Targeting lysosomal quality control as a therapeutic strategy against aging and diseases.

Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.

In vitro study to identify ligand-independent function of estrogen receptor-α in suppressing DNA damage-induced chondrocyte senescence.

In osteoarthritis (OA), chondrocytes undergo many pathological alternations that are linked with cellular senescence. However, the exact pathways that lead to the generation of a senescence-like phenotype in OA chondrocytes are not clear. Previously, we found that loss of estrogen receptor-α (ERα) was associated with an increased senescence level in human chondrocytes. Since DNA damage is a common cause of cellular senescence, we aimed to study the relationship among ERα levels, DNA damage, and senescence in chondrocytes. We first examined the levels of ERα, representative markers of DNA damage and senescence in normal and OA cartilage harvested from male and female human donors, as well as from male mice. The influence of DNA damage on ERα levels was studied by treating human chondrocytes with doxorubicin (DOX), which is an often-used DNA-damaging agent. Next, we tested the potential of overexpressing ERα in reducing DNA damage and senescence levels. Lastly, we explored the interaction between ERα and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Results indicated that the OA chondrocytes contained DNA damage and displayed senescence features, which were accompanied by significantly reduced ERα levels. Overexpression of ERα reduced the levels of DNA damage and senescence in DOX-treated normal chondrocytes and OA chondrocytes. Moreover, DOX-induced the activation of NF-κB pathway, which was partially reversed by overexpressing ERα. Taken together, our results demonstrated the critical role of ERα in maintaining the health of chondrocytes by inhibiting DNA damage and senescence. This study also suggests that maintaining the ERα level may represent a new avenue to prevent and treat OA.

Donepezil promotes skin flap survival through activation of the HIF-1α/VEGF signalling pathway.

Flaps are mainly used to repair wounds in the clinical setting but can sometimes experience ischaemic necrosis postoperatively. This study investigated whether donepezil, an acetylcholinesterase inhibitor, can enhance the survival rate of flaps. We randomly allocated 36 rats into control, low-dose (3 mg/kg/day), and high-dose (5 mg/kg/day) groups. On Postoperative day 7, we assessed flap viability and calculated the mean area of viable flap. After euthanizing the rats, we employed immunological and molecular biology techniques to examine the changes in flap tissue vascularization, apoptosis, autophagy, and inflammation. Donepezil enhanced the expression of hypoxia-inducible factor and vascular endothelial growth factor to facilitate angiogenesis. In addition, it elevated the expression of LC3B, p62, and beclin to stimulate autophagy. Furthermore, it increased the expression of Bcl-2 while reducing the expression of Bax, thus inhibiting apoptosis. Finally, it had anti-inflammatory effects by reducing the levels of IL-1ß, IL-6, and TNF-α. The results suggest that donepezil can enhance the viability of randomly generated skin flaps by upregulating HIF-1α/VEGF signalling pathway, facilitating vascularization, inducing autophagy, suppressing cell apoptosis, and mitigating inflammation within the flap tissue.

Efficacy and safety of subcutaneous immunotherapy combined with omalizumab in children with dust mite-induced asthma.

OBJECTIVE: To evaluate the benefits of combining omalizumab with specific immunotherapy (SCIT) in the treatment of children with bronchial asthma. METHODS: In this study, 83 children with asthma were treated at the Allergy Department of Qingdao University from January 2019 to February 2020. Participants were divided into three groups: SCIT, combination (omalizumab + SCIT), and control (standard asthma medications). We assessed Asthma Control Questionnaire (ACQ) scores, Visual Analogue Scale (VAS) scores, and lung function at baseline, 24 wk, and 48 wk. Additionally, asthma medication scores were compared at 24 and 48 wk. Adverse reactions were monitored in both the SCIT and combination groups. RESULTS: The combination group demonstrated lower ACQ scores at both 24 and 48 wk, and improved VAS scores at 48 wk compared to the other groups. Additionally, lung function parameters (FEV1 and FEF50) showed significant improvement in the combination group. Reduced asthma medication scores were noted in the combination group at 24 and 48 wk. Local adverse reactions were fewer in the combination group, and no systemic adverse reactions were reported. CONCLUSION: Combining omalizumab with SCIT provides quicker asthma control, lowers medication requirements, and enhances lung function with fewer adverse effects, making it a safe and effective treatment for children with bronchial asthma.

