a ROS inhibitor. Nerolidol treatment also increased the percentage of cells for which tail moment could be calculated using an alkaline comet assay, and induced p-γH2AXser139 expression, which indicated induction of DNA damage. We also observed downregulation of ATM and its phosphorylation after nerolidol treatment; furthermore, treatment with KU-55933, an ATM kinase inhibitor, mimicked the inhibitory effects of nerolidol treatment on cell proliferation and Akt phosphorylation. In conclusion, nerolidol displayed anti-UF activity in a leiomyoma cell model via ROS-induced DNA damage and G1 phase cell cycle arrest by inhibiting the expression and activation of the ATM/Akt pathway. Our data suggests that nerolidol is a potential therapeutic agent for UF. [Display omitted] • Nerolidol induces G1 phase arrest to reduce the proliferation of rat leiomyoma cells. • The inhibitory effect of nerolidol depends on reactive oxygen species generation. • Nerolidol induces DNA damage in rat leiomyoma cells. • Nerolidol reduces the activation of ATM/Akt kinases. • Inhibition of ATM mimics the effect of nerolidol in leiomyoma cells. [ABSTRACT FROM AUTHOR]

Designing appropriate support for noble metal-based catalyst has consistently been an effective strategy to improve the catalytic activity of ethanol electrooxidation reaction (EOR). Here, a novel heteroatom-doped carbon (HDC) material has been prepared by calcination of Schiff base metal complex precursor. The HDC-750 prepared at the optimum temperature (750 °C) has a three-dimensional structure with large specific surface area and unique pores. When the HDC-750 is used as a support for palladium nanoparticles, it can improve the conductivity of catalysts, the permeability of electrolyte and intermediates, and increase the number of anchoring points of palladium nanoparticles. Due to its unique three-dimensional structure and the synergistic enhancement effect of strong metal support interaction between Pd and HDC-750, the Pd/HDC-750 catalyst exhibits high electrochemical active surface area (23.94 m2 g Pd −1) and excellent EOR activity (146.3 mA cm−2), which is as high as 2.1 and 3.0 times of that for the Pd/C. After 3600 s durability test, the Pd/HDC-750 shows a high current density of 9.9 mA cm−2, while Pd/C shows only 1.3 mA cm−2. [ABSTRACT FROM AUTHOR]

• The solid electrolyte of iron compound powder ingots can enhance battery capacity. • The ferrous chloride will be converted into Fe 8 O 8 (OH) 8 Cl 1.35 during the charge-discharge cycle. • After charging-discharging, an abnormal layer forms at the interface of solid electrolyte and electrode, leading to interface expansion, cracks, and reduced electrode adhesion. This study investigates a Fe/SSE/GF battery. Iron (Fe) as cathode material contains higher electrical capacity and competitive advantages. The solid-state electrolyte (SSE) material is sodium silicate powder mixed with iron compound powders. There are four types of iron compounds: 1) iron oxide, 2) chlorinated/Na-rich iron oxide, 3) Cl-rich iron oxide, 4) ferrous chloride, which are compared with sodium silicate powder. The negative electrode material is graphite film (GF). According to experiments, converting iron into iron oxide or ferric chloride can enhance battery capacity (beyond 200 mAh/g) and cycle life. The reliability of the Fe/SSE/GF battery was assessed by substituting sodium silicate powder with an iron compound electrolyte and adding binder (Polyvinyl Alcohol, PVA) into powder to enhance the performance of Fe/SSE/GF. This experimental research is not only innovative but also represents a significant milestone in the field of solid-state energy storage. [ABSTRACT FROM AUTHOR]

