Microplastics exposure disrupts nephrogenesis and induces renal toxicity in human iPSC-derived kidney organoids.

Microplastics (MPs) have emerged as a pervasive environmental pollutant of global concern. Their detection within the human placenta and fetal organs has prompted apprehension regarding the potential hazards of MPs during early organogenesis. The kidney, a vital multifunctional organ, is susceptible to damage from MPs in adulthood. However, the precise adverse effects of MP exposure on human nephrogenesis remain ambiguous due to the absence of a suitable model. Here, we explore the potential impact of MPs on early kidney development utilizing human kidney organoids in vitro. Human kidney organoids were subjected to polystyrene-MPs (PS-MPs, 1 µm) during the nephron progenitor cell (NPC) stage, a critical phase in early kidney development and patterning. We delineate the effects of PS-MPs on various stages of nephrogenesis, including NPC, renal vesicle, and comma-shaped body, through sequential examination of kidney organoids. PS-MPs were observed to adhere to the surface of cells during the NPC stage and accumulate within glomerulus-like structures within kidney organoids. Moreover, both short- and long-term exposure to PS-MPs resulted in diminished organoid size and aberrant nephron structure. PS-MP exposure heightened reactive oxygen species (ROS) production, leading to NPC apoptosis during early kidney development. Increased apoptosis, diminished cell viability, and NPC reduction likely contribute to the observed organoid size reduction under PS-MP treatment. Transcriptomic analysis at both NPC and endpoint stages revealed downregulation of Notch signaling, resulting in compromised proximal and distal tubular structures, thereby disrupting normal nephron patterning following PS-MP exposure. Our findings highlight the significant disruptive impact of PS-MPs on human kidney development, offering new insights into the mechanisms underlying PS-MP-induced nephron toxicity.

Przewaquinone A inhibits Angiotensin II-induced endothelial diastolic dysfunction activation of AMPK.

BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.

Hemispherical Retina Emulated by Plasmonic Optoelectronic Memristors with All-Optical Modulation for Neuromorphic Stereo Vision.

Binocular stereo vision relies on imaging disparity between two hemispherical retinas, which is essential to acquire image information in three dimensional environment. Therefore, retinomorphic electronics with structural and functional similarities to biological eyes are always highly desired to develop stereo vision perception system. In this work, a hemispherical optoelectronic memristor array based on Ag-TiO2 nanoclusters/sodium alginate film is developed to realize binocular stereo vision. All-optical modulation induced by plasmonic thermal effect and optical excitation in Ag-TiO2 nanoclusters is exploited to realize in-pixel image sensing and storage. Wide field of view (FOV) and spatial angle detection are experimentally demonstrated owing to the device arrangement and incident-angle-dependent characteristics in hemispherical geometry. Furthermore, depth perception and motion detection based on binocular disparity have been realized by constructing two retinomorphic memristive arrays. The results demonstrated in this work provide a promising strategy to develop all-optically controlled memristor and promote the future development of binocular vision system with in-sensor architecture.

Sinomenine ameliorates bleomycin-induced pulmonary fibrosis by inhibiting the differentiation of fibroblast into myofibroblast.

Idiopathic pulmonary fibrosis (IPF) represents a severe interstitial lung disease characterized by limited therapeutic interventions. Recent study has suggested that sinomenine (SIN), an alkaloid derived from the roots of Sinomenium acutum, demonstrates efficacy in interrupting aerobic glycolysis, a predominant metabolic pathway in myofibroblasts. However, its pharmacological potential in the context of pulmonary fibrosis remains inadequately explored. In the present study, we established a bleomycin (BLM)-induced pulmonary fibrosis mouse model and subjected the mice to a one-week regimen of SIN treatment to assess its efficacy. Additionally, a TGF-ß1-induced primary lung fibroblast model was employed to investigate the molecular mechanism underlying the effects of SIN. Our observations revealed robust anti-pulmonary fibrosis properties associated with SIN treatment, as evidenced by reduced extracellular matrix deposition, diminished hydroxyproline contents, improved Ashcroft scores, and enhanced lung function parameters. Furthermore, SIN administration significantly impeded TGF-ß1-induced fibroblast-to-myofibroblast differentiation. Mechanistically, SIN exerted its beneficial effects by mitigating aerobic glycolysis, achieved through the inhibition of the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (Pfkfb3). Notably, the protective effects of SIN on fibroblasts were reversed upon ectopic overexpression of Pfkfb3. In conclusion, our data underscore the potential of SIN to attenuate fibroblast-to-myofibroblast differentiation by modulating Pfkfb3-associated aerobic glycolysis and SIN emerges as a promising anti-fibrotic agent for pulmonary fibrosis in clinical practice.