Serum Lactate Is an Indicator for Short-Term and Long-Term Mortality in Patients with Acute Pancreatitis.

BACKGROUND: Serum lactate, as a single and an easily available biomarker, has been applied in various diseases. AIMS: In this study, we aimed to explore the predictive value of serum lactate for short-term and long-term prognosis in acute pancreatitis (AP) admitted in intensive care unit (ICU) based on a large-scale database. METHODS: AP patients admitted in ICU in the MIMIC-IV database were included. We constructed three different models to investigate the relationships between serum lactate and clinical outcomes, including 30-day, 180-day and 1-year mortality in AP. Smooth fitting curves were performed for intuitively demonstrating the relationship between serum lactate and different outcomes in AP by the generalized additive model. RESULTS: A total of 895 AP patients admitted in ICU were included. The mortalities of 30 days, 180 days, and 1 year were 12.63% (n = 113), 16.87% (n = 151), and 17.54% (n = 157). In model B, with 1-mmol/L increment in serum lactate, the values of OR in 30-day, 180-day and 1-year mortality were 1.20 (95%CI 1.04-1.37, P = 0.0094), 1.21 (95%CI 1.06-1.37, P = 0.0039), and 1.21 (95%CI 1.07-1.38, P = 0.0035). The AUCs of serum lactate for predicting 30-day, 180-day, and 1-year mortality in AP were 0.688 (95%CI 0.633-0.743), 0.655 (95%CI 0.605-0.705), and 0.653 (95%CI 0.603-0.701), respectively. The cut-off value of serum lactate predicting 30-day, 180-day and 1-year mortality in AP was 2.4 mmol/L. CONCLUSION: Serum lactate could be an indicator for short-term and long-term mortality in patients with AP admitted in ICU.

Mediating effect of gestational weight gain on the preventive effect of exercise during pregnancy on macrosomia: a randomized clinical trial.

OBJECTIVE: We sought to investigate the impact of individualized exercise guidance during pregnancy on the incidence of macrosomia and the mediating effect of gestational weight gain (GWG). DESIGN: A prospective randomized clinical trial. SETTING: A Hospital in Xingtai District, Hebei Province. POPULATION: Older than 20 years of age, mid-pregnancy, and singleton pregnant women without contraindications to exercise during pregnancy. METHODS: A randomized clinical trial was conducted from December 2021 to September 2022 to compare the effects of standard prenatal care with individualized exercise guidance on the incidence of macrosomia. MAIN OUTCOME MEASURE: Incidence of macrosomia. RESULTS: In all, 312 singleton women were randomized into an intervention group (N = 162) or a control group (N = 150). Participants who received individualized exercise guidance had a significantly lower incidence of macrosomia (3.73% vs. 13.61%, P = 0.002) and infants large for gestational age (9.94% vs. 19.73%, P = 0.015). However, no differences were observed in the rate of preterm birth (1.86% vs. 3.40%, P = 0.397) or the average gestational age at birth (39.14 ± 1.51 vs. 38.69 ± 1.85, P = 0.258). Mediation analysis revealed that GWG mediated the effect of exercise on reducing the incidence of macrosomia. CONCLUSION: Individualized exercise guidance may be a preventive tool for macrosomia, and GWG mediates the effect of exercise on reducing the incidence of macrosomia. However, evidence does not show that exercise increases the rate of preterm birth or affects the average gestational age at birth. TRIAL REGISTRATION: The trial is registered at www.clinicaltrails.gov [registration number: NCT05760768; registration date: 08/03/2023 (retrospectively registered)].

Per- and polyfluoroalkyl substances inhibit human and rat 17ß-hydroxysteroid dehydrogenase 1: Quantitative structure-activity relationship and molecular docking analysis.