Background: Hyaluronic acid (HA) gel is a widely used dermal filler for the correction of facial volume loss. The relationship between the characteristics of HA and clinical efficacy remains unclear. The aim of this systematic review and meta‐analysis was to compare the efficacy and safety of monophasic and biphasic HA in the treatment of nasolabial folds (NLFs). Methods: Studies were identified by searching the electronic databases PubMed, Embase, and Web of Science from inception to May 2021. Randomized controlled trials (RCTs) were selected according to the inclusion criteria. Outcomes included the Wrinkle Severity Rating Scale (WSRS) score, Global Aesthetic Improvement Scale score, and incidence of adverse events. Results: A total of 1190 patients from 14 RCTs were included in the meta‐analysis. The mean WSRS score improvement in the biphasic HA group was much lower than that in the monophasic HA group (MD = 0.18, 95% CI: 0.16–0.20, p < 0.00001). The subject satisfaction percentage was significantly higher for monophasic than biphasic HA (RR = 1.95, 95% CI: 1.09–3.48, p = 0.02). There was no significant difference in the adverse event rate between the monophasic and biphasic HA groups (RR = 0.96, 95% CI: 0.75–1.24, p = 0.77). Conclusions: Regardless of whether improvement in NLFs or patient satisfaction is considered, monophasic HA is better than biphasic HA. Regarding the adverse event rate, there is no difference between monophasic and biphasic HA. [ABSTRACT FROM AUTHOR]

• The batteries in this study can be assembled in ambient air and can be packaged easily. • Powder surface area increases by activating with HCl, demonstrating high capacity. • This study synthesizes a unique structure Simonkolleite. • The battery exhibits excellent electrical performance and cyclic stability. Zn solid-state batteries offer a novel and environmentally friendly energy storage solution with excellent safety features. This study explores the material characteristics and electrochemical mechanisms of the Zn anode and sodium silicate solid electrolyte powder after HCl chlorination. Results reveal the formation of Zn chloride hydroxide monohydrate (Zn 5 OH 8 Cl 2 ⋅H 2 O, known as Simonkolleite) in the zinc anode post HCl treatment. The compound's layered structure enhances ion transport. The sodium silicate electrolyte exhibits increased surface area after HCl treatment. In engineering applications, a solid-state battery assembled with Simonkolleite anode, electrolyte (HB), and graphite film (GF) cathode demonstrates a high capacity (>5000 mAh/g) in the first discharging cycle and impressive stability over 30–100 cycles, highlighting its promising potential for energy storage. [ABSTRACT FROM AUTHOR]

This study examined the cognitive-linguistic and literacy-related correlates of dyslexia in three Chinese cities and the English word reading and mathematics performances of Chinese children with dyslexia. Chinese children with/without dyslexia were measured with an equivalent test battery of literacy and mathematics in Beijing, Hong Kong, and Taipei. Univariate analysis results suggested that phonological sensitivity distinguished those with and without dyslexia across all three cities in group comparisons. In Taipei and Hong Kong, morphological awareness, delayed copying, and spelling also distinguished the groups. Logistic regression analyses demonstrated that Chinese character reading, as directly compared to Chinese word reading, also distinguished the groups particularly well. In addition, in Beijing and Hong Kong, children with dyslexia performed significantly less well in English word reading than those without dyslexia. In Hong Kong and Taipei, children with dyslexia also had difficulties in mathematics performance. Findings highlight the fundamental importance of some cognitive-linguistic skills for explaining Chinese dyslexia across cultures, the utility of recognizing the individual Chinese character as a foundational unit of analysis in Chinese across cultures, and the generalizability of the comorbidity of both English as a second language (L2) and mathematics with dyslexia in Chinese children in both Beijing and Hong Kong. [ABSTRACT FROM AUTHOR]

