Hydrogel morphogenesis induced by force-controlled growth.

Morphogenesis is one of the most marvelous natural phenomena. The morphological characteristics of biological organs develop through growth, which is often triggered by mechanical force. In this study, we propose a bioinspired strategy for hydrogel morphogenesis through force-controlled chemical reaction and growth under isothermal conditions. We adopted a double network (DN) hydrogel with sacrificial bonds. Applying mechanical force to the gel caused deformation and sacrificial bond rupture. By supplying monomers to the gel, the radicals generated by the bond rupture triggered the formation of a new network inside the deformed gel. This new network conferred plasticity to the elastic gel, allowing it to maintain its deformed shape, along with increased volume and strength. We demonstrated that sheet-shaped DN hydrogels rapidly adopted various three-dimensional shapes at ambient temperature when subjected to forces such as drawing and blowing. This mechanism enables morphogenesis of elastic hydrogels and will promote the application of these materials in biomedical fields and soft machines.

Unique stick-slip crack dynamics of double-network hydrogels under pure-shear loading.

In this work, we have found that a prenotched double-network (DN) hydrogel, when subjected to tensile loading in a pure-shear geometry, exhibits intriguing stick-slip crack dynamics. These dynamics synchronize with the oscillation of the damage (yielding) zone at the crack tip. Through manipulation of the loading rate and the predamage level of the brittle network in DN gels, we have clarified that this phenomenon stems from the significant amount of energy dissipation required to form the damage zone at the crack tip, as well as a kinetic contrast between the rapid crack extension through the yielding zone (slip process) and the slow formation of a new yielding zone controlled by the external loading rate (stick process).

Regional homogeneity alterations in patients with functional constipation and their associations with gene expression profiles.

Functional constipation, a highly prevalent functional gastrointestinal disorder, often accompanies by mental and psychological disorders. Previous neuroimaging studies have demonstrated brain functional and structural alterations in patients with functional constipation. However, little is known about whether and how regional homogeneity is altered in these patients. Moreover, the potential genetic mechanisms associated with these alterations remain largely unknown. The study included 73 patients with functional constipation and 68 healthy controls, and regional homogeneity comparison was conducted to identify the abnormal spontaneous brain activities in patients with functional constipation. Using Allen Human Brain Atlas, we further investigated gene expression profiles associated with regional homogeneity alterations in functional constipation patients with partial least squares regression analysis applied. Compared with healthy controls, functional constipation patients demonstrated significantly decreased regional homogeneity in both bilateral caudate nucleus, putamen, anterior insula, thalamus and right middle cingulate cortex, supplementary motor area, and increased regional homogeneity in the bilateral orbitofrontal cortex. Genes related to synaptic signaling, central nervous system development, fatty acid metabolism, and immunity were spatially correlated with abnormal regional homogeneity patterns. Our findings showed significant regional homogeneity alterations in functional constipation patients, and the changes may be caused by complex polygenetic and poly-pathway mechanisms, which provides a new perspective on functional constipation's pathophysiology.

Role of dynamic bonds on fatigue threshold of tough hydrogels.

SignificanceDynamic bonds have been found to enhance fracture toughness of hydrogels as sacrificial bonds, but the role of dynamic bonds to fatigue threshold of hydrogels is poorly understood because the wide dynamic range of viscoelastic response imposes a challenge on fatigue experiments. Here, by using polyampholyte hydrogels, we adopted a time-salt superposition principle to access a wide range of time scales that are otherwise difficult to access in fatigue tests. Relations between fatigue threshold and strain rate in elastic and viscoelastic regimes and the corresponding mechanism correlated to permanent/dynamic bonds were revealed. We believe that this work gives important insight into the design and development of fatigue-resistant soft materials composed of dynamic bonds.

Mechanism of temperature-induced asymmetric swelling and shrinking kinetics in self-healing hydrogels.