Per- and polyfluoroalkyl (PFAS) substances are enduring industrial materials. 17ß-Hydroxysteroid dehydrogenase isoform 1 (17ß-HSD1) is an estrogen metabolizing enzyme, which transforms estrone into estradiol in human placenta and rat ovary. Whether PFAS inhibit 17ß-HSD1 and what the structure-activity relationship (SAR) remains unexplored. We screened 18 PFAS for inhibiting human and rat 17ß-HSD1 in microsomes and studied their SAR and mode of action(MOA). Of the 11 perfluorocarboxylic acids (PFCAs), C8-C14 PFCAs at a concentration of 100 µM substantially inhibited human 17ß-HSD1, with order of C11 (half-maximal inhibition concentration, IC50, 8.94 µM) > C10 (10.52 µM) > C12 (14.90 µM) > C13 (30.97 µM) > C9 (43.20 µM) > C14 (44.83 µM) > C8 (73.38 µM) > others. Of the 7 per- and poly-fluorosulfonic acids (PFSAs), the potency was C8S (IC50, 14.93 µM) > C7S (80.70 µM) > C6S (177.80 µM) > others. Of the PFCAs, C8-C14 PFCAs at 100 µM markedly reduced rat 17ß-HSD1 activity, with order of C11 (IC50, 9.11 µM) > C12 (14.30 µM) > C10 (18.24 µM) > C13 (25.61 µM) > C9 (67.96 µM) > C8 (204.39 µM) > others. Of the PFSAs, the potency was C8S (IC50, 37.19 µM) > C7S (49.38 µM) > others. In contrast to PFOS (C6S), the partially fluorinated compound 6:2 FTS with an equivalent number of carbon atoms demonstrated no inhibition of human and rat 17ß-HSD1 activity at a concentration of 100 µM. The inhibition of human and rat enzymes by PFAS followed a V-shaped trend from C4 to C14, with a nadir at C11. Moreover, human 17ß-HSD1 was more sensitive than rat enzyme. PFAS inhibited human and rat 17ß-HSD1 in a mixed mode. Docking analysis revealed that they bind to the NADPH and steroid binding site of both 17ß-HSD1 enzymes. The 3D quantitative SAR (3D-QSAR) showed that hydrophobic region, hydrogen bond acceptor and donor are key factors in binding to 17ß-HSD1 active sites. In conclusion, PFAS exhibit inhibitory effects on human and rat 17ß-HSD1 depending on factors such as carbon chain length, degree of fluorination, and the presence of carboxylic acid or sulfonic acid groups, with a notable V-shaped shift observed at C11.

Induction and Stabilization of Columnar Mesophases in Fluorinated Polycyclic Aromatic Hydrocarbons by Arene-Perfluoroarene Interactions.

The straightforward synthesis of several Fluorinated Polycyclic Aromatic Hydrocarbons by the efficient, transition-metal-free, arene fluorine nucleophilic substitution reaction is described, and the full investigation of their liquid crystalline and optical properties reported. The key precursors for this study, i. e. 2,2'-dilithio-4,4',5,5'-tetraalkoxy-1,1'-biphenyl derivatives, were obtained in two steps from the highly selective Scholl oxidative homo-coupling of 3,4-dialkoxy-1-bromobenzene, followed by quantitative double-lithiation. In situ room temperature nucleophilic annulation with either perfluorobenzene or perfluoronaphthalene leads to 1,2,3,4-tetrafluoro-6,7,10,11-tetraalkxoytriphenylenes and 9,10,11,12,13,14-hexafluoro-2,3,6,7-tetraalkoxybenzo[f]tetraphenes, respectively, in good yields. Exploiting the same strategy, subsequent double annulations resulted in the formation of 9,18-difluoro-2,3,6,7,11,12,15,16-octa(alkoxy)tribenzo[f,k,m]tetraphenes and 9,10,19,20-tetrafluoro-2,3,6,7,12,13,16,17-octakis(hexyloxy)tetrabenzo[a,c,j,l]tetracenes, respectively. Despite the presence of only four alkoxy chains, the polar "Janus" mesogens display a columnar hexagonal mesophase over broad temperature ranges, with higher mesophase stability than the archetypical 2,3,6,7,10,11-hexa(alkoxy)triphenylenes and their hydrogenated counterparts. The improvement or induction of mesomorphism is attributed to efficient antiparallel face-to-face π-stacking driven by the establishment of non-covalent perfluoroarene-arene intermolecular interactions. The larger lipophilic discotic π-extended compounds also exhibit columnar mesomorphism, over similar temperature ranges and stability than their hydrogenated homologs. Finally, these fluorinated molecules form stringy gels in various solvents, and show interesting solvatochromic emission properties in solution as well as strong emission in thin films and gels.

Effect of different cement distribution in bilateral and unilateral Percutaneous vertebro plasty on the clinical efficacy of vertebral compression fractures.

