Transformable Superisostatic Crystals Self-Assembled from Segment Colloidal Rods.

Transformable mechanical structures can switch between distinct mechanical states. Whether this kind of structure can be self-assembled from simple building blocks at microscale is a question to be answered. In this work, we propose a self-assembly strategy for these structures based on a nematic monolayer of segmented colloidal rods with lateral cutting. By using Monte Carlo simulation, we find that rods with different cutting degrees can self-assemble into different crystals characterized by bond coordination z that varies from 3 to 6. Among these, we identify a transformable superisostatic structure with pgg symmetry and redundant bonds (z = 5). We show that this structure can support either soft bulk modes or soft edge modes depending on its Poisson's ratio, which can be tuned from positive to negative through a uniform soft deformation. We also prove that the bulk soft modes are associated with states of self-stress along the direction of zero strain during uniform soft deformation. The self-assembled transformable structures may act as mechanical metamaterials with potential applications in micromechanical engineering.

Clinical and electromyographic signals analysis about the effect of space-adjustment splint on overerupted maxillary molars.

BACKGROUND: Overerupted maxillary molars is common in adults, which can lead to insufficient intermaxillary vertical space ,great difficulty in prosthetic reconstruction ,and cause occlusal interference in movements.To reconstruct occlusal function, it is necessary to prepare enough space for prostheses. The aim of the present study was to evaluate the effect of space-adjustment occlusal splint on overerupted maxillary molars by clinical and electromyographic signals analysis. METHODS: Eighteen patients with overerupted maxillary molars were selected to wear space-adjustment occlusal splint suppressing overerupted maxillary molars for three months. Satisfaction was assessed by 5-point Likert; intermaxillary vertical space and the teeth transportation distance were measured in models; clinical periodontal status were evaluated by periodontal probing depth (PPT) and bleeding index (BI); electromyographic recordings of the masseter and anterior temporal muscles were monitored by Cranio-Mandibular K7 Evaluation System. RESULTS: All the patients were satisfied with the treatment effect (Likert scale ≧ 4). The intermaxillary space in edentulous areas after treatment showed statistically significant increasing when compared with those before treatment. PPT and BI showed no significant difference. No statistically significant differences were found in electromyographic activity of anterior temporal muscles, while a reduction of muscle activity in masseter in the contralateral side were detected in post-treatment evaluations compared with pre-treatment at mandibular rest position. CONCLUSIONS: Space-adjustment occlusal splint is an efficient treatment option on overerupted maxillary molars by intruding the maxillary molar to obtain adequate intermaxillary space for prostheses.

ABHD7-mediated depalmitoylation of lamin A promotes myoblast differentiation.

LMNA gene mutation can cause muscular dystrophy, and post-translational modification plays a critical role in regulating its function. Here, we identify that lamin A is palmitoylated at cysteine 522, 588, and 591 residues, which are reversely catalyzed by palmitoyltransferase zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) and depalmitoylase α/ß hydrolase domain 7 (ABHD7). Furthermore, the metabolite lactate promotes palmitoylation of lamin A by inhibiting the interaction between it and ABHD7. Interestingly, low-level palmitoylation of lamin A promotes, whereas high-level palmitoylation of lamin A inhibits, murine myoblast differentiation. Together, these observations suggest that ABHD7-mediated depalmitoylation of lamin A controls myoblast differentiation.

Clinical Application Value of left Ventricular Pressure-Strain Loop Examination of Myocardial Dysfunction in Patients with Hypertension at Various Risk Levels.

