Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.

Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice.

Ablation of Dual-Specificity Phosphatase 6 Protects against Nonalcoholic Fatty Liver Disease via Cytochrome P450 4A and Mitogen-Activated Protein Kinase.

Dual-specificity phosphatase 6 (DUSP6) is a specific phosphatase for mitogen-activated protein kinase (MAPK). This study used a high-fat diet (HFD)-induced murine nonalcoholic fatty liver disease model to investigate the role of DUSP6 in this disease. Wild-type (WT) and Dusp6-haploinsufficiency mice developed severe obesity and liver pathology consistent with nonalcoholic fatty liver disease when exposed to HFD. In contrast, Dusp6-knockout (KO) mice completely eliminated these phenotypes. Furthermore, primary hepatocytes isolated from WT mice exposed to palmitic and oleic acids exhibited abundant intracellular lipid accumulation, whereas hepatocytes from Dusp6-KO mice showed minimal lipid accumulation. Transcriptome analysis revealed significant down-regulation of genes encoding cytochrome P450 4A (CYP4A), known to promote ω-hydroxylation of fatty acids and hepatic steatosis, in Dusp6-KO hepatocytes compared with that in WT hepatocytes. Diminished CYP4A expression was observed in the liver of Dusp6-KO mice compared with WT and Dusp6-haploinsufficiency mice. Knockdown of DUSP6 in HepG2, a human liver-lineage cell line, also promoted a reduction of lipid accumulation, down-regulation of CYP4A, and up-regulation of phosphorylated/activated MAPK. Furthermore, inhibition of MAPK activity promoted lipid accumulation in DUSP6-knockdown HepG2 cells without affecting CYP4A expression, indicating that CYP4A expression is independent of MAPK activation. These findings highlight the significant role of DUSP6 in HFD-induced steatohepatitis through two distinct pathways involving CYP4A and MAPK.

Assessing health behavior change and comparing remote, hybrid and in-person implementation of a school-based health promotion and coaching program for adolescents from low-income communities.

To assess the impact of a school-based health intervention on adolescents' health knowledge, psychosocial assets and health behaviors, including comparisons of implementation mode: remote, hybrid or in-person. The Stanford Youth Diabetes Coaches Program, an 8-week, school-based health promotion and coaching skills program, was offered to adolescents (ages 14-18 years) from four low-income US communities. Mode of program implementation was remote, hybrid or in-person. Participants completed online pre- and postsurveys. Analysis included paired t-tests, linear regression and qualitative coding. From Fall 2020 to Fall 2021, 262 adolescents enrolled and 179 finished the program and completed pre- and postsurveys. Of the 179, 80% were female, with a mean age of 15.9 years; 22% were Asian; 8% were Black or African American; 25% were White; and 40% were Hispanic. About 115 participants were remote, 25 were hybrid and 39 were in-person. Across all participants, significant improvements (P < 0.01) were reported in health knowledge, psychosocial assets (self-esteem, self-efficacy and problem-solving) and health behaviors (physical activity, nutrition and stress reduction). After adjusting for sex and age, these improvements were roughly equivalent across the three modes of delivery. Participation was associated with significant improvements in adolescent health behaviors. Furthermore, remote mode of instruction was just as effective as in-person and hybrid modes.

Associations of different isomeric forms of serum lycopene with cardiovascular disease and all-cause mortality.

Background: The effect of serum lycopene on the progression of cardiovascular diseases (CVDs) and their longevity remains a controversial topic. The purpose of this study was to evaluate the associations of different isomeric forms of serum lycopene with CVD and all-cause mortality in the American population. Methods: The National Health and Nutrition Examination Survey (NHANES) is a large population survey to investigate public health in the US. We analyzed data from 2003-2006 linked with mortality data obtained in 2015. Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to assess the risk of CVD and all-cause mortality caused by serum lycopene. Results: Among 7452 participants (aged 20-85 years, 46.7% male), 298 died from CVDs among the total 1213 deaths during a median follow-up of 10.7 years. Serum lycopene is a protective factor for all-cause and CVD mortality. In multivariable-adjusted models, the hazard ratio (with 95% confidence intervals) associated with Q4 compared to Q1 of serum total-lycopene, trans-lycopene and cis-lycopene was 0.49 (0.38,0.63), 0.49 (0.39,0.63) and 0.55 (0.43,0.70) for all-cause mortality (Ptrend<0.05), and was 0.53 (0.32,0.96), 0.48 (0.32,0.72) and 0.63 (0.41,0.97) for CVD mortality (Ptrend<0.05). The subgroup analyses showed that different isomeric forms of lycopene showed varied associations with CVD and all-cause mortality based on age, drinking status, history of hypertension and diabetes. Conclusions: Serum lycopene concentration was significantly associated with the risk of CVD and all-cause mortality. Cis-lycopene had a U-shaped relationship with mortality, while trans-lycopene had an inverse relationship with it.