Metal powder metallurgy (PM) is widely utilized in the tool and automotive industries due to its near-net forming advantages. While PM aluminum alloys have been explored in numerous studies, their practical engineering applications are still limited. Thus, this research delves into the nuanced aspects of PM Al-Si-Mg-Fe alloy. By employing hot-rolled dynamic recrystallization to control the metallurgical texture and introducing T6 treatment to refine the microstructure. These optimizations aim to enhance the properties of PM aluminum alloy materials. Results revealed that grain coarsening in the PM Al-Si-Mg-Fe alloy hampers the grain boundary strengthening effects, thus limiting the strength. Moreover, the solid-solution treatment applied to the PM specimens efficiently disperses silicon particles within the matrix, preventing the aggregation of silicon particles and the associated brittle effect caused by interface peeling. By implementing a three-stage process, sintering-rolling-T6 treatment, the rolled-T6 exhibited impressive tensile strength (291 MPa) and ductility (17 %), highlighting the excellent engineering applicability of PM Al-alloys. TEM analysis confirmed the presence of nanoprecipitation Al 3 Mg and Al 9 Fe 2 hard components within the matrix, contributing to the strength enhancement. These findings not only represent a significant milestone in the advancement but also provide valuable references for engineering applications in the field of PM Al-alloys. • PM technology enhances Al-Si-Mg-Fe alloy applications. • Three-stage process optimizes microstructure and properties. • Microstructural effects and phase distribution are compared. • Reveals Al 9 Fe 2 and Al(Si) 3 Mg strengthening mechanisms. [ABSTRACT FROM AUTHOR]

The article discusses the routine testing and reporting of piperacillin/tazobactam susceptibility in Elizabethkingia species, which are increasingly prevalent pathogens in Asia. The study found that there is variability in the results of different susceptibility assays, leading to inconsistent reporting of susceptibility rates. In addition, the presence of a specific gene, blaB, in Elizabethkingia species was found to increase resistance to piperacillin/tazobactam and reduce its efficacy in vivo. The authors suggest that routine testing and reporting of piperacillin/tazobactam susceptibility in Elizabethkingia species may not be informative for treatment decisions. [Extracted from the article]

Allium victorialis L. (Family: Liliaceae) is an herb with nutritional and medicinal properties. In Jilin Province, China, A. victorialis is mainly distributed in the Changbai Mountains and grows in various habitat conditions. However, the relationship between habitat factors and the nutritional quality of A. victorialis in the Changbai Mountains has not yet been examined. We assessed the nutritional quality of five A. victorialis populations growing in five different habitats in the Changbai Mountains and analyzed the relationship between nutritional quality and habitat factors. Allium victorialis populations in this region were primarily found in the undergrowth at elevations above 500 m and within specific ranges of air temperature, air relative humidity, soil temperature, and soil water content. Among the habitat factors investigated, canopy density significantly affected several nutritional components of A. victorialis; however, elevation had a significant effect only on the total flavonoid content, and the vitamin C content was not strongly associated with the main habitat factors in this study. During germplasm selection and artificial cultivation, it is important to simulate the growth conditions of the original habitat. Our results provide useful information for site selection and environmental condition optimization for the artificial cultivation of A. victorialis. [ABSTRACT FROM AUTHOR]

• The stomatal distribution pattern of 90 plant species in Loess Plateau was studied. • Phylogeny affected stomatal density and distribution pattern to some extent. • Most stomatal patterns were similar, but there were some exceptions. • Stomatal density may affect stomatal distribution pattern. Stomata are the valves controlling carbon and water exchange between plant leaves and the atmosphere. Stomatal position changes throughout the whole growth of leaves, and the position is gradually fixed until the leaves mature, whether stomatal spatial distributions exhibit clear patterning remains unclear. In this study, we measured stomatal density and stomatal position of 90 widespread plants from the Loess Plateau, quantifying the spatial patterns of stomatal distribution using replicated spatial point pattern analysis. The results showed that the stomatal distribution pattern was similar in all plants except five species (Ginkgo biloba , Festuca glauca , Hemerocallis fulva , Hylotelephium spectabile and Kochia scoparia). Stomatal density, aggregation and uniform distribution were slightly affected by phylogeny and depended on spatial scale of analysis. At small spatial scales (0–60 μm), were regularly distributed but at large spatial scales (60–400 µm) they were randomly distributed. Stomatal density was negatively correlated (p < 0.001) with the proportion of randomly distributed and positively correlated (p < 0.001) with the proportion of stomatal aggregated distributed, and no significant effect on the proportion of stomatal uniform distribution. These results highlight the linkages between stomatal distribution and phylogeny, which may provide reference for future optimization of transpiration models. [ABSTRACT FROM AUTHOR]

