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The primary objective of the paper is the numerical and experimental investigation related to the damage recognition effects for CFRP tubes of four dynamic parameters. Four damage identification indexes consisting of natural frequency‐based index, Mode Shape‐based index (MS), Mode Shape Curvature‐based index (MSC), and Modal Flexibility Curvature‐based index (MFC) are established by analyzing the dynamic parameter data obtained before and after damage occurs. The performances of dynamic parameters are thoroughly discussed in the context of numerical simulations and experiment. The results indicate that the effect of natural frequency is not as significant as that of mode shape. MFC has the most notable effectiveness out of the four indexes. The simulation peak index pair is predicted to rise from 0.3 to 0.6 as the damage in the simulation model increases by 25% from 12.5%, indicating that MFC can feedback the damage degree. Moreover, the circumferential curvature index exhibits superior performance compared to the axial curvature index. To enhance the accuracy of the axial curvature index, it is proposed to increase the number of measuring sites along the tube's long direction. Highlights: Damage identification indexes of four dynamic parameters are established.Discuss the identification ability of dynamic parameters by simulation and test.Two numerical models of CFRP tube with delamination damage are established.Impact and modal tests are executed to study the ability of four indexes. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to determine whether inhibition of mitophagy affects seizures through Clathrin‐mediated endocytosis (CME). Methods: Pentylenetetrazol (PTZ) was intraperitoneally injected daily to establish a chronic PTZ‐kindled seizure. The Western blot (WB) was used to compare the differences in Parkin protein expression between the epilepsy group and the control group. Immunofluorescence was used to detect the expression of MitoTracker and LysoTracker. Transferrin‐Alexa488 (Tf‐A488) was injected into the hippocampus of mice. We evaluated the effect of 3‐methyladenine (3‐MA) on epilepsy behavior through observation in PTZ‐kindled models. Results: The methylated derivative of adenine, known as 3‐MA, has been extensively utilized in the field of autophagy research. The transferrin protein is internalized from the extracellular environment into the intracellular space via the CME pathway. Tf‐A488 uses a fluorescent marker to track CME. Western blot showed that the expression of Parkin was significantly increased in the PTZ‐kindled model (p < 0.05), while 3‐MA could reduce the expression (p < 0.05). The fluorescence uptake of MitoTracker and LysoTracker was increased in the primary cultured neurons induced by magnesium‐free extracellular fluid (p < 0.05); the fluorescence uptake of Tf‐A488 was significantly decreased in the 3‐MA group compared with the control group (p < 0.05). Following hippocampal injection of Tf‐A488, both the epilepsy group and the 3‐MA group exhibited decreased fluorescence uptake, with a more pronounced effect observed in the 3‐MA group. Inhibition of mitophagy by 3‐MA from day 3 to day 9 progressively exacerbated seizure severity and shortened latency. Significance: It is speculated that the aggravation of seizures by 3‐MA may be related to the failure to remove damaged mitochondria in time and effectively after inhibiting mitochondrial autophagy, affecting the vesicle endocytosis function of CME and increasing the susceptibility to epilepsy. Summary: Abnormal mitophagy was observed in a chronic pentylenetetrazol‐induced seizure model and a Mg2+‐free‐induced spontaneous recurrent epileptiform discharge model. A fluorescent transferrin marker was utilized to track clathrin‐mediated endocytosis. Using an autophagy inhibitor (3‐methyladenine) on primary cultured neurons, we discovered that inhibition of autophagy led to a reduction in fluorescent transferrin uptake, while impairing clathrin‐mediated endocytosis function mediated by mitophagy. Finally, we examined the effects of 3‐methyladenine in an animal model of seizures showing that it exacerbated seizure severity. Ultimately, this study provides insights into potential mechanisms through which mitophagy regulates clathrin‐mediated endocytosis in epilepsy. [ABSTRACT FROM AUTHOR]

Improving polarizability is an important strategy for designing high‐performance mid‐infrared (mid‐IR) nonlinear optical (NLO) materials. The substitution of equivalent or aliovalent atoms can manipulate the polarizability by adjusting the symmetry of the polyhedron. Herein, the Li+ and Cd2+ are introduced into the Cu3PS4 as the equivalent and aliovalent dopants for the Cu site. As a result, Li+ can significantly improve the bandgap (Eg) of LixCu3−xPS4 from 2.38 to 2.88 eV, leading to a higher laser‐induced damage threshold (LIDT) of 4.9 times than AgGaS2 (AGS) with a comparable second harmonic generation (SHG) response of AGS (26−45 µm). Interestingly, Cd2+ can improve the SHG response and enlarge the Eg simultaneously. As a result, Cd0.4Cu2.2PS4 has a large SHG response of 10 × AGS at 2050 nm (26−45 µm) and a LIDT of 2.6 × AGS. Theoretical calculations reveal that lattice vacancies induced by Cd2+ significantly boost polarizability compared to LixCu3−xPS4 with no vacancy, leading to a strong NLO response. [ABSTRACT FROM AUTHOR]