Detection of Multi-Layered Bond Delamination Defects Based on Full Waveform Inversion.

This study aimed to address the challenges encountered in traditional bulk wave delamination detection methods characterized by low detection efficiency. Additionally, the limitations of guided wave delamination detection methods were addressed, particularly those utilizing reflected waves, which are susceptible to edge reflections, thus complicating effective defect extraction. Leveraging the full waveform inversion algorithm, an innovative approach was established for detecting delamination defects in multi-layered structures using ultrasonic guided wave arrays. First, finite element modeling was employed to simulate guided wave data acquisition by a circular array within an aluminum-epoxy bilayer structure with embedded delamination defects. Subsequently, the full waveform inversion algorithm was applied to reconstruct both regular and irregular delamination defects. Analysis results indicated the efficacy of the proposed approach in accurately identifying delamination defects of varying shapes. Furthermore, an experimental platform for guided wave delamination defect detection was established, and experiments were conducted on a steel-cement bilayer structure containing an irregular delamination defect. The experimental results validated the exceptional imaging precision of our proposed technique for identifying delamination defects in multi-layered boards. In summary, the proposed method can accurately determine both the positions and sizes of defects with higher detection efficiency than traditional pulse-echo delamination detection methods.

The promoting effect of exercise motivation on physical fitness in college students: a mediation effect model.

BACKGROUND: In recent years, the physical fitness situation of college students is worrying in China. Exercise motivation is of great importance for the physical activity and physical fitness. However, existing studies have paid limited attention to the specific effect between exercise motivation, physical activity and physical fitness, and even less to the different genders and exercise motivation dimensions. This study aimed to investigate the promoting effect of sport motivation on physical fitness with different gender and dimension in college students. METHODS: Physical fitness levels of 2544 college students in Wuhan and Jingzhou city were measured. Exercise motivation and physical activity was assessed using the Chinese version of the motives for physical activities measure-revised scale and the physical activity survey scale, respectively. Correlation analysis and structural equation model were used to explore the relationship between exercise motivation, physical activity and physical fitness. Bootstrap method was used to test the mediating effect. Multilevel regression analysis was used to examine the effects of different dimensions of exercise motivation on PF. RESULTS: The exercise motivation of college students was directly related to physical fitness (effect value: 0.307) or indirectly related through the mediating effect of physical activity (effect value: 0.092). The mediation effect percentage of physical activity on exercise motivation and physical fitness in male (51.20%) was greater than female (27.18%), and the standardized regression coefficient of the health dimension to PF was ß = 0.151, P < 0.001, and the competence dimension to PF was ß = 0.189, P < 0.001. CONCLUSIONS: The exercise motivation of college students can directly influence PF or indirectly influence PF through the mediating effect of PA. The promoting effect of exercise motivation and PA on PF in college students is related to gender and dimensions of exercise motivation. Therefore, we can improve physical fitness levels of college students by promoting their exercise motivation (especially for health motivation and competence motivation) and increasing their participation in physical activity. This study provides new strategies for improving physical fitness in college students.

High-Precision Corrosion Detection via SH1 Guided Wave Based on Full Waveform Inversion.

Corrosion detection for industrial settings is crucial for safe and efficient operations. Due to its high imaging resolution, the guided-wave full-waveform inversion tomography technique has significant potential for corrosion detection of plate metals. Limited by the long wavelengths of A0 and S0 mode waves, this method exhibits inadequate detection resolution for the earlier shallow and small corrosion defects. Based on the relatively short wavelength characteristics of the SH1 mode wave, we propose a high-precision corrosion detection method via SH1 guided wave using the full waveform inversion algorithms. By conducting finite element simulations of ultrasonic-guided waves on aluminum plates with varying corrosion defects, a comparison was made to assess the detection precision across A0, S0, and SH1 modes. The comparison results showed that, whether for regular or irregular defects, the SH1 mode wave always exhibited higher imaging accuracy than the A0 and S0 mode waves for shallow and small-sized defects. The corresponding experiments were conducted on an aluminum plate with simple or complex defects. The results of the experiments reconfirmed that the full waveform inversion method using SH1 guided wave can effectively reconstruct the shape and size of small and shallow corrosion defects within aluminum plates.