Pan-cancer analysis and experimental validation reveal FAM72D as a potential novel biomarker and therapeutic target in lung adenocarcinoma.

BACKGROUND: Cancers, particularly lung adenocarcinoma (LUAD), represent a major global health concern. However, the role of FAM72D in various cancers, including LUAD, remains poorly understood. METHODS: We utilized databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx) and online tools to investigate the correlation between FAM72D expression and its prognostic, diagnostic, and mutational significance, as well as its impact on immune cell infiltration across multiple cancers. Additionally, we developed LUAD cell lines overexpressing FAM72D to confirm its oncogenic role. RESULTS: FAM72D expression was elevated in cancerous tissues compared to noncancerous tissues, with diagnostic and prognostic implications in many cancers, including LUAD. Moreover, associations were identified between FAM72D expression and diverse immune subtypes, alongside factors such as microsatellite instability, neoantigens, and tumour mutational burden across pan-cancers. Additionally, FAM72D was associated with immune infiltration and various immune checkpoint-related genes in LUAD. In vitro experiments demonstrated that FAM72D promoted cell proliferation, colony formation, and migration, while inhibiting apoptosis in LUAD cells. CONCLUSIONS: Our study establishes associations between FAM72D expression and diagnosis, prognosis, and tumour immunity across multiple cancers, as well as its oncogenic effects in LUAD. FAM72D shows promise as a biomarker and therapeutic target in LUAD.

Engineered in vivo and in vitro tumor model recapitulates vasculogenic mimicry signatures in melanoma.

Vasculogenic mimicry (VM) describes a process by which tumor cells formed a novel microcirculation pattern in an endothelial cell-free manner. Clinically, VM is associated with aggressive phenotype and poor patient survival. However, the current models for investigating VM include 2D monolayer cultures, Matrigel-based cultures, and animal models, each of which has limitations. Matrigel-based models often exhibit batch-to-batch variations, while in vivo tumor models currently produce insufficient amounts of VM. There is currently no suitable tumor model to discover new therapeutic targets against VM. Herein, we establish an extracellular matrix (ECM)-based engineered tumor model in vivo and in vitro. In this study, we demonstrate that matrix proteins enhanced the VM formation in the engineered xenograft model. Furthermore, we also investigated the role of collagen/fibronectin (FN) in melanoma progression and VM formation. Compared with cells cultured on TCPS plates, the B16F10 cells cultured on collagen/FN coated plates showed increased proliferation and stemness, and significantly enhanced invasion and formation of VM networks. Molecular mechanism analysis showed that Integrin/VE-cadherin/EphA2/PI3K/MMP-2 signaling pathways are responsible for VM formation. Our results indicate that collagen/FN matrix plays an important role in VM formation in melanoma, suggesting that ECM protein is a potential therapeutic target for anti-VM therapy for melanoma.

Development and evaluation of interpretable machine learning regressors for predicting femoral neck bone mineral density in elderly men using NHANES data.