Objective: This study aims to determine the variations in myocardial work among patients with essential hypertension at varying risk levels by analyzing the left ventricular pressure-strain loop. Additionally, this research aims to investigate the potential diagnostic significance of myocardial work parameters in identifying myocardial dysfunction in patients with essential hypertension. Methods: We conducted a study with 79 patients who have essential hypertension and 30 healthy adults. The essential hypertension patients were categorized according to their risk level, with 10 patients in the low-risk group, 11 in the medium-risk group, 23 in the high-risk group, and 35 in the very high-risk group. We included 30 healthy adults in the study as a control group. Clinical data such as height, weight, and blood pressure were collected for all groups. Routine echocardiographic dynamic images were collected, and speck tracking echocardiography was performed to analyze global longitudinal strain and myocardial work parameters were detected by the left ventricular pressure-strain loop. Finally, the global work index, global constructive work, global wasted work, global work efficiency, and global longitudinal strain were calculated and compared among groups. The correlation between blood pressure and myocardial work parameters was analyzed. Results: Compared with the control group, inter-ventricular septum thickness was thickened in the medium-risk groups, high-risk groups,and very high-risk groups, P < .001). There was a negative linear correlation between global work efficiency and blood pressure (systolic and diastolic, and a positive linear correlation was observed between blood pressure and global work index, global constructive work, and global wasted work. Conclusion: Left ventricular pressure-strain loop can be used to evaluate changes in left ventricular myocardial work of essential hypertension patients in the early stage and with different risk stratifications.

Feedback regulation of ubiquitination and phase separation of HECT E3 ligases.

Lipid homeostasis is essential for normal cellular functions and dysregulation of lipid metabolism is highly correlated with human diseases including neurodegenerative diseases. In the ubiquitin-dependent autophagic degradation pathway, Troyer syndrome-related protein Spartin activates and recruits HECT-type E3 Itch to lipid droplets (LDs) to regulate their turnover. In this study, we find that Spartin promotes the formation of Itch condensates independent of LDs. Spartin activates Itch through its multiple PPAY-motif platform generated by self-oligomerization, which targets the WW12 domains of Itch and releases the autoinhibition of the ligase. Spartin-induced activation and subsequent autoubiquitination of Itch lead to liquid-liquid phase separation (LLPS) of the poly-, but not oligo-, ubiquitinated Itch together with Spartin and E2 both in vitro and in living cells. LLPS-mediated condensation of the reaction components further accelerates the generation of polyubiquitin chains, thus forming a positive feedback loop. Such Itch-Spartin condensates actively promote the autophagy-dependent turnover of LDs. Moreover, we show that the catalytic HECT domain of Itch is sufficient to interact and phase separate with poly-, but not oligo-ubiquitin chains. HECT domains from other HECT E3 ligases also exhibit LLPS-mediated the promotion of ligase activity. Therefore, LLPS and ubiquitination are mutually interdependent and LLPS promotes the ligase activity of the HECT family E3 ligases.

TET2 is required to suppress mTORC1 signaling through urea cycle with therapeutic potential.

Tumor development, involving both cell growth (mass accumulation) and cell proliferation, is a complex process governed by the interplay of multiple signaling pathways. TET2 mainly functions as a DNA dioxygenase, which modulates gene expression and biological functions via oxidation of 5mC in DNA, yet whether it plays a role in regulating cell growth remains unknown. Here we show that TET2 suppresses mTORC1 signaling, a major growth controller, to inhibit cell growth and promote autophagy. Mechanistically, TET2 functions as a 5mC "eraser" by mRNA oxidation, abolishes YBX1-HuR binding and promotes decay of urea cycle enzyme mRNAs, thus negatively regulating urea cycle and arginine production, which suppresses mTORC1 signaling. Therefore, TET2-deficient tumor cells are more sensitive to mTORC1 inhibition. Our results uncover a novel function for TET2 in suppressing mTORC1 signaling and inhibiting cell growth, linking TET2-mediated mRNA oxidation to cell metabolism and cell growth control. These findings demonstrate the potential of mTORC1 inhibition as a possible treatment for TET2-deficient tumors.

Aldolase A Accelerates Cancer Progression by Modulating mRNA Translation and Protein Biosynthesis via Noncanonical Mechanisms.

