Identification and transcriptional response of ATP-binding cassette transporters to beta-cypermethrin in the poultry red mite, Dermanyssus gallinae.

Dermanyssus gallinae, a worldwide pest in birds, has developed varying degrees of resistance to insecticides. The ATP-binding cassette (ABC) transporters are essential for the removal of xenobiotics from arthropods. However, our knowledge about ABC transporter proteins in D. gallinae is limited. Forty ABC transporters were identified in the transcriptome and genome of D. gallinae. The resistant population displayed an augmented metabolic rate for beta-cypermethrin compared to the susceptible group, with a remarkable increase in the content of ABC transporters. Verapamil was found able to increase the toxicity of beta-cypermethrin in the resistant population. Results from qRT-PCR analysis showed that eleven ABC transcripts were more highly expressed in the resistant population than the susceptible group at all stages of development, and beta-cypermethrin was observed to be able to induce the expression of DgABCA5, DgABCB4, DgABCD3, DgABCE1 and DgABCG5 in D. gallinae. RNAi-mediated knockdown of the five genes was observed to increase the susceptibility of resistant mites to beta-cypermethrin. These results suggest that ABC transporters, DgABCA5, DgABCB4, DgABCD3, DgABCE1 and DgABCG5 genes, may be related to beta-cypermethrin resistance in D. gallinae. This research will serve as a foundation for further studies on mechanism of insecticide resistance, which could be beneficial for controlling D. gallinae.

Mediation of FOXA2/IL-6/IL-6R/STAT3 signaling pathway mediates benzo[a]pyrene-induced airway epithelial mesenchymal transformation in asthma.

Benzo [a]pyrene (BaP), a toxic pollutant, increases the incidence and severity of asthma. However, the molecular mechanisms underlying the effects of BaP in asthma remain unclear. In terms of research methods, we used BaP to intervene in the animal model of asthma and the human bronchial epithelial (16HBE) cells, and the involved mechanisms were found from the injury, inflammation, and airway epithelial to mesenchymal transition (EMT) in asthma. We also constructed small interfering RNAs and overexpression plasmids to knockdown/overexpress IL-6R and FOXA2 in 16HBE cells and a serotype 9 adeno-associated viral vector for lung tissue overexpression of FOXA2 in mice to determine the mechanism of action of BaP-exacerbated asthma airway EMT. We observed that BaP aggravated inflammatory cell infiltration into the lungs, reduced the Penh value, increased collagen fibres in the lung tissue, and increased serum IgE levels in asthmatic mice. After BaP intervention, the expression of FOXA2 in the lung tissue of asthmatic mice decreased, the production and secretion of IL-6 were stimulated, and STAT3 phosphorylation and nuclear translocation increased, leading to changes in EMT markers. However, EMT decreased after increasing FOXA2 expression and decreasing that of IL-6R and was further enhanced after low FOXA2 expression. Our results revealed that BaP exacerbated airway epithelial cell injury and interfered with FOXA2, activating the IL-6/IL-6R/STAT3 signaling pathway to promote airway EMT in asthma. These findings provide toxicological evidence for the mechanism underlying the contribution of BaP to the increased incidence of asthma and its exacerbations.

Establishment and validation of a novel disulfidptosis-related immune checkpoint gene signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal tumors and is associated with a unfavorable prognosis. Disulfidptosis is a recently identified form of cell death mediated by disulfide bonds. Numerous studies have highlighted the significance of immune checkpoint genes (ICGs) in ccRCC. Nevertheless, the involvement of disulfidptosis-related immune checkpoint genes (DRICGs) in ccRCC remains poorly understood. METHODS: The mRNA expression profiles and clinicopathological data of ccRCC patients were obtained from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. The associations between disulfidptosis-related genes (DRGs) and immune checkpoint genes (ICGs) were assessed to identify DRICGs. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were conducted to construct a risk signature. RESULTS: A total of 39 differentially expressed immune-related candidate genes were identified. A prognostic signature was constructed utilizing nine DRICGs (CD276, CD80, CD86, HLA-E, LAG3, PDCD1LG2, PVR, TIGIT, and TNFRSF4) and validated using GEO data. The risk model functioned as an independent prognostic indicator for ccRCC, while the associated nomogram provided a reliable scoring system for ccRCC. Gene set enrichment analysis indicated enrichment of phospholipase D, antigen processing and presentation, and ascorbate and aldarate metabolism-related signaling pathways in the high-risk group. Furthermore, the DRICGs exhibited correlations with the infiltration of various immune cells. It is noteworthy that patients with ccRCC categorized into distinct risk groups based on this model displayed varying sensitivities to potential therapeutic agents. CONCLUSIONS: The novel DRICG-based risk signature is a reliable indicator for the prognosis of ccRCC patients. Moreover, it also aids in drug selection and correlates with the tumour immune microenvironment in ccRCC.