Osteoporotic femoral neck fractures (OFNFs) pose a significant orthopedic challenge in the elderly population, accounting for up to 40% of all osteoporotic fractures and leading to considerable health deterioration and increased mortality. In addressing the critical need for early identification of osteoporosis through routine screening of femoral neck bone mineral density (FNBMD), this study developed a user-friendly prediction model aimed at men aged 50 years and older, a demographic often overlooked in osteoporosis screening. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), the study involved outlier detection and handling, missing value imputation via the K nearest neighbor (KNN) algorithm, and data normalization and encoding. The dataset was split into training and test sets with a 7:3 ratio, followed by feature screening through the least absolute shrinkage and selection operator (LASSO) and the Boruta algorithm. Eight different machine learning algorithms were then employed to construct predictive models, with their performance evaluated through a comprehensive metric suite. The random forest regressor (RFR) emerged as the most effective model, characterized by key predictors such as age, body mass index (BMI), poverty income ratio (PIR), serum calcium, and race, achieving a coefficient of determination (R²) of 0.218 and maintaining robustness in sensitivity analyses. Notably, excluding race from the model resulted in sustained high performance, underscoring the model's adaptability. Interpretations using Shapley additive explanations (SHAP) highlighted the influence of each feature on FNBMD. These findings indicate that our predictive model effectively aids in the early detection of osteoporosis, potentially reducing the incidence of OFNFs in this high-risk population.

Logistic regression modeling of cytokines for cerebrospinal fluid evaluation in primary central nervous system lymphoma.

BACKGROUND: The diagnostic utility of cerebrospinal fluid (CSF) cytology encounters impediments stemming from variability in cell collection techniques and pathologists' morphological acumen, resulting in wide-ranging CSF positivity rates for primary central nervous system lymphomas (PCNSL). Such disparity impacts patient evaluation, treatment stratagem, and prognostication. Thus, this study endeavors to explore liquid biomarkers complementary to CSF cytology or immunophenotype analysis in the diagnosis of CSF involvement. METHODS: 398 newly diagnosed PCNSL patients were categorized into CSF involvement and non-involvement groups based on CSF cytology and immunophenotype analysis. Binary logistic regression analysis was performed on 338 patients to investigate factors predicting CSF involvement and to develop a joint prediction model. An additional cohort of 60 PCNSL patients was recruited for model validation. Statistical analyses included the Mann-Whitney U test for comparing various CSF parameters between two groups. ROC curve analyses were performed for each biomarker to identify PCNSL CSF involvement. RESULTS: The cytokine IL-10 level in CSF has emerged as the most promising biomarker for CSF evaluation, boasting an ROC AUC of 0.922. C-TNFα and soluble C-IL2R demonstrate efficacy in quantifying tumor burden within the CSF. Logistic regression identified C-IL10lg (OR = 30.103, P < 0.001), C-TNC (OR = 1.126, P < 0.001), C-IL2Rlg (OR = 3.743, P = 0.029) as independent predictors for CSF involvement, contributing to a joint predictive model with an AUC of 0.935, sensitivity of 74.1 %, and specificity of 93.0 %. Validation of the model in an independent cohort confirmed its effectiveness, achieving an AUC of 0.9713. CONCLUSIONS: The identification of these feasible biomarkers and the development of an accurate prediction model may facilitate the precise evaluation of CSF status in PCNSL, offering significant advancements in patient management.

Tranexamic acid efficacy in geriatric hip fractures: impact of nutritional status on blood loss, transfusion rates, and safety.

BACKGROUND: Tranexamic acid (TXA) is a widely employed intervention in orthopedic surgeries to minimize blood loss and the need for postoperative transfusions. This study focuses on assessing the efficacy and safety of TXA specifically in undernourished older adults undergoing hip fracture procedures. METHODS: A total of 216 patients were classified into two groups based on the Geriatric Nutritional Risk Index: undernourished and normal. In total, 82 patients received intravenous TXA at a dosage of 15 mg/kg before incision, with an additional 1 g administered intravenously over a 3-hour period postoperatively. Postoperative hemoglobin (Hb) drop, blood transfusion rate, and the incidence of deep venous thrombosis (DVT) were assessed in each group according to the presence or absence of TXA. Additionally, demographic factors including age, sex, body mass index, and serum albumin were investigated. RESULTS: 51.9% patients were identified as undernourished, experiencing progressive anemia (Hb: 10.9 ± 1.5 g/dL) and hypoalbuminemia (serum albumin: 31.9 ± 8 g/L). In comparison with the normal group, undernourished individuals were more likely to sustain femoral neck fractures (undernutrition vs. normal: 56.2 vs. 42.3%) and less likely to incur trochanteric fractures (undernutrition vs. normal: 43.8 vs. 57.7%) (P = 0.043). TXA administration significantly reduced the transfusion rate (P = 0.014) and Hb drop (P = 0.001) in the normal nutritional group, while its impact on the undernourished group remained less pronounced. There was no significant association between TXA administration and the rate of DVT complications, irrespective of the nutritional status. CONCLUSIONS: Undernutrition not only diminishes muscle strength and gait function, leading to various types of hip fractures, but it may also hinder the efficacy of TXA in reducing blood transfusion rates and blood loss.