Understanding the physical principle that governs the stimuli-induced swelling and shrinking kinetics of hydrogels is indispensable for their applications. Here, we show that the shrinking and swelling kinetics of self-healing hydrogels could be intrinsically asymmetric. The structure frustration, formed by the large difference in the heat and solvent diffusions, remarkably slows down the shrinking kinetics. The plateau modulus of viscoelastic gels is found to be a key parameter governing the formation of structure frustration and, in turn, the asymmetric swelling and shrinking kinetics. This work provides fundamental understandings on the temperature-triggered transient structure formation in self-healing hydrogels. Our findings will find broad use in diverse applications of self-healing hydrogels, where cooperative diffusion of water and gel network is involved. Our findings should also give insight into the molecular diffusion in biological systems that possess macromolecular crowding environments similar to self-healing hydrogels.

Gluing blood into gel by electrostatic interaction using a water-soluble polymer as an embolic agent.

Liquid embolic agents are widely used for the endovascular embolization of vascular conditions. However, embolization based on phase transition is limited by the adhesion of the microcatheter to the embolic agent, use of an organic solvent, unintentional catheter retention, and other complications. By mimicking thrombus formation, a water-soluble polymer that rapidly glues blood into a gel without triggering coagulation was developed. The polymer, which consists of cationic and aromatic residues with adjacent sequences, shows electrostatic adhesion with negatively charged blood substances in a physiological environment, while common polycations cannot. Aqueous polymer solutions are injectable through clinical microcatheters and needles. The formed blood gel neither adhered to the catheter nor blocked the port. Postoperative computed tomography imaging showed that the polymer can block the rat femoral artery in vivo and remain at the injection site without nontarget embolization. This study provides an alternative for the development of waterborne embolic agents.

Real-Space Visualization of Charged Polymer Network of Hydrogel by Double Network Strategy and Mineral Staining.

Hydrogels consist of three-dimensional (3D) and complicated polymer networks that determine their physical properties. Among the methods for structural analyses of hydrogels, the real-space imaging of a polymer network of hydrogels on a nanometer scale is one of the optimal methods; however, it is highly challenging. In this study, we propose a direct observation method for cationic polymer networks using transmission electron microscopy (TEM). By combining the double network strategy and the mineral staining technique, we overcame the challenges of polymer aggregation and the low electron density of the polymer. An objective cationic network was incorporated into a neutral skeleton network to suppress shrinkage during subsequent staining. Titania mineralization along the cationic polymer strands provided sufficient electron density for the objective polymer network for TEM observation. This observation method enables the visualization of local structures in real space and plays a complementary role to scattering methods for soft matter structure analysis.

Effect of the Activation Force of Mechanophore on Its Activation Selectivity and Efficiency in Polymer Networks.

In recent decades, more than 100 different mechanophores with a broad range of activation forces have been developed. For various applications of mechanophores in polymer materials, it is crucial to selectively activate the mechanophores with high efficiency, avoiding nonspecific bond scission of the material. In this study, we embedded cyclobutane-based mechanophore cross-linkers (I and II) with varied activation forces (fa) in the first network of the double network hydrogels and quantitively investigated the activation selectivity and efficiency of these mechanophores. Our findings revealed that cross-linker I, with a lower activation force relative to the bonds in the polymer main chain (fa-I/fa-chain = 0.8 nN/3.4 nN), achieved efficient activation with 100% selectivity. Conversely, an increase of the activation force of mechanophore II (fa-II/fa-chain = 2.5 nN/3.4 nN) led to a significant decrease of its activation efficiency, accompanied by a substantial number of nonspecific bond scission events. Furthermore, with the coexistence of two cross-linkers, significantly different activation forces resulted in the almost complete suppression of the higher-force one (i.e., I and III, fa-I/fa-III = 0.8 nN/3.4 nN), while similar activation forces led to simultaneous activations with moderate efficiencies (i.e., I and IV, fa-I/fa-IV = 0.8 nN/1.6 nN). These findings provide insights into the prevention of nonspecific bond rupture during mechanophore activation and enhance our understanding of the damage mechanism within polymer networks when using mechanophores as detectors. Besides, it establishes a principle for combining different mechanophores to design multiple mechanoresponsive functional materials.

Research progress on the mechanism and signalling pathway of ferroptosis and its potential role in dermatosis research.

