Ultra-Fast-Healing Glassy Hyperbranched Plastics Capable of Restoring 26.4†MPa Tensile Strength within One Minute at Room Temperature.

The growing concern regarding widespread plastic pollution has propelled the development of sustainable self-healing plastics. Although considerable efforts have been dedicated to fabricating self-healing plastics, achieving rapid healing at room temperature is extremely challenging. Herein, we have developed an ultra-fast-healing glassy polyurethane (UGPU) by designing a hyperbranched molecular structure with a high density of multiple hydrogen bonds (H-bonds) on compliant acyclic heterochains and introducing trace water to form water bridge across the fractured surfaces. The compliant acyclic heterochains allow the dense multiple hydrogen bonds to form a frozen network, enabling tensile strength of up to 70 MPa and storage modulus of 2.5 GPa. The hyperbranched structure can drive the reorganization of the H-bonding network through the high mobility of the branched chains and terminals, thereby leading to self-healing ability at room temperature. Intriguingly, the presence of trace water vapor facilitates the formation of activated layers and the rearrangement of networks across the fractured UGPU sections, thereby enabling ultra-fast self-healing at room temperature. Consequently, the restored tensile strength after healing for 1 minute achieves a historic-record of 26.4 MPa. Furthermore, the high transparency (>90 %) and ultra-fast healing property of UGPU make it an excellent candidate for advanced optical and structural materials.

Thermomechanically stable supramolecular elastomers inspired by heat shock proteins.

Supramolecular polymers are usually thermomechanically unstable, as their mechanical strength decreases drastically upon heating, which is a fatal shortcoming for their application. Herein, inspired by heat shock proteins (HSPs) which enable living organisms to tolerate lethal high temperatures, we design an HSP-like response to impart a supramolecular elastomer with high thermomechanical stability. The HSP-like response relies on the reversible hydrolysis of boronic acid and the tunable association strength of boron dative bonds. As the temperature increases, the boronic acid dehydrates and transforms into boroxane. The boroxane, acting as a heat shock chemical, prevents the disintegration of the supramolecular network through formation of multiple and stronger dative bonds with imidazole-containing polymers, thereby enabling the material to retain its mechanical strength at high temperatures. Such chemical transformation and network change induced by the HSP-like response are fully reversible during the heating and cooling processes. Moreover, due to the dynamic nature of the supramolecular network, the elastomer possesses recycling and self-healing abilities.

Impact-Resistant Adhesive Based on the Shear-Stiffening Effect via Dynamic B-O Linkages.

The occurrence of adhesive failure under impact poses significant risks, including property damage, structural collapse, and even loss of life. Herein, we have developed a series of impact-resistant adhesives by incorporating dynamic B-O linkages into linear polymeric chains. These adhesives not only possess broad-area adhesion and superior adhesive strength compared to 3 M commercial products but also exhibit a shear-stiffening effect. The shear-stiffening effect provided by the B-O linkages endows the adhesives with remarkable impact resistance, achieving a force attenuation efficiency of 84.3-86.3%. Additionally, when they are bonded to target materials, the resulting sandwich structures retain their excellent impact resistance. Therefore, this class of impact-resistant adhesives with a shear-stiffening effect shows significant potential for applications in protecting precision instruments and buildings.

A Shear-Stiffening Mouthguard with Excellent Shock Absorption Capability and Remoldability via a Dynamic Dual Network.

Mouthguards are used to reduce injuries and the probability of them to orofacial tissues when impacted during sports. However, the usage of a mouthguard is low due to the discomfort caused by the thickness of the mouthguard. Herein, we have constructed a dynamic dual network to fabricate a shear-stiffening mouthguard with remoldability, which are called remoldable shear-stiffening mouthguards (RSSMs). Based on diboron/oxygen dative bonds, RSSMs show a shear-stiffening effect and excellent shock absorption ability, which can absorb more than 90% of the energy of a blank. Even reducing the thickness to half, RSSMs can reduce approximately 25% of the transmitted force and elongate by about 1.6-fold the buffer time compared to commercial mouthguard materials (Erkoflex and Erkoloc-pro). What is more, owing to the dynamic dual network, RSSMs show good remolding performance with unchanged shear-stiffening behavior and impact resistance, which conforms to the existing vacuum thermoforming mode. In addition, RSSMs exhibit stability in artificial saliva and biocompatibility. In conclusion, this work will broaden the range of mouthguard materials and offer a platform to apply shear-stiffening materials to biomedical applications and soft safeguarding devices.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases: A case report.