Polyvinyl acetate-based soil stabilization for rock slope ecological restoration.

External-soil spray seeding (ESSS) is a method often used for the ecological restoration of bare rock slopes. However, the direct use of ESSS is normally less satisfactory due to the erosion of sprayed soil and low survival rate of the plants on rock slopes. This study proposes a novel approach to addressing this issue through the combined use of ESSS with polyvinyl acetate (PVA) based soil stabilization. The PVA solutions are added to the soil to stabilize soil and improve soil strength while possessing high water and nutrient retention favorable for plant growth. A series of experimental tests on the mechanical properties, water stability, erosion resistance, water retention, and plant growth of the PVA-stabilized soil were conducted to assess the efficacy of the proposed method. The results showed that the proposed method could be promising for rock slope ecological restoration. A proper curing time (e.g., >3 days) was required to achieve beneficial effects of PVA on the soil properties. A shorter curing time would otherwise result in the decrease in the strength with the increased PVA content. It was found that the optimum PVA content was 3% for achieving the maximum water stability, erosion resistance, water retention, and plant growth. The cohesion increased by up to 50% and the internal friction angle increased by 3.5° compared to the natural soil. The disintegration rate of the stabilized soil was generally < 3e-3%/min. The maximum reduction in erosion was up to 83% when the PVA content ≥3%. The mechanisms behind the findings are also discussed.

Comparison of Different Volatile Extraction Methods for the Identification of Fishy Off-Odor in Fish By-Products.

This study was conducted to analyze volatile odor compounds and key odor-active compounds in the fish soup using fish scarp and bone. Five extraction methods, including solid-phase microextraction (SPME), dynamic headspace sampling (DHS), solvent-assisted flavor evaporation (SAFE), stir bar sorptive extraction (SBSE), liquid-liquid extraction (LLE), were compared and SPME was finally selected as the best extraction method for further study. The volatile odor compounds were analyzed by gas chromatography-olfactometry-mass spectrometry (GC-O-MS) and comprehensive two-dimensional gas chromatography-olfactometry-mass spectrometry (GC × GC-O-MS) techniques, and the key odor-active compounds were identified via aroma extract dilution analysis (AEDA) and relative odor activity value (r-OAV) calculation. A total of 38 volatile compounds were identified by GC-O-MS, among which 10 were declared as odor-active compounds. Whereas 39 volatile compounds were identified by GC × GC-O-MS, among which 12 were declared as odor-active compounds. The study results revealed that 1-octen-3-one, 2-pentylfuran, (E)-2-octenal, 1-octen-3-one, hexanal, 1-octen-3-ol, 6-methylhept-5-en-2-one, (E,Z)-2,6-nondienal and 2-ethyl-3,5-dimethylpyrazine were the key odor-active compounds in the fish soup.

Lateral approach is a more aesthetical option for radical resection of BSCC: assessment of its surgical, oncological, functional, and aesthetic outcomes.

BACKGROUND: The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. METHODS: This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. RESULTS: Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. CONCLUSION: The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.

Metabolic effects and safety of Roux-en-Y gastric bypass surgery vs. conventional medication in obese Chinese patients with type 2 diabetes.

AIM: To assess metabolic effects and safety of Roux-en-Y gastric bypass (RYGB) versus conventional medication (CM) in obese Chinese patients with type 2 diabetes (T2DM). METHODS: This retrospective cohort study included 40 patients who underwent RYGB (mean age 44.1 years, body mass index [BMI] 33.3 kg/m2 ) and 36 patients administered CM (mean age 49.4 years, BMI 32.1 kg/m2 ). The primary endpoint was achievement of the triple endpoint (haemoglobin A1C [HbA1c] < 7.0%, low-density lipoprotein cholesterol < 2.6 mmol/L, and systolic blood pressure < 130 mmHg). Changes in weight, BMI, medication usage, complications, and adverse events were assessed. RESULTS: After 1-year follow-up, 35% of RYGB patients and 8% of CM patients achieved the triple endpoint (P = 0.005). More patients in the RYGB group achieved complete (48% vs 3%, P < 0.001) and partial (23% vs 0%, P = 0.007) remission of diabetes, and complete remission of hypertension (58% vs 24%, P = 0.019). Patients in the RYGB group had greater weight loss and decrease in BMI, waist circumference, fasting and postprandial of blood glucose and insulin levels, HbA1c, blood pressure, triglycerides, and increased high-density cholesterol (P < 0.001- < 0.05). A lower proportion of the RYGB group received antidiabetics, antihypertensives, or antilipemic treatments, and had non-alcoholic fatty liver disease (NAFLD) than the CM group during follow-up. More patients had nutrient deficiency-related diseases in the RYGB group over 1-year follow-up. CONCLUSIONS: For obese Chinese patients with T2DM, RYGB resulted in better metabolic control, greater weight loss, and lower medication usage and NAFLD, but more frequently resulted in diseases related to nutrient deficiency.