Effects of two fillers and process conditions on the water treatment efficiency of a continuous packed bed biofilm reactor.

This study evaluated the treatment efficiency of two selected fillers and their combination for improving the water quality of aquaculture wastewater using a packed bed biofilm reactor (PBBR) under various process conditions. The fillers used were nanosheet (NS), activated carbon (AC), and a combination of both. The results indicated that the use of combined fillers and the hydraulic retention time (HRT) of 4 h significantly enhanced water quality in the PBBR. The removal rates of chemical oxygen demand, NO2-─N, total suspended solids（TSS）, and chlorophyll a were 63.55%, 74.25%, 62.75%, and 92.85%, respectively. The microbiota analysis revealed that the presence of NS increased the abundance of microbial phyla associated with nitrogen removal, such as Nitrospirae and Proteobacteria. The difference between the M1 and M2 communities was minimal. Additionally, the microbiota in different PBBR samples displayed similar preferences for carbon sources, and carbohydrates and amino acids were the most commonly utilized carbon sources by microbiota. These results indicated that the combination of NS and AC fillers in a PBBR effectively enhanced the treatment efficiency of aquaculture wastewater when operated at an HRT of 4 h. The findings provide valuable insights into optimizing the design of aquaculture wastewater treatment systems.

Best evidence summary of sleep protection in premature infants in the neonatal intensive care unit: a narrative review.

Background and Objective: Sleep influences the interaction between infants and their environment, as well as the achievement of crucial milestones in motor and language development. This is particularly significant for preterm infants in vulnerable positions. However, prematurely born infants in the neonatal intensive care unit (NICU) are exposed to various stimuli such as noise and light, which disrupt their normal sleep patterns. This study assesses and consolidates the existing evidence on non-pharmacological strategies for protecting and promoting sleep in preterm infants. By providing an evidence-based data repository, it offers a valuable reference for clinical interventions. Methods: We conducted computer-based searches using various databases and resources, including UpToDate, BMJ Best Practice, Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), National Guideline Clearinghouse (NGC), Registered Nurses Association of Ontario (RNAO), Joanna Briggs Institute (JBI), World Health Organization (WHO), Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data, and China Biology Medicine disc (CBM). The search period spanned from January 2014 to May 2024. Key Content and Findings: We have included a total of 22 articles in our review, comprising two guidelines, 11 systematic reviews, 1 evidence summary, 1 technical report, 2 practice recommendations, and 5 randomized controlled trials. The evidence was synthesized from eight domains: sleep team construction, risk factor assessment, sleep assessment tools, positional management, noise control, light management, sensory stimulation, and hospital-home transition sleep management, resulting in 27 pieces of evidence. Conclusions: This study summarizes the optimal evidence for the management of sleep in premature infants, providing empirical support for standardizing the management of sleep in premature infants. It is recommended that healthcare professionals judiciously apply the best evidence while considering the clinical context, thus promoting safe sleep for premature infants.

A Simple Prognostic Scoring System for Hepatocellular Carcinoma Treated with DEB-TACE.

Objective: To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC). Methods: Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems. Results: The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0-4 points), medium-risk (DTH-B, 5-6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73±0.62 months, 12.73±0.10 months, and 6.93±0.19 months, respectively (p<0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems. Conclusion: The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.

A Fe2O3/CNx cascade nanoreactor with dual-enzyme-mimetic activities for cancer hypoxia relief to amplify chemo/photodynamic therapy.