Sepsis causes multiple organ injuries, among which the heart is one most severely damaged organ. Melatonin (MEL) alleviates septic myocardial injury, although a systematic and comprehensive approach is still lacking to understand the precise protective machinery of MEL. This study aimed to examine the underlying mechanisms of MEL on improvement of septic myocardial injury at a systematic level. This study integrated three analytic modalities including database investigations, RNA-seq analysis, and weighted gene co-expression network analysis (WCGNA), in order to acquire a set of genes associated with the pathogenesis of sepsis. The Drugbank database was employed to predict genes that may serve as pharmacological targets for MEL-elicited benefits, if any. A pharmacological protein-protein interaction network was subsequently constructed, and 66 hub genes were captured which were enriched in a variety of immune response pathways. Notably, PIK3CG, one of the hub genes, displayed high topological characteristic values, strongly suggesting its promise as a novel target for MEL-evoked treatment of septic myocardial injury. Importantly, molecular docking simulation experiments as well as in vitro and in vivo studies supported an essential role for PIK3CG in MEL-elicited effect on septic myocardial injury. This study systematically clarified the mechanisms of MEL intervention in septic myocardial injury involved multiple targets and multiple pathways. Moreover, PIK3CG-governed signaling cascade plays an important role in the etiology of sepsis and septic myocardial injury. Findings from our study provide valuable information on novel intervention targets for the management of septic myocardial injury. More importantly, this study has indicated the utility of combining a series of techniques for disease target discovery and exploration of possible drug targets, which should shed some light on elucidation of experimental and clinical drug action mechanisms systematically. [ABSTRACT FROM AUTHOR]

Urological cancers are among the most common malignancies around the world. In particular, bladder cancer severely threatens human health due to its aggressive and heterogeneous nature. Various therapeutic modalities have been considered for the treatment of bladder cancer although its prognosis remains unfavorable. It is perceived that treatment of bladder cancer depends on an interdisciplinary approach combining biology and engineering. The nanotechnological approaches have been introduced in the treatment of various cancers, especially bladder cancer. The current review aims to emphasize and highlight possible applications of nanomedicine in eradication of bladder tumor. Nanoparticles can improve efficacy of drugs in bladder cancer therapy through elevating their bioavailability. The potential of genetic tools such as siRNA and miRNA in gene expression regulation can be boosted using nanostructures by facilitating their internalization and accumulation at tumor sites and cells. Nanoparticles can provide photodynamic and photothermal therapy for ROS overgeneration and hyperthermia, respectively, in the suppression of bladder cancer. Furthermore, remodeling of tumor microenvironment and infiltration of immune cells for the purpose of immunotherapy are achieved through cargo-loaded nanocarriers. Nanocarriers are mainly internalized in bladder tumor cells by endocytosis, and proper design of smart nanoparticles such as pH-, redox-, and light-responsive nanocarriers is of importance for targeted tumor therapy. Bladder cancer biomarkers can be detected using nanoparticles for timely diagnosis of patients. Based on their accumulation at the tumor site, they can be employed for tumor imaging. The clinical translation and challenges are also covered in current review. [ABSTRACT FROM AUTHOR]

The article offers information that the Betta fish is indigenous to central Thailand and the lower Mekong and is mostly known for its domesticated forms appreciated as an ornamental fish but was originally bred for its use in gambling matches similar to cock fights. It also mentions that researchers have examined the inheritance of body color, fin length, and sex determination in classic crosses in the 1930s to 1940s.