Point mutations in the voltage-gated sodium channel gene conferring pyrethroid resistance in China populations of the Dermanyssus gallinae.

BACKGROUND: Dermanyssus gallinae, the poultry red mite (PRM), is a worldwide ectoparasite posing significant economic challenges in poultry farming. The extensive use of pyrethroids for PRM control has led to the emergence of pyrethroid resistance. The objective of this study is to detect the pyrethroid resistance and explore its associated point mutations in the voltage-gated sodium channel (VGSC) gene among PRM populations in China. RESULTS: Several populations of D. gallinae, namely CJF-1, CJP-2, CJP-3, CSD-4 and CLD-5, displayed varying degrees of resistance to beta-cypermethrin compared to a susceptible field population (CBP-5). Mutations of VGSC gene in populations of PRMs associated with pyrethroid resistance were identified through sequencing its fragments IIS4-IIS5 and IIIS6. The mutations I917V, M918T/L, A924G and L925V were present in multiple populations, while no mutations were found at positions T929, I936, F1534 and F1538. CONCLUSION: The present study confirmed the presence of extremely high levels of pyrethroid resistance in PRM populations in China, and for the first time detected four pyrethroid resistance mutations in the VGSC gene. Identifying pyrethroid resistance in the field population of PRM in China can be achieved through screening for VGSC gene mutations as an early detection method. Our findings underscore the importance of implementing chemical PRM control strategies based on resistance evidence, while also considering the management of acaricide resistance in the control of PRMs. © 2024 Society of Chemical Industry.

No causal association between insomnia and bladder cancer: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Previous observational studies have indicated a potential link between insomnia and bladder cancer, yet the underlying causal relationship remains uncertain. The current study employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate this association. METHODS: A two-sample MR analysis was conducted utilizing publicly available summary data from genome-wide association studies (GWAS) on insomnia and bladder cancer. Various regression methods including the inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode methods were employed for the MR analysis. The presence of pleiotropy and heterogeneity in the MR results was also assessed. Furthermore, additional sensitivity tests were performed to mitigate potential biases. RESULTS: No significant causal relationship was detected between insomnia and bladder cancer using IVW method (OR = 0.761, 95% CI 0.996-1.005; P = 0.76). Similarly, the IVW model did not reveal any causal effect of bladder cancer on the risk of insomnia (OR = 1.47, 95% CI 0.772-2.799; P = 0.24). Consistent results were obtained from the other four methods employed. There was no evidence of horizontal pleiotropy or heterogeneity in our MR analysis (P > 0.05). The sensitivity analyses further supported the reliability of the estimated causal effects. CONCLUSIONS: This study presents no evidence for a causal relationship between insomnia and bladder cancer.

Band-like transport in solution-processed perylene diimide dianion films with high Hall mobility.

It is crucial to prepare high-mobility organic polycrystalline film through solution processing. However, the delocalized carrier transport of polycrystalline films in organic semiconductors has rarely been investigated through Hall-effect measurement. This study presents a strategy for building strong intermolecular interactions to fabricate solution-crystallized p-type perylene diimide (PDI) dianion films with a closer intermolecular π-π stacking distance of 3.25 Å. The highly delocalized carriers enable a competitive Hall mobility of 3 cm2 V-1 s-1, comparable to that of the reported high-mobility organic single crystals. The PDI dianion films exhibit a high electrical conductivity of 17 S cm-1 and typical band-like transport, as evidenced by the negative temperature linear coefficient of mobility proportional to T-3/2. This work demonstrates that, as the intermolecular π-π interactions become strong enough, they will display high mobility and conductivity, providing a new approach to developing high-mobility organic semiconductor materials.