Aldolase A (ALDOA), a crucial glycolytic enzyme, is often aberrantly expressed in various types of cancer. Although ALDOA has been reported to play additional roles beyond its conventional enzymatic role, its nonmetabolic function and underlying mechanism in cancer progression remain elusive. Here, it is shown that ALDOA promotes liver cancer growth and metastasis by accelerating mRNA translation independent of its catalytic activity. Mechanistically, ALDOA interacted with insulin- like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to facilitate its binding to m6 A-modified eIF4G mRNA, thereby increasing eIF4G protein levels and subsequently enhancing overall protein biosynthesis in cells. Importantly, administration of GalNAc-conjugated siRNA targeting ALDOA effectively slows the tumor growth of orthotopic xenografts. Collectively, these findings uncover a previously unappreciated nonmetabolic function of ALDOA in modulating mRNA translation and highlight the potential of specifically targeting ALDOA as a prospective therapeutic strategy in liver cancer.

Increased α-HB links colorectal cancer and diabetes by potentiating NF-κB signaling.

Sufficient evidence has linked many different types of cancers and T2D through shared risk factors; however, the underlying mechanisms are not fully understood. α-Hydroxybutyrate (α-HB), a byproduct metabolite increased in diabetes and cancer, including colorectal cancer (CRC), triggers lactate dehydrogenase A (LDHA) nuclear translocation. Nuclear LDHA markedly extends NF-κB nuclear retention by interacting with phosphorylated p65, leading to an increase in TNF-α production, impaired insulin secretion and the exacerbation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC and high-fat diet (HFD)-induced type 2 diabetes. Furthermore, metformin interrupted this process by inhibiting the transcription of FOXM1 and c-MYC, the resultant downregulation of LDHA expression and α-HB-induced LDHA nuclear translocation. Thus, the results reveal the elevated α-HB level could be a novel shared risk factor of linking CRC, diabetes and the use of metformin treatment, as well as highlight the importance of preventing NF-κB activation for protecting against cancer and diabetes.

Enhanced BCAT1 activity and BCAA metabolism promotes RhoC activity in cancer progression.

Increased expression of branched-chain amino acid transaminase 1 or 2 (BCAT1 and BCAT2) has been associated with aggressive phenotypes of different cancers. Here we identify a gain of function of BCAT1 glutamic acid to alanine mutation at codon 61 (BCAT1E61A) enriched around 2.8% in clinical gastric cancer samples. We found that BCAT1E61A confers higher enzymatic activity to boost branched-chain amino acid (BCAA) catabolism, accelerate cell growth and motility and contribute to tumor development. BCAT1 directly interacts with RhoC, leading to elevation of RhoC activity. Notably, the BCAA-derived metabolite, branched-chain α-keto acid directly binds to the small GTPase protein RhoC and promotes its activity. BCAT1 knockout-suppressed cell motility could be rescued by expressing BCAT1E61A or adding branched-chain α-keto acid. We also identified that candesartan acts as an inhibitor of BCAT1E61A, thus repressing RhoC activity and cancer cell motility in vitro and preventing peritoneal metastasis in vivo. Our study reveals a link between BCAA metabolism and cell motility and proliferation through regulating RhoC activation, with potential therapeutic implications for cancers.

Association between obstructive sleep apnea symptoms and gout in US population, a cross-sectional study.

The results of association between Obstructive Sleep Apnea (OSA) and gout are not consistent. Participants aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2015-2018 were included. Weighted univariable and multivariable logistic regressions were used to evaluate the association between OSA symptoms and gout. The subgroup and sensitivity analyses were also performed. Among the 15,947 participants in this study, the mean age was 47.8 years old, 48.87% of whom were male, 4891 had OSA symptoms, and 842 had gout. In multivariable logistic regression analyses, OSA symptoms were positively associated with gout in all models. The odds ratio (OR) was 1.315 and 95% confidence interval (CI) was 1.070-1.616 in fully adjusted model 4. In the subgroup analyses, we found a considerable interaction between OSA symptoms and gender with gout (P for interaction = 0.003). In the sensitivity analyses, the association between OSA symptoms and gout remained stable after adjustment for congestive heart failure and diuretics using. OSA symptoms were associated with an increased likelihood of gout. This association could especially be found in female participants.

Neuromuscular and occlusion analysis to evaluate the efficacy of three splints on patients with bruxism.

