Gender-specific effects of polystyrene nanoplastic exposure on triclosan-induced reproductive toxicity in zebrafish (Danio rerio).

Nanoplastics (NPs) and triclosan (TCS) are ubiquitous emerging environmental contaminants detected in human samples. While the reproductive toxicity of TCS alone has been studied, its combined effects with NPs remain unclear. Herein, we employed Fourier transform infrared spectroscopy and dynamic light scattering to characterize the coexposure of polystyrene nanoplastics (PS-NPs, 50 nm) with TCS. Then, adult zebrafish were exposed to TCS at environmentally relevant concentrations (0.361-48.2 µg/L), with or without PS-NPs (1.0 mg/L) for 21 days. TCS biodistribution in zebrafish tissues was investigated using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Reproductive toxicity was assessed through gonadal histopathology, fertility tests, changes in steroid hormone synthesis and gene expression within the hypothalamus-pituitary-gonad-liver (HPGL) axis. Transcriptomics and proteomics were applied to explore the underlying mechanisms. The results showed that PS-NPs could adsorb TCS, thus altering the PS-NPs' physical characteristics. Our observations revealed that coexposure with PS-NPs reduced TCS levels in the ovaries, livers, and brains of female zebrafish. Conversely, in males, coexposure with PS-NPs increased TCS levels in the testes and livers, while decreasing them in the brain. We found that co-exposure mitigated TCS-induced ovary development inhibition while exacerbated TCS-induced spermatogenesis suppression, resulting in increased embryonic mortality and larval malformations. This co-exposure influenced the expression of genes linked to steroid hormone synthesis (cyp11a1, hsd17ß, cyp19a1) and attenuated the TCS-decreased estradiol (E2) in females. Conversely, testosterone levels were suppressed, and E2 levels were elevated due to the upregulation of specific genes (cyp11a1, hsd3ß, cyp19a1) in males. Finally, the integrated analysis of transcriptomics and proteomics suggested that the aqp12-dctn2 pathway was involved in PS-NPs' attenuation of TCS-induced reproductive toxicity in females, while the pck2-katnal1 pathway played a role in PS-NPs' exacerbation of TCS-induced reproductive toxicity in males. Collectively, PS-NPs altered TCS-induced reproductive toxicity by disrupting the HPGL axis, with gender-specific effects.

Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis.

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg-1·d-1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1ß. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1ß, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

3D printing-based lateral flow visual assay utilizing the dual-excitation property of nitrogen-doped carbon dots for the ratiometric determination and chemometric discrimination of flavonoids.

A ratiometric fluorescence sensor has been established based on dual-excitation carbon dots (D-CDs) for the detection of flavonoids (morin is chosen as the typical detecting model for flavonoids). D-CDs were prepared using microwave radiation with o-phenylenediamine and melamine and exhibit controllable dual-excitation behavior through the regulation of their concentration. Remarkably, the short-wavelength excitation of D-CDs can be quenched by morin owing to the inner filter effect, while the long-wavelength excitation remains insensitive, serving as the reference signal. This contributes to the successful design of an excitation-based ratiometric sensor. Based on the distinct and differentiated variation of excitation intensity, morin can be determined from 0.156 to 110 µM with a low detection limit of 0.156 µM. In addition, an intelligent and visually lateral flow sensing device is developed for the determination  of morin content in real samples with satisfying recoveries, which indicates the potential application for human health monitoring.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

From cradle to grave: Deciphering sex-specific disruptions of the nervous and reproductive systems through interactions of 4-methylbenzylidene camphor and nanoplastics in adult zebrafish.

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4832 µg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish.

Exposure of Peregrine Falcons to Halogenated Flame Retardants: A 30 Year Retrospective Biomonitoring Study across North America.

