In vitro heterochronic parabiosis identifies pigment epithelium-derived factor as a systemic mediator of rejuvenation by young blood.

Several decades of heterochronic parabiosis (HCPB) studies have demonstrated the restorative impact of young blood, and deleterious influence of aged blood, on physiological function and homeostasis across tissues, although few of the factors responsible for these observations have been identified. Here we develop an in vitro HCPB system to identify these circulating factors, using replicative lifespan (RLS) of primary human fibroblasts as an endpoint of cellular health. We find that RLS is inversely correlated with serum donor age and sensitive to the presence or absence of specific serum components. Through in vitro HCPB, we identify the secreted protein pigment epithelium-derived factor (PEDF) as a circulating factor that extends RLS of primary human fibroblasts and declines with age in mammals. Systemic administration of PEDF to aged mice reverses age-related functional decline and pathology across several tissues, improving cognitive function and reducing hepatic fibrosis and renal lipid accumulation. Together, our data supports PEDF as a systemic mediator of the effect of young blood on organismal health and homeostasis and establishes our in vitro HCPB system as a valuable screening platform for the identification of candidate circulating factors involved in aging and rejuvenation.

A Multimodal Self-Propelling Tensegrity Structure.

Tensegrity structure is composed of tensile cables and compressive rods, offering high stiffness-to-mass ratio, deploy ability, and excellent energy damping capability. The active and dynamic tensegrity designs demonstrate great potential for soft robots. In previous designs, the movement has relied on carefully controlled input power or manually controlled light irradiation, limiting their potential applications. Here, a hybrid tensegrity structure (HTS) is constructed by integrating thermally responsive cables, nonresponsive cables, and stiff rods. The HTS can self-propel continuously on a hot surface due to its unique geometry. The HTS allows for the easy achievement of multimodal self-propelled locomotive modes, which has been challenging for previously demonstrated self-propelling structures. Additionally, using Velcro tapes to adhere the rods and cables together, a modulable and reassemblable HTS is created. The HTS introduced in this study presents a new strategy and offers a large design space for constructing self-propelling and modulable robots.

Mechanochromic Hydrogel Fibers with Multiple Fluorescent Colors.

Mechanochromic polymers can change their color in response to external force and have shown promising applications in stress sensing and failure warning. They are usually obtained as thin films or bulky specimens. The mechanochromic fibers, which can be used to make smart fabrics, have been seldom reported due to the lack of efficient fabrication techniques. In this work, a general method using photo-polymerization of microgel solution in a template tube to produce mechanochromic hydrogel fibers is reported. The obtained hydrogel fibers can generate visible and fluorescent color changes upon deformation. The diameter of the mechanochromic fibers can be easily adjusted by using different template tubes. The mechanochromic fibers can be fabricated as long as 1 m. By reducing the fiber diameter or increasing the microgel concentration, the mechanical properties of the mechanochromic fibers can be improved, leading to more obvious mechanochromic behavior. The polymethacrylate (PMA) is further used to coat the hydrogel fibers, prevent the loss of water in the fibers, and increase the storage time. The mechanochromic fibers with multiple fluorescent colors are further fabricated by utilizing different microgel solutions. This work provides an easy and effective method to fabricate mechanochromic fibers with different color change abilities.

Associations among Parental Phubbing, Self-esteem, and Adolescents' Proactive and Reactive Aggression: A Three-Year Longitudinal Study in China.

Parental phubbing, as a new risk factor for adolescents' healthy development, has been noticed by scholars. However, few studies have clarified the associations between parental phubbing and adolescents' proactive and reactive aggression and the potential mediating mechanisms. To address the gaps, the current study explored the longitudinal associations among parental phubbing, self-esteem, and adolescents' proactive and reactive aggression by using the parallel process latent growth curve model and the cross-lagged panel model. The current study involved 2407 Chinese adolescents (girls were 1202, Mage = 12.75, SD = 0.58 at baseline, range = 11-16). Results indicated that parental phubbing significantly positively predicted adolescents' reactive aggression but not proactive aggression. Self-esteem significantly predicted the adolescents' reactive and proactive aggression. Self-esteem significantly mediated the associations between parental phubbing and adolescents' proactive and reactive aggression, respectively. These findings suggest that intervening with parental phubbing is a promising way to reduce adolescents' reactive aggression, and promoting adolescents' self-esteem is an effective approach to prevent their proactive and reactive aggression.