The Brassicaceae is an important plant family. We built a user-friendly, web-based, comparative, and functional genomic database, The Brassicaceae Genome Resource (TBGR, http://www.tbgr.org.cn), based on 82 released genomes from 27 Brassicaceae species. The TBGR database contains a large number of important functional genes, including 4,096 glucosinolate genes, 6,625 auxin genes, 13,805 flowering genes, 36,632 resistance genes, 1,939 anthocyanin genes, and 1,231 m6A genes. A total of 1,174,049 specific guide sequences for clustered regularly interspaced short palindromic repeats and 5,856,479 transposable elements were detected in Brassicaceae. TBGR also provides information on synteny, duplication, and orthologs for 27 Brassicaceae species. The TBGR database contains 1,183,851 gene annotations obtained using the TrEMBL, Swiss-Prot, Nr, GO, and Pfam databases. The BLAST, Synteny, Primer Design, Seq_fetch, and JBrowse tools are provided to help users perform comparative genomic analyses. All the genome assemblies, gene models, annotations, and bioinformatics results can be easily downloaded from the TBGR database. We plan to improve and continuously update the database with newly assembled genomes and comparative genomic studies. We expect the TBGR database to become a key resource for the study of the Brassicaceae. [ABSTRACT FROM AUTHOR]

Variety identification plays an important role in protecting the intellectual property of varieties, ensuring seed quality, and encouraging breeding innovation. Currently, morphological evaluation in the field, such as distinctness, uniformity, and stability (DUS) testing, and DNA fingerprinting in the laboratory using molecular markers are two dominant methods used for variety identification. Few studies have compared the results of these approaches, and the relationship between the two methods is obscure. In this study, 134 dominant cucumber varieties were evaluated using 50 DUS testing traits and genotyped by 40 single nucleotide polymorphisms (SNPs). The 40 SNPs were developed in our previous study and are well suited for variety identification. In the DUS testing, significant positive or negative correlations among 50 DUS traits were observed, and 20 core traits, including 15 fruit traits, were further selected to increase field inspection efficiency. This suggested that fruit shape plays an important role in variety identification. The ratio of fruit length/diameter was the most important trait, explaining 9.2% of the phenotypic variation. In the DNA fingerprinting test, the 40 SNPs were highly polymorphic and could distinguish all of the 134 cucumber varieties, and 14 core SNPs were selected to improve the identification rate. Interestingly, the population structure analysis of 134 cucumber varieties by phenotypic data in the DUS test was in accordance with the genotypic data from the DNA fingerprinting, indicating that all varieties could be divided into the same four subgroups: European type, North China type, South China type, and hybrids of the North China and South China types. Moreover, linear correlativity of distinguishment for each pair of varieties was observed between the DUS test and the DNA fingerprinting. These results indicated that these two methods have good application in future research, especially for the scaled-up analysis of hundreds of varieties. [ABSTRACT FROM AUTHOR]

On analyzing the results of cell-based assays, we have previously shown that perilla (Perilla frutescens) leaf extract (PLE), a food supplement and orally deliverable traditional Chinese medicine approved by the Taiwan Food and Drug Administration, effectively inhibits SARS-CoV-2 by directly targeting virions. PLE was also found to modulate virusinduced cytokine expression levels. In this study, we explored the anti-SARS-CoV-2 activity of PLE in a hamster model by examining viral loads and virus-induced immunopathology in lung tissues. Experimental animals were intranasally challenged with different SARS-CoV-2 doses. Jugular blood samples and lung tissue specimens were obtained in the acute disease stage (3-4 post-infection days). As expected, SARS-CoV-2 induced lung inflammation and hemorrhagic effusions in the alveoli and perivascular areas; additionally, it increased the expression of several immune markers of lung injury -- including lung Ki67-positive cells, Iba-1-positive macrophages, and myeloperoxidase-positive neutrophils. Virus-induced lung alterations were significantly attenuated by orally administered PLE. In addition, pretreatment of hamsters with PLE significantly reduced viral loads and immune marker expression. A purified active fraction of PLE was found to confer higher antiviral protection. Notably, PLE prevented SARS-CoV-2-induced increase in serum markers of liver and kidney function as well as the decrease in serum high-density lipoprotein and total cholesterol levels in a dose-dependent fashion. Differently from lung pathology, monitoring of serum biomarkers in Syrian hamsters may allow a more humane assessment of the novel drugs with potential anti-SARS-CoV-2 activity. Our results expand prior research by confirming that PLE may exert an in vivo therapeutic activity against SARS-CoV-2 by attenuating viral loads and lung tissue inflammation, which may pave the way for future clinical applications. [ABSTRACT FROM AUTHOR]