Ferroptosis is a novel type of cell death that is dependent on lipid peroxidation and iron accumulation, which distinguishes it from other types of programmed cell death. Current research indicates a significant association between ferroptosis and various pathological conditions, including cancer, neurological disorders, and cardiovascular diseases, albeit with a relatively unexplored role in dermatological afflictions. This paper elaborates on the mechanisms and signalling pathways of ferroptosis, summarizing the recent studies on ferroptosis and its related factors in dermatosis. Our objective is to shed light on novel perspectives and therapeutic strategies for dermatosis, enhancing the understanding of this under-researched area through this comprehensive review.

Visual deterioration outcomes following optic pathway glioma treatment: a 12-year single institution retrospective study.

OBJECTIVE: The surgical treatment of optic pathway gliomas (OPG) remains controversial, with visual outcomes often unpredictable. The present study explored surgical and clinical factors influencing visual acuity (VA) after OPG treatment and developed anatomical subtypes correlated with clinical symptoms. METHODS: Children with OPG who underwent initial partial tumor resection at Beijing Tiantan Hospital from January 2011 to December 2022 were retrospectively analyzed. Multivariate logistic regression and random forest analyses were performed to identify risk factors for post-treatment VA deterioration and a decision tree model was created based on significant factors. RESULTS: A total of 140 patients were enrolled. Multivariate logistic regression analysis identified surgical approach and initial VA as independent predictors of post-treatment VA deterioration (P < 0.05). Surgical approach, initial VA, and extent of tumor resection were the most significant factors for risk assessment and were included in the decision tree model, with surgical approach as the most important "root" node. The model demonstrated good predictive performance, with area under the curve values of 0.75 and 0.66 for the training and test datasets, respectively. A simple anatomical classification was developed, which revealed clinical characteristic differences among OPG types. Meanwhile, a correlation analysis of post-treatment visual deterioration was performed for each of the three anatomical types. CONCLUSION: This study offers a predictive model for visual outcomes following initial tumor-reduction surgery in OPG patients, which may help in visual outcomes risk stratification. Additionally, the anatomical classification effectively indicates OPG growth direction, offering potential insights into clinical symptoms.

Oxylipins biosynthesis and the regulation of bovine postpartum inflammation.

Uncontrolled or dysregulated inflammation has adverse effects on the reproduction, production and health of animals, and is a major pathological cause of increased incidence and severity of infectious and metabolic diseases. To achieve successful transition from a non-lactation pregnant state to a non-pregnant lactation state, drastic metabolic and endocrine alteration have taken place in dairy cows during the periparturient period. These physiological changes, coupled with decreased dry matter intake near calving and sudden change of diet composition after calving, have the potential to disrupt the delicate balance between pro- and anti-inflammation, resulting in a disordered or excessive inflammatory response. In addition to cytokines and other immunoregulatory factors, most oxylipins formed from polyunsaturated fatty acids (PUFAs) via enzymatic and nonenzymatic oxygenation pathways have pro- or anti-inflammatory properties and play a pivotal role in the onset, development and resolution of inflammation. However, little attention has been paid to the possibility that oxylipins could function as endogenous immunomodulating agents. This review will provide a detailed overview of the main oxylipins derived from different PUFAs and discuss the regulatory role that oxylipins play in the postpartum inflammatory response in dairy cows. Based on the current research, much remains to be illuminated in this emerging field. Understanding the role that oxylipins play in the control of postpartum inflammation and inflammatory-based disease may improve our ability to prevent transition disorders via Management, pharmacological, genetic selection and dietary intervention strategies.

Room-temperature ferromagnetism, half-metallicity and spin transport in monolayer CrSc2Te4-based magnetic tunnel junction devices.

The discovery of novel two-dimensional (2D) half-metallic materials with a robust ferromagnetic (FM) order and a high Curie temperature (Tc) is attractive for the advancement of next-generation spintronic devices. Here, we propose a monolayer with stable 2D intrinsic FM half-metallicity, i.e., the CrSc2Te4 monolayer, which was constructed by intercalating a monolayer of 1T-CrTe2-type sandwiched between two layers of 2H-ScTe2 monolayers. Our calculations reveal that it exhibits exceptional dynamical, thermal, and mechanical stabilities accompanied by a robust half-metallicity characterized by a wide bandgap of 1.02 eV and FM ordering with a high Tc of 326 K. Notably, these properties remain intact in almost the entire range of the biaxial strain from -5% to 5%. Furthermore, our investigations demonstrate excellent spin transport capabilities, including an outstanding spin-filtering effect, and a remarkably high tunneling magnetoresistance ratio peaking at 6087.07%. The remarkable magnetic features of the 2D CrSc2Te4 monolayer with room temperature FM, intrinsic half-metallicity, and 100% spin-polarization make it a promising candidate for the next-generation high-performance spintronic nanodevices as well as high-density magnetic recording and sensors.