Although orthorhombic GeSe is predicted to have an ultrahigh figure of merit, ZT ≈ 2.5, up to now, the highest experimental value is ≈0.2 due to the low carrier concentration (nH ≈ 1018 cm−3). Improving symmetry is an effective approach for enhancing the ZT of GeSe‐based materials. With Te‐alloying, Ge4Se3Te displays the two‐dimensional hexagonal structure and high nH ≈ 1.23 × 1021 cm−3. Interestingly, Ge4Se3Te transformed from the hexagonal into the rhombohedral phase with only ≈2% I–V–VI2‐alloying (I = Li, Na, K, Cu, Ag; V = Sb, Bi; VI = Se, Te). According to the calculated results of Ge0.82Ag0.09Bi0.09Se0.614Te0.386 single‐crystal grown via AgBiTe2‐alloying, it exhibits a higher valley degeneracy than the hexagonal Ge4Se3Te. For instance, AgBiTe2‐alloying induces a strong band convergence and band inversion effect, resulting in a significantly enhanced Seebeck coefficient and power factor with a similar nH from 17 µV K−1 and 0.63 µW cm−1 K−2 for pristine Ge4Se3Te to 124 µV K−1 and 5.97 µW cm−1 K−2 for 12%AgBiTe2‐alloyed sample, respectively. Moreover, the sharply reduced phonon velocity, nano‐domain wall structure, and strong anharmonicity lead to low lattice thermal conductivity. As a result, a record‐high average ZT ≈0.95 over 323–773 K with an excellent ZT ≈ 1.30 is achieved at 723 K. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) remains an essential challenge in the clinics due to the ferroptosis of nucleus pulposus cells (NPCs) and the imbalance of extracellular matrix (ECM) metabolism. Here, a dynamic hydrogel (HPGO) based on oxidized hyaluronic acid (OHA) and polyvinyl alcohol (PVA) for the integration of oridonin (Ori)‐loaded NPC membrane‐based nanovesicles is proposed, which is further grafted with growth and differentiation factor 5 (GDF5) on the OHA chain via Schiff base ligation. The precursors can rapidly form mechanically resilience hydrogels after injection into nucleus pulposus (NP) through the formation of various dynamic bonds. Meanwhile, the acidic pH in the degenerated NP can trigger the responsive release of GDF5, which may cooperate with Ori to alleviate inflammation in the microenvironment for restoring the metabolic homeostasis of ECM. In addition, the Schiff base moieties in HPGO hydrogel can scavenge free ferrous ions in the microenvironment to strengthen the dynamic bonds for self‐regulated reinforcement, thus providing mechanical support for the degenerated intervertebral discs (IVDs). Furthermore, HPGO hydrogel can enhance ferroptosis resistance of NPCs by activating the nuclear factor erythoid 2‐related factor 2 signaling pathway. Overall, HPGO hydrogel can mechanically support the damaged IVDs as well as reversing their degenerative status through cooperative ferroptosis inhibition, which provides an approach for the clinical treatment of IDD. [ABSTRACT FROM AUTHOR]

Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα‐negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc‐finger transcriptional factor, recruited lysine‐specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα‐positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα‐positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression‐induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse‐free survival and overall survival in ERα‐positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial–mesenchymal transition in BC. [ABSTRACT FROM AUTHOR]

Flexible conductive materials capable of simulating transparent ocean organisms have garnered interest in underwater motion monitoring and covert communication applications. However, the creation of underwater flexible conductors that possess mechanical robustness, adhesion, and self‐healing properties remains a challenge. Herein, hydrophobic interaction is combined with electrostatic interaction to obtain a solvent‐free transparent poly(ionic liquid) elastomer (PILE) fabricated using soft acrylate monomers and acrylate ionic liquids. The synergy of hydrophobic and electrostatic interactions can eliminate the hydration of water molecules underwater, giving the PILE adjustable fracture strength, good elasticity, high stretchability, high toughness, fatigue resistance, underwater self‐healing ability, underwater adhesion, and ionic conductivity. As a result, the transparent iontronic sensor generated from the PILE can achieve multifunctional sensing and human motion detection with high sensitivity and stability. In particular, the sensor can also transmit information underwater through stretching, pressing, and non‐contact modes, demonstrating its huge potential in underwater flexible iontronic devices. [ABSTRACT FROM AUTHOR]

In light of the rapid development of intelligence and miniaturization in electronics, the growing demand for sustainable energy sources gives rise to a plethora of environmental/mechanical energy harvesters. However, the fluctuating nature of these generated energies frequently presents a challenge to their immediate usability. Although electrolytic capacitors can smooth fluctuating energy, lacking miniaturization and flexibility constrain their potential applications. Conversely, electrochemical capacitors (ECs), particularly fiber‐shaped electrochemical capacitors (FSECs), can offer superior flexibility. Nevertheless, the inherent trade‐off between ion transport and charge storage in fibrous electrodes poses a significant obstacle to their filtering capability. Here, a hierarchically 3D fibrous electrode that effectively balances ion transport and charge storage through its unhindered primary framework and intertwined secondary frameworks is presented. The resulting FSEC exhibits an exceptional specific areal capacitance of 1.37 mF cm−2 with a phase angle of −82° at 120 Hz, surpassing that of fiber‐shaped filter capacitors and most non‐fibrous filter ECs previously reported. Additionally, the FSEC displays excellent flexibility and high‐frequency response, rendering it well‐suited for filtering arbitrary ripple voltage and compatible with environmental/mechanical energy harvesters. These results demonstrate a promising approach for designing fibrous high‐frequency response electrodes and a foundation for portable environmental energy harvesting devices. [ABSTRACT FROM AUTHOR]