Reactive oxygen species (ROS)-mediated therapeutic strategies, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and their combination, are effective for treating cancer. Developing a nanoreactor with combined functions of catalase (CAT) and peroxidase (POD) that can simultaneously convert excess H2O2 in tumors into O2 required for type II PDT and hydroxyl radicals (•OH) for CDT can help achieve combined therapy. Here, we reported on a safe Fe2O3/CNx nanoreactor with dual enzyme simulated activity, in which CNx sheet was the carrier and reducing agent to convert Fe2O3 to Fe2+. After modified by MgO2 and photosensitizer Ce6, MgO2-Fe2O3/CNx-Ce6 (MFCC) platform integrated multiple functions, including photosensitizer delivery, compensated H2O2 continuous supply, relieve of hypoxia, generation of •OH and consumption of GSH into a single formulation. Under 660 nm irradiation for 4 min, MFCC actives more ROS to conduct PDT/CDT, leading to the remarkable reduced survival rate of breast cancer cells to 14 %. Due to the enhanced permeability and retention (EPR) effect, MFCC can retain and accumulate at the tumor site of mice for a longer period that inhibit the expression of tumor angiogenic factors, suppress tumor neovascularization, and suppress the proliferation and growth of tumor cells.

A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report.

Pseudohypoparathyroidism (PHP) type 1a (PHP 1a) is a rare hereditary disorder characterized by target organ resistance to hormonal signaling and the Albright hereditary osteodystrophy (AHO) phenotype, which features round facial features, short fingers, subcutaneous calcifications, short stature, obesity, and intellectual disability. Progressive osseous heteroplasia (POH) is another rare disorder characterized by heterotopic ossification (HO) that progressively affects skin, subcutaneous tissues, and deep skeletal muscle. PHP 1a is inherited maternally due to a GNAS mutation, while pure POH is inherited paternally. This case study presented a Chinese boy with congenital hypothyroidism, tonic-clonic seizures, hypoparathyroidism, AHO, POH, and joint fixation deformity. Sequencing analysis of GNAS-Gsα revealed a heterozygous C.432+2T>C(P.?) variant (NM_000516.7) affecting the canonical splice donor site of intron 5 in the boy and his mother, indicating maternal inheritance of a GNAS mutation. The patient was diagnosed with POH overlap syndrome (POH/PHP 1a). Following calcium and calcitriol supplementation, he experienced a reduction in seizures, and surgery was performed to correct the joint fixation deformity caused by HO. This case report provided valuable insights into the genotype-phenotype correlations of POH overlap syndrome and underscored the significance of genetic testing in diagnosing rare diseases.

Microrna-605-3p Inhibited the Growth and Chemoresistance of Osteosarcoma Cells via Negatively Modulating RAF1.

BACKGROUND: Osteosarcoma (OS) is the leading cancer-associated mortality in childhood and adolescence. Increasing evidence has demonstrated the key function of microRNAs (miRNAs) in OS development and chemoresistance. Among them, miRNA-605-3p acted as an important tumor suppressor and was frequently down-regulated in multiple cancers. However, the function of miR-650-3p in OS has not been reported. OBJECTIVE: The aim of this work is to explore the novel role of miR-605-3p in osteosarcoma and its possible involvement in OS chemotherapy resistance. METHOD: The expression levels of miR-605-3p in OS tissues and cells were assessed by reverse transcription quantitative PCR (RT-qPCR). The relevance of miR-605-3p with the prognosis of OS patients was determined by the Kaplan-Meier analysis. Additionally, the influence of miR-605-3p on OS cell growth was analyzed using the cell counting kit-8, colony formation assay, and flow cytometry. The mRNA and protein expression of RAF1 were detected by RT-qPCR and western blot. The binding of miR-605-3p with the 3'-UTR of RAF1 was confirmed by dual-luciferase reporter assay. RESULTS: Our results showed that miR-605-3p was markedly decreased in OS tissues and cells. A lower level of miR-605-3p was strongly correlated with lymph node metastasis and poor 5-year overall survival rate of OS patients. In vitro assay found that miR-605-3p suppressed OS cell proliferation and promoted cell apoptosis. Mechanistically, the proto-oncogene RAF1 was seen as a target of miR-605-3p and strongly suppressed by miR-605-3p in OS cells. Restoration of RAF1 markedly eliminated the inhibitory effect of miR-605-3p on OS progression, suggesting RAF1 as a key mediator of miR-605-3p. Consistent with the decreased level of RAF1, miR-605-3p suppressed the activation of both MEK and ERK in OS cells, which are the targets of RAF1. Moreover, lower levels of miR-605-3p were found in chemoresistant OS patients, and downregulated miR-605-3p increased the resistance of OS cells to therapeutic agents. CONCLUSION: Our data revealed that miR-605-3p serves as a tumor suppressor gene by regulating RAF1 and increasing the chemosensitivity of OS cells, which provided the novel working mechanism of miR-605-3p in OS. Engineering stable nanovesicles that could efficiently deliver miR-605-3p with therapeutic activity into tumors could be a promising therapeutic approach for the treatment of OS.

