Safety and efficacy of an anti-human APC antibody for prophylaxis of congenital factor deficiencies in preclinical models.

Rebalance of coagulation and anticoagulation to achieve a hemostatic effect has recently gained attention as an alternative therapeutic strategy for hemophilia. We engineered a humanized chimeric antibody, SR604, based on a previously published murine antibody, HAPC1573, which selectively blocks the anticoagulant activity of human activated protein C (APC). SR604 effectively blocked the anticoagulation activities of APC in human plasma deficient in various coagulation factors in vitro with affinities ∼60 times greater than that of HAPC1573. SR604 exhibited prophylactic and therapeutic efficacy in the tail-bleeding and knee-injury models of hemophilia A and B mice expressing human APC (humanized hemophilic mice). SR604 did not interfere with the cytoprotection and endothelial barrier function of APC, nor were there obvious toxicity effects in humanized hemophilic mice. Pharmacokinetic study showed a high bioavailability (106%) of subcutaneously injected SR604 in cynomolgus monkeys. These results demonstrate that SR604 is expected to be a safe and effective therapeutic and/or prophylactic agent with a prolonged half-life for patients with congenital factor deficiencies including hemophilia A and B.

Comparative genomics reveals insights into anuran genome size evolution.

BACKGROUND: Amphibians, particularly anurans, display an enormous variation in genome size. Due to the unavailability of whole genome datasets in the past, the genomic elements and evolutionary causes of anuran genome size variation are poorly understood. To address this, we analyzed whole-genome sequences of 14 anuran species ranging in size from 1.1 to 6.8 Gb. By annotating multiple genomic elements, we investigated the genomic correlates of anuran genome size variation and further examined whether the genome size relates to habitat types. RESULTS: Our results showed that intron expansions or contraction and Transposable Elements (TEs) diversity do not contribute significantly to genome size variation. However, the recent accumulation of transposable elements (TEs) and the lack of deletion of ancient TEs primarily accounted for the evolution of anuran genome sizes. Our study showed that the abundance and density of simple repeat sequences positively correlate with genome size. Ancestral state reconstruction revealed that genome size exhibits a taxon-specific pattern of evolution, with families Bufonidae and Pipidae experiencing extreme genome expansion and contraction events, respectively. Our result showed no relationship between genome size and habitat types, although large genome-sized species are predominantly found in humid habitats. CONCLUSIONS: Overall, our study identified the genomic element and their evolutionary dynamics accounting for anuran genome size variation, thus paving a path to a greater understanding of the size evolution of the genome in amphibians.

Transplanted mesenchymal stromal cells are unable to migrate to the bone surface and subsequently improve osteogenesis in glucocorticoid-induced osteoporosis.

Long-term or high-dose use of glucocorticoids causes bone loss and low bone formation. We previously demonstrated that dexamethasone (Dex) administration caused the shifted differentiation balance of mesenchymal stromal cells (MSCs) to favor adipogenic lineage over osteoblastic lineage, which is one of the key mechanisms for Dex-induced osteoporosis (DIO). These findings indicate that supplementing functional allogeneic MSCs could be a therapeutic strategy for DIO. Here, we found that transplanting MSCs by intramedullary injection had little effect in promoting new bone formation. Fluorescent-labeled lineage tracing revealed that 1 week after transplantation, green fluorescent protein (GFP)-MSCs were found to migrate to the bone surface (BS) in control mice but not in DIO mice. As expected, GFP-MSCs on the BS were mostly Runx2-positive; however, GFP-MSCs located away from the BS failed to differentiate into osteoblasts. We further discovered that the levels of transforming growth factor beta 1 (TGF-ß1), one of the main chemokines for MSC migration, is significantly decreased in the bone marrow fluid of DIO mice, which is insufficient to direct MSC migration. Mechanistically, Dex inhibits TGF-ß1 expression by down-regulating its promoter activity, which decreases bone matrix-deposited TGF-ß1 as well as active TGF-ß1 released during osteoclast-mediated bone resorption. This study indicates that blocking MSC migration in osteoporotic BM contributes to bone loss and suggests that MSC mobilization to the BS may be a promising target for treating osteoporosis.

The Effect of Face-Voice Gender Consistency on Impression Evaluation.