Aim: To assess whether small‐for‐gestational‐age (SGA) – an indicator of poor fetal growth, may affect metabolic health biomarkers in infancy and explore the predictors. Methods: This was a nested matched (1:2) prospective observational study of 65 SGA (birth weight < 10th percentile) and 130 optimal‐for‐gestational‐age (OGA, birth weight 25th‐75th percentiles, control) infants in the 3D birth cohort with subjects recruited in Canada from 1 May 2010 to 31 August 2012. The outcomes included homeostasis model assessment of insulin resistance (HOMA‐IR) and beta‐cell function (HOMA‐β), circulating leptin and adiponectin concentrations at age 2 years. Results: HOMA‐IR, HOMA‐β, leptin and adiponectin concentrations were similar in SGA versus OGA infants. Female sex and accelerated growth in length during mid‐infancy (3–12 months) were associated with higher HOMA‐IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12–24 months) were associated with lower HOMA‐IR. Current BMI was positively associated with circulating adiponectin in SGA infants only (+13.4% [4.0%–23.7%] per BMI z score increment). Conclusion: Insulin resistance and secretion, circulating leptin and adiponectin levels were normal in SGA subjects in infancy at age 2 years. The novel observation in SGA‐specific positive association between current BMI and circulating adiponectin suggests dysfunctional adiposity‐adiponectin negative feedback loop development during infancy in SGA subjects. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a common inflammatory bowel disease driven by the dyshomeostasis of intestinal immune system and microbiota, but its treatment options are limited due to impaired epithelial barrier integrity and function. Herein, a multifunctional biomimetic hydrogel is developed as artificial colonic mucosa, which can readily establish a bioadhesive barrier at the ulcer site and restore local immune and microbial homeostasis to exert potent anti‐inflammatory effect. The hydrogel framework is generated through the thrombin‐mediated activation and polymerization of fibrinogen that resembles natural blood coagulation mechanism. During this process, the antibacterial agent Ag+ is used for the crosslinking between the generated fibrin units and dopamine/thiol‐modified hyaluronic acid biopolymers via Ag+‐thiol coordination to convey enhanced bioadhesiveness, while the interconnected porous network is employed to encapsulate basic fibroblast growth factor (bFGF) and alanyl‐glutamine (ALG) for mucosa regeneration. The hydrogel stably adheres to the ulcer site to protect and repair the damaged epithelium and establishes an anti‐inflammatory microenvironment by inducing locoregional M1‐to‐M2 macrophage repolarization while eliminating harmful gut flora, which can act in a cooperative manner to substantially alleviate UC symptoms. The biomimetic hydrogel here presents a promising approach for effective UC therapy in the clinics. [ABSTRACT FROM AUTHOR]

The alloy materials of automotive chassis are subjected to sequential time‐varying loads due to road unevenness. The continuous change of the loading mode and the stress ratio leads to cyclic plasticity of the material, which induces cyclic hardening. The estimation of hardening effects seriously affects the structural's fatigue properties. Therefore, herein, a hardening model and the corresponding fatigue life prediction model are proposed. Then, the loading sequence effect's influence on an Al–Mg–Si alloy's cyclic hysteretic characteristics is analyzed. The steering knuckle is taken as the verification object. The acquired load spectrum is transformed into three sequential forms according to the equivalent damage principle for the verification test. The test results verify the conjecture of the loading sequence effect and confirm the accuracy of the proposed prediction model. [ABSTRACT FROM AUTHOR]

This study investigates Ga‐doped n‐type PbTe thermoelectric materials and the dynamic phase conversion process of the second phases via Cu2Se alloying. Introducing Cu2Se enhances its electrical transport properties while reducing its lattice thermal conductivity (κlat) via weak electron–phonon coupling. Cu2Te and CuGa(Te/Se)2 (tetragonal phase) nanocrystals precipitate during the alloying process, resulting in Te vacancies and interstitial Cu in the PbTe matrix. At room temperature, Te vacancies and interstitial Cu atoms serve as n‐type dopants, increasing the carrier concentration and electrical conductivity from ≈1.18 × 1019 cm−3 and ≈1870 S cm−1 to ≈2.26 × 1019 cm−3 and ≈3029 S cm−1, respectively. With increasing temperature, the sample exhibits a dynamic change in Cu2Te content and the generation of a new phase of CuGa(Te/Se)2 (cubic phase), strengthening the phonon scattering and obtaining an ultralow κlat. Pb0.975Ga0.025Te‐3%CuSe exhibits a maximum figure of merit of ≈1.63 at 823 K, making it promising for intermediate‐temperature device applications. [ABSTRACT FROM AUTHOR]