BACKGROUND: Small cell lung cancer (SCLC) is a common and aggressive subtype of lung cancer. It is characterized by rapid growth and a high mortality rate. Approximately 10% of patients with SCLC present with brain metastases at the time of diagnosis, which is associated with a median survival of 5 mo. This study aimed to summarize the effect of bevacizumab on the progression-free survival (PFS) and overall survival of patients with brain metastasis of SCLC. CASE SUMMARY: A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks. The patient was diagnosed with limited-stage SCLC. He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo. CONCLUSION: The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Cell death dependent on holins LrgAB repressed by a novel ArsR family regulator CdsR.

The cell death and survival paradox in various biological processes requires clarification. While spore development causes maternal cell death in Bacillus species, the involvement of other cell death pathways in sporulation remains unknown. Here, we identified a novel ArsR family transcriptional regulator, CdsR, and found that the deletion of its encoding gene cdsR causes cell lysis and inhibits sporulation. To our knowledge, this is the first report of an ArsR family transcriptional regulator governing cell death. We found that CdsR directly repressed lrgAB expression. Furthermore, lrgAB overexpression resulted in cell lysis without sporulation, akin to the cdsR mutant, suggesting that LrgAB, a holin-like protein, induces cell death in Bacillus spp. The lrgAB mutation increases abnormal cell numbers during spore development. In conclusion, we propose that a novel repressor is vital for inhibiting LrgAB-dependent cell lysis.

ßAR-mTOR-lipin1 pathway mediates PKA-RIIß deficiency-induced adipose browning.

Background: Enhancing white adipose tissue (WAT) browning combats obesity. The RIIß subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RIIß gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored. Methods: This study investigates the mechanisms underlying WAT browning in RIIß-KO mice. Genetic approaches such as ß3-adrenergic receptors (ß3ARs) deletion and sympathetic denervation of WAT were utilized. Genome-wide transcriptomic sequencing and bioinformatic analysis were employed to identify potential mediators of WAT browning. siRNA assays were employed to knock down mTOR and lipin1 in vitro, while AAV-shRNAs were used for the same purpose in vivo. Results: We found that WAT browning substantially contributes to the lean and obesity-resistant phenotypes of RIIß-KO mice. The WAT browning can be dampened by ß3ARs deletion or WAT sympathetic denervation. We identified that adipocytic mTOR and lipin1 may act as mediators of the WAT browning. Inhibition of mTOR or lipin1 abrogates WAT browning and hinders the lean phenotype of RIIß-KO mice. In human subcutaneous white adipocytes and mouse white adipocytes, ß3AR stimulation can activate mTOR and causes lipin1 nuclear translocation; knockdown of mTOR and Lipin1 mitigates WAT browning-associated gene expression, impedes mitochondrial activity. Moreover, mTOR knockdown reduces lipin1 level and nuclear translocation, indicating that lipin1 may act downstream of mTOR. Additionally, in vivo knockdown of mTOR and Lipin1 diminished WAT browning and increased adiposity. Conclusions: The ß3AR-activated mTOR-lipin1 axis mediates WAT browning, offering new insights into the molecular basis of PKA-regulated WAT browning. These findings provide potential adipose target candidates for the development of drugs to treat obesity.

A Qualitative Study on Parental Experience of Involvement in the Transition from Kindergarten to Primary School for Chinese Children with Intellectual and Developmental Disabilities.

Parental involvement plays a vital role in the transition from kindergarten to primary school among children with intellectual and developmental disabilities (IDDs); this study aims to explore Chinese parents' experiences of parental involvement during this period. Informed by interpretive phenomenological analysis, semi-structured, one-on-one interviews were held with 10 parents. Three major themes were identified: (1) "aggressive" involvement; (2) factors in transforming parental involvement; and (3) "rational" involvement. Participants reported their perceptions, attitudes, and parenting behaviors in different phases of involvement in the transition to primary school. These findings highlight the need to support parents of children with IDDs during this time of change.

The relationship between parental involvement and psychological adjustment among Chinese children with autism spectrum disorder in the transition from kindergarten to primary school: A chain-mediating model.