BACKGROUND: The ramifications of osteoporotic fractures and their subsequent complications are becoming progressively detrimental for the elderly population. This study evaluates the clinical ramifications of postoperative bone cement distribution in patients with osteoporotic vertebral compression fractures (OVCF) who underwent both bilateral and unilateral Percutaneous Vertebroplasty (PVP). OBJECTIVE: The research aims to discern the influence of bone cement distribution on the clinical outcomes of both bilateral and unilateral Percutaneous Vertebroplasty. The overarching intention is to foster efficacious preventive and therapeutic strategies to mitigate postoperative vertebral fractures and thereby enhance surgical outcomes. METHODS: A comprehensive evaluation was undertaken on 139 patients who received either bilateral or unilateral PVP in our institution between January 2018 and March 2022. These patients were systematically classified into three distinct groups: unilateral PVP (n = 87), bilateral PVP with a connected modality (n = 29), and bilateral PVP with a disconnected modality (n = 23). Several operational metrics were juxtaposed across these cohorts, encapsulating operative duration, aggregate hospital expenses, bone cement administration metrics, VAS (Visual Analogue Scale) scores, ODI (Oswestry Disability Index) scores relative to lumbar discomfort, postoperative vertebral height restitution rates, and the status of the traumatized and adjacent vertebral bodies. Preliminary findings indicated that the VAS scores for the January and December cohorts were considerably reduced compared to the unilateral PVP group (P = 0.015, 0.032). Furthermore, the recurrence of fractures in the affected and adjacent vertebral structures was more pronounced in the unilateral PVP cohort compared to the bilateral PVP cohorts. The duration of the procedure (P = 0.000) and the overall hospitalization expenses for the unilateral PVP group were markedly lesser than for both the connected and disconnected bilateral PVP groups, a difference that was statistically significant (P = 0.015, P = 0.024, respectively). Nevertheless, other parameters, such as the volume of cement infused, incidence of cement spillage, ODI scores for lumbar discomfort, post-surgical vertebral height restitution rate, localized vertebral kyphosis, and the alignment of cement and endplate, did not exhibit significant statistical deviations (P > 0.05). CONCLUSION: In juxtaposition with unilateral PVP, the employment of bilateral PVP exhibits enhanced long-term prognostic outcomes for patients afflicted with vertebral compression fractures. Notably, bilateral PVP significantly curtails the prevalence of subsequent vertebral injuries. Conversely, the unilateral PVP cohort is distinguished by its abbreviated operational duration, minimal invasiveness, and reduced overall hospitalization expenditures, conferring it with substantial clinical applicability and merit.

Pyrene-Fused Poly-Aromatic Regioisomers: Synthesis, Columnar Mesomorphism, and Optical Properties.

π-Extended pyrene compounds possess remarkable luminescent and semiconducting properties and are being intensively investigated as electroluminescent materials for potential uses in organic light-emitting diodes, transistors, and solar cells. Here, the synthesis of two sets of pyrene-containing π-conjugated polyaromatic regioisomers, namely 2,3,10,11,14,15,20,21-octaalkyloxypentabenzo[a,c,m,o,rst]pentaphene (BBPn) and 2,3,6,7,13,14,17,18-octaalkyloxydibenzo[j,tuv]phenanthro [9,10-b]picene (DBPn), is reported. They were obtained using the Suzuki-Miyaura cross-coupling in tandem with Scholl oxidative cyclodehydrogenation reactions from the easily accessible precursors 1,8- and 1,6-dibromopyrene, respectively. Both sets of compounds, equipped with eight peripheral aliphatic chains, self-assemble into a single hexagonal columnar mesophase, with one short-chain BBPn homolog also exhibiting another columnar mesophase at a lower temperature, with a rectangular symmetry; BBPn isomers also possess wider mesophase ranges and higher mesophases' stability than their DBPn homologs. These polycyclic aromatic hydrocarbons all show a strong tendency of face-on orientation on the substrate and could be controlled to edge-on alignment through mechanical shearing of interest for their implementation in photoelectronic devices. In addition, both series BBPn and DBPn display green-yellow luminescence, with high fluorescence quantum yields, around 30%. In particular, BBPn exhibit a blue shift phenomenon in both absorption and emission with respect to their DBPn isomers. DFT results were in good agreement with the optical properties and with the stability ranges of the mesophases by confirming the higher divergence from the flatness of DBPn compared with BBPn. Based on these interesting properties, these isomers could be potentially applied not only in the field of fluorescent dyes but also in the field of organic photoelectric semiconductor materials as electron transport materials.