Bone Marrow Mesenchymal Stem Cells Alleviate Acute Severe Pancreatitis and Promote Lung Repair via Inhibiting NLRP3 Inflammasome in Rat.

BACKGROUND: Acute severe pancreatitis (SAP) is a severe acute abdominal disease, which can lead to pancreatic infection and necrosis as well as distant organ damage. Bone marrow mesenchymal stem cells (BMSCs) can exert anti-inflammatory effect on SAP, while NLRP3 inflammasomes play an important role in the inflammatory response. This study aimed to investigate whether BMSCs exert anti-inflammatory effect on SAP by inhibiting NLRP3 inflammasome. METHODS: The rat SAP model was established. Serum amylase, lipase and inflammatory factor levels were measured by ELISA, and the level of tissue injury was assessed by HE staining. The expression of NLRP3 inflammasome was detected by PCR, Western Blot and immunohistochemistry. ML385 was used to block Nrf2 pathway, aiming to investigate whether Nrf2 pathway was involved in the therapeutic effect of BMSCs on SAP by regulating NLRP3 inflammasome expression. RESULTS: In SAP rats, NLRP3 inflammasome was activated, which became more evident over time. After transplantation of BMSCs, the NLRP3 inflammasome expression decreased at both mRNA and protein levels, the serum levels of amylase, lipase and inflammatory factors decreased, and the pathological scores of the pancreas and lung were both improved. After blocking the Nrf2 pathway, the NLRP3 inflammasome expression increased in the injured pancreas and lung, and the inflammation deteriorated, which inhibited the therapeutic effects of BMSCs on SAP. CONCLUSION: The therapeutic effect of BMSC on SAP is at least partially ascribed to the inhibition of NLRP3 inflammasome, and Nrf2 pathway mediates the therapeutic effect of BMSC on SAP by inhibiting NLRP3 inflammasome.

Risk Factors for Rebleeding After Endoscopic Injection of Cyanoacrylate Glue for Gastric Varices: A Systematic Review and Meta-Analysis.

BACKGROUND: Rebleeding is a significant complication of endoscopic injection of cyanoacrylate in gastric varices in cirrhotic patients. AIM: This systematic review and meta-analysis aimed to evaluate the efficiency of endoscopic cyanoacrylate injection and summarized the risk factors for rebleeding. METHODS: Databases were searched for articles published between January 2012 and December 2022. Studies evaluating the efficiency of endoscopic injection of cyanoacrylate glue for gastric varices and the risk factors for rebleeding were included. RESULTS: The final analysis included data from 24 studies. The hemostatic rates ranged from 65 to 100%. The pooled rate of gastric varices recurrence was 34% [95% CI 21-46, I2 = 61.4%], early rebleeding rate was 16% [95% CI 11-20, I2 = 37.4%], late rebleeding rate was 39% [95% CI 36-42, I2 = 90.9%], mild and moderate adverse events rate were 28% [95% CI 24-31, I2 = 91.6%], 3% [95% CI - 2 to 8, I2 = 15.3%], rebleeding-related mortality rate was 6% [95% CI 2-10, I2 = 0%], all-cause mortality rate was 17% [95% CI 12-22, I2 = 63.6%]. Independent risk factors for gastric variceal rebleeding included portal venous thrombosis, ascites, cyanoacrylate volume, fever/systemic inflammatory response syndrome, red Wale sign, previous history of variceal bleeding, active bleeding and paragastric veins. The use of proton pump inhibitors could be a protective factor. CONCLUSIONS: Endoscopic cyanoacrylate glue injection is an effective and safe treatment for gastric varices. Cirrhotic patients with the above risk factors may benefit from treatment aimed at reducing portal hypertension, antibiotic prophylaxis, and anticoagulation if they meet the indications.