The regulation of Insulin/IGF-1 signaling by miR-142-3p associated with human longevity.

MicroRNAs (miRNAs) have been demonstrated to modulate life span in the invertebrates C. elegans and Drosophila by targeting conserved pathways of aging, such as insulin/IGF-1 signaling (IIS). However, a role for miRNAs in modulating human longevity has not been fully explored. Here we investigated novel roles of miRNAs as a major epigenetic component of exceptional longevity in humans. By profiling the miRNAs in B-cells from Ashkenazi Jewish centenarians and 70-year-old controls without a longevity history, we found that the majority of differentially expressed miRNAs were upregulated in centenarians and predicted to modulate the IIS pathway. Notably, decreased IIS activity was found in B cells from centenarians who harbored these upregulated miRNAs. miR-142-3p, the top upregulated miRNA, was verified to dampen the IIS pathway by targeting multiple genes including GNB2, AKT1S1, RHEB and FURIN . Overexpression of miR-142-3p improved the stress resistance under genotoxicity and induced the impairment of cell cycle progression in IMR90 cells. Furthermore, mice injected with a miR-142-3p mimic showed reduced IIS signaling and improved longevity-associated phenotypes including enhanced stress resistance, improved diet/aging-induced glucose intolerance, and longevity-associated change of metabolic profile. These data suggest that miR-142-3p is involved in human longevity through regulating IIS-mediated pro-longevity effects. This study provides strong support for the use of miR-142-3p as a novel therapeutic to promote longevity or prevent aging/aging-related diseases in human.

Multi-material 3D Printing of Mechanochromic Double Network Hydrogels for On-Demand Patterning.

Cephalopods can change their color and patterns by activating the skin chromatophores for camouflage. However, in the man-made soft material systems, it is greatly challenging to fabricate the color-change structure in the desired patterns and shapes. Herein, we employ a multi-material microgel direct ink writing (DIW) printing method to make mechanochromic double network hydrogels in arbitrary shapes. We prepare the microparticles by grinding the freeze-dried polyelectrolyte hydrogel and immobilize the microparticles in the precursor solution to produce the printing ink. The polyelectrolyte microgels contain mechanophores as the cross-linkers. We adjust the rheological and printing properties of the microgel ink by tailoring the grinding time of freeze-dried hydrogels and microgel concentration. The multi-material DIW 3D printing technique is utilized to fabricate various 3D hydrogel structures which could change into a colorful pattern in response to applied force. The microgel printing strategy shows great potential in the fabrication of the mechanochromic device with arbitrary patterns and shapes.

The moderating roles of peer pressure and family economic stress in the longitudinal links between adolescent trait anger and cyberbullying perpetration.

In adolescence, individuals are at high risk for cyberbullying perpetration. Although the role of trait anger in cyberbullying perpetration has attracted attention in the research literature, it is unclear the temporal sequence between trait anger and adolescents' cyberbullying perpetration and whether stressful environments could interact synergistically with trait anger to create a profile of the particularly severe risk to adolescents' cyberbullying perpetration. This study contributed to existing knowledge by examining the longitudinal and reciprocal relationships between trait anger and cyberbullying perpetration and exploring whether peer pressure and family economic stress would moderate these relationships across 2 years (3 time points) with a cohort of Chinese adolescents (N = 2,407, Mage = 12.75 at baseline). The cross-lagged model revealed that prior trait anger was associated with later self-reported cyberbullying perpetration (ßT1 → T2 = 0.09 and ßT2 → T3 = 0.10), whereas earlier self-reported cyberbullying perpetration was not associated with subsequent trait anger. Peer pressure moderated the link between trait anger and self-reported cyberbullying perpetration. Family economic stress did not play a moderating role in the link between trait anger and self-reported cyberbullying perpetration. Findings suggest that cyberbullying perpetration prevention and intervention programs should attach importance to adolescents' trait anger and the way of getting along with their peers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Genetic Structure of an East Asian Minnow (Toxabramis houdemeri) in Southern China, with Implications for Conservation.