Face and voice are important information cues of interpersonal interaction. Most previous studies have investigated the cross-modal perception of face and voice from the perspective of cognitive psychology, but few empirical studies have focused on the effect of gender consistency of face and voice on the impression evaluation of the target from the perspective of social cognition. Based on the two-stage model of stereotype activation and the stereotype content model, this research examined the effects of face-voice gender consistency on impression evaluation (gender categorization and warmth competence evaluation) by using a cross-modal priming paradigm (Study 1, 20 males and 23 females, Mage = 21.00, SDage = 2.59), a sequential presentation task (Study 2a, 57 males and 70 females, Mage = 18.54, SDage = 1.54; Study 2b, 52 males and 51 females, Mage = 18.54, SDage = 1.36), and a simultaneous presentation task (Study 3, 51 males and 55 females, Mage = 23.58, SDage = 3.20), respectively. The results showed that: (1) there was a face-voice gender consistency preference in gender categorization, and the response of face-voice consistent condition was faster than that of inconsistent condition; (2) compared with the face-voice gender-inconsistent individuals, the participants showed a higher and more stable evaluation of the warmth and competence of the gender-consistent individuals, indicating the effect of matching preference of the face-voice gender consistency on the impression evaluation; (3) people paid more attention to the gender information of faces in the impression evaluation, and the female face could improve people's evaluation on the target's warmth and competence; (4) males were more intolerant of face-voice gender inconsistency when presented sequentially; the "voice needs to match face" effect was stronger for females when presented simultaneously. These findings, on the one hand, enrich and expand previous theories and research on cross-modal processing of face and voice from the perspective of social cognitive impression evaluation; on the other hand, these findings have important practical implications for impression management and decision-making in social interaction.

Social essentialism in the United States and China: How social and cognitive factors predict within- and cross-cultural variation in essentialist thinking.

People intuitively view some social groups (such as Black people, Muslims, and women) as having biological underpinnings and discrete boundaries. Essentialist beliefs about social groups shape how people view themselves and others, leading to a number of negative social consequences. Whereas previous research has demonstrated variations in social essentialism within some Western societies, less is known about how social essentialism manifests in East Asian cultures that have well-documented differences in social values and cognitive styles from Western cultures. The current research investigated cultural variations in social essentialist thinking in the United States and China to reveal how cultural ideologies and social belief systems shape people's basic representations of the social world. Analyses revealed several cultural and social correlates of social essentialism both between and within the cultures and demonstrated the mediating role of collectivistic values in predicting cultural differences in essentialist beliefs about group coherence.

Effect of attribution on the emotions and behavioral intentions of third-party observers toward intergroup discriminators during the COVID-19 pandemic.

The global outbreak of novel coronavirus disease COVID-19 has caused intergroup discrimination associated with the disease to become increasingly prominent. Research demonstrates that the attitudes and behaviors of third-party observers significantly impact the progression of discrimination incidents. This study tested a parallel mediating model in which the attribution tendencies of observers influence their behavioral intentions through the mediating effect of the emotions of anger and contempt. The first two studies confirmed the proposed model with discrimination incidents reported against "returnees from Wuhan" and "returning workers from Hubei." Study 3 further manipulated the attribution tendencies of observers, providing empirical evidence for the causality from attribution tendencies to emotions, confirming the validity of the model. These findings enrich the cognitive (attribution)-emotion-action model, further enhancing our understanding of the role of third parties in intergroup conflicts, with implications for the management of people's emotions and behaviors in social crises.

[Analysis of clinical phenotype and genetic variants among four Chinese pedigrees affected with Waardenburg syndrome].