Prolactin improves hepatic steatosis via CD36 pathway.

BACKGROUND & AIMS: Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD). METHODS: The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells. RESULTS: Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9-10.3] µg/L; women: 8.7 [range, 6.1-12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8-13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2-16.1] µg/L, p <0.001). PRL levels in patients with biopsy-proven severe hepatic steatosis were lower compared with those with mild-to-moderate hepatic steatosis in both men (8.3 [range, 5.4-9.5] µg/L vs. 9.7 [range, 7.1-12.3] µg/L, p = 0.031) and women (8.5 [range, 4.2-10.6] µg/L vs. 9.8 [range, 8.2-15.7] µg/L, p = 0.027). Furthermore, hepatic PRLR gene expression was significantly reduced in patients with NAFLD and negatively correlated with CD36 gene expression. In FFA-induced HepG2 cells, PRL treatment or PRLR overexpression significantly reduced the expression of CD36 and lipid content, effects that were abrogated after silencing of PRLR. Furthermore, overexpression of CD36 significantly reduced the PRL-mediated improvement in lipid content. CONCLUSIONS: Our results reveal a novel association between the central nervous system and the liver, whereby PRL/PRLR improved hepatic lipid accumulation via the CD36 pathway. LAY SUMMARY: Our clinical study suggests a negative association between prolactin (PRL)/prolactin receptor (PRLR) and the presence of non-alcoholic fatty liver disease (NAFLD). Using cell experiments, we found that PRL ameliorates hepatic steatosis via the hepatic PRLR and fatty acid translocase (FAT)/CD36, a key transporter of free fatty acid uptake in liver. Our findings suggest a novel approach to improving NAFLD using PRL and PRLR. Clinical trial number: NCT03296605.

A gold electrode modified with a nanoparticulate film composed of a conducting copolymer for ultrasensitive voltammetric sensing of hydrogen peroxide.

A film consisting of poly(γ-glutamic acid) modified with 3-aminothiophene (ATh-γ-PGA) was prepared by macromolecular self-assembly and electropolymerization. ATh-γ-PGA is amphiphilic and electrically conductive. The copolymers undergo self-assembly to form nanoparticles (NPs) on decreasing the pH value of an aqueous solution. A conducting film of NPs was formed on the surface of a gold electrode by casting the ATh-γ-PGA NPs and subsequently electropolymerizing the thiophene units. Next, horseradish peroxidase and Nafion were cast onto the film to obtain an enzymatic biosensor for H2O2. Due to the electropolymerization step, a cross-conjugated polymer network is created that improves electron transfer rates and thus enhances the response. This endows the biosensor with high sensitivity. Two linear ranges are present, the first ranging from 1 × 10-11 to 1 × 10-8 mol·L-1, and the second from 1 × 10-8 to 1 × 10-5 mol·L-1. The detection limit is as low as 3 × 10-12 mol·L-1. The sensor is stable, repeatable, and was successfully applied to the determination of H2O2 in a commercial disinfecting solution. Graphical abstract Preparation of a conducting nanoparticle (NP) film on the gold electrode (GE) by self-assembly of poly(γ-glutamic acid) that was modified with electroactive 3-aminothiophene (ATh-γ-PGA). It served as a platform for the fabricationof an ultrasensitive voltammetric enzyme-based biosensor for H2O2.

Short- and Long-term Therapeutic Efficacies of Intravenous Transplantation of Bone Marrow Stem Cells on Cardiac Function in Rats with Acute Myocardial Infarction: A Meta-analysis of Randomized Controlled Trials.