Introduction: This study examined the impact of parental involvement on the psychological adjustment of children with autism spectrum disorder (ASD), and the role of parenting self-efficacy and parenting stress in the transition from kindergarten to primary school. Methods: Using the questionnaires, we collected data from 237 Chinese parents of children with ASD. Results: Mediation analyses showed that parental involvement partially promoted the psychological adjustment of children with ASD, which was reflected in the fact that parental involvement promoted children's prosocial behavior but did not reduce their emotional/behavioral problems. Mediation analyses also revealed the role of the mediator in parenting stress between parental involvement and the psychological adjustment of children. Additionally, the results suggested that parenting self-efficacy and parenting stress played a chain-mediating role in the association between parental involvement and psychological adjustment in children with ASD. Discussion: These findings enhance our understanding of the mechanisms underlying the relationship between parental involvement and psychological adjustment in children with ASD in the transition from kindergarten to primary school.

Family Socioeconomic Status and Parental Involvement in Chinese Parents of Children with Autism Spectrum Disorder: A Moderated Mediation Model.

Parental involvement benefits children with autism spectrum disorder (ASD) in multiple developmental areas. We conducted the present study to examine the role of parenting stress and ASD symptom severity in the relationship between family socioeconomic status (SES) and parental involvement. A total of 165 Chinese parents of children with ASD participated in this study. Mediation analyses indicated that family SES was positively related to parental involvement; parenting stress partially mediated the relationship between family SES and parental involvement. The analyses also found that ASD symptom severity moderated the influence of parenting stress on parental involvement. Specifically, the decreased parenting stress improved parental involvement when ASD symptom severity was low. The findings enhanced our understanding of the mechanism underlying the relationship between family SES and parental involvement among parents facing considerable child-rearing challenges. Implications for devising evidenced-based interventions to promote parental involvement for low SES children with ASD are discussed.

The development and validation of a questionnaire on parental involvement in the transition from kindergarten to primary school for children with developmental disabilities in China.

BACKGROUND: At present, there is a lack of valid and reliable instruments that can measure parental involvement in the transition from kindergarten to primary school of children with developmental disabilities (DD) in China. AIM: This study seeks to develop and validate the questionnaire on Parental Involvement in Transition from Kindergarten to Primary School (PITKPS) for children with DD in China. METHODS: A total of 241 parents of children with DD participated in Study 1, and another 247 parents participated in Study 2. In study 1, we used item analysis and exploratory factor analysis to screen items and explore the factor structure of the PITKPS questionnaire. In study 2, three types of validity were examined: construct validity; convergent and discriminative validity; and criterion-related validity. Internal consistency was used to measure reliability. RESULTS: The final version of the PITKPS questionnaire comprised 37 items that examined six factors. Confirmatory factor analysis supported the use of the six-factor model, and the results indicated that the questionnaire had good reliability and validity. CONCLUSIONS: The PITKPS questionnaire can be used as a valid tool to assess the involvement of Chinese parents in the transition from kindergarten to primary school of children with DD.

Hyperprogression after anti-programmed death-1 therapy in a patient with urothelial bladder carcinoma: A case report.

BACKGROUND: Immune checkpoint inhibitors, including programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) have recently been approved to treat locally advanced and metastatic urothelial carcinoma (UC). However, some patients experience rapid tumor progression rather than any clinical benefit from anti-PD-L1/PD-1 therapy. CASE SUMMARY: A 73-year-old woman with bladder UC showed the progression of multiple metastases after surgery and chemotherapy for over 12 mo. The patient could not tolerate further chemotherapy. Next-generation sequencing was performed, and the results indicated that the tumor mutational burden was 6.4 mutations/Mb. The patient received the anti-PD-L1 agent toripalimab combined with albumin-bound paclitaxel. Compared with the baseline staging before immunotherapy, the patient had a treatment failure time of < 2 mo, an increase in tumor burden of > 50%, and a > 2-fold increase in progression, indicating hyperprogression. CONCLUSION: Selecting patients most likely to respond to treatment with immunotherapeutic agents remains challenging. For older patients with advanced UC who have already exhausted multi-line chemotherapy options, immunotherapy should be used prudently if no effective biomarker is available. Further studies are required to clarify the causes and mechanisms of hyperprogression.

WNT ligands in non-small cell lung cancer: from pathogenesis to clinical practice.