Pollination precision and efficiency have been deemed to be important driving forces in floral evolution. Herkogamy reduction is a main mechanism to increase pollination precision. Secondary pollen presentation (SPP), by which pollen is presented on other floral organs especially pistils, has been widely accepted as a special mechanism to increase pollen transfer precision through spatial reduction of the anther–stigma distance, that is, minimized herkogamy. This overlooks a potential driving force, that is expanding the pollination niche through converting pollen thieves and nectar robbers into effective pollinators. We selected two species as study models with typical pistillate SPP, Pavetta hongkongensis Bremek. (Rubiaceae) and Scaevola taccada (Gaertn.) Roxb. (Goodeniaceae). In both species, two distinct pollinator functional groups were recognized. Short‐tongued bees and flies fed on pollen on stigmas but also stole pollen from anthers and robbed nectar, whereas long‐tongued hawkmoths and butterflies only collected nectar. Emasculation had no influence on long‐tongued pollinators, but significantly decreased the visitation frequency of short‐tongued visitors and fruit set, compared to intact flowers, demonstrating short‐tongued visitors did not effectively pollinate and acted merely as pollen thieves or nectar robbers when SPP was absent. Data from the two plant species clearly indicated pistillate SPP has additional adaptive advantages of converting ineffective visitors into pollinators and consequently widening the pollination niche, which could help plants overcome environmental stochasticity. Our results suggest that multiple selective forces drive the evolution of SPP and the minimization of herkogamy. [ABSTRACT FROM AUTHOR]

Regulated cell death (RCD) is a vital event in various physiological and pathological processes. Ferroptosis is a newly described RCD, which is driven by iron accumulation and unrestricted lipid peroxidation. The interaction between ferroptosis and immunity has been a topic of substantial interest since its discovery in 2012. It has become increasingly evident that ferroptosis is critically involved in the regulation of antitumor immunity and may provide potential strategies in immunotherapy. Ferroptosis could release various damage‐associated molecular patterns (DAMPs) or lipid metabolites to regulate the cellular immune response, validating its role as a form of immunogenic cell death (ICD). Specifically, the oxygenated membrane lipids on ferroptotic cells could mediate the phagocytosis by macrophages to maintain the immune responses. Additionally, immune checkpoint inhibitor therapy may sensitize cancer cells to ferroptosis, while ferroptosis might contribute to tumor immune evasion by directly interfering with the function of various immune cells. Based on these insights, we provided a comprehensive review on the interaction patterns between ferroptosis and immunity, which may not only offer insight into the underlying regulatory mechanisms but also facilitating the development of ferroptosis‐based antitumor therapeutics. [ABSTRACT FROM AUTHOR]

Both Alzheimer's disease (AD) and osteoporosis (OP) are common age‐associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCYYoung‐EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. These benefits of OCYYoung‐EVs are diminished in aged osteocyte‐derived EVs (OCYAged‐EVs). Based on the self‐constructed OCY‐EVs tracer transgenic mouse models and the in vivo fluorescent imaging system, OCY‐EVs have been observed to be transported to the brain under physiological and pathological conditions. In the hippocampal administration of Aβ40 induced young AD model mice, the intramedullary injection of Rab27a‐shRNA adenovirus inhibits OCYYoung‐EVs secretion from bone and aggravates cognitive impairment. Proteomic quantitative analysis reveals that OCYYoung‐EVs, compared to OCYAged‐EVs, enrich multiple protective factors of AD pathway. The study uncovers the role of OCY‐EV as a regulator of brain health, suggesting a novel mechanism in bone‐brain communication. [ABSTRACT FROM AUTHOR]

A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new form of regulated cell death, which is characterized by the iron‐dependent accumulation of lethal lipid peroxides and involved in many critical diseases. Recent reports revealed that cellular energy metabolism activities such as glycolysis, pentose phosphate pathway (PPP), and tricarboxylic acid cycle are involved in the regulation of key ferroptosis markers such as reduced nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and reactive oxygen species (ROS), therefore imposing potential regulatory roles in ferroptosis. Remarkably, tumor cells can activate adaptive metabolic responses to inhibit ferroptosis for self‐preservation such as the upregulation of glycolysis and PPP. Due to the rapid proliferation of tumor cells and the intensified metabolic rate, tumor energy metabolism has become a target for disrupting the redox homeostasis and induce ferroptosis. Based on these emerging insights, regulatory impact of those‐tumor specific metabolic aberrations is systematically characterized, such as rewired glucose metabolism and metabolic compensation through glutamine utilization on ferroptosis and analyzed the underlying molecular mechanisms. Additionally, those ferroptosis‐based therapeutic strategies are also discussed by exploiting those metabolic vulnerabilities, which may open up new avenues for tumor treatment in a clinical context. [ABSTRACT FROM AUTHOR]