Roxadustat promotes hypoxia-inducible factor-1α/vascular endothelial growth factor signalling to enhance random skin flap survival in rats.

Random skin flaps have limited clinical application as a broad surgical reconstruction treatment because of distal necrosis. The prolyl hydroxylase domain-containing protein inhibitor roxadustat (RXD) enhances angiogenesis and reduces oxidative stress and inflammation. This study explored the function of RXD in the survival of random skin flaps. Thirty-six male Sprague-Dawley rats were randomly divided into low-dose RXD group (L-RXD group, 10 mg/kg/2 day), high-dose RXD group (H-RXD group, 25 mg/kg/2 day), and control group (1 mL of solvent, 1:9 DMSO:corn oil). The proportion of surviving flaps was determined on day 7 after surgery. Angiogenesis was assessed by lead oxide/gelatin angiography, and microcirculation blood perfusion was evaluated by laser Doppler flow imaging. Specimens in zone II were obtained, and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured as indicators of oxidative stress. Histopathological status was evaluated with haematoxylin and eosin staining. The levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and the inflammatory factors interleukin (IL)-1ß, IL-6, and tumour necrosis factor-α (TNF-α) were detected by immunohistochemistry. RXD promoted flap survival and microcirculatory blood perfusion. Angiogenesis was detected distinctly in the experimental group. SOD activity increased and the MDA level decreased in the experimental group. Immunohistochemistry indicated that the expression levels of HIF-1α and VEGF were increased while the levels of IL-6, IL-1ß, and TNF-α were decreased after RXD injection. RXD promoted random flap survival by reinforcing vascular hyperplasia and decreasing inflammation and ischaemia-reperfusion injury.

Interlayer directional coupling thermo-optic waveguide switches based on functionalized epoxy-crosslinking polymers.

In this study, interlayer directional coupling (DC) thermo-optic (TO) waveguide switches were designed and fabricated using functionalized epoxy-crosslinking polymers. Fluorinated SU-8 (FSU-8) with a photo-initiating epoxy-crosslinking network was self-synthesized as a waveguide core material. A copolymer of methyl methacrylate and glycidyl methacrylate P(MMA-co-GMA) with a thermo-initiating epoxy crosslinking structure was self-synthesized as a waveguide cladding material. Compared with commercial pure SU-8 and PMMA, FSU-8 exhibited a lower absorption loss and P(MMA-co-GMA) exhibited a higher thermal stability. Using epoxy-crosslinking functionalized polymers, the structure of the waveguides and electrode heaters were optimized, and the performance parameters of the interlayer DC TO switches were simulated. At a signal wavelength of 1550 nm, the insertion loss, extinction ratio, and power consumption of the actual interlayer devices were measured as 6.7 dB, 15.6 dB, and 9 mW, respectively. The rising and falling response times of the TO switches were obtained as 631.6 µs and 362 µs, respectively. The self-leveling ability and solvent resistance characteristic of the epoxy-crosslinking network for FSU-8 and P(MMA-co-GMA) may guarantee the realization of interlayer DC TO waveguide switches. The proposed technique will be suitable for photonic integrated waveguide chips with multilayer stacking dynamic optical information interactions.

K+-doping-induced highly efficient red emission in CsPb(Br,I)3 quantum dot glass toward Rec. 2020 displays.

It is demonstrated that the incorporation of K+ into CsPb(Br,I)3 perovskite quantum dot glass leads to the simultaneous increases of quantum efficiency and phase stability. The latent mechanism is analyzed via the microstructural and spectroscopic studies. The constructed prototype white-light-emitting diode device yields an ultra-wide color gamut attaining 96% Rec. 2020 standard.

Toward high-power-density laser-driven lighting: enhancing heat dissipation in phosphor-in-glass film by introducing h-BN.

In this work,  hexagonal boron nitride (h-BN) nanocrystals as functional additives in a phosphor-in-glass film are shown to substantially increase the luminous performance driven by a blue laser. Microstructural and spectroscopic studies reveal that h-BN particles distributed over the whole glass matrix build in situ a local heat conductive path which effectively accelerates heat dissipation and so greatly relieves the "thermal run-away effect". The developed composite material with fine thermal manipulation may be a promising phosphor color converter for high-power-density laser-driven lighting.

Metal-printing tunable interlayer waveguide coupler using low-loss fluorinated polycarbonate.