Non-small cell lung cancer (NSCLC) is the malignant tumor with the highest morbidity and leading cause of death worldwide, whereas its pathogenesis has not been fully elucidated. Although mutations in some crucial genes in WNT pathways such as ß-catenin and APC are not common in NSCLC, the abnormal signal transduction of WNT pathways is still closely related to the occurrence and progression of NSCLC. WNT ligands (WNTs) are a class of secreted glycoproteins that activate WNT pathways through binding to their receptors and play important regulatory roles in embryonic development, cell differentiation, and tissue regeneration. Therefore, the abnormal expression or dysfunction of WNTs undoubtedly affects WNT pathways and thus participates in the pathogenesis of diseases. There are 19 members of human WNTs, WNT1, WNT2, WNT2b, WNT3, WNT3a, WNT4, WNT5a, WNT5b, WNT6, WNT7a, WNT7b, WNT8a, WNT8b, WNT9a, WNT9b, WNT10a, WNT10b, WNT11 and WNT16. The expression levels of WNTs, binding receptors, and activated WNT pathways are diverse in different tissue types, which endows the complexity of WNT pathways and multifarious biological effects. Although abundant studies have reported the role of WNTs in the pathogenesis of NSCLC, it still needs further study as therapeutic targets for lung cancer. This review will systematically summarize current research on human WNTs in NSCLC, from molecular pathogenesis to potential clinical practice.

Mouthguards Based on the Shear-Stiffening Effect: Excellent Shock Absorption Ability with Softness Perception.

Mouthguards are used to prevent craniomaxillofacial injuries when collisions happen during contact and high-speed sports. However, poor compliance with mouthguard wear in athletes is attributed to discomfort because of its thickness and hardness. These drawbacks significantly restrict their protective performance for oral tissues and applications during contact sports; as a result, the incidence of craniomaxillofacial injuries increases. In this study, non-Newton material is introduced into mouthguard material and then a mouthguard with shear-stiffening behavior is fabricated, which is named the shear-stiffening mouthguard (SSM). Compared with commercial mouthguard materials (Erkoflex and Erkoloc-pro), SSMs show remarkable enhancement of shock absorption ability with an approximately 60% reduction in peak force relative to commercial materials and approximately 3-fold extensive buffer time. Moreover, Young's modulus of SSMs (average 0.48 MPa) is extremely lower compared to commercial materials (22.88 MPa for Erkoflex and 26.71 MPa for Erkoloc-pro). This manifests that SSMs have not only excellent shock absorption ability but also softness perception. Moreover, SSMs show biocompatibility in vitro. In conclusion, this work provides a platform to develop a new type of thin and soft mouthguard with a shear-stiffening effect and broadens the horizon in protecting oral tissues with shear-stiffening materials.

RIIß-PKA in GABAergic Neurons of Dorsal Median Hypothalamus Governs White Adipose Browning.

The RIIß subunit of  cAMP-dependent protein kinase A (PKA) is expressed in the brain and adipose tissue. RIIß-knockout mice show leanness and increased UCP1 in brown adipose tissue. The authors have previously reported that RIIß reexpression in hypothalamic GABAergic neurons rescues the leanness. However, whether white adipose tissue (WAT) browning contributes to the leanness and whether RIIß-PKA in these neurons governs WAT browning are unknown. Here, this work reports that RIIß-KO mice exhibit a robust WAT browning. RIIß reexpression in dorsal median hypothalamic GABAergic neurons (DMH GABAergic neurons) abrogates WAT browning. Single-cell sequencing, transcriptome sequencing, and electrophysiological studies show increased GABAergic activity in DMH GABAergic neurons of RIIß-KO mice. Activation of DMH GABAergic neurons or inhibition of PKA in these neurons elicits WAT browning and thus lowers body weight. These findings reveal that RIIß-PKA in DMH GABAergic neurons regulates WAT browning. Targeting RIIß-PKA in DMH GABAergic neurons may offer a clinically useful way to promote WAT browning for treating obesity and other metabolic disorders.

Direct, Indirect, and Buffering Effect of Social Support on Parental Involvement Among Chinese Parents of Children with Autism Spectrum Disorders.

Parental involvement plays a pivotal role in promoting developmental and educational outcomes for children with autism spectrum disorder (ASD). This study aimed to examine the relationships between social support, parenting stress, and parental involvement by investigating a sample of 245 Chinese parents of children with ASD. Mediation analyses indicated that the relationships between support from family and friends and parental involvement were partially mediated by parenting stress, and support from significant others was directly, positively related to parental involvement. Additionally, support from family and friends moderated the influence of parenting stress on parental involvement in their children's education. The direct, indirect, and buffering effects of social support on parental involvement were discussed finally.

Leptin signaling and leptin resistance.