Examining the causal association between psoriasis and bladder cancer: A two-sample Mendelian randomization analysis.

BACKGROUND: Previous epidemiological observational studies have potentially associated psoriasis with bladder cancer, but the results are inconsistent, and the causality remains unknown. The present study aimed to examine whether there are causal associations between psoriasis and bladder cancer using bidirectional two-sample Mendelian randomization (MR) analysis. MATERIALS AND METHODS: A two-sample MR analysis was conducted using publicly available genome-wide association study (GWAS) data for individuals diagnosed with psoriasis and bladder cancer. The inverse variance weighted (IVW) method was the primary method. The complementary methods used included the weighted median, MR-Egger, weighted mode, and simple mode methods. Heterogeneity and pleiotropy of the MR results were detected. Moreover, leave-one-out sensitivity analysis was also employed to evaluate the robustness and validity of the findings. RESULTS: No significant causal association was detected between psoriasis incidence and the risk of bladder cancer using the IVW method (OR = 0.999, 95% CI 0.977-1.022; P = 0.956). Similarly, the IVW model revealed no evidence of a causal relationship between bladder cancer and the risk of psoriasis (OR = 0.979, 95%CI = 0.873-1.098; P = 0.716). The results of the complementary methods were consistent with those of the IVW method. There was no notable horizontal pleiotropy or heterogeneity (P > 0.05) in our MR analysis. The results of sensitivity analysis confirmed that the MR estimates were not driven by single-nucleotide polymorphisms (SNPs). CONCLUSION: This study does not support a causal relationship between psoriasis and bladder cancer.

A group-targeting biosensor for sensitive and rapid detection of quinolones in water samples.

BACKGROUND: Quinolones (QNs) widely exist in the environment due to their wide range of applications and poor metabolic properties, resulting in the generation and spread of resistance genes, posing a potential threat to human health. Traditional analytical methods cannot detect all broad ranges of QNs simultaneously. The development of facile, efficient and reliable method for quantification and assessment of the total QNs is a long-lasting challenge. RESULTS: We hereby provide a simple, sensitive and instantaneous group-targeting biosensor for the detection of total QNs in environmental water samples. The biosensor is based on a group-specific antibodies with high affinity against QNs. Fluorescent labeled antibodies bound to the coated antigen modified on the surface of the transducer, and excited by the evanescent waves. The detected fluorescent signal is inversely proportional to the QNs concentration. This biosensor exhibited excellent performance with detection limits lower than 0.15 µg L-1 for all five QNs variants, and even lower than 0.075 µg L-1 for ciprofloxacin (CIP) and ofloxacin (OFL). Environmental water samples can be detected after simple pretreatment, and all detection steps can be completed in 10 min. The transducer has a high regenerative capacity and shows no significant signal degradation after two hundred detection cycles. The recoveries of QNs in a variety of wastewater range from 105 to 119%, confirming its application potential in the measurement of total QNs in reality. SIGNIFICANCE: The biosensor can realize rapid and sensitive detection of total QNs in water samples by simple pretreatment, which overcomes the disadvantage of the traditional methods that require complex pretreatment and time-consuming, and pave the groundwork for expansive development centered around this technology.

Activation of CncC pathway by ROS burst regulates ABC transporter responsible for beta-cypermethrin resistance in Dermanyssus gallinae (Acari:Dermanyssidae).