Contamination by pathogens, such as bacteria, can irritate a wound and prevent its healing, which may affect the physical fitness of the infected person. As such, the development of more novel nano-biomaterials able to cope with the inflammatory reaction to bacterial infection during the wound healing process to accelerate wound healing is required. Herein, a halofuginone‑silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. HTPM&AgNPs-gel was characterized based on thermogravimetric analysis, differential scanning calorimetry, morphology, injectability, and rheological mechanics that reflected its exemplary nature. Moreover, HTPM&AgNPs-gel was further tested for its ability to facilitate healing of skin fibroblasts and exert antibacterial activity. Finally, HTPM&AgNPs-gel was tested for its capacity to accelerate general wound healing and treat bacterially induced wound damage. HTPM&AgNPs-gel appeared spherical under a transmission electron microscope and showed a grid structure under a scanning electron microscope. Additionally, HTPM&AgNPs-gel demonstrated excellent properties, including injectability, temperature-dependent swelling behavior, low loss at high temperatures, and appropriate rheological properties. Further, HTPM&AgNPs-gel was found to effectively promote healing of skin fibroblasts and inhibit the proliferation of Escherichia coli and Staphylococcus aureus. An evaluation of the wound healing efficacy demonstrated that HTPM&AgNPs-gel had a more pronounced ability to facilitate wound repair and antibacterial effects than HTPM-gel or AgNPs-gel alone, and exhibited ideal biocompatibility. Notably, HTPM&AgNPs-gel also inhibited inflammatory responses in the healing process. HTPM&AgNPs-gel exhibited antibacterial, anti-inflammatory, and scar repair features, which remarkably promoted wound healing. These findings indicated that HTPM&AgNPs-gel holds great clinical potential as a promising and valuable wound healing treatment. [Display omitted] • Halofuginone‑silver thermosensitive nanohydrogels (HTPM&AgNPs-gel) had excellent properties, including injectable, thermosensitive, favorable hemocompatibility, and a slow-release. • HTPM&AgNPs-gel exhibited excellent antibacterial and anti-inflammatory properties with scar removal compared with commercial thermosensitive nanohydrogels. • HTPM&AgNPs-gel effectively contributes to the wound-repair process and is a potential candidate bioactive wound dressing that may support full-thickness skin wound healing. [ABSTRACT FROM AUTHOR]

Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair-proficient (pMMR) CRCs make up about 95% of metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models of orthotopic pMMR CRC liver metastasis accurately recapitulate the inefficacy of ICB therapy in patients, whereas the same pMMR CRC tumors are sensitive to ICB therapy when grown subcutaneously. To reveal local, nonmalignant components that determine CRC sensitivity to treatment, we compared the microenvironments of pMMR CRC cells grown as liver metastases and subcutaneous tumors. We found a paucity of both activated T cells and dendritic cells in ICB-treated orthotopic liver metastases, when compared with their subcutaneous tumor counterparts. Furthermore, treatment with Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 ligand (Flt3L) plus ICB therapy increased dendritic cell infiltration into pMMR CRC liver metastases and improved mouse survival. Lastly, we show that human CRC liver metastases and microsatellite stable (MSS) primary CRC have a similar paucity of T cells and dendritic cells. These studies indicate that orthotopic tumor models, but not subcutaneous models, should be used to guide human clinical trials. Our findings also posit dendritic cells as antitumor components that can increase the efficacy of immunotherapies against pMMR CRC. [ABSTRACT FROM AUTHOR]