New biomaterials with antitumor and tissue repair function have become increasingly important for the postoperative care of melanoma surgery, which could prolong the tumor‐free survival of patients while simultaneously facilitating the reconstruction of the trauma tissue. For this purpose, a bioresorbable composite scaffold is designed which is fabricated by depositing therapeutic amorphous calcium carbonate (ACC)‐based nanoformulations in gelatin/polycaprolactone (GP) nanofibers via electrospinning. The ACC nanoformulations are integrated with Fe2+‐preactivated bleomycin to deliver biocatalytically enhanced therapeutic effect while the hydrolysable ACC contents can act as proton scavengers to ameliorate the tumor tissue acidity in situ, leading to sustained inhibition on tumor recurrence and metastasis. The acid‐triggered ACC decomposition also releases Ca2+ to activate the downstream Wnt/β‐catenin signaling pathways, which can cooperate with the healing effect of the GP substrate and accelerate wound regeneration. The nanoengineered scaffold can be useful as a supplementary treatment for the postoperative management of melanoma. [ABSTRACT FROM AUTHOR]

Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)‐induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX‐induced reduction of Akkermansia muciniphila (Akk). Direct replenishment of Akk is sufficient to correct the OVX‐induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM‐ and Akk‐induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX‐induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium Akk mediates the CGM‐induced anti‐osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new form of regulated cell death that shows promise for tumor treatment. Most current ferroptosis tumor therapies are based on the intrinsic pathological features of the malignancies, and it would be of clinical significance to develop ferroptosis‐inducing strategies with improved tumor specificity and modulability. Here we report a polydopamine‐based nanoplatform (FeIIPDA@LAP‐PEG‐cRGD) for the efficient loading of Fe2+ and β‐lapachone (LAP), which could readily initiate ferroptosis in tumor cells upon treatment with near‐infrared light. PDA nanostructures could generate mild hyperthermia under NIR irritation and trigger the release of the ferroptosis‐inducing Fe2+ ions. The NIR‐actuated photothermal effect would also activate cellular heat shock response and upregulate the downstream NQO1 via HSP70/NQO1 axis to facilitate bioreduction of the concurrently released β‐lapachone and enhance intracellular H2O2 formation to promote the Fe2+‐mediated lipid peroxidation. [ABSTRACT FROM AUTHOR]

We present an effective approach to favorably modify the electronic structure of PbSe using Ag doping coupled with SrSe or BaSe alloying. The Ag 4d states make a contribution to in the top of the heavy hole valence band and raise its energy. The Sr and Ba atoms diminish the contribution of Pb 6s2 states and decrease the energy of the light hole valence band. This electronic structure modification increases the density‐of‐states effective mass, and strongly enhances the thermoelectric performance. Moreover, the Ag‐rich nanoscale precipitates, discordant Ag atoms, and Pb/Sr, Pb/Ba point defects in the PbSe matrix work together to reduce the lattice thermal conductivity, resulting a record high average ZTavg of around 0.86 over 400–923 K. [ABSTRACT FROM AUTHOR]

A sequentially responsive photosensitizer‐integrated biopolymer is developed for tumor‐specific photodynamic therapy, which is capable of forming long‐retained aggregates in situ inside tumor tissues. Specifically, the photosensitizer zinc phthalocyanine (ZnPc) is conjugated with polyethylene glycol (PEG) via pH‐labile maleic acid amide linker and then immobilized onto the hyaluronic acid (HA) chain using a redox‐cleavable disulfide linker. The PEG segment can enhance blood circulation of the molecular carrier after intravenous administration and be shed after reaching the acidic tumor microenvironment, allowing the remaining fragment to self‐assemble into large clusters in situ to avoid backward diffusion and improve tumor retention. This process is driven by hydrophobic interactions and does not require additional external actuation. The aggregates are then internalized by the tumor cells via HA‐facilitated endocytosis, and the high glutathione level in tumor cells eventually leads to the intracellular release of ZnPc to facilitate its interaction with the subcellular lipid structures. This tumor‐triggered morphology‐based delivery platform is constructed with clinically tested components and could potentially be applied to other hydrophobic therapeutics. [ABSTRACT FROM AUTHOR]

The Ordos Basin, as the second largest petroliferous basin of China, contains abundant oil and gas resources, oil shale, and sandstone‐type uranium mineral resources. Chang 7 shale is not only the major source rock of the Mesozoic petroliferous system of the Basin, but is also crucial in determining the space‐time distribution relationship of the shale section for the effective exploration and development of the Basin's oil and gas resources. To obtain a highly precise age of the shale development section, we collected tuff samples from the top and bottom profile of the Chang 7 Member, Yishi Village, Yaoqu Town, Tongchuan District, on the southern margin of the Ordos Basin and performed high‐precision chemical abrasion (CA)–isotope dilution (ID)–thermal ionization mass spectrometry (TIMS) zircon U‐Pb dating on the basis of extensive laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) zircon U‐Pb dating data. Our results show the precise ages of the top and bottom zircon in the Chang 7 shale to be 241.06±0.12 Ma and 241.558±0.093 Ma, respectively. We first obtained Chang 7 age data with Grade 0.1‐Ma precision and then determined the age of the shale development in the Chang 7 Member to be the early‐Middle Triassic Ladinian. This result is supported by paleontological evidence. The deposition duration of the Chang 7 shale is 0.5Ma with an average deposition rate of the shale section being 5.3 cm/ka. Our research results provide time scale and basic data for further investigation of the basin–mountain coupling relation of the shale section, the sedimentary environment and volcanic ash and organic‐matter‐rich shale development relation, and the organism break‐out and organic‐matter enrichment mechanism. [ABSTRACT FROM AUTHOR]