The drug resistance of poultry red mites to chemical acaricides is a global issue in the control of the mites, which presents an ongoing threat to the poultry industry. Though the increased production of detoxification enzymes has been frequently implicated in resistance development, the overexpression mechanism of acaricide-resistant related genes in mites remains unclear. In the present study, it was observed that the transcription factor Cap 'n' Collar isoform-C (CncC) and its partner small muscle aponeurosis fibromatosis (Maf) were highly expressed in resistant strains compared to sensitive strains under the stress of beta-cypermethrin. When the CncC/Maf pathway genes were down-regulated by RNA interference (RNAi), the expression of the ABC transporter genes was down-regulated, leading to a significant increase in the sensitivity of resistant strains to beta-cypermethrin, suggesting that CncC/Maf played a crucial role in mediating the resistance of D.gallinae to beta-cypermethrin by regulating ABC transporters. Furthermore, it was observed that the content of H2O2 and the activities of peroxidase (POD) and catalase (CAT) enzymes were significantly higher in resistant strains after beta-cypermethrin stress, indicating that beta-cypermethrin activates reactive oxygen species (ROS). In ROS scavenger assays, it was found that the expression of CncC/Maf significantly decreased, along with a decrease in the ABC transporter genes. The present study showed that beta-cypermethrin seemed to trigger the outbreak of ROS, subsequently activated the CncC/Maf pathway, as a result induced the ABC transporter-mediated resistance to the drug, shedding more light on the resistance mechanisms of D.gallinae to pyrethroids.

One-step synthesis of N, S-doped carbon dots with green emission and their application in 4-NP detection, pH sensing, and cell imaging.

Using p-aminophenol and dithioacetamide as precursors, green luminescent nitrogen (N) and sulfur (S) co-doped carbon dots (N, S-CDs) are prepared by hydrothermal method with the quantum yield (QY) of 7.1 %. Superior properties of the N, S-CDs including high photostability, outstanding biocompatibility, and desirable biological penetration were found, which could realize the monitor of 4-nitrophenol (4-NP) and pH. The N, S-CDs can be designed as a fluorescent probe for sensitive detection of 4-NP in water samples with linear ranges of 0-85 µM and a detection limit of 0.037 µM. Moreover, the fluorescence intensity of N, S-CDs is sensitive to pH and shows a linear relationship with pH values ranging from 3.50 to 7.25 and 7.25-12.00, accompanied with a significant color variation of the N, S-CDs solution from colorless to brown. Finally, the proposed N, S-CDs have also been applied to monitor the 4-NP in oocysts due to its low cytotoxicity, providing a great capacity for various targets molecules detection.

Extremely Stable Perylene Bisimide-Bridged Regioisomeric Diradicals and Their Redox Properties.

Excellent stability is an essential premise for organic diradicals to be used in organic electronic and spintronic devices. We have attached two tris(2,4,6-trichlorophenyl)methyl (TTM) radical building blocks to the two sides of perylene bisimide (PBI) bridges and obtained two regioisomeric diradicals (1,6-TTM-PBI and 1,7-TTM-PBI). Both of the isomers show super stability rather than the monomeric TTM under ambient conditions, due to the increased conjugation and the electron-withdrawing effects of the PBI bridges. The diradicals show distinct and reversible multistep redox processes, and a spectro-electrochemistry investigation revealed the generation of organic mixed-valence (MV) species during reduction processes. The two diradicals have singlet ground states, very small singlet-triplet energy gaps (ΔES-T ) and a pure open-shell character (with diradical character y0 =0.966 for 1,6-TTM-PBI and 0.967 for 1,7-TTM-PBI). This work opens a window to developing very stable diradicals and offers the opportunity of their further application in optical, electronic and magnetic devices.

A novel cuproptosis-related prognostic gene signature in adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor associated with poor outcomes. Cuproptosis, a new pattern of cell death, relies on mitochondrial respiration and is associated with protein lipoylation. Increasing evidence has demonstrated the potential roles of cuproptosis in several tumor entities. However, the relationship between cuproptosis and ACC remains unclear. METHODS: In total, 10 cuproptosis-related genes (CRGs) of patients with ACC were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and differential expression analysis of CRGs was analyzed. Functional enrichment of the CRGs was performed and protein-protein interaction analysis was utilized to explore the association between the CRGs. Cuproptosis-related risk score (CRRS) was constructed by Lasso Cox regression and validated. RESULTS: In the current study, the alteration and expression patterns of 10 CRGs in TCGA-ACC datasets were analyzed. We identified different expression patterns of CRGs in ACCs, discovered strong associations between CRGs and ACCs, and found that the CRGs were associated with immune infiltration in ACCs. A CRRS was created thereafter to predict overall survival (OS). CRRS = (0.083103718) *FDX1 + (-0.278423862) *LIAS+(0.090985682) *DLAT+(-0.018784047) *PDHA1 + (0.297218951) *MTF1 + (0.310197964) *CDKN2A. Patients were divided into high- and low-risk groups based on their CRRS, and independent prognostic factors were investigated. Finally, CDKN2A and FDX1 were found to be independent prognostic predictors of patients with ACC. CONCLUSIONS: CDKN2A and FDX1 are independent prognostic predictors of patients with ACC. Cuproptosis may play a role in the development of ACC, providing a new perspective on therapeutic strategies related to CRGs for cancer prevention and treatment.