OBJECTIVE: Occlusal splints are always applied on individuals with bruxism to reduce tooth wear and relieve orofacial symptoms such as myofascial pain. The stomatognathic system is mainly composed of tooth, occlusion, masticatory muscles, and temporomandibular joint. The occlusion and masticatory muscles function are regarded as the important parameters for evaluating the stomatognathic system state objectively. However, the effects of occlusal splints on individuals with bruxism is rarely elucidated from accurate neuromuscular analysis and occlusion evaluation. The aim of the present study was to estimate the effects of three different splints (two clinically common full coverage occlusal splint and an modified anterior splint) on subjects with bruxism using K7-J5 neuromuscular analysis system and Dental Prescale II (DP2) to evaluate occlusion. METHODS: Sixteen subjects claimed to be suffering from nocturnal bruxism,with complete dentition and stable occlusal relationship, were selected for study.The intermaxillary space and the baselines of EMG-activity of the anterior temporalis and masseter were recorded for all the subjects. The participants was treated with three different splints, and outcomes were estimated by comfort index, occlusion and surface electromyography of anterior temporalis and masseter. RESULTS: At teeth clenched position, EMG data were significantly lower in the participants with use of modified anterior splint than with hard, soft occlusal splint or without splint (p < 0.05). The maximum bite force and bite area occur in subjects without use of splint, while the minimal occur in subjects with use of modified anterior splint. Intermaxillary space increased and masticatory muscles presented significant reduction of EMG data at rest position as a result of J5 (p < 0.05). CONCLUSION: Modified anterior splint seems to be more comfortable and effective in reducing occlusion force and electromyographic activity of anterior temporalis and masseter for subjects with bruxism.

A metabolic clue for STING suppression.

A recent report by Heath et al. reveals that obesity could impair cancer immunogenicity and foster a type I interferon (IFN-I)-deprived tumor microenvironment through saturated fatty acid-mediated stimulator of interferon genes (STING) inhibition.

Association between nonalcoholic fatty liver disease and peripheral neuropathy in US population, a cross-sectional study.

Nonalcoholic fatty liver disease (NAFLD) has become an important risk of type 2 diabetes mellitus (T2DM). Peripheral neuropathy (PN) is regarded as one of the main microvascular complications of diabetes. But the association of NAFLD with PN is still unclear. We aimed to investigate the association between NAFLD and PN in US population by conducting a cross-sectional study. We enrolled 3029 participants aged 40-85 years from National Health and Nutrition Examination Survey (NHANES) 1999-2004. NAFLD was defined as a US Fatty Liver Index (FLI) score ≥ 30, and PN was defined as having one or more insensate areas on either foot. Participants were divided into two groups (with or without PN). We performed multivariate logistic regression models to evaluate the association between NAFLD and PN. Subgroup analyses were used to find out whether the association was stable in different stratified groups. Sensitivity analyses were conducted to assess the robustness of the results. All the analyses were weighted. Among the individuals, 524 (17.3%) had PN and 1250 (41.27%) had NAFLD. In the multivariate logistic regression models, NAFLD was associated with an increased risk of PN (OR 1.44 [1.03 ~ 2.02]) after fully adjusting for covariates. In the subgroup analyses, NAFLD was significantly associated with PN in the age group (40-64 years), compared with those in the age group (65-85 years), (P for interaction: 0.004). The results of association of NAFLD with PN were stable in sensitivity analyses. In this cross-sectional study among US adults aged 40-85 years old, NAFLD was associated with an increased likelihood of prevalent PN.

S-adenosyl-L-methionine supplementation alleviates damaged intestinal epithelium and inflammatory infiltration caused by Mat2a deficiency.