Therapeutic effects of curculigoside on cyclophosphamide-induced premature ovarian failure in mice.

OBJECTIVE: The main purpose of this study was to elucidate the anti-apoptotic effects of curculigoside (CUR) on ovarian granulosa cells (GCs) in a mouse model of cyclophosphamide (CTX)-induced premature ovarian failure (POF). METHOD: Intraperitoneal injection of CTX (100 mg/kg body weight) induced POF in mice. Thirty-six female mice were divided into six groups: blank group; POF model group; low-dose CUR group; medium-dose CUR group; high-dose CUR group; and estradiol benzoate group. Mice were orally administered for 28 consecutive days. Twenty-four hours after the completion of treatment, mice were weighed and euthanized, and blood was collected from the eyeball under anesthesia. The ovaries were surgically separated and weighed, and the ovarian index was calculated. Hematoxylin-eosin (HE) staining was used to observe follicular development and corpus luteum morphology in the ovaries. Serum levels of follicle stimulating hormone (FSH), anti-Müllerian hormone (AMH) and estradiol (E2) were measured. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) content and malondialdehyde (MDA) levels in ovarian tissue were determined. The GC apoptosis level was measured. Western blotting was used to detect protein expression levels of Beclin-1, LC3, P62, AKT, p-AKT, mTOR and p-mTOR in the ovaries. RESULTS: The results showed that CUR can improve body weight and ovarian index; promote follicular development and reduce follicular atresia; improve FSH, AMH and E2 levels; downregulate MDA levels and restore antioxidant enzyme activity; inhibit the autophagy level; activate the AKT/mTOR signaling pathway; and alleviate GC apoptosis. CONCLUSION: CUR improves POF by activating the AKT/mTOR signaling pathway, inhibiting autophagy and alleviating GC apoptosis.

Effects of gender-affirming hormone therapy on body fat: a retrospective case‒control study in Chinese transwomen.

BACKGROUND: There is insufficient research on how gender-affirming hormone therapy (GAHT) affects body fat modifications in transwomen from China. It is unclear whether hormone therapy affects the prevalence of obesity and blood lipid levels within this population. The current research aimed to assess how GAHT and treatment duration had an impact on the change in and redistribution of body fat in Chinese transwomen. METHODS: This study included 40 transwomen who had not received GAHT and 59 who had. Body fat, blood lipid, and blood glucose levels were measured. GAHT is mainly a pharmacologic (estrogen and anti-androgen) treatment. The study also stratified participants based on the duration of GAHT to assess its impact on body fat distribution. The duration of GAHT was within one year, one to two years, two to three years, or more than three years. RESULTS: After receiving GAHT, total body fat increased by 19.65%, and the percentage of body fat increased by 17.63%. The arm, corrected leg, and leg regions showed significant increases in fat content (+ 24.02%, + 50.69%, and + 41.47%, respectively) and percentage (+ 25.19%, + 34.90%, and + 30.39%, respectively). The total visceral fat content decreased (-37.49%). Based on the diagnostic standards for a body mass index ≥ 28 or total body fat percentage ≥ 25% or 30%, the chance of developing obesity did not change significantly. Blood glucose levels significantly increased (+ 12.31%). Total cholesterol levels (-10.45%) decreased significantly. Fat changes in those who received GAHT for one to two years were significantly different from those who did not receive GAHT. CONCLUSION: After receiving GAHT, total body fat and regional fat increased in Chinese transwomen, and the body fat distribution changed from masculine to feminine, especially during the first two years. However, neither the increase in total body fat percentage nor the decrease in visceral fat content didn't bring about significant changes in the incidence of obesity, nor did triglycerides or low-density lipoprotein-cholesterol.

Assessment of whole-body and regional body fat using abdominal quantitative computed tomography in Chinese women and men.