Compared to aquatic ecosystem, terrestrial systems have been subjected to fewer investigations on the exposure to halogenated flame retardants (HFRs). Our study utilized peregrine falcon eggs collected from multiple habitats across North America to retrospectively explore both spatial distribution and temporal changes in legacy (e.g., polybrominated diphenyl ethers) and alternative HFRs over a 30 year period (1984-2016). The results reveal intensive HFR exposure in terrestrial ecosystems and chemical-specific spatiotemporal distribution patterns. The correlations between egg levels of the selected HFRs and human population density clearly illustrated a significant urban influence on the exposure of this wildlife species to these HFRs and subsequent maternal transfer to their eggs. Temporal analyses suggest that, unlike aquatic systems, terrestrial ecosystems may undergo continual exposure to consistently high levels of legacy HFRs for a long period of time. Our findings collectively highlight the effectiveness of using peregrine eggs to monitor terrestrial exposure to HFRs and other bioaccumulative chemicals and the need for continuous monitoring of HFRs in terrestrial ecosystems.

Comparing Equil patch versus traditional catheter insulin pump in type 2 diabetes using continuous glucose monitoring metrics and profiles.

AIMS: It is not clear whether there are differences in glycemic control between the Equil patch and the MMT-712 insulin pump. Our objective was to compare two types of insulin pumps in the treatment of type 2 diabetes mellitus (T2DM), using continuous glucose monitoring (CGM) metrics and profiles. METHODS: This was a randomized case-crossover clinical trial. Participants were hospitalized and randomly allocated to two groups and underwent two types of insulin pump treatments (group A: Equil patch-Medtronic MMT-712 insulin pump; group B: Medtronic MMT-712-Equil patch insulin pump) separated by a 1-day washout period. Glycemic control was achieved after 7-8 days of insulin pump therapy. Each patient received CGM for 5 consecutive days (from day 1 to day 5). On day 3 of CGM performance, the Equil patch insulin pump treatment was switched to Medtronic MMT-712 insulin pump treatment at the same basal and bolus insulin doses or vice versa. CGM metrics and profiles including glycemic variability (GV), time in range (TIR, 3.9-10.0 mmol/L), time below range (TBR, <3.9 mmol/L), time above range (TAR, >10.0 mmol/L), and postprandial glucose excursions, as well as incidence of hypoglycemia. RESULTS: Forty-six T2DM patients completed the study. There was no significant difference in parameters of daily GV and postprandial glucose excursions between the Equil patch insulin pump treatment and the Medtronic insulin pump treatment. Similarly, there was no between-treatment difference in TIR, TBR, and TAR, as well as the incidence of hypoglycemia. CONCLUSION: The Equil patch insulin pump was similar to the traditional MMT-712 insulin pump in terms of glycemic control. Equil patch insulin pump is a reliable tool for glycemic management of diabetes mellitus.

Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors. AIM: To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients. METHODS: This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA). RESULTS: The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit. CONCLUSION: Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.

Transcriptomic and physiological analyses of Symphytum officinale L. in response to multiple heavy metal stress.

Soil heavy metal contamination has become a global environmental issue, which threaten soil quality, food security and human health. Symphytum officinale L. have exhibited high tolerance and restoration capacity to heavy metals (HMs) stress. However, little is known about the mechanisms of HMs in S. officinale. In this study, transcriptomic and physiological changes of S. officinale response to different HMs (Pb, Cd and Zn) were analyzed and investigated the key genes and pathways involved in HMs uptake patterns. The results showed that phenotypic effects are not significant, and antioxidant enzyme activities were all upregulated. Transcriptome analysis indicated that 1247 differential genes were up-regulated, and 1963 differential genes were down-regulated under Cd stress, while 3752 differential genes were up-regulated, and 7197 differential genes were down-regulated under Pb stress; and 527 differential genes were up-regulated; and 722 differential genes were down-regulated under Zn stress. Based on their expression, we preliminarily speculate that different HMs resistance of S. officinale may be regulated by the differential expression of key genes. These results provide a theoretical basis for determining the exact expression of genes in plants under different heavy metal stress, the processes involved molecular pathways, and how they can be efficiently utilized to improve plant tolerance to toxic metals and improve phytoremediation efficiency.