River dynamics have been hypothesized to substantially influence the genetic structure of freshwater fish taxa. Southern China harbors abundant independent river systems, which have undergone historical rearrangements. This river system is thus an excellent model with which to test the abovementioned hypothesis. In this study, a cyprinid widespread in many independent rivers in southern China, Toxabramis houdemeri, was chosen as an exemplar species with which to explore the effects of river configuration changes on spatial genetic structure using mitochondrial and nuclear markers. The results indicated that the T. houdemeri populations fell into four mitochondrial haplotype groups, each genetically endemic to a single river or two adjacent river systems. The mitochondrial haplotype network recovered a clear genetic boundary between Hainan Island populations and mainland populations. Notable genetic differentiation was observed within populations from distinct river systems in both mitochondrial and nuclear loci. River system separation, mountain barriers, and mobility were the key factors shaping the genetic structure of T. houdemeri populations. Late Pleistocene divergence and historical immigration were identified within the four mitochondrial haplotype groups, indicating that river rearrangements triggered by the Late Pleistocene glacial cycles were important drivers of the complex genetic structure and demographic history of T. houdemeri. Historical demographics suggested that T. houdemeri populations expanded during the Late Pleistocene. The present study has important consequences for the management and conservation of T. houdemeri.

A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A.

Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in aging and metabolism regulation. Targeted sequencing of SIRT6 locus in a population of 450 Ashkenazi Jewish (AJ) centenarians and 550 AJ individuals without a family history of exceptional longevity identified enrichment of a SIRT6 allele containing two linked substitutions (N308K/A313S) in centenarians compared with AJ control individuals. Characterization of this SIRT6 allele (centSIRT6) demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double-strand break repair, and more robustly kill cancer cells compared with wild-type SIRT6. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+ concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which was correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA.

Hybrid Phenol-Rhodamine Dye Based Mechanochromic Double Network Hydrogels with Tunable Stress Sensitivity.

Mechanochromic hydrogels, which can switch their color in response to the applied external force, have shown great potential in stress visualization and damage indication. However, the kinds of colors in the reported mechanochromic hydrogels are limited. It is challenging to develop mechanochromic hydrogels with new kinds of color changes. Herein, a kind of mechanochromic double network (DN) hydrogel is reported based on the hybrid phenol-rhodamine mechanophore. The hydrogels turn into orange color with an emission wavelength of around 566/574 nm in response to tensile and compressive stress. The DN hydrogels show great reversibility. The color of DN hydrogels vanishes slowly after releasing the stress. The stress sensitivity can be tailored by the crosslinking density and the mechanophore concentration of the first network. In addition, the influence of the pH on the mechanochromic properties of DN hydrogels is also studied. This study provides an insightful study in tuning the stress sensitivity in the mechanochromic hydrogel, which will be beneficial for the development of mechanochromic materials.

Large-scale DNA barcoding of the subfamily Culterinae (Cypriniformes: Xenocyprididae) in East Asia unveils a geographical scale effect, taxonomic warnings and cryptic diversity.