Toltrazuril alkalizer-modifying solid dispersions against Toxoplasma gondii: A pharmacotechnical strategy to improve the efficacy of the drug.

Toxoplasma gondii is a zoonotic protozoan that can parasitize nucleated cells of all warm-blooded animals, and seriously harm human and livestock. Toltrazuril (TOL) has insecticidal activity against parasites of the phylum Apicomplexan at multiple development stages, but the clinical application is limited by its poor water solubility. To improve the dissolution of TOL, nine ternary solid dispersions (SD) were prepared with PEG6000 as the carrier and various alkalizers as the pH modifier. Compared with the binary SD, all ternary SDs had improved TOL dissolution although dissolution rates differed. The complete dissolution was achieved for the Ca(OH)2-SD, associated with a gradual release of the alkalizer and adequate pH regulation of the microenvironment. DSC, PXRD and FTIR analyses indicated that TOL in the Ca(OH)2-SD was present in an amorphous form and had a strong hydrogen bond with Ca(OH)2. Within the drug concentration of 100 µg/mL, Ca(OH)2-SD was proved to have no damage to host cells by in vitro cytotoxicity analysis, and its anti-T. gondii efficacy was significantly higher than that of TOL and binary SD. The in vivo efficacy of Ca(OH)2-SD against T. gondii in mice further confirmed that Ca(OH)2-SD could be used as a new strategy to prevent T. gondii from killing mice and treat toxoplasmosis. In conclusion, Ca(OH)2-SD is expected to eventually turn into a clinical candidate for toxoplasmosis treatment in the future.

Combined use of microbubbles of various sizes and single-transducer dual-frequency ultrasound for safe and efficient inner ear drug delivery.

We have previously applied ultrasound (US) with microbubbles (MBs) to enhance inner ear drug delivery, with most experiments conducted using single-frequency, high-power density US, and multiple treatments. In the present study, the treatment efficacy was enhanced and safety concerns were addressed using a combination of low-power-density, single-transducer, dual-frequency US (I SPTA = 213 mW/cm2) and MBs of different sizes coated with insulin-like growth factor 1 (IGF-1). This study is the first to investigate the drug-coating capacity of human serum albumin (HSA) MBs of different particle sizes and their drug delivery efficiency. The concentration of HSA was adjusted to produce different MB sizes. The drug-coating efficiency was significantly higher for large-sized MBs than for smaller MBs. In vitro Franz diffusion experiments showed that the combination of dual-frequency US and large MB size delivered the most IGF-1 (24.3 ± 0.47 ng/cm2) to the receptor side at the second hour of treatment. In an in vivo guinea pig experiment, the efficiency of IGF-1 delivery into the inner ear was 15.9 times greater in animals treated with the combination of dual-frequency US and large MBs (D-USMB) than in control animals treated with round window soaking (RWS). The IGF-1 delivery efficiency was 10.15 times greater with the combination of single-frequency US and large size MBs (S-USMB) than with RWS. Confocal microscopy of the cochlea showed a stronger distribution of IGF-1 in the basal turn in the D-USMB and S-USMB groups than in the RWS group. In the second and third turns, the D-USMB group showed the greatest IGF-1 distribution. Hearing assessments revealed no significant differences among the D-USMB, S-USMB, and RWS groups. In conclusion, the combination of single-transducer dual-frequency US and suitably sized MBs can significantly reduce US power density while enhancing the delivery of large molecular weight drugs, such as IGF-1, to the inner ear.