Effector enrichment by Candidatus Liberibacter promotes Diaphorina citri feeding via Jasmonic acid pathway suppression.

BACKGROUND: Citrus huanglongbing (HLB) is a devastating disease caused by Candidatus Liberibacter asiaticus (CLas) that affects the citrus industry. In nature, CLas relies primarily on Diaphorina citri Kuwayama as its vector for dissemination. After D. citri ingests CLas-infected citrus, the pathogen infiltrates the insect's body, where it thrives, reproduces, and exerts regulatory control over the growth and metabolism of D. citri. Previous studies have shown that CLas alters the composition of proteins in the saliva of D. citri, but the functions of these proteins remain largely unknown. RESULTS: In this study, we detected two proteins (DcitSGP1 and DcitSGP3) with high expression levels in CLas-infected D. citri. Quantitative PCR and Western blotting analysis showed that the two proteins were highly expressed in the salivary glands and delivered into the host plant during feeding. Silencing the two genes significantly decreased the survival rate for D. citri, reduced phloem nutrition sucking and promoted jasmonic acid (JA) defenses in citrus. By contrast, after overexpressing the two genes in citrus, the expression levels of JA pathway-associated genes decreased. CONCLUSION: Our results suggest that CLas can indirectly suppress the defenses of citrus and support feeding by D. citri via increasing the levels of effectors in the insect's saliva. This discovery facilitates further research into the interaction between insect vectors and pathogens. © 2024 Society of Chemical Industry.

METTL3 Promotes Osteosarcoma Metastasis via an m6A-dependent Epigenetic Activity of CBX4.

BACKGROUND: Osteosarcoma cells are prone to metastasis, and the mechanism of N6-methyladenosine (m6A) methylation modification in this process is still unclear. Methylation modification of m6A plays an important role in the development of osteosarcoma, which is mainly due to abnormal expression of enzymes related to methylation modification of m6A, which in turn leads to changes in the methylation level of downstream target genes messenger RNA (mRNA) leading to tumor development. METHODS: We analyzed the expression levels of m6A methylation modification-related enzyme genes in GSE12865 whole-genome sequencing data. And we used shRNA (short hairpin RNA) lentiviral interference to interfere with METTL3 (Methyltransferase 3) expression in osteosarcoma cells. We studied the cytological function of METTL3 by Cell Counting Kit-8 (CCK8), flow cytometry, migration and other experiments, and the molecular mechanism of METTL3 by RIP (RNA binding protein immunoprecipitation), Western blot and other experiments. RESULTS: We found that METTL3 is abnormally highly expressed in osteosarcoma and interferes with METTL3 expression in osteosarcoma cells to inhibit metastasis, proliferation, and apoptosis of osteosarcoma cells. We subsequently found that METTL3 binds to the mRNA of CBX4 (chromobox homolog 4), a very important regulatory protein in osteosarcoma metastasis, and METTL3 regulates the mRNA and protein expression of CBX4. Further studies revealed that METTL3 inhibited metastasis of osteosarcoma cells by regulating CBX4. METTL3 has been found to be involved in osteosarcoma cells metastasis by CBX4 affecting the protein expression of matrix metalloproteinase 2 (MMP2), MMP9, E-Cadherin and N-Cadherin associated with osteosarcoma cells metastasis. CONCLUSIONS: These results suggest that the combined action of METTL3 and CBX4 plays an important role in the regulation of metastasis of osteosarcoma, and therefore, the METTL3-CBX4 axis pathway may be a new potential therapeutic target for osteosarcoma.

Regulation of soldier caste differentiation by microRNAs in Formosan subterranean termite (Coptotermes formosanus Shiraki).