Geographical scale might be expected to impact significantly the efficiency of DNA barcoding as spatially comprehensive sampling provides opportunities to uncover intricate relationships among closely related species and to detect cryptic diversity for widespread taxa. Here, we present a DNA barcoding study on a Xencyprididae subfamily (Culterinae) involving the production of 998 newly generated DNA barcodes from East Asian drainages (80 localities). Together with 513 barcodes mined from BOLD and GenBank, a reference library consisting of 1511 DNA barcodes (116 localities) for 42 species was assembled, accounting for 66% of known Culterinae species. Intraspecific genetic distances are positively correlated to geographical scale, while a negative correlation is detected between interspecific genetic distances and geographical scale. The present study demonstrates that geographical scale influences the efficiency of DNA barcoding by narrowing the width of the barcoding gap. DNA-based species delimitation analyses delimited 44 molecular operational taxonomic units (MOTUs). Rampant cryptic diversity is detected within eight species with multiple MOTUs, whereas 25 species present mismatch between morphological and molecular delimitations. A total of 18 species are lumped into nine MOTUs due to low interspecific divergence and/or mixed lineages. Several MOTU divergences are hypothesized to relate to known biogeographical barriers and geological events during the Pliocene and Pleistocene. This study provides new insights into the taxonomy and phylogeography of the subfamily Culterinae.

R-D-A and R-D-π-A Structured AIEgens: Relationship between Electronic, Conformational Characteristics and Photophysical Properties.

The design of new aggregation-induced emission luminogens (AIEgens) has aroused continuous attention. The relationship between structure and performance plays an important role in guiding such efforts. In this contribution, two R-D-A- and R-D-π-A-type AIEgens were facilely designed and synthesized, that is, DPE-PTZ-CN and DPE-PTZ-PCN, with diphenylethylene as the twisted rotor structure (R), phenothiazine as electron-donor (D), and the (aryl) cyano group as electron-acceptor (A) fragments. Both luminophores were endowed with typical AIE properties, while their αAIE (PL intensity ratio of AIEgen in a mixed solution with water fraction (fw) = 90 vol % to that with fw = 0) were quite different. The αAIE for DPE-PTZ-CN was as high as 41, but it was only 3 for DPE-PTZ-PCN, in which the π-bridge (aryl linker) was introduced between its D and A groups. In addition, the push-pull electronic effect endowed both molecules with the feature of intramolecular charge transfer (ICT). The solvatochromism effect observed in solutions with different polarities confirmed the existence of the ICT process. The theoretical calculation and single crystal structure analysis revealed that the electronic structure and molecular conformation characteristics had a decisive influence on the differences in photophysical behaviors.

ß-Hydroxybutyrate Alleviates Low Glucose-Induced Apoptosis via Modulation of ROS-Mediated p38 MAPK Signaling.

Hypoglycemia has emerged as a prominent complication in anti-diabetic drug therapy or negative energy balance of animals, which causes brain damage, cognitive impairment, and even death. Brain injury induced by hypoglycemia is closely related to oxidative stress and the production of reactive oxygen species (ROS). The intracellular accumulation of ROS leads to neuronal damage, even death. Ketone body ß-hydroxybutyrate (BHBA) not only serves as alternative energy source for glucose in extrahepatic tissues, but is also involved in cellular signaling transduction. Previous studies showed that BHBA reduces apoptosis by inhibiting the excessive production of ROS and activation of caspase-3. However, the effects of BHBA on apoptosis induced by glucose deprivation and its related molecular mechanisms have been seldom reported. In the present study, PC12 cells and primary cortical neurons were used to establish a low glucose injury model. The effects of BHBA on the survival and apoptosis in a glucose deficient condition and related molecular mechanisms were investigated by using flow cytometry, immunofluorescence, and western blotting. PC12 cells were incubated with 1 mM glucose for 24 h as a low glucose cell model, in which ROS accumulation and cell mortality were significantly increased. After 24 h and 48 h treatment with different concentrations of BHBA (0 mM, 0.05 mM, 0.5 mM, 1 mM, 2 mM), ROS production was significantly inhibited. Moreover, cell apoptosis rate was decreased and survival rate was significantly increased in 1 mM and 2 mM BHBA groups. In primary cortical neurons, at 24 h after treatment with 2 mM BHBA, the injured length and branch of neurites were significantly improved. Meanwhile, the intracellular ROS level, the proportion of c-Fos+ cells, apoptosis rate, and nuclear translocation of NF-κB protein after treatment with BHBA were significantly decreased when compared with that in low glucose cells. Importantly, the expression of p38, p-p38, NF-κB, and caspase-3 were significantly decreased, while the expression of p-ERK was significantly increased in both PC12 cells and primary cortical neurons. Our results demonstrate that BHBA decreased the accumulation of intracellular ROS, and further inhibited cell apoptosis by mediating the p38 MAPK signaling pathway and caspase-3 apoptosis cascade during glucose deprivation. In addition, BHBA inhibited apoptosis by activating ERK phosphorylation and alleviated the damage of low glucose to PC12 cells and primary cortical neurons. These results provide new insight into the anti-apoptotic effect of BHBA in a glucose deficient condition and the related signaling cascade.