Objective: To determine whether pre-eclampsia is associated with polymorphisms in superoxide dismutase (SOD) genes among mother-father-infant triads.Methods: We did this follow-up cohort study at 17 urban hospitals in Canada between October 1, 2008, and September 30, 2010. We recruited Canadian participants who had participated in the International Trial of Antioxidant Supplementation for the Prevention of Pre-eclampsia. Saliva specimens were collected for DNA extraction. The SOD1 +35A/C (rs2234694) and SOD2 Ala16Val C/T (rs4880) single-nucleotide polymorphisms (SNPs) were genotyped.Results: Dual presence of the SOD2 Ala16Val TT variant among mother-father pairs (n=657) was associated with an increased risk of pre-eclampsia when compared with the absence of the TT variant among the mother-father pairs (7/48 [14.6%] vs 11/339 [3.2%]; adjusted odds ratio 6.80, 95% confidence interval 2.32-19.95; P<0.001). By contrast, presence of a single T variant in mother-father pairs (16/270 [5.9%]) or mother-infant pairs (8/179 [4.5%]) was not associated with pre-eclampsia. The SOD1 +35A/CSNP was not associated with pre-eclampsia.Conclusion: The SOD2 Ala16Val SNP might be involved in paternal influence on the maternal predisposition to pre-eclampsia. Genotyping of mother-father pairs could be a promising strategy to identify pre-eclampsia genes. [ABSTRACT FROM AUTHOR]

Abstract: Sb‐doped and GeTe‐alloyed n‐type thermoelectric materials that show an excellent figure of merit ZT in the intermediate temperature range (400–800 K) are reported. The synergistic effect of favorable changes to the band structure resulting in high Seebeck coefficient and enhanced phonon scattering by point defects and nanoscale precipitates resulting in reduction of thermal conductivity are demonstrated. The samples can be tuned as single‐phase solid solution (SS) or two‐phase system with nanoscale precipitates (Nano) based on the annealing processes. The GeTe alloying results in band structure modification by widening the bandgap and increasing the density‐of‐states effective mass of PbTe, resulting in significantly enhanced Seebeck coefficients. The nanoscale precipitates can improve the power factor in the low temperature range and further reduce the lattice thermal conductivity (κlat). Specifically, the Seebeck coefficient of Pb0.988Sb0.012Te–13%GeTe–Nano approaches −280 µV K−1 at 673 K with a low κlat of 0.56 W m−1 K−1 at 573 K. Consequently, a peak ZT value of 1.38 is achieved at 623 K. Moreover, a high average ZTavg value of ≈1.04 is obtained in the temperature range from 300 to 773 K for n‐type Pb0.988Sb0.012Te–13%GeTe–Nano. [ABSTRACT FROM AUTHOR]

Abstract: The checkpoint blockade‐based immunotherapy has recently emerged as a promising approach for tumor treatment, but its clinical implementation has been impeded by poor tumor penetration of the nanocarriers and activation of antitumor immune response. To overcome the obstacles, a tumor acidity‐responsive micellar nanocomplex co‐loaded with programmed death‐ligand 1 (PD‐L1)‐blockade siRNA and mitochondrion‐targeting photosensitizer for the synergistic integration of photodynamic therapy and immunotherapy is reported in the present study. The nanosystem is coated with long‐circulating polyethylene glycol (PEG) shells, which can be shed in response to the weakly acidic tumor microenvironment and lead to significant size reduction and increasing positive charge. These transitions facilitate penetration and uptake of nanocarriers against tumors. Subsequently, under the mild acidic endo/lysosome condition, the micellar nanocomplexes are rapidly protonated and disintegrated to release the PD‐L1‐blockade siRNA and photosensitizer through sponge effect. Results from in vitro and in vivo experiments collectively reveal that the nanosystem efficiently activates a photodynamic therapy‐induced immune response and silences immune resistance mediated by the checkpoint gene PD‐L1. In consequence, melanoma growth is inhibited and the recurrence rate is reduced via triggering systemic antitumor immune responses. This study offers an alternative strategy for the development of efficient antitumor immune therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE Cholestyramine ( CHO), as a bile acid sequestering exchange resin, has been widely used to treat hypercholesterolemia. The aim of this study was to explore how CHO regulated serum cholesterol amounts and bile acid levels in animal models. METHODS New Zealand White rabbits were randomly assigned to the control (given distilled water) and CHO-treated (given CHO solution 1 g/kg per day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were constructed in five rabbits in each group. Serum cholesterol levels and biliary and fecal bile outputs were determined. Liver cholesterol 7α-hydroxylase ( CYP7A1), small heterodimer partner ( SHP), bile salt export pump ( BSEP), ileal bile acid-binding protein ( IBABP) and LDL receptor ( LDL-R) m RNA expressions were assessed by real-time polymerase chain reaction. CYP7A1 activity was also determined. RESULTS CHO treatment decreased serum cholesterol levels by 12.1%. Although CHO did not change the bile acid pool size and biliary bile acid output, it significantly increased fecal bile acid output. Interestingly, CHO also significantly increased the expression and activity of CYP7A1, as well as IBABP and LDL-R m RNA expressions, but decreased hepatic SHP and BSEP gene expressions. CONCLUSION CHO markedly alters bile acid and cholesterol amounts in rabbit intestinal and liver tissues, downregulating genes responsible for cholesterol homeostasis. [ABSTRACT FROM AUTHOR]