Strain-Temperature Dual Sensor Based on Deep Learning Strategy for Human-Computer Interaction Systems.

Thermoelectric (TE) hydrogels, mimicking human skin, possessing temperature and strain sensing capabilities, are well-suited for human-machine interaction interfaces and wearable devices. In this study, a TE hydrogel with high toughness and temperature responsiveness was created using the Hofmeister effect and TE current effect, achieved through the cross-linking of PVA/PAA/carboxymethyl cellulose triple networks. The Hofmeister effect, facilitated by Na+ and SO42- ions coordination, notably increased the hydrogel's tensile strength (800 kPa). Introduction of Fe2+/Fe3+ as redox pairs conferred a high Seebeck coefficient (2.3 mV K-1), thereby enhancing temperature responsiveness. Using this dual-responsive sensor, successful demonstration of a feedback mechanism combining deep learning with a robotic hand was accomplished (with a recognition accuracy of 95.30%), alongside temperature warnings at various levels. It is expected to replace manual work through the control of the manipulator in some high-temperature and high-risk scenarios, thereby improving the safety factor, underscoring the vast potential of TE hydrogel sensors in motion monitoring and human-machine interaction applications.

Nano-Titanium Oxide-Coated Carbon Nanotubes for Photothermal Therapy in the Treatment of Colorectal Cancer.

Recent studies have shown that carbon nanotubes display good potential in tumor photothermal therapy. In this study, we aimed to investigate the therapeutic potential of nano-titanium oxide-coated multi-walled carbon nanotubes (MCNTs) against colorectal cancer (CRC). Firstly, we modified TiO2 nanosheets on the surface of MCNTs to obtain nano-TiO2-coated MCNTs. Next, we conducted cell compatibility validation on nano-TiO2-coated MCNTs, and found that nano-TiO2-coated MCNTs were safe within a certain concentration range (0∼200 µg/ml). Interestingly, nano-TiO2-coated MCNTs displayed a good killing effect in CRC cells under NIR laser irradiation. Subsequently, nano-TiO2-coated MCNTs markedly promoted the proapoptotic effects of NIR laser irradiation, and significantly inhibited the expression of cell cycle proteins CCNA1 and CCND1 in CRC cells under NIR laser irradiation, which indicated that nano-TiO2-coated MCNTs exerted anti-CRC effects under NIR laser irradiation by regulating cell apoptosis and cell cycle. Furthermore, nano-TiO2-coated MCNTs accelerated inhibitory effects on the AKT signaling pathway under NIR laser irradiation. Finally, a cell line-derived xenograft model was established, and the results showed that nano-TiO2-coated MCNTs significantly exhibited superior tumor-killing ability under NIR laser irradiation in vivo. Collectively, our results demonstrate that nano-TiO2-coated MCNTs with NIR laser irradiation may serve as an effective strategy for the treatment of CRC. This article is protected by copyright. All rights reserved.

Comparison of the efficacy and safety of MAKO robot-assisted total knee arthroplasty versus conventional manual total knee arthroplasty in uncomplicated unilateral total knee arthroplasty a single-centre retrospective analysis.