Cyclic dimeric guanosine monophosphate (c-di-GMP) is an important second messenger in bacteria. It regulates a wide range of bacterial functions and behaviors including biofilm formation that causes chronic infections and antibiotic resistance. C-di-GMP being as a signal transducer in bacteria is known to exist in monomer and dimer form. Recent studies also discover that c-di-GMP can form higher-order oligomers, such as tetramer and octamer, which may have physiological roles in bacterial cells. Moreover, the tetrameric c-di-GMP structure was reported to link two subunits of a transcription factor (BldD), which controls the progression of multicellular differentiation in sporulating actinomycete bacteria and then mediates the dimerization process. Current understanding on higher-order oligomers of c-di-GMP is relatively limited compared to its monomer or dimer structure. To probe and visualize the higher-order structure of c-di-GMP and its associated biofunctions in live bacterial cells with fluorescence techniques for mechanistic study and cellular investigation is important. Nonetheless, the sensitive and selective fluorescent probe with a rapid signal response for higher-order oligomers of c-di-GMP is currently lacking. In the present study, a series of fluorescent probes that preferentially interacted with tetrameric c-di-GMP and generated red fluorescence signal promptly were synthesized and investigated. The interaction mechanism was studied with 1H NMR and molecular docking. In addition, the ligand was demonstrated as an excellent molecular fluorescent probe for bioimaging of tetrameric c-di-GMP structure and monitoring of biofilm formation on both biotic and abiotic surfaces with pathogenic bacteria including Pseudomonas aeruginosa PAO1 and Bacillus subtilis 168. [Display omitted] • A novel c-di-GMP tetramer-specific red fluorescent probe was developed. • Monitoring of bacterial biofilm formation on biotic and abiotic surfaces. • Naked-eye visualization of biofilms with a portable blue LED illuminator. • Real-time imaging of tetrameric c-di-GMP structure in live bacterial cells. • Visualizing biofilm of pathogenic bacterial cells such as PAO1 and B. subtilis. [ABSTRACT FROM AUTHOR]

Cyclic dimeric guanosine monophosphate (c-di-GMP) is an important second messenger in bacteria. It regulates a wide range of bacterial functions and behaviors including biofilm formation that causes chronic infections and antibiotic resistance. C-di-GMP being as a signal transducer in bacteria is known to exist in monomer and dimer form. Recent studies also discover that c-di-GMP can form higher-order oligomers, such as tetramer and octamer, which may have physiological roles in bacterial cells. Moreover, the tetrameric c-di-GMP structure was reported to link two subunits of a transcription factor (BldD), which controls the progression of multicellular differentiation in sporulating actinomycete bacteria and then mediates the dimerization process. Current understanding on higher-order oligomers of c-di-GMP is relatively limited compared to its monomer or dimer structure. To probe and visualize the higher-order structure of c-di-GMP and its associated biofunctions in live bacterial cells with fluorescence techniques for mechanistic study and cellular investigation is important. Nonetheless, the sensitive and selective fluorescent probe with a rapid signal response for higher-order oligomers of c-di-GMP is currently lacking. In the present study, a series of fluorescent probes that preferentially interacted with tetrameric c-di-GMP and generated red fluorescence signal promptly were synthesized and investigated. The interaction mechanism was studied with 1H NMR and molecular docking. In addition, the ligand was demonstrated as an excellent molecular fluorescent probe for bioimaging of tetrameric c-di-GMP structure and monitoring of biofilm formation on both biotic and abiotic surfaces with pathogenic bacteria including Pseudomonas aeruginosa PAO1 and Bacillus subtilis 168. [Display omitted] • A novel c-di-GMP tetramer-specific red fluorescent probe was developed. • Monitoring of bacterial biofilm formation on biotic and abiotic surfaces. • Naked-eye visualization of biofilms with a portable blue LED illuminator. • Real-time imaging of tetrameric c-di-GMP structure in live bacterial cells. • Visualizing biofilm of pathogenic bacterial cells such as PAO1 and B. subtilis. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel mitochondria-specific fluorescent turn-on probe with high photostability was developed. • Selectively interacting with G-quadruplexes of mitochondrial DNA and giving red emission signal. • The probe showed high selectivity and sensitivity and good linear relationship toward mitochondrial G4-DNA. • The probe can be used to monitor the dynamic process of mitochondrial autophagy. A series of new mitochondrial-selective fluorescent probe was designed and synthesized based on the integration of two planar molecular scaffolds of benzo-indole/indole with a p -substituted styrene moiety. The small-sized probes are flexible and rotatable via an ethylene bridge. The restriction of free rotation upon interaction with targeting biomolecules of G-quadruplexes in mitochondria generates strong emission in visible range (575–615 nm). Cell imaging study showed that the ligands are targeting mitochondria but not nucleus. Competition experiments showed that the ligand BYM is highly selective towards mitochondrial G4-DNA structures against other non-G4 nucleic acid structures including single-/double-stranded DNA and hairpin. The equilibrium binding constant (K eq) of BYM interacting with mitochondrial G4-DNA (mt6363, K eq = 10.8 × 106 M−1) is almost 1000-fold higher than that of mitochondrial double-stranded DNA (K eq = 0.01 × 106 M−1). The probe also showed high sensitivity (LOD = 1.52 nM) and good linear relationship (R2 = 0.9983) with the mitochondrial G4-DNA. The delivery of BYM to mitochondria is not mitochondrial membrane potential dependent but mainly through the permeability transition pore on the mitochondrial inner membrane. In addition, BYM exhibits low cytotoxicity against a number of human cancer and noncancerous cells, indicating that BYM could be a good ligand for bioorthogonal study in live cells by targeting the mitochondrial G4-DNA structures. In the present study, BYM was demonstrated in monitoring the dynamic process of mitochondrial autophagy. The small-sized fluorescent probe possessing high photostability, selectivity and sensitivity targeting mitochondrial G-quadruplexes may able to provide a useful chemical tool for real-time study of mitochondrial functions in live cells. [ABSTRACT FROM AUTHOR]