Antibiotic resistance genes in gut of breast-fed neonates born by caesarean section originate from breast milk and hospital ward air.

The human gut is a reservoir of antibiotic resistance genes (ARGs). Even in the absence of antibiotics, ARGs are present in large quantities in faeces of adults, children and even newborns. However, where and when ARGs are acquired remains unclear, as does the types of ARGs acquired. Herein, we recruited 82 pairs of women and their caesarean section newborns. Conventional culture methods and quantitative PCR were employed to detect nine species and six ARG types in meconia, faeces from 3-day-old newborns, amniotic fluid, colostrum, and hospital ward air samples. Furthermore, ARG transfer was explored by tracking Staphylococcus epidermidis isolated from faeces of 3-day-old newborns, colostrum and ward air samples using multi-locus sequence typing (MLST). No ARGs or microorganisms were detected in meconia or amniotic fluid. One or more ARGs were detected in 90.2% of faeces from 3-day-old newborns, and the mecA gene exhibited the highest detection rate (45.1%). ARGs were detected in 85.4% of colostra consistent with ARGs in faeces from 3-day-old newborns. Some ARGs were detected in ward air, and might also be a source of ARGs in neonatal faeces. Isolation of S. epidermidis from neonatal faeces was consistent with antibiotic resistance and gene profiles for colostrum samples. Traceability analysis of S. epidermidis showed that ARGs in neonatal faeces mainly originated from colostrum, and partly from ward air. After birth, neonates born by caesarean section obtain a variety of ARGs mainly from colostrum, and partly from ward air.

How is Trait Anger Related to Adolescents' Cyberbullying Perpetration? A Moderated Mediation Analysis.

Although trait anger has been shown to play an important role in cyberbullying perpetration, little is known about mediating and moderating mechanisms underlying this relationship. In the present study, we examined whether moral disengagement mediated the relationship between trait anger and cyberbullying perpetration, and whether this mediating process was moderated by empathy. Four hundred and fifty-five Chinese adolescents completed the measures of trait anger, moral disengagement, cyberbullying perpetration, and empathy. The results indicated that trait anger was significantly and positively associated with cyberbullying perpetration and this relationship was partially mediated by moral disengagement. Moderated mediation analysis further indicated that empathy moderated the relationship between moral disengagement and cyberbullying perpetration. This relationship became weaker for adolescents with higher levels of empathy. Results highlight the significance of identifying the mechanisms that moderate the mediated paths between trait anger and adolescents' cyberbullying perpetration.

Childhood Maltreatment and Adolescent Cyberbullying Perpetration: A Moderated Mediation Model of Callous-Unemotional Traits and Perceived Social Support.

Although childhood maltreatment has been shown to play an important role in adolescent cyberbullying perpetration, little is known about mediating and moderating mechanisms underlying this relationship. The current study investigated the mediating role of callous-unemotional (CU) traits in the association between childhood maltreatment and adolescent cyberbullying perpetration, as well as the moderating role of perceived social support. A total of 2,407 Chinese adolescents (aged 11-16 years, Mage = 12.75 years, SD = 0.58) completed the measures of childhood maltreatment, CU traits, cyberbullying perpetration, and perceived social support. The results showed that CU traits partially mediated the relationship between childhood maltreatment and adolescent cyberbullying perpetration. Furthermore, perceived social support moderated the relationship between childhood maltreatment and CU traits, as well as CU traits and cyberbullying perpetration. Specifically, childhood maltreatment had a greater impact on CU traits for adolescents with higher levels of perceived social support and the predictive function of CU traits on cyberbullying perpetration was stronger for adolescents with low levels of perceived social support.