A drug co-delivery platform made of magnesium-based micromotors enhances combination therapy for hepatoma carcinoma cells.

Combination therapy is an emerging strategy to overcome multidrug resistance (MDR) in hepatocellular carcinoma (HCC) chemotherapy treatment. However, the passive diffusion in traditional delivery systems greatly retards the approach and penetration of drugs into hepatocellular carcinoma cells and thus hinders the efficacy of combination therapy. Micro/nanomotors with autonomous locomotion in a tiny scale provide the possibility of tackling this issue. Herein, an active drug delivery micromotor platform delicately designed to load drugs with different physicochemical properties and enhance the drug permeability of cells is demonstrated for HCC chemotherapy treatment. The biocompatible micromotor platform Mg/PLGA/CHI comprised magnesium (Mg) coated with two polymer layers made of poly(lactic-co-glycolic acid) (PLGA) and chitosan (CHI), where the hydrophobic and hydrophilic drugs doxorubicin (Dox) and Curcumin (Cur) were loaded, respectively. The autonomous motion of the micromotors with velocity up to 45 µm s-1 greatly enhanced the diffusion of chemotherapeutic drugs and led to higher extracellular and intracellular drug distribution. Moreover, hydrogen produced during the motion eliminated the excess reactive oxygen species (ROS) in the human hepatocellular carcinoma (HepG2) cells. Compared with inert groups, the absorption of Dox and Cur from the active micromotors was about 2.9 and 1.5 times higher in human hepatocellular carcinoma (HepG2) cells. In addition, the anti-tumor activity also obviously improved at the micromotor concentration of 1 mg mL-1 (cell proliferation was reduced by almost 30%). Overall, this work proposes an approach based on loading different chemotherapy agents on an active delivery system to enhance drug permeability and overcome MDR and provides a potentially effective therapeutic strategy for the treatment of HCC.

Acaricidal activity of bioactive compounds isolated from Aspergillus oryzae against poultry red mites, Dermanyssus gallinae (Acari: Dermanyssidae).

Dermanyssus gallinae, the poultry red mite (PRM), is an obligate ectoparasite feeding on poultry blood, seriously affecting the health of layers and egg production. The control of PRMs mainly relies on chemical drugs, which is facing several challenges such as the environment pollution and drug resistance. Using fungal metabolites is an environmentally friendly alternative for the control of pests. However, few studies have been conducted on the efficacy of fungal metabolites against D. gallinae. In this study, five strains of fungi were isolated from D. gallinae under laboratory conditions, and their extracts with ethyl acetate were tested for acaricidal activity on D. gallinae. The crude extract of Aspergillus oryzae caused 75.55 ± 6.94% mortality of mites at a concentration of 12.5 mg/mL, showing the highest acaricidal effect in all extracts. Subsequently, the extract of A. oryzae was isolated by bio-guided fractionation, and ten major compounds were identified by LC-MS/MS analysis. The results of bioassays indicated that five compounds exhibited acaricidal activity against D. gallinae. N, N-dimethyldecylamine N-oxide was the optimal acaricidal compound with LC50 of 0.568 mg/mL. Additionally, palmitic acid, triethanolamine, cuminaldehyde, and 2,4-dimethylbenzaldehyde also showed acaricidal activity. These compounds have great application potential in the mite control, and the analysis of these fungal acaricidal substances provides a new idea and basis for the subsequent development of PRM control technology.

EZH2 in hepatocellular carcinoma: progression, immunity, and potential targeting therapies.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death. The accumulation of genetic and epigenetic changes is closely related to the occurrence and development of HCC. Enhancer of zeste homolog 2 (EZH2, a histone methyltransferase) is suggested to be one of the principal factors that mediates oncogenesis by acting as a driver of epigenetic alternation. Recent studies show that EZH2 is widely involved in proliferation and metastasis of HCC cells. In this review, the functions of EZH2 in HCC progression, the role of EZH2 in tumor immunity and the application of EZH2-related inhibitors in HCC therapy are summarized.

Large-Strain Surface Modeling Using Plasticity.