The soldier caste is one of the most distinguished castes inside the termite colony. The mechanism of soldier caste differentiation has mainly been studied at the transcriptional level, but the function of microRNAs (miRNAs) in soldier caste differentiation is seldom studied. In this study, the workers of Coptotermes formosanus Shiraki were treated with methoprene, a juvenile hormone analog which can induce workers to transform into soldiers. The miRNomes of the methoprene-treated workers and the controls were sequenced. Then, the differentially expressed miRNAs (DEmiRs) were corrected with the differentially expressed genes DEGs to construct the DEmiR-DEG regulatory network. Afterwards, the DEmiR-regulated DEGs were subjected to GO enrichment and KEGG enrichment analysis. A total of 1,324 miRNAs were identified, among which 116 miRNAs were screened as DEmiRs between the methoprene-treated group and the control group. A total of 4,433 DEmiR-DEG pairs were obtained. No GO term was recognized as significant in the cellular component, molecular function, or biological process categories. The KEGG enrichment analysis of the DEmiR-regulated DEGs showed that the ribosome biogenesis in eukaryotes and circadian rhythm-fly pathways were enriched. This study demonstrates that DEmiRs and DEGs form a complex network regulating soldier caste differentiation in termites.

Properties of Cementitious Materials Utilizing Seashells as Aggregate or Cement: Prospects and Challenges.

Nowadays, the sustainable development of the construction industry has become a focus of attention. Crushing and grinding waste seashells originating from the fishery industry, such as oyster shells, cockle shells, mussel shells, and scallop shells, into different particle sizes for usage as aggregate and cement in concrete or mortar provides an effective and sustainable solution to environmental problems by reducing natural resource dependence. Numerous studies have attempted to analyze the suitability of waste seashell as a possible alternative to natural aggregates and cement in concrete or mortar. This paper presents an up-to-date review of the characteristics of different types of waste seashell, as well as the physical, mechanical, durability, and other notable functional properties of seashell concrete or mortar. From the outcome of the research, waste seashell could be an inert material, and it is important to conduct a series of proper treatment for a better-quality material. It is also seen from the results that although the mechanical properties of seashell concrete have been reduced, they all meet the required criteria set by various international standards and codes. Therefore, it is recommended that the replacement of seashells as aggregate and cement should not exceed 20% and 5%, respectively. Seashell concrete or mortar would then have sufficient workability and strength for non-structural purposes. However, there is still a lack of investigation concerning the different properties of reinforced concrete members using seashells as the replacement of aggregate or cement. Further innovative research can solidify its utilization towards sustainable development.

FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta-analysis.

Numerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity-associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle-based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z-score, BMI, waist circumference, waist-to-hip ratio, and body fat percentage after interventions. These obesity-related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random-effect meta-analysis models. The results from single-group interventions showed no evidence of associations between FTO risk allele and changes in obesity-related outcomes after interventions (e.g., BMI Z-score: -0.01; 95% CI: -0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity-related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children.

Effect of liver cancer on the accumulation and hepatobiliary transport of per- and polyfluoroalkyl substances.

In this study, we examined the distribution of per- and polyfluoroalkyl substances (PFASs) in liver and bile tissues from the patients with liver cancer (n = 202) and healthy controls (n = 30), and calculated the hepatobiliary transport efficiency (TB-L) of PFASs. Among 21 PFASs, 13 PFASs were frequently detected in the liver (median: 8.80-16.3 ng/g) and bile (median: 11.03-14.26 ng/mL) samples. PFAS concentrations in liver were positively correlated with age, with higher levels of PFASs in the older. Variance analysis showed that gender and BMI (Body Mass Index) have an important impact on the distribution of PFASs. A U-shaped trend in TB-L of PFASs with the increasing of carbon chain length was found for the first time, and the TB-L of most PFASs in the control was higher than that of those in cases (p < 0.05), suggesting that hepatic injury would affect their transport. PFASs were positively associated with liver injury biomarkers, including γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), and total bilirubin (TB) levels (p < 0.05). This is the first study on examining the hepatobiliary transport characteristics of PFASs, which may help understand the connection between PFAS accumulation and liver cancer risk.

The role of ABCC10/MRP7 in anti-cancer drug resistance and beyond.