0D transition metal phosphides (TMPs) nanocrystals (NCs)-2D ultrathin black phosphorus (BP) heterostructure (Ni2P@BP) have been synthesized via a facile sonication-assisted exfoliation followed by a solvothermal process. Compared with the bare BP, the specially designed Ni2P@BP architecture can enhance the electrical conductivity (from 2.12 × 102 to 6.25 × 104 S m-1), tune the charge carrier concentration (from 1.25 × 1017 to 1.37 × 1020 cm-3), and reduce the thermal conductivity (from 44.5 to 7.69 W m-1 K-1) at 300 K, which can be considered for multiple applications. As a result, the Ni2P@BP exhibits excellent Li storage properties and high hydrogen evolution reaction electrocatalytic activities. The Ni2P@BP shows improved Li diffusion kinetics (e.g., the Li ions diffusion coefficient increases from 1.14 × 10-14 cm2 s-1 for pure BP nanosheets to 8.02 × 10-13 cm2 s-1 for Ni2P@BP). In addition, the Ni2P@BP electrode sustains hydrogen production with almost unchanged activity over 3000 cycles, which indicates its good chemical stability when operating under strong reducing environment. [ABSTRACT FROM AUTHOR]

Rapid developments in materials science and biological mechanisms have greatly boosted the research discoveries of new drug delivery systems. In the past few decades, hundreds of nanoparticle-based drug carriers have been reported almost on a daily basis, in which new materials, structures, and mechanisms are proposed and evaluated. Standing out among the drug carriers, the hybrid nanoparticle systems offer a great opportunity for the optimization and improvement of conventional chemotherapy. By combining several features of functional components, these hybrid nanoparticles have shown excellent promises of improved biosafety, biocompatibility, multifunctionality, biodegradability, and so forth. In this Personal Account, we highlight the recent research advances of some representative hybrid nanoparticles as drug delivery systems and discuss their design strategies and responsive mechanisms for controlled drug delivery. [ABSTRACT FROM AUTHOR]

To enhance long-term survival of titanium implants in patients with osteoporosis, chitosan/gelatin multilayers containing bone morphogenetic protein 2(BMP2) and an antiosteoporotic agent of calcitonin (CT) are deposited on the Ti6Al4V (TC4) implants through layer-by-layer (LBL) electrostatic assembly technique. Here, the obtained titanium alloy implant (TC4/LBL/CT/BMP2) can regulate the release of loaded calcitonin and BMP2 agents in a sustaining manner to accelerate the bone formation and simultaneously inhibit bone resorption. In vitro results show that the bone-related cells on TC4/LBL/CT/BMP2 present the lowest production level of tartrate resistant acid phosphatase (TRAP) but the highest ( p < 0.05) level of alkaline phosphatase (ALP) activity, osteocalcin production, mineralization capacity and osteoblast-related gene expression among all groups after treatment for 7 or 21 days, respectively. Besides, in vivo studies of micro-CT analysis, routine histological and immunohistochemical analysis also collectively demonstrate that the TC4/LBL/CT/BMP2 implant can dramatically promote the formation and remodeling of new bone in osteoporotic rabbits after implantation for 30 days and 90 days, respectively. In vivo push-out testing further confirms that the TC4/LBL/CT/BMP2 implant has the highest ( p < 0.01) interfacial shear strength and favorable bone-implant osseointegration. Overall, this study establishes a simple and profound methodology to fabricate a biofunctional TC4 implant for the treatment of local osteoporotic fractures in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1437-1451, 2016. [ABSTRACT FROM AUTHOR]