OBJECTIVE: To explore the genetic basis for four Chinese pedigrees affected with Waardenburg syndrome (WS). METHODS: Four WS probands and their pedigree members who had presented at the First Affiliated Hospital of Zhengzhou University between July 2021 and March 2022 were selected as the study subjects. Proband 1, a 2-year-and-11-month female, had blurred speech for over 2 years. Proband 2, a 10-year-old female, had bilateral hearing loss for 8 years. Proband 3, a 28-year-old male, had right side hearing loss for over 10 years. Proband 4, a 2-year-old male, had left side hearing loss for one year. Clinical data of the four probands and their pedigree members were collected, and auxiliary examinations were carried out. Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: Proband 1, with profound bilateral sensorineural hearing loss, blue iris and dystopia canthorum, was found to have harbored a heterozygous c.667C>T (p.Arg223Ter) nonsense variant of the PAX3 gene, which was inherited from her father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PM2_Supporting+PP4), and the proband was diagnosed with WS type I. Proband 2, with moderate sensorineural hearing loss on the right side and severe sensorineural hearing loss on the left side, has harbored a heterozygous frameshifting c.1018_1022del (p.Val340SerfsTer60) variant of the SOX10 gene. Neither of her parents has harbored the same variant. Based on the ACMG guidelines, it was classified as pathogenic (PVS1+PM2_Supporting+PP4+PM6), and the proband was diagnosed with WS type II. Proband 3, with profound sensorineural hearing loss on the right side, has harbored a heterozygous c.23delC (p.Ser8TrpfsTer5) frameshifting variant of the SOX10 gene. Based on the ACMG guidelines, it was classified as pathogenic (PVS1+PM2_Supporting+PP4), and the proband was diagnosed with WS type II. Proband 4, with profound sensorineural hearing loss on the left side, has harbored a heterozygous c.7G>T (p.Glu3Ter) nonsense variant of the MITF gene which was inherited from his mother. Based on the ACMG guidelines, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP4), and the proband was diagnosed with WS type II. CONCLUSION: By genetic testing, the four probands were all diagnosed with WS. Above finding has facilitated molecular diagnosis and genetic counseling for their pedigrees.

Adenosine improves LPS-induced ROS expression and increasing in monolayer permeability of endothelial cell via acting on A2AR.

Blood-labyrinth barrier (BLB) disruption plays a crucial role in the development of otitis media. The aims of our study was to explore the role and action mechanism of adenosine in LPS-induced endothelial cells (ECs) damage, which are one of the major principal cell type for blood-labyrinth barrier (BLB), and so as to assess the potential of adenosine to be used in the treatment of BLB disruption in animal experiment. In our study, ECs were treated with LPS to mimic BLB damage in vitro. Our data showed that adenosine at dosage of 1, 10, and 20 µM had no influence on the cell viability of ECs. LPS treatment obviously suppressed the expression of Occludin and Zonula occludens-1 (ZO-1) in ECs, which was partly recused by adenosine treatment. Meantime, LPS-induced increasing in reactive oxygen species (ROS) production and ECs permeability also was rescued by adenosine treatment. However, inhibition the A2A receptor (A2AR) could attenuate the influence of adenosine on LPS-treated ECs, indicating that adenosine alleviated LPS-induced BLB damage by activating A2AR. Moreover, the inhibition of adenosine to LPS-induced inactivation of AMPK/AKT signaling pathway was partly recused by A2AR suppression. In addition, Compound C (an AMPK inhibitor) decreased the expression of Occludin and ZO-1 in ECs following LPS combined with adenosine treatment. In conclusion, adenosine alleviates LPS-induced BLB damage via AMPK/AKT pathway through activation of A2AR. This work suggests that adenosine may be a candidate drug for the treatment of BLB dysfunction-related diseases.

(cRGD)2 peptides modified nanoparticles increase tumor-targeting therapeutic effects by co-delivery of albendazole and iodine-131.

Albendazole (ABZ), a clinical antiparasitic drug, has shown potential antitumor effects in various tumors. Herein, we prepared dimeric cRGD [(cRGD)2] modified human serum albumin (HSA) nanosystem to co-delivery of albendazole (ABZ) and iodine-131 (131I) for chemoradiotherapy of triple-negative breast cancer (TNBC). HSA@ABZ NPs were synthesized by the self-assembly method. 131I-(cRGD)2/HSA@ABZ NPs were fabricated through covalently binding HSA@ABZ NPs with (cRGD)2 peptides, followed by chloramine T direct labeling with 131I. In vitro therapeutic effects on TNBC (MDA-MB-231 and 4T1 cells) were determined using MTT assay, crystal violet assay, wound-healing assay and western blotting analysis. In vivo treatment was performed using 4T1-bearing mice, and the tumor-targeting efficacy was assessed by gamma imaging. The distribution of NPs was quantitatively analyzed by detecting the gamma counts in tumor and main organs. The nanoparticles possessed negative charge, moderate size and good polydispersity index. Dual responding to pH and redox, the in vitro release rate of ABZ was more than 80% in 72 h. In vitro, NPs inhibited the proliferation of TNBC cells in a concentration-dependent manner and decreased cell migration. Western blotting analysis showed that the NPs, as well as free ABZ, cell-dependently induced autophagy and apoptosis by restraining or promoting the expression of p-p38 and p-JNK MAPK. In vivo, gamma imaging exhibited an earlier and denser radioactivity accumulation in tumor of 131I-(cRGD)2/HSA@ABZ NPs compared to NPs free of (cRGD)2 conjugating. Furthermore, 131I-(cRGD)2/HSA@ABZ NPs significantly suppressed tumor growth by restraining proliferation and promoting apoptosis in vivo. Our study suggested that the nanoparticles we developed enhanced tumor-targeting of ABZ and increased antitumor effects by combination of chemotherapy and radiotherapy.