PURPOSE: To compare the efficacy and safety of MAKO robot-assisted total knee arthroplasty (MA-TKA) with conventional manual total knee arthroplasty (CM-TKA) in patients with end-stage knee osteoarthritis (KOA) during the early postoperative period. METHOD: A retrospective analysis was conducted on 22 patients with KOA who underwent MA-TKA and 26 patients who underwent CM-TKA from April 2023 to July 2023. Hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), American Knee Society Score (AKSS), Forgotten Joint Score-12 (FJS-12), visual analogue scale (VAS), and postoperative complications were recorded and compared between the two groups. RESULT: Both groups successfully completed the surgeries. In terms of radiographic parameters, postoperative one month LDFA and HKA in the MA-TKA group were significantly lower than those in the CM-TKA group (P < 0.05). At the one month follow-up, 19 patients (86.4%) in the MA-TKA group had an HKA less than 3°, compared to 20 patients (76.9%) in the CM-TKA group. Clinically, VAS scores at 24 h, 48 h, and 72 h postoperatively were lower in the MA-TKA group both at rest and during activity. At one month and three months postoperatively, AKSS Function Scores and FJS-12 scores in the MA-TKA group were significantly higher than those in the CM-TKA group (P < 0.05). Regarding postoperative complications, no complications occurred in the MA-TKA group, while one patient in the CM-TKA group experienced postoperative knee stiffness, which resolved after physical therapy, with no statistically significant difference (P > 0.05). CONCLUSION: Compared with conventional manual total knee arthroplasty, MAKO robot-assisted TKA demonstrates better short-term clinical efficacy, achieves better alignment planning, and maintains good safety.

Modulation of the gut microbiota by processed food and natural food: evidence from the Siniperca chuatsi microbiome.

Habitual dietary changes have the potential to induce alterations in the host's gut microbiota. Mandarin fish (Siniperca chuatsi), an aquatic vertebrate species with distinct feeding habits, were fed with natural feeds (NF) and artificial feeds (AF) to simulate the effects of natural and processed food consumption on host gut microbiota assemblages. The results showed that the alpha diversity index was reduced in the AF diet treatment, as lower abundance and diversity of the gut microbiota were observed, which could be attributed to the colonized microorganisms of the diet itself and the incorporation of plant-derived proteins or carbohydrates. The ß-diversity analysis indicated that the two dietary treatments were associated with distinct bacterial communities. The AF diet had a significantly higher abundance of Bacteroidota and a lower abundance of Actinomycetota, Acidobacteriota, and Chloroflexota compared to the NF group. In addition, Bacteroidota was the biomarker in the gut of mandarin fish from the AF treatment, while Acidobacteriota was distinguished in the NF treatments. Additionally, the increased abundance of Bacteroidota in the AF diet group contributed to the improved fermentation and nutrient assimilation, as supported by the metabolic functional prediction and transcriptome verification. Overall, the present work used the mandarin fish as a vertebrate model to uncover the effects of habitual dietary changes on the evolution of the host microbiota, which may provide potential insights for the substitution of natural foods by processed foods in mammals.

Targeting ferroptosis regulators by natural products in colorectal cancer.

Colorectal cancer (CRC) poses a significant global health challenge, ranking as the third most diagnosed cancer and the second leading cause of cancer-related deaths. Despite advancements in treatment, challenges such as delayed diagnosis, multidrug resistance, and limited therapeutic effectiveness persist, emphasizing the need for innovative approaches. This review explores the potential of natural products, nutraceuticals, and phytochemicals for targeting ferroptosis-related regulators as a novel strategy in CRC. Ferroptosis, a form of regulated cell death characterized by iron-dependent lethal lipid peroxide accumulation, holds substantial importance in CRC progression and therapy resistance. Natural products, known for their diverse bioactive effects and favorable safety profiles, emerge as promising candidates to induce ferroptosis in CRC cells. Exploring amino acid, iron, lipid metabolism regulators, and oxidative stress regulators reveals promising avenues for inducing cell death in CRC. This comprehensive review provides insights into the multifaceted effects of natural products on proteins integral to ferroptosis regulation, including GPX4, SLC7A11, ACSL4, NCOA4, and HO-1. By elucidating the intricate mechanisms through which natural products modulate these proteins, this review lays the foundation for a promising therapeutic strategy in CRC.