With the prevalence of obesity and associated comorbidities, studies aimed at revealing mechanisms that regulate energy homeostasis have gained increasing interest. In 1994, the cloning of leptin was a milestone in metabolic research. As an adipocytokine, leptin governs food intake and energy homeostasis through leptin receptors (LepR) in the brain. The failure of increased leptin levels to suppress feeding and elevate energy expenditure is referred to as leptin resistance, which encompasses complex pathophysiological processes. Within the brain, LepR-expressing neurons are distributed in hypothalamus and other brain areas, and each population of the LepR-expressing neurons may mediate particular aspects of leptin effects. In LepR-expressing neurons, the binding of leptin to LepR initiates multiple signaling cascades including janus kinase (JAK)-signal transducers and activators of transcription (STAT) phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT), extracellular regulated protein kinase (ERK), and AMP-activated protein kinase (AMPK) signaling, etc., mediating leptin actions. These findings place leptin at the intersection of metabolic and neuroendocrine regulations, and render leptin a key target for treating obesity and associated comorbidities. This review highlights the main discoveries that shaped the field of leptin for better understanding of the mechanism governing metabolic homeostasis, and guides the development of safe and effective interventions to treat obesity and associated diseases.

Effect of Counterions on the Physicomechanical Properties of Copper-Nitrogen-Coordinated Metallosupramolecular Elastomers.

Metallosupramolecular elastomers have attracted much attention due to their excellent mechanical properties, flexible tailoring of performance, and responsiveness to photo and thermal stimuli. The physicomechanical properties of metallosupramolecular elastomers are highly dependent on metal salts and ligand units; however, the role of counterions lacks practical exploration. To this end, we synthesized a simple acrylate copolymer model and introduced copper salts with different counterions to construct dynamic copper-nitrogen coordination cross-linked networks. This approach generated a series of elastomers with a tensile strength of over 10 MPa and a laser self-healing efficiency of over 90% within 2 min. In particular, we studied the effects of counterions on the thermodynamic, viscoelastic, mechanical, photothermal, and self-healing properties of the materials. Therefore, this work can provide instruction for the preparation and performance tailoring of metallosupramolecular elastomers.

Bioinspired Design of High Vibration-Damping Supramolecular Elastomers Based on Multiple Energy-Dissipation Mechanisms.

Suppressing vibrations and noises is essential for our automated society. Here, inspired by the hierarchical dynamic bonds and phase separation of mussel byssal threads, we synthesize high-damping supramolecular elastomers (HDEs) via simple one-pot radical polymerization of butyl acrylate (BA), acrylic acid (AA), and vinylimidazole (VI). Interestingly, AA and VI not only form hydrogen bonds and ionic bonds simultaneously but also segregate into aggregates of different sizes, thereby successfully mimicking the hierarchical structure of mussel byssal threads. When applying external forces, the weak hydrogen bonds are broken at first and then the ionic bonds and aggregates are disrupted progressively from small to large deformations. Such multiple energy-dissipation mechanisms lead to the outstanding damping property of the HDEs. Therefore, the HDEs outperform commercially available rubbers in terms of sound absorption and vibration damping. Furthermore, the multiple energy-dissipation mechanisms impart the HDEs with high toughness (41.1 MJ/m3), tensile strength (21.3 MPa), and self-healing ability.

Protective effect of endoplasmic reticulum stress inhibition on 5-fluorouracil-induced oral mucositis.

5-Fluorouracil (5-FU)-induced oral mucositis has a severe negative impact on the patient's quality of life. This study aimed to investigate the role of endoplasmic reticulum stress (ERS) in the occurrence of 5-FU-induced oral mucositis in vivo and in the clinic. In vivo, 5-FU-induced oral mucositis model mice showed a higher level of glucose-regulated protein 78 kD (GRP78, a marker of ERS) than control mice. The inhibition of ERS could effectively reduce 5-FU-induced oxidative stress, inflammatory factor mRNA and cell apoptosis. Moreover, inhibition of ERS significantly decreased the activation of nuclear factor kappa-B (NF-κB) in 5-FU-induced oral mucositis model mice following tissue damage reduction. In the clinic, 5-FU could increase cell apoptosis and cause oral mucosa damage while increasing the expression of the ERS marker genes GRP78 and C/EBP-homologous protein (CHOP). Our study found that 5-FU could induce severe ERS, upregulate the expression of GRP78 and CHOP, raise oxidative stress and increase the expression of inflammatory factors by activating the NF-κB pathway, thus causing cell apoptosis and finally leading to oral mucosal injury.