Methionine is important for intestinal development and homeostasis in various organisms. However, the underlying mechanisms are poorly understood. Here, we demonstrate that the methionine adenosyltransferase gene Mat2a is essential for intestinal development and that the metabolite S-adenosyl-L-methionine (SAM) plays an important role in intestinal homeostasis. Intestinal epithelial cell (IEC)-specific knockout of Mat2a exhibits impaired intestinal development and neonatal lethality. Mat2a deletion in the adult intestine reduces cell proliferation and triggers IEC apoptosis, leading to severe intestinal epithelial atrophy and intestinal inflammation. Mechanistically, we reveal that SAM maintains the integrity of differentiated epithelium and protects IECs from apoptosis by suppressing the expression of caspases 3 and 8 and their activation. SAM supplementation improves the defective intestinal epithelium and reduces inflammatory infiltration sequentially. In conclusion, our study demonstrates that methionine metabolism and its intermediate metabolite SAM play essential roles in intestinal development and homeostasis in mice.

Research on Adaptability Evaluation Method of Polymer by Nuclear Magnetic Resonance Technology.

In order to study the matching relationship between polymer(HPAM) molecular weight and reservoir permeability, in this paper, the injection performance of polymers with different molecular weights in rock cores with different permeability is studied. Using nuclear magnetic resonance technology combined with conventional core displacement equipment, the change law of the displacement process was analyzed from three aspects of nuclear magnetic resonance T2 spectrum, core layering, and imaging. Finally, the fluidity of the polymer solution in the core was analyzed by injection pressure control features. The experimental results show that the polymer solution with a molecular weight of 25 million has the best retention effect in the core flooding experiment and can stay in the dominant channel of the core for a long time to control the water flooding mobility. In rocks with a permeability of 500, 1000, and 2000 mD, subsequent water flooding can expand the swept volume by about 25% compared with polymer flooding. This method can effectively establish the adaptability matching relationship between the polymer molecular weight and the reservoir permeability.

Analysis of the Induced Stress Fields Around Hydraulic Fractures Considering the Influence of Natural Fractures and Bedding Planes.

Natural fractures (NFs) and bedding planes (BPs) are well developed in shale reservoirs. The propagation of hydraulic fractures (HFs) and the opening of NFs and BPs can produce induced stress fields (ISFs) within the fracturing process, causing interference to the in situ stress field. Aiming at the "stress shadow" effect among HFs in horizontal wells, the calculation models of HFs, BPs, and NFs for induced stress distributions are established based on displacement discontinuity theory, which can quantitatively characterize the composite ISF of the three under different connecting states. In addition, the interference coefficient of stress intensity factor (ICSIF) is introduced to quantitatively evaluate the interference degree of the composite ISF to the propagation of HFs. The results show that: (1) the ISF forms a "tensile stress concentration zone" near the fracture surface to promote the HFs opening and a "compressive stress concentration zone" at the fracture tips to suppress the propagation of HFs; (2) the ISF forms an elliptical effective swept area around the fracture, which is affected by the propagation height of HFs, while NFs or BPs generate local disturbances to the ISF; (3) the in situ stress reverses in the swept area, and the stress reversal interval is related to the in situ stress difference, fracture propagation height, Poisson's ratio, fracture net pressure, and fracture spacing; (4) the reasonable fracture spacing and fracture propagation height of horizontal wells can be determined by the ICSIF. The study can provide theoretical guidance for optimizing the fracture spacing and promoting the uniform propagation of multiple fractures in staged fracturing of horizontal wells.

Facilitated dynamics of an active polymer in 2D crowded environments with obstacles.

Understanding the behaviors of a single active chain in complex environments is not only an interesting topic in non-equilibrium physics but also has applicative implications in biological/medical engineering. In this work, by using molecular simulations, we systematically study the dynamical and conformational behaviors of an active polymer in crowded environments, i.e., a single active chain confined in 2D space with randomly arranged obstacles. We found that the competition between the chain's activity and rigidity in the presence of obstacles leads to many interesting dynamical and conformational states, such as the diffusive expanded state, the diffusive collapsed state, and the localized collapsed state. Importantly, we found a counter-intuitive phenomenon, i.e., crowded environments facilitate the diffusion of the active polymer within a large parameter space. As the crowdedness (packing fraction of obstacles) increases, the parameter space in which crowding-enhanced diffusion occurs still remains. This abnormal dynamics is attributed to a structural reason that the obstacles prevent active chains from collapsing. Our findings capture some generic features of active polymers in complex environments and provide insights into the design of novel drug delivery systems.