Tunable three-dimensional (3D) integrated optical waveguide chips with optical interconnection function are beneficial to expand the application of optical devices in a 3D integrated photonic module. Here, we propose a thermo-optic (TO) tunable interlayer waveguide coupler based on the metal-printing technique. Low-loss fluorinated polycarbonate (AF-Ali-PC MA) and poly (methyl methacrylate-glycidyl methacrylate) [P(MMA-co-GMA)] are synthesized as waveguide core and cladding layer, respectively. The thermal stability and optical adsorption characteristics of AF-Ali-PC MA are analyzed. Optical signal transmission features of the interlayer coupling waveguides are simulated. The optical response properties and fabrication process flows of a dynamic multilayer waveguide chip can be greatly improved by the metal-printing technique. The on-off time of the TO interlayer coupling chip is obtained as 250 µs, and the electrical power consumption is measured as 7.6 mW. To the best of our knowledge, this is the first time that a TO tunable interlayer waveguide coupler is achieved by an efficient metal-printing method, which is suitable for large-scale photonic integrated circuit (PIC) systems and multilayer optical interconnection (OXC) networks.

Enhancing the potential of aged human articular chondrocytes for high-quality cartilage regeneration.

Autologous chondrocyte implantation (ACI) is a regenerative procedure used to treat focal articular cartilage defects in knee joints. However, age has been considered as a limiting factor and ACI is not recommended for patients older than 40-50 years of age. One reason for this may be due to the reduced capacity of aged chondrocytes in generating new cartilage. Currently, the underlying mechanism contributing to aging-associated functional decline in chondrocytes is not clear and no proven approach exists to reverse chondrocyte aging. Given that chondrocytes in healthy hyaline cartilage typically display a spherical shape, believed to be essential for chondrocyte phenotype stability, we hypothesize that maintaining aged chondrocytes in a suspension culture that forces the cells to adopt a round morphology may help to "rejuvenate" them to a younger state, thus, leading to enhanced cartilage regeneration. Chondrocytes isolated from aged donors displayed reduced proliferation potential and impaired capacity in generating hyaline cartilage, compared to cells isolated from young donors, indicated by increased hypertrophy and cellular senescence. To test our hypothesis, the "old" chondrocytes were seeded as a suspension onto an agarose-based substratum, where they maintained a round morphology. After the 3-day suspension culture, aged chondrocytes displayed enhanced replicative capacity, compared to those grown adherent to tissue culture plastic. Moreover, chondrocytes subjected to suspension culture formed new cartilage in vitro with higher quality and quantity, with enhanced cartilage matrix deposition, concomitant with lower levels of hypertrophy and cellular senescence markers. Mechanistic analysis suggested the involvement of the RhoA and ERK1/2 signaling pathways in the "rejuvenation" process. In summary, our study presents a robust and straightforward method to enhance the function of aged human chondrocytes, which can be conveniently used to generate a large number of high-quality chondrocytes for ACI application in the elderly.

Enhancement of Upconversion Luminescence by the Construction of a 3Yb-Er-Hf Sublattice Energy Cluster and Surface Defect Elimination.

Nanotetragonal LiYF4:RE (Tm,Er,Ho) is a kind of excellent upconversion luminescence (UCL) material potentially used in many fields, while the enhancement of UC emission and regulation of luminescence lifetime are still a challenge. Herein, a strategy was reported to enhance UCL performance with the aid of the construction of a 3Yb-Er-Hf sublattice energy cluster with the introduction of Hf4+ and the interception of surface defect fluorescence quenching. UCL was obviously decreased by Hf4+ doping without surface defect elimination, but after the interception of surface defect quenching, UCL was dramatically enhanced more than 300-fold with an Er3+/Hf4+ mole ratio of 1:1. The contribution of UCL enhancement by the construction of a 3Yb-Er-Hf sublattice energy cluster is about 1.5 times of the sample without energy cluster construction. Interestingly, the lifetime of UCL can also be regulated by this strategy. According to the results of systematical microstructure analyses and UCL performance behaviors examined by X-ray powder diffraction (XRD), small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), and fluorescence spectrophotometry (FS) methods, the possible mechanism of UCL enhancement was proposed. This work may be an inspiration for researchers to design and develop high-performance UCL nanomaterials.

Design and Research of an Underactuated Manipulator Based on the Metamorphic Mechanism.