Culture influences the development of children's gender-related peer preferences: Evidence from China and Thailand.

Current understanding of how culture relates to the development of children's gender-related peer preferences is limited. To investigate the role of societal acceptance of gender nonconformity, this study compared children from China and Thailand. Unlike China and other cultures where the conceptualization of gender as binary is broadly accepted, individuals who identify as a nonbinary "third" sex/gender have been highly visible and tolerated in Thai society for at least several decades. Chinese and Thai 4- to 9-year-olds (N = 458) viewed vignettes of four hypothetical peers who varied on gender (i.e., boy vs. girl) and gender-typed toy play behavior (i.e., masculine vs. feminine), and were asked to give a friendship preference rating for each peer. Chinese, compared with Thai, children evidenced gender-related peer preferences that emerged earlier, remained more stable across age groups, and were relatively more biased against gender-nonconforming behavior. The only cultural similarity was in children's preference for peers who were of the same gender and/or displayed same-gender-typed behavior. Thus, while preference for peers who are of the same gender and/or display same-gender-typed behavior is common among children across cultures, the developmental onset and course of these preferences vary by culture. Moreover, societal acceptance of gender nonconformity might be key to limiting children's bias against gender-nonconforming peers.

NGF monoclonal antibody DS002 alleviates chemotherapy-induced peripheral neuropathy in rats.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the pervasive side effects of chemotherapy, leading to poor quality of life in cancer patients. Discovery of powerful analgesics for CIPN is an urgent and substantial clinical need. Nerve growth factor (NGF), a classic neurotrophic factor, has been identified as a potential therapeutic target for pain. In this study, we generated a humanized NGF monoclonal antibody (DS002) that most effectively blocked the interaction between NGF and tropomyosin receptor kinase A (TrkA). We showed that DS002 blocked NGF binding to TrkA in a dose-dependent manner with an IC50 value of 6.6 nM; DS002 dose-dependently inhibited the proliferation of TF-1 cells by blocking the TrkA-mediated downstream signaling pathway. Furthermore, DS002 did not display noticeable species differences in its binding and blocking abilities. In three chemotherapy-induced rat models of CIPN, subcutaneous injection of DS002 produced a significant prophylactic effect against paclitaxel-, cisplatin- and vincristine-induced peripheral neuropathy. In conclusion, we demonstrate for the first time that an NGF inhibitor effectively alleviates pain in animal models of CIPN. DS002 has the potential to treat CIPN pain in the clinic.

Dominance or Integration? Influence of Sexual Dimorphism and Clothing Color on Judgments of Male and Female Targets' Attractiveness, Warmth, and Competence.

The face is an important source of information in social interactions. Prior studies exploring the mechanism of face perception were consistent with either dominance or integration theory. Studies have shown that both sexually dimorphic features and background cues play essential roles in the formation of impressions and the perception of facial attractiveness. In this study, we conducted two experiments to examine 539 participants' appraisal of attractiveness, warmth, and competence of the target faces of masculine and feminine men and women dressed in red, blue, or white. The results showed that: (1) feminized male/female faces were considered to have a higher degree of attractiveness, warmth, and competence, (2) people rated feminine faces wearing red higher in terms of attractiveness perception, while there was no significant effect of red on attractiveness perception of masculine faces, (3) when evaluating the warmth of targets, the promotion effect of red was found for feminine faces but not for masculine faces. This study, conducted in a pathogen disgust environment, provides direct evidence to support the integration theory over the dominance theory. Feminized red preference found in this study matches Chinese collectivism and the red cultural heritage, which has an important value for people's daily impression management and consumption decisions.

Influence of smartphone use motives on smartphone addiction during the COVID-19 epidemic in China: the moderating effect of age.