Nanotechnology-based diagnostics and therapeutics usually suffer from long-term retention of nanosized devices in the major organs, which may cause unwanted side effects. Herein, we describe the development of ultra-small silica-polymer hybrid dots (Sdots) through the self-assembly between a polyethylene oxide-poly(propylene oxide)-polyethylene oxide (PEO-PPO-PEO) triblock copolymer and a silica precursor. Sdots feature a silica particle size of 4.2 nm and a hydrated size of 14 nm. The larger hydrated size is related to their polyethylene glycol (PEG) surface ligands, which evolve from the PEO blocks in the copolymer. The densely packed PEG corona can effectively shield the hybrid from reticuloendothelial uptake, which gives rise to rapid and thorough hepatobiliary clearance. In vivo experiments demonstrated that, upon intravenous injection, almost complete clearance of Sdots from mouse bodies could be realized through hepatobiliary excretion within only 5 days. Compared to renal clearable nanoparticles with short blood-circulation times, the proposed Sdots have a prolonged blood-circulation half-life of 19 h, so that the Sdots could effectively accumulate at a subcutaneous transplanted tumor through enhanced penetration and retention. As the PPO core of the Sdots can be utilized to accommodate hydrophobic guest molecules, such as anticancer drugs, these Sdots can prospectively serve as fast-clearable drug carriers for targeted cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: High prepregnancy body mass index (BMI), excessive gestational weight gain (GWG), and gestational diabetes mellitus (GDM) are associated with the risk of childhood obesity. This study aims to examine the extent to which these effects may be mediated through the placenta.Methods: Data included 33,893 mothers and their singleton infants from birth to 7 years old (total 154,590 visits) in the Collaborative Perinatal Project, a U.S. multicenter prospective cohort study from 1959 to 1976. The placentas were weighed after removing cord and membranes. We performed sequential generalized estimating equation-linear models excluding and including placental weight to evaluate its mediation effect.Results: In this population, 21.7% of mothers had overweight or obesity, 17.3% had excessive GWG, and 350 (1%) had diagnosed GDM; in addition, 7.2% children had obesity. After adjustment for prepregnancy BMI and other covariates, childhood BMI was 0.23 (95% CI: 0.05, 0.40) kg/m(2) higher for children born to mothers with GDM versus those without GDM. Inclusion of placental weight in the model attenuated the association by 52% to 0.11 (95% CI: -0.06, 0.28) and similarly attenuated the associations with childhood BMI for GWG by 25% and maternal prepregnancy BMI by 17%.Conclusions: Placental weight partly mediates the effects of prepregnancy BMI, excessive GWG, and GDM on childhood BMI. [ABSTRACT FROM AUTHOR]

Although near-infrared (NIR) light-absorbing organic dyes have recently been proposed for photothermal ablation of tumors, their clinical applications have often been hampered by problems such as low water solubility and minimal tissue absorption. Rapid development of nanotechnology provides various novel nanostructures to address these issues. In this work, doxorubicin (DOX)-loaded stealth liposomes are engineered through the incorporation of an NIR-absorptive heptamethine indocyanine dye IR825 into the thermoresponsive liposomes for photothermal/chemo combined cancer therapy. It is demonstrated that the lipid nanostructure can enhance the bioavailability of water-insoluble IR825 for efficient photothermal treatment, while delivering the anticancer drug doxorubicin to achieve simultaneous anticancer medication. The combined treatment of photothermal ablation and chemotherapy synergistically improves the overall cancer cell killing efficiency, which can be of future clinical interest. [ABSTRACT FROM AUTHOR]

Glutamate receptor antagonists have been known to play a crucial role in the treatment of many neuronal diseases. Recently, these antagonists have also shown therapeutic effects in the treatment of cancer. In this study, an ionotropic glutamate (iGlu) receptor antagonist, 4-hydroxyphenylacetyl spermine ( L1), was used concurrently with a common anticancer drug, doxorubicin (Dox), for simultaneous cancer therapy. Mesoporous silica nanoparticles (MSNPs) were employed as the delivery vehicle for both L1 and Dox by conjugating the iGlu receptor antagonist on the surface and encapsulating Dox within the mesopores. Dox was then trapped within the mesopores by functionalizing a redox-cleavable capping group on the MSNP surface, and it could be released upon exposure to the reductive glutathione. In vitro studies on B16F10 and NIH3T3 cell lines revealed that the iGlu receptor antagonist L1 exhibited therapeutic as well as targeting effects. In addition, the simultaneous use of therapeutic L1 and Dox proved to be synergistic in the treatment of cancer. The present work demonstrated the feasibility of employing a delivery system to deliver both neuroprotective drug and anticancer drug for efficient anticancer treatment. [ABSTRACT FROM AUTHOR]

Amphiphobic surfaces are being promisingly applied in numerous fundamental and industrial applications. A transparent amphiphobic coating was fabricated by combining fluoroalkyl silane copolymer (PFAS) with SiO2 nanoparticles. Dodecafluoroheptylmethacrylate (DFMA) and γ-methacryloxypropyltrimethoxysilane (γ-MPS) were monomers, and PFAS was prepared via free-radical polymerization. Tetraethoxysilane (TEOS) and SiO2 nanoparticles were added in PFAS solution to obtain a homogeneous hybrid sol. The hybrid sol was coated on glass surfaces. After drying, a transparent and amphiphobic hybrid coating was obtained. The visible-light transmittance of the hybrid coating on the glass surface ranged from 85% to 90%. The contact angle (CA) of the hybrid coating for water, ethylene glycol and hexadecane were 153°, 150°, 115°. The hybrid coating had a great thermal stability below 280 °C. The hardness and adhesion of the hybrid coating could reach 1 grade and H, respectively. This is expected to be a facile, cost-effective method to obtain transparent amphiphobic surfaces. [ABSTRACT FROM AUTHOR]