Modeling arbitrarily large deformations of surfaces smoothly embedded in three-dimensional space is challenging. We give a new method to represent surfaces undergoing large spatially varying rotations and strains, based on differential geometry, and surface first and second fundamental forms. Methods that penalize the difference between the current shape and the rest shape produce sharp spikes under large strains, and variational methods produce wiggles, whereas our method naturally supports large strains and rotations without any special treatment. For stable and smooth results, we demonstrate that the deformed surface has to locally satisfy compatibility conditions (Gauss-Codazzi equations) on the first and second fundamental forms. We then give a method to locally modify the surface first and second fundamental forms in a compatible way. We use those fundamental forms to define surface plastic deformations, and finally recover output surface vertex positions by minimizing the surface elastic energy under the plastic deformations. We demonstrate that our method makes it possible to smoothly deform triangle meshes to large spatially varying strains and rotations, while meeting user constraints.

EDC-DTI: An end-to-end deep collaborative learning model based on multiple information for drug-target interactions prediction.

Innovations in drug-target interactions (DTIs) prediction accelerate the progression of drug development. The introduction of deep learning models has a dramatic impact on DTIs prediction, with a distinct influence on saving time and money in drug discovery. This study develops an end-to-end deep collaborative learning model for DTIs prediction, called EDC-DTI, to identify new targets for existing drugs based on multiple drug-target-related information including homogeneous information and heterogeneous information by the way of deep learning. Our end-to-end model is composed of a feature builder and a classifier. Feature builder consists of two collaborative feature construction algorithms that extract the molecular properties and the topology property of networks, and the classifier consists of a feature encoder and a feature decoder which are designed for feature integration and DTIs prediction, respectively. The feature encoder, mainly based on the improved graph attention network, incorporates heterogeneous information into drug features and target features separately. The feature decoder is composed of multiple neural networks for predictions. Compared with six popular baseline models, EDC-DTI achieves highest predictive performance in the case of low computational costs. Robustness tests demonstrate that EDC-DTI is able to maintain strong predictive performance on sparse datasets. As well, we use the model to predict the most likely targets to interact with Simvastatin (DB00641), Nifedipine (DB01115) and Afatinib (DB08916) as examples. Results show that most of the predictions can be confirmed by literature with clear evidence.

Temperature changes of renal calyx during high-power flexible ureteroscopic Moses holmium laser lithotripsy: a case analysis study.

PURPOSE: The risk of thermal damage increases with the introduction of high-power lasers during holmium laser lithotripsy. This study aimed to quantitatively evaluate the temperature change of renal calyx in the human body and the 3D printed model during high-power flexible ureteroscopic holmium laser lithotripsy and map out the temperature curve. METHODS: The temperature was continuously measured by a medical temperature sensor secured to a flexible ureteroscope. Between December 2021 and December 2022, willing patients with kidney stones undergoing flexible ureteroscopic holmium laser lithotripsy were enrolled. High frequency and high-power settings (24 W, 80 Hz/0.3 J and 32 W, 80 Hz/0.4 J) were performed for each patient with room temperature (25 °C) irrigation. In the 3D printed model, we studied more holmium laser settings (24 W, 80 Hz/0.3 J, 32 W, 80 Hz/0.4 J and 40 W, 80 Hz/0.4 J) with warmed (37 °C) and room temperature (25 °C) irrigation. RESULTS: Twenty-two patients were enrolled in our study. With 30 ml/min or 60 ml/min irrigation, the local temperature of the renal calyx did not reach 43 °C in any patient under 25 °C irrigation after 60 s laser activation. There were similar temperature changes in the 3D printed model with the human body under the irrigation of 25 °C. Under the irrigation of 37 °C, the temperature rise slowed down, but the temperature in the renal calyces was close to or even exceeded the 43 °C at the setting of 32 W, 30 ml/min and 40 W, 30 ml/min after continuing laser activation. CONCLUSION: In the irrigation of 60 ml/min, the temperature in the renal calyces can still be maintained within a safe range after continuous activation of a holmium laser up to 40 W. However, continuous activation of 32 W or higher power holmium laser in the renal calyces for more than 60 s in the limited irrigation of 30 ml/min can cause excessive local temperature, in such situation room temperature perfusion at 25 ℃ may be a relatively safer option.