With the development of science and technology, the phenomenon of smartphone addiction has become very common. However, smartphone addiction has adverse consequences. To date, few studies have examined psychological crises and smartphone use motives during the coronavirus disease 2019 (COVID-19) pandemic according to age. Therefore, this study aimed to examine the influences of different types of smartphone use motives on smartphone addiction and explore the moderating effect of age on adolescents and adults. A total of 1346 participants (600 adults and 746 adolescents) completed questionnaires on their motives for smartphone use and smartphone addiction. Results indicated significant positive correlations between smartphone use motives and smartphone addiction. In the moderation model, mood regulation, social relations, pastime, and conformity significantly and directly predicted smartphone addiction; however, perceived enjoyment did not. Age played a moderating role in the prediction of smartphone addiction. Teenagers and adults have different motives for smartphone use, and different motives have different effects on adolescents and adults. Adolescents have higher coping motivation and conformity motivation than adults, and for adolescents, perceived pleasure motivation has a significant impact on smartphone addiction. For adults, perceived pleasure and social relationship motivation have a significant impact on smartphone addiction. Therefore, interventions for smartphone addiction can be developed by investigating the motives of use among different people, and age should be considered when developing interventions for smartphone addiction.

Magnetic mesoporous nanomaterials with AIE properties for selective detection and removal of CN- from water under magnetic conditions.

We have prepared a type of magnetic mesoporous nanomaterial with aggregation-induced emission properties (Fe3O4@mSiO2@TPA@BA, hence abbr. FSTB) to detect and remove cyanide ions (CN-) under magnetic conditions. FSTB has a large specific surface area and improved fluorescence performance to identify CN-, and its superparamagnetic behavior plays an important role in removing CN-. The magnetic sensor FSTB shows excellent selectivity and anti-interference for the detection of CN- in aqueous solutions. It is obvious from the equation LOD = 3δ/S that the limit of detection (LOD) of FSTB for CN- is significantly lower than the permissible level of CN- in drinkable water recommended by the World Health Organization. Therefore, the magnetic sensor FSTB has a wide range of applications for detecting and removing harmful CN-.

Non-Pregnant and Pregnant Women's Femininity Preferences in Male Faces: Tests Based on Within- and Between-Sex Sexual Dimorphism Facial Manipulations.

Past research on women's preferences for male facial masculinity in Western cultures has produced inconsistent results. Some inconsistency may be related to the use of different facial stimulus manipulations (e.g., between-sex sexual dimorphic facial manipulation or within-sex sexual dimorphic facial manipulation) that do not perfectly avoid non-facial cues, and pregnancy status may also influence women's face preferences. We therefore recruited pregnant and nonpregnant Chinese women and manipulated the sexual dimorphism of male facial stimuli to explore the influences of manipulation methods, non-facial cues, and pregnancy status on face preferences. Results showed that: (1) in contrast with a general masculinity preference observed in Western cultures, both pregnant and nonpregnant Chinese women preferred feminized and neutral male faces generally; (2) pregnant women's preference for feminized male faces was stable across manipulation methods, while nonpregnant women preferred feminized male faces except under between-sex sexual dimorphism manipulation; and (3) manipulation methods, rather than non-facial cues, influenced participants' face preferences. Specifically, women showed the strongest preferences for femininity when face stimuli were manipulated by within-sex sexual dimorphic facial manipulation, followed by unmanipulated faces and between-sex sexual dimorphic facial manipulation. This effect was stronger for nonpregnant women in the unmanipulated condition and for pregnant women in the between-sex sexual dimorphic facial manipulation. This research provides empirical evidence of women's preferences for sexual dimorphism in male faces in a non-Western culture, as well as the effects of facial manipulation methods, pregnancy status, and the interactions between these factors.

The Effects of Race, Gender, and Gender-Typed Behavior on Children's Friendship Appraisals.

From a young age, children's peer appraisals are influenced by the social categories to which peers belong based on factors such as race and gender. To date, research regarding the manner in which race- and gender-related factors might interact to influence these appraisals has been limited. The present study employed an experimental vignette paradigm to investigate the relative influences of target peers' race, gender, and gender-typed behavior toward 4- to 6-year-old Chinese children's (N = 119, 62 girls, 57 boys) peer appraisals. Appraisals were assessed via (1) a rating scale measuring children's interest in being friends with a range of hypothetical target peers varying in race, gender, and gender-typed behavior, and (2) a forced-choice rank-order task in which children indicated their preferences for four hypothetical target peers who varied from themselves on either race, gender, or gender-typed behavior, or were similar to themselves on all three traits. There was little evidence to suggest children's rank-ordered peer preferences in relation to race were influenced by whether the other-race presented was White (preferred relatively more) or Black (preferred relatively less). In contrast, gender-related factors (i.e., rater gender, target gender, target gender-typed behavior) had more robust influences on peer preferences for both outcome measures. Gender-conforming peers were preferred over gender-nonconforming peers, and target boys displaying feminine behavior were less preferred than target girls displaying masculine behavior. The results help characterize cross-cultural (in)consistencies in children's social preferences in relation to peers' race and gender.