Objective To investigate the short- and long-term therapeutic efficacies of intravenous trans- plantation of bone marrow stem cells (MSCs) in rats with experimental myocardial infarction by meta- analysis. Methods Randomized controlled trials were systematically searched from PubMed, Science Citation Index (SCI), Chinese journal full-text database (CJFD) up to December 2014. While the experimental groups (MSCs groups) were injected MSCs intravenously, the control groups were injected Delubecco's minimum essential medium (DMEM) or phosphate buffered saline (PBS). Subgroup analysis for each outcome measure was performed for the observing time point after the transplantation of MSCs. Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated for outcome parameters including ejection fraction (EF) and fractional shortening (FS), which were measured by echocardiogram after intravenous injection and analyzed by RevMan 5.2 and STATA 12.0. Results Data from 9 studies (190 rats) were included in the meta-analysis. As compared to the control groups, the cardiac function of the experimental groups were not improved at day 7 (EF: WMD=0.08, 95%CI -1.32 to 1.16, P>0.01; FS: WMD=-0.12, 95%CI -0.90 to 0.65, P>0.01) until at day 14 after MSCs' transplantation (EF: WMD=10.79, 95%CI 9.16 to 12.42, P<0.01; FS: WMD=11.34, 95%CI 10.44 to 12.23, P<0.01), and it lasted 4 weeks or more after transplantation of MSCs (EF: WMD=13.94, 95%CI 12.24 to 15.64, P<0.01; FS: WMD=9.64, 95%CI 7.98 to 11.31, P<0.01). Conclusion The therapeutic efficacies of MSCs in rats with myocardid infarction become increasing apparent as time advances since 2 weeks after injection.

Anterior tibial artery perforator flap for reconstruction of intraoral defects.

PURPOSE: The present clinical study assessed the feasibility of using an anterior tibial artery perforator (ATAP) flap for the reconstruction of an intraoral defect after ablative surgery for oral cancer. PATIENTS AND METHODS: A cohort of consecutive patients with oral cancer requiring reconstruction of an intraoral defect using an ATAP flap were enrolled after ablative surgery for oral cancer and ipsilateral neck dissection. RESULTS: Twelve patients had primary oral squamous cell carcinoma (8 with tongue cancer and 4 with buccal cancer). All patients received intraoral defect repair using an ATAP flap from the lower left leg. The flap measured 7 × 4 to 8 × 6 cm(2). Flap thickness was approximately 4.8 mm (3 to 6 mm). Anastomosis of all ATAP flaps was straightforward because of the long and high-caliber vessel pedicle. All flaps survived and yielded excellent esthetic results for intraoral reconstruction. No major complications occurred in any patient. CONCLUSION: The main advantages of the ATAP flap included the thin and pliable tissue characteristics and a long and high-caliber pedicle. For small and medium-size intraoral defects, the ATAP flap is a reliable alternative to the radial forearm free flap.

Efficacy and Safety of Epidural Chloroprocaine for Breakthrough Pain During Labor Analgesia: A Prospective, Double-Blind, Randomized Trial.

INTRODUCTION: A significant number of women who undergo neuraxial labor analgesia experience breakthrough pain. Prompt mitigation of breakthrough pain is essential to improve maternal and fetal outcomes. We evaluated epidural chloroprocaine compared with ropivacaine in alleviating labor breakthrough pain. METHODS: We performed a double-blind randomized controlled clinical trial between May and July 2023. Eligible parturients received epidural analgesia with ropivacaine and sufentanil. Those with breakthrough pain were randomized to receive either 0.125% epidural ropivacaine (group R) or chloroprocaine at concentrations of 0.5% (group C1), 1.0% (group C2), or 1.5% (group C3), all in a volume of 6 mL. The primary outcome was the treatment success rate, indicated by a decrease of at least 4 points on the numerical rating scale pain score 9 min after analgesic injection. Secondary outcomes and adverse effects were also recorded. RESULTS: Out of 323 patients receiving epidural analgesia, 192 experienced breakthrough pain. After exclusion of three patients because of protocol deviation, there were 47, 48, 47, and 47 patients in group R, C1, C2, and C3, respectively. Group C3 demonstrated a higher treatment success rate (39/47, 83.0%) in managing breakthrough pain than group R (26/47, 55.3%), group C1 (12/48, 25.0%), and group C2 (30/47, 63.8%) (p < 0.001). Group C3 had lower numerical rating scale scores at 6 and 9 min after injection and required fewer patient-controlled epidural boluses than other groups. In addition, group C3 reported greater satisfaction than the other groups (p < 0.001). No significant differences were observed in obstetric or neonatal outcomes across these groups. CONCLUSION: Parturients experiencing breakthrough pain could receive 1.5% epidural chloroprocaine, rather than lower chloroprocaine concentrations and ropivacaine, to achieve more rapid and better pain relief with higher patient satisfaction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300071069, http://www.chictr.org.cn/index.aspx .