Multidrug resistance protein 7 (MRP7), also known as ATP-binding cassette (ABC) transporter subfamily C10 (ABCC10), is an ABC transporter that was first identified in 2001. ABCC10/MRP7 is a 171 kDa protein located on the basolateral membrane of cells. ABCC10/MRP7 consists of three transmembrane domains and two nucleotide binding domains. It mediates multidrug resistance of tumor cells to a variety of anticancer drugs by increasing drug efflux and results in reducing intracellular drug accumulation. The transport substrates of ABCC10/MRP7 include antineoplastic drugs such as taxanes, vinca alkaloids, and epothilone B, as well as endobiotics such as leukotriene C4 (LTC4) and estradiol 17 ß-D-glucuronide. A variety of ABCC10/MRP7 inhibitors, including cepharanthine, imatinib, erlotinib, tariquidar, and sildenafil, can reverse ABCC10/MRP7-mediated MDR. Additionally, the presence or absence of ABCC10/MRP7 is also closely related to renal tubular dysfunction, obesity, and other diseases. In this review, we discuss: 1) Structure and functions of ABCC10/MRP7; 2) Known substrates and inhibitors of ABCC10/MRP7 and their potential therapeutic applications in cancer; and 3) Role of ABCC10/MRP7 in non-cancerous diseases.

Improving the Resolution of Flexible Large-Area Tactile Sensors through Machine-Learning Perception.

Industrial robots are the main piece of equipment of intelligent manufacturing, and array-type tactile sensors are considered to be the core devices for their active sensing and understanding of the production environment. A great challenge for existing array-type tactile sensors is the wiring of sensing units in a limited area, the contradiction between a small number of sensing units and high resolution, and the deviation of the overall output pattern due to the difference in the performance of each sensing unit itself. Inspired by the human somatosensory processing hierarchy, we combine tactile sensors with artificial intelligence algorithms to simplify the sensor architecture while achieving tactile resolution capabilities far greater than the number of signal channels. The prepared 8-electrode carbon-based conductive network achieves high-precision identification of 32 regions with 97% classification accuracy assisted by a quadratic discriminant analysis algorithm. Notably, the output of the sensor remains unchanged after 13,000 cycles at 60 kPa, indicating its excellent durability performance. Moreover, the large-area skin-like continuous conductive network is simple to fabricate, cost-effective, and can be easily scaled up/down depending on the application. This work may address the increasing need for simple fabrication, rapid integration, and adaptable geometry tactile sensors for use in industrial robots.

Paper-based colorimetric sensor using bimetallic Nickel-Cobalt selenides nanozyme with artificial neural network-assisted for detection of H2O2 on smartphone.

Paper-based analytical devices (PADs) integrated with smartphones have shown great potential in various fields, but they also face challenges such as single signal reading, complex data processing and significant environmental impacting. In this study, a colorimetric PAD platform has been proposed using bimetallic nickel-cobalt selenides as highly active peroxidase mimic, smartphone with 3D-printing dark-cavity as a portable detector and an artificial neural network (ANN) model as multi-signal processing tool. Notably, the optimized nickel-cobalt selenides (Ni0.75Co0.25Se with Ni to Co ratio of 3/1) exhibit excellent peoxidase-mimetic activities and are capable of catalyzing the oxidation of four chromogenic reagents in the presence of H2O2. Using a smartphone with image capture function as a friendly signal readout tool, the Ni0.75Co0.25Se based four channel colorimetric sensing paper is used for multi-signal quantitative analysis of H2O2 by determining the Grey, red (R), green (G) and blue (B) channel values of the captured pictures. An intelligent on-site detection method for H2O2 has been constructed by combining an ANN model and a self-programmed easy-to-use smartphone APP with a dynamic range of 5 µM to 2 M. Noteworthy, machine learning-assisted smartphone sensing devices based on nanozyme and 3D printing technology provide new insights and universal strategies for visual ultrasensitive detection in a variety of fields, including environments monitoring, biomedical diagnosis and safety screening.

Inhibition of RhoGEF/RhoA alleviates regorafenib resistance and cancer stemness via Hippo signaling pathway in hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.