Robot hands play an important role in the interaction between robots and the environment, and the precision and complexity of their tasks in work production are becoming higher and higher. However, because the traditional manipulator has too many driving components, complex control, and a lack of versatility, it is difficult to solve the contradiction between the degrees of freedom, weight, flexibility, and grasping ability. The existing manipulator has difficulty meeting the diversified requirements of a simple structure, a large grasping force, and the ability to automatically adapt to shape when grasping an object. To solve this problem, we designed a kind of underactuated manipulator with a simple structure and strong generality based on the metamorphic mechanism principle. First, the mechanism of the manipulator was designed on the basis of the metamorphic mechanism principle, and a kinematics analysis was carried out. Then, the genetic algorithm was used to optimize the size parameters of the manipulator finger structure. Finally, for different shapes of objects, the design of the control circuit binding force feedback control was carried out with a grasping experiment. The experimental results show that the manipulator has simple control and can grasp objects of different sizes, positions, and shapes.

[Effects of Low-dose Antibiotic Exposure on Fetal Growth and Development].

Objective To analyze maternal blood exposure to non-therapeutic antibiotics in late pregnancy and explore the effects of low-dose antibiotics on fetal growth and development.Methods A total of 104 pregnant women in late pregnancy (28-32 weeks) without serious pregnancy complications were enrolled,who had regular antenatal examination and delivery in Peking Union Medical College Hospital and did not use therapeutic antibiotics 2 months before pregnancy and in the whole pregnant process.The levels of antibiotics in the maternal blood were detected by liquid chromatography-tandem mass spectrometry,and the pregnant women were assigned into an antibiotic exposure group (antibiotic positive) and a non-exposure group (antibiotic negative).The length,weight,placental weight,and placental volume of the newborns in the two groups were measured,and the data were statistically analyzed by t test or χ2 test.Results The maternal blood antibiotic test showed 7 positive cases (6.73%,antibiotic exposure group) and 97 negative cases (93.27%,non-exposure group). The average length of newborns in the antibiotic exposure group and the non-exposure group was (49.57±1.40) cm and (48.85±1.77) cm,respectively,with no significant difference (t=1.060,P=0.363).The average weight of newborns in the antibiotic exposure group and the non-exposure group was (3558.57±382.95) g and (3275.36±356.41) g,respectively,with significant difference (t=2.021,P=0.046).The mean placental weight in the antibiotic exposure group and the non-exposure group was (676.43±124.59) g and (631.96±129.25) g,respectively,with no significant difference (t=0.881,P=0.380).The mean placental volume in the antibiotic exposure group and the non-exposure group was (724.67±174.91) cm3 and (676.82±220.86) cm3,respectively,with no significant difference (t=0.560,P=0.388).Compared with those in the non-exposure group,the neonatal length,neonatal weight,placental weight,and placental volume in the antibiotic exposure group increased by 1.47%,8.65%,7.04%,and 7.07%,respectively.Conclusion There are antibiotics in the environment,and maternal blood exposure to non-therapeutic antibiotics can promote the growth and development of the fetus and placenta,especially increasing the fetal weight.

The impacts of digital finance development on household income, consumption, and financial asset holding: an extreme value analysis of China's microdata.

This paper examines the roles of digital finance development in household income, consumption, and financial asset holding from an extreme value theory perspective. Three types of extreme pairs (Min to Min, Max to Max, and Max to Min) are constructed, corresponding to the three aspects of the economic welfare of digital finance: fairness, efficiency, and their trade-off. Using panel data from the Peking University Digital Financial Inclusion Index of China (PKU-DFIIC) and China Family Panel Studies (CFPS) over time span 2014-2018, this paper models the block maxima and minima of variables by fitting them with generalized extreme value (GEV) distribution. The binary expansion testing (BET) is used to detect the nonlinear dependence between digital finance and household economic variables. The tail quotient correlation coefficient (TQCC) is used to quantify the tail dependencies. The results show that: (1) digital finance has significant fairness effects in reducing poverty, increasing consumption, and promoting financial asset holding; (2) digital finance shows effects of promoting incentives and efficiency in household income and financial asset holding, but this effect is relatively limited in household consumption; (3) digital finance generally increases efficiency without harming fairness in terms of all cases of household income and consumption, and most of the cases regarding household financial asset holding; (4) the positive spatial externality of digital finance exists for all household economic variables; and, for pairs regarding household income and consumption, the wider the scope, the greater the spatial spillover effect. The result of this paper implies many novel policy implications.