Biomimetic Electronic Skin Based on a Stretchable Ionogel Mechanoreceptor Composed of Crumpled Conductive Rubber Electrodes for Synchronous Strain, Pressure, and Temperature Detection.

Electronic skin (e-skin) is showing a huge potential in human-computer interaction, intelligent robots, human health, motion monitoring, etc. However, it is still challenging for e-skin to realize distinguishable detection of stretching strain, vertical pressure, and temperature through a simple noncoupling structure design. Here, a stretchable multimodal biomimetic e-skin was fabricated by integrating layer-by-layer self-assembled crumpled reduced graphene oxide/multiwalled carbon nanotubes film on natural rubber (RGO/MWCNTs@NR) as stretchable conductive electrodes and polyacrylamide/NaCl ionogel as a dielectric layer into an ionotropic capacitive mechanoreceptor. Unlike natural skin receptors, the sandwich-like stretchable ionogel mechanoreceptor possessed a distinct ionotropic capacitive behavior for strain and pressure detection. The results showed that the biomimetic e-skin displayed a negative capacitance change with superior stretchability (0-300%) and a high gauge factor of 0.27 in 180-300% strain, while exhibiting a normal positive piezo-capacitance behavior in vertical pressure range of 0-15 kPa with a maximal sensitivity of 1.759 kPa-1. Based on this feature, the biomimetic e-skin showed an excellent synchronous detection capability of planar strain and vertical pressure in practical wearable applications such as gesture recognition and grasping movement detection without a complicated mathematical or signal decoupling process. In addition, the biomimetic e-skin exhibited a quantifiable linear responsiveness to temperature from 20-90 °C with a temperature coefficient of 0.55%/°C. These intriguing properties gave the biomimetic e-skin the ability to perform a complete function similar to natural skin but beyond its performance for future wearable devices and artificial intelligence devices.

Cellular Aging and Senescence in Cancer: A Holistic Review of Cellular Fate Determinants.

This comprehensive review navigates the complex relationship between cellular aging, senescence, and cancer, unraveling the determinants of cellular fate. Beginning with an overview of cellular aging's significance in cancer, the review explores processes, changes, and molecular pathways influencing senescence. The review explores senescence as a dual mechanism in cancer, acting as a suppressor and contributor, focusing on its impact on therapy response. This review highlights opportunities for cancer therapies that target cellular senescence. The review further examines the senescence-associated secretory phenotype and strategies to modulate cellular aging to influence tumor behavior. Additionally, the review highlights the mechanisms of senescence escape in aging and cancer cells, emphasizing their impact on cancer prognosis and resistance to therapy. The article addresses current advances, unexplored aspects, and future perspectives in understanding cellular aging and senescence in cancer.

Closed-loop recycling of tough epoxy supramolecular thermosets constructed with hyperbranched topological structure.

The regulation of topological structure of covalent adaptable networks (CANs) remains a challenge for epoxy CANs. Here, we report a strategy to develop strong and tough epoxy supramolecular thermosets with rapid reprocessability and room-temperature closed-loop recyclability. These thermosets were constructed from vanillin-based hyperbranched epoxy resin (VanEHBP) through the introduction of intermolecular hydrogen bonds and dual dynamic covalent bonds, as well as the formation of intramolecular and intermolecular cavities. The supramolecular structures confer remarkable energy dissipation capability of thermosets, leading to high toughness and strength. Due to the dynamic imine exchange and reversible noncovalent crosslinks, the thermosets can be rapidly and effectively reprocessed at 120 °C within 30 s. Importantly, the thermosets can be efficiently depolymerized at room temperature, and the recovered materials retain the structural integrity and mechanical properties of the original samples. This strategy may be employed to design tough, closed-loop recyclable epoxy thermosets for practical applications.

Hallmarks of cancer resistance.

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.