Coding mutations in NUS1 contribute to Parkinson's disease.

Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson's disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD. We identified 12 genes with de novo mutations (MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2), which could be functionally relevant to PD pathogenesis. Further analyses of two independent case-control cohorts (1,852 patients and 1,565 controls in one cohort and 3,237 patients and 2,858 controls in the other) revealed that NUS1 harbors significantly more rare nonsynonymous variants (P = 1.01E-5, odds ratio = 11.3) in PD patients than in controls. Functional studies in Drosophila demonstrated that the loss of NUS1 could reduce the climbing ability, dopamine level, and number of dopaminergic neurons in 30-day-old flies and could induce apoptosis in fly brain. Together, our data suggest that de novo mutations could contribute to early onset PD pathogenesis and identify NUS1 as a candidate gene for PD.

The relationship of perceived social support to feelings of hopelessness under COVID-19 pandemic: The effects of epidemic risk and meaning in life.

Lockdown orders were issued on January 23, 2020 in Wuhan, China, for the purpose of preventing and controlling COVID-19, which led to severe psychological problems for residents. The present study aimed to investigate the recovery model of hopelessness through interpersonal pathways during the COVID-19 epidemic. An online survey was conducted in 34 provinces (those in autonomous regions and municipalities) of China. This survey investigated residents' hopelessness and the impact of three factors on it, including their perceived social support, meaning in life, and epidemic risk levels. Results showed that both perceived social support and meaning in life negatively predicted hopelessness, while meaning in life played a partial mediating role between perceived social support and hopelessness. Further, epidemic risk level played a moderating role between perceived social support and meaning in life, indicating a "marginal zone effect." Specifically, when comparing other province, perceived social support showed a stronger positive relationship with meaning in life among residents living in other regions of Hubei province. In sum, this study extends the recovery model of hopelessness through interpersonal pathways, and has important implications for public health emergency management.

Facial expression stereotypes of rich and poor adults and children.

Facial expression stereotypes can affect the perception of other people's facial expressions. This study examined facial expression stereotypes of poor and rich adults and children. Experiment 1 found that the adult participants associated rich adults with positive emotions (i.e., happiness) and poor adults with negative emotions (i.e., sadness). In Experiments 2-4, adult participants still thought that rich 4-, 6-, and 10-year-old children would show positive facial expressions (happiness) but did not think that poor 4-, 6-, and 10-year-old children would show negative emotions (sadness). These finding have implications concerning how adults communicate with poor and rich adults and children.

The long noncoding RNA H19 attenuates force-driven cartilage degeneration via miR-483-5p/Dusp5.

Developmental dysplasia of the hip (DDH) is a common hip disease characterized by abnormal development of the acetabulum and femoral head. In most cases, DDH ultimately leads to osteoarthritis. Anomalous biomechanical force plays an important role in cartilage degeneration in DDH. However, in addition to mechanical wear, the underlying molecular mechanisms in cartilage degeneration in DDH remain unclear. This study analyzed the effect of long noncoding RNA (lncRNA)-H19 on DDH cartilage degradation. To elucidate the specific role of lncRNA H19, we established an intermittent cyclic mechanical stress (ICMS) cell force model to simulate abnormal biomechanical environment in vitro. Then, the roles of lncRNA-H19 were also determined in vivo by establishing a model of swaddling DDH. We observed that patients with DDH possessed low levels of lncRNA-H19, COL2A1, and Aggrecan but high levels of MMP3 and Adamts5. The same results were also obtained in a DDH rat model. Furthermore, the data suggested that ICMS promoted cartilage degeneration and caused reorientation of the cytoskeleton, and lncRNA H19 helped inhibit cartilage degeneration. Bioinformatics analysis and lncRNA sequencing were performed, and luciferase assays showed that lncRNA H19 and Dusp5 are both direct targets of miR-483-5p. Moreover, Dups5 plays a negative role in ICMS-induced cartilage degradation by activating the Erk and p38 pathways. In vivo, lncRNA H19 had protective effects on the swaddling DDH model. These findings indicate that lncRNA-H19 played a positive role in cartilage degradation in DDH through the lncRNA H19/miR-483-5p/Dusp5 axis.