BACKGROUND: Being overweight or obese has become a serious public health concern, and accurate assessment of body composition is particularly important. More precise indicators of body fat composition include visceral adipose tissue (VAT) mass and total body fat percentage (TBF%). Study objectives included examining the relationships between abdominal fat mass, measured by quantitative computed tomography (QCT), and the whole-body and regional fat masses, measured by dual energy X-ray absorptiometry (DXA), as well as to derive equations for the prediction of TBF% using data obtained from multiple QCT slices. METHODS: Whole-body and regional fat percentage were quantified using DXA in Chinese males (n = 68) and females (n = 71) between the ages of 24 and 88. All the participants also underwent abdominal QCT measurement, and their VAT mass and visceral fat volume (VFV) were assessed using QCT and DXA, respectively. RESULTS: DXA-derived TBF% closely correlated with QCT abdominal fat percentage (r = 0.89-0.93 in men and 0.76-0.88 in women). Stepwise regression showed that single-slice QCT data were the best predictors of DXA-derived TBF%, DXA android fat percentage and DXA gynoid fat percentage. Cross-validation analysis showed that TBF% and android fat percentage could be accurately predicted using QCT data in both sexes. There were close correlations between QCT-derived and DXA-derived VFV (r = 0.97 in men and 0.93 in women). CONCLUSION: Clinicians can assess the TBF% and android and gynoid fat percentages of Chinese women and men by analysing existing abdominal CT-derived data using the QCT technique.

How chain dynamics affects crack initiation in double-network gels.

Double-network gels are a class of tough soft materials comprising two elastic networks with contrasting structures. The formation of a large internal damage zone ahead of the crack tip by the rupturing of the brittle network accounts for the large crack resistance of the materials. Understanding what determines the damage zone is the central question of the fracture mechanics of double-network gels. In this work, we found that at the onset of crack propagation, the size of necking zone, in which the brittle network breaks into fragments and the stretchable network is highly stretched, distinctly decreases with the increase of the solvent viscosity, resulting in a reduction in the fracture toughness of the material. This is in sharp contrast to the tensile behavior of the material that does not change with the solvent viscosity. This result suggests that the dynamics of stretchable network strands, triggered by the rupture of the brittle network, plays a role. To account for this solvent viscosity effect on the crack initiation, a delayed blunting mechanism regarding the polymer dynamics effect is proposed. The discovery on the role of the polymer dynamic adds an important missing piece to the fracture mechanism of this unique material.

Molecular mechanism of abnormally large nonsoftening deformation in a tough hydrogel.

Tough soft materials usually show strain softening and inelastic deformation. Here, we study the molecular mechanism of abnormally large nonsoftening, quasi-linear but inelastic deformation in tough hydrogels made of hyperconnective physical network and linear polymers as molecular glues to the network. The interplay of hyperconnectivity of network and effective load transfer by molecular glues prevents stress concentration, which is revealed by an affine deformation of the network to the bulk deformation up to sample failure. The suppression of local stress concentration and strain amplification plays a key role in avoiding necking or strain softening and endows the gels with a unique large nonsoftening, quasi-linear but inelastic deformation.

Identifying the risk of depression in a large sample of adolescents: An artificial neural network based on random forest.

BACKGROUND: This study aims to develop an artificial neural network (ANN) prediction model incorporating random forest (RF) screening ability for predicting the risk of depression in adolescents and identifies key risk factors to provide a new approach for primary care screening of depression among adolescents. METHODS: The data were from a large cross-sectional study conducted in China from July to September 2021, enrolling 8635 adolescents aged 10-17 with their parents. We used the Patient health questionnaire (PHQ-9) to rate adolescent depression symptoms, using scales and single-item questions to collect demographic information and other variables. Initial model variables screening used the RF importance assessment, followed by building prediction model using the screened variables through the ANN. RESULTS: The rate of depression symptoms in adolescents was 24.6%, and the depression risk prediction model was built based on 70% of the training set and 30% of the test set. Ten variables were included in the final prediction model with a model accuracy of 85.03%, AUC of 0.892, specificity of 89.79%, and sensitivity of 70.81%. The top 10 significant factors of depression risk were adolescent rumination, adolescent self-esteem, adolescent mobile phone addiction, peer victimization, care in parenting styles, overprotection in parenting styles, academic pressure, conflict in parent-child relationship, parental rumination, and relationship between parents. CONCLUSIONS: The ANN model based on the RF effectively identifies depression risk in adolescents and provides a methodological reference for large-scale primary screening. Cross-sectional studies and single-item scales limit further improvements in model accuracy.