Parental Phubbing and Adolescents' Cyberbullying Perpetration: A Moderated Mediation Model of Moral Disengagement and Online Disinhibition.

The current study sought to examine whether parental phubbing was significantly related to adolescents' cyberbullying perpetration and if moral disengagement mediated this relationship. We further examined whether online disinhibition moderated the direct and indirect relationships between parental phubbing and adolescents' cyberbullying perpetration. The participants included 2,407 adolescents from seven middle schools in China who completed the questionnaires regarding their experience with parental phubbing, moral disengagement, cyberbullying perpetration, and online disinhibition. Results indicated that adolescents with a high level of parental phubbing were likely to cyberbully others. Moral disengagement significantly mediated the relationship between parental phubbing and adolescents' cyberbullying perpetration. Furthermore, online disinhibition moderated the indirect relationship between parental phubbing and adolescents' cyberbullying perpetration. Specifically, the paths from parental phubbing to moral disengagement and from moral disengagement to cyberbullying perpetration became strengthened when adolescents experienced high levels of online disinhibition.

Childhood Maltreatment and Adolescents' Aggression: A Moderated Mediation Model of Callous-Unemotional Traits and Friendship Quality.

A growing body of research has documented that childhood maltreatment is associated with increased risk of child aggression. However, little is known about the mediating and moderating mechanisms underlying the relationships between childhood maltreatment and reactive and proactive functions of aggression. Therefore, the present study examined whether callous-unemotional traits mediated the relationships between childhood maltreatment and two subtypes of aggression and whether these mediating processes were moderated by friendship quality. A cross-sectional study was conducted among 2407 adolescents between 11 and 16 years (M age = 12.75, SD = .58) in Shanxi province, China. Participants filled out questionnaires regarding childhood maltreatment, callous-unemotional traits, aggression, and friendship quality. The results indicated that childhood maltreatment was significantly and positively associated with proactive and reactive aggression, and these relationships were partially mediated by callous-unemotional traits after controlling for demographic variables. Friendship quality moderated the relationship between childhood maltreatment and proactive aggression as well as callous-unemotional traits and proactive aggression. These relationships became weaker for adolescents with high levels of friendship quality. Friendship quality did not moderate the effects of childhood maltreatment and callous-unemotional traits on reactive aggression.

Phenothiazine-Based Luminophores with AIE, Solvatochromism, and Mechanochromic Characteristics.

Aggregation-induced emission (AIE) fluorescent molecules with unique photoelectric properties have received extensive attention due to the wide range of applications. In this work, two novel phenothiazine-based luminophores DPE-PTZ-Cl and DPE-PTZ-CF3 were designed based on the frontier molecular orbital (FMO) theory and construction strategy of AIEgens. As expected, both of the luminophores displayed typical AIE behavior and realized the spatial separation of FMOs, which was confirmed by the positive solvatochromism behavior. Their AIE properties could be attributed to the twisted three-dimensional (3D) conformation. Such a conformation resulted from "butterfly-like" phenothiazine and a multirotor structure of diphenylethylene. The spatial separation of FMOs originated from the push-pull electronic synergistic effect of the donor-acceptor (D-A) architecture. Interestingly, DPE-PTZ-Cl also showed a rare blue-shifted mechanochromic (MC) luminescence property. Single-crystal X-ray diffraction (SCXRD) and powder X-ray diffraction (PXRD) experiments were carried out to reveal that the phase transformation between crystalline and amorphous states was responsible for the peculiar solid-state luminescence phenomenon.