Skin Interstitial Fluid (ISF) is an alternative source for biomarkers. Herein, a highly swellable microneedle patch (MNP) to rapidly extract ISF painlessly and bloodlessly is presented. The MNP is made of crosslinked methacrylated hyaluronic acid (MeHA) and dissolvable hyaluronic acid (HA) with the optimal balance of mechanical strength (0.6 N/MN) and absorption capability (16.22 μL in 20 min). Incorporated with wax-patterned and sensing-reagent-decorated test paper (TP) for multiplexed colorimetric detection of metabolites (glucose, lactate, cholesterol, and pH), this TP-MNP biosensor gives rapid color change in biomarker concentration-dependent manner based on specific enzymatic reactions, whereby allowing diagnosis by the naked eye or quantitative RGB analysis. Both the in vitro and in vivo experiments demonstrate the feasibility of TP-MNPs to detect multiple biomarkers in skin interstitial fluid within minutes. Such convenient and self-administrable profiling of metabolites shall be instrumental for home-based long-term monitoring and management of metabolic diseases. [ABSTRACT FROM AUTHOR]

Cisplatin-based chemotherapy is the standard treatment for bladder urothelial carcinoma (UC). Most patients experience chemoresistance, the primary cause of treatment failure, which leads to disease relapse. The underlying mechanism of chemoresistance involves reduced apoptosis. In this study, we investigated the antitumor effect of the deubiquitylating enzyme inhibitor PR-619 in cisplatin-resistant bladder UC. Deubiquitinase (ubiquitin-specific protease 14 (USP14) and USP21) immunohistochemical staining demonstrated that deubiquitination is related to chemoresistance in patients with metastatic UC and may be a target for overcoming chemoresistance. Cytotoxicity and apoptosis were assessed using fluorescence-activated flow cytometry and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay, and PR-619 was found to enhance the cytotoxic and apoptotic effects of cisplatin in cisplatin-resistant T24/R cells. Mitigated cisplatin chemoresistance was associated with the concurrent suppression of c-Myc expression in T24/R cells. Moreover, the expression of c-Myc was upregulated in human bladder UC specimens from patients with chemoresistance. Experiments in a xenograft nude mouse model confirmed that PR-619 enhanced the antitumor effects of cisplatin. These results are promising for the development of therapeutic strategies to prevent UC chemoresistance through the combined use of chemotherapeutic agents/deubiquitination inhibitors (PR-619) by targeting the c-Myc pathway. [ABSTRACT FROM AUTHOR]