Printed Self-Healing Stretchable Electronics for Bio-signal Monitoring and Intelligent Packaging.

Integrating self-healing capabilities into printed stretchable electronic devices is important for improving performance and extending device life. However, achieving printed self-healing stretchable electronic devices with excellent device-level healing ability and stretchability while maintaining outstanding electrical performance remains challenging. Herein, a series of printed device-level self-healing stretchable electronic devices is achieved by depositing liquid metal/silver fractal dendrites/polystyrene-block-polyisoprene-block-polystyrene (LM/Ag FDs/SIS) conductive inks onto a self-healing thermoplastic polyurethane (TPU) film via screen printing method. Owing to the fluidic properties of the LM and the interfacial hydrogen bonding and disulfide bonds of TPU, the as-obtained stretchable electronic devices maintain good electronic properties under strain and exhibit device-level self-healing properties without external stimulation. Printed self-healing stretchable electrodes possess high electrical conductivity (1.6 × 105 S m-1), excellent electromechanical properties, and dynamic stability, with only a 2.5-fold increase in resistance at 200% strain, even after a complete cut and re-healing treatment. The printed self-healing capacitive stretchable strain sensor shows good linearity (R2 ≈0.9994) in a wide sensing range (0%-200%) and is successfully applied to bio-signal detection. Furthermore, the printed self-healing electronic smart label is designed and can be used for real-time environmental monitoring, which exhibits promising potential for practical application in food preservation packaging.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Tyrosine Mutation in the Characteristic Motif of the Amorphous Region of Spidroin for Self-Assembly Capability Enhancement.

Spidroin, with robust mechanical performance and good biocompatibility, could fulfill broad applications in material science and biomedical fields. Development of miniature spidroin has made abundant fiber production economically feasible, but the mechanical properties of artificial silk still fall short of natural silk. The mechanism behind mechanical properties of spidroin usually focuses on ß-microcrystalline regions; the effect of amorphous regions was barely studied. In this study, residue tyrosines (Y) were designed to replace asparagine (N)/glutamic acid (Q) in the characteristic motifs (GGX)n in amorphous regions for performance enhancement of spidroin; the mutants presented lower free energy and significantly exhibited stronger van der Waals and electrostatic interactions, which might result from π-π stacking interactions between the phenyl rings in the side chain of tyrosine. Additionally, the soluble expressions of wild-type spidroin and mutant spidroin were achieved when heterologously expressed in E. coli, with yields of 560 mg/L (2REP), 590 mg/L (2REPM), 240 mg/L (4REP), and 280 mg/L (4REPM). Significantly, secondary structure analysis confirmed that the mutant spidroin more avidly forms more ß-sheets than the wild-type spidroin, and aggregation morphology suggested that mutant spidroin displayed better self-assembly capacity and was easier to form artificial spider silk fibers; in particular, self-assembled 4REPM nanofibrils had an average modulus of 11.2 ± 0.35 GPa, about 2 times higher than self-assembled B. mori silk nanofibrils and almost the same as that of native spider dragline silk fibers (10-15 GPa). Thus, we first demonstrated a new influence mechanism of the amorphous region's characteristic motif on the self-assembly and material properties of spidroin. Our study provides a reference for the design of high-performance material proteins and their heterologous preparation.

The positive impact of smoking on poor sleep quality is moderated by IGF1 levels in cerebrospinal fluid: a case-control study among Chinese adults.

Objective: Previous research indicates associations between cigarette smoking, insulin-like growth factor-1 (IGF1), and sleep disturbances. This study aimed to examine the association between smoking and sleep quality and investigate the moderating role of IGF1. Methods: This case-control study involved 146 Chinese adult males (53 active smokers and 93 non-smokers) from September 2014 to January 2016. Sleep quality and disturbances were evaluated using the Pittsburgh Sleep Quality Index (PSQI), which includes seven scales. Pearson correlation analysis and logistic regression analysis were utilized to examine the link between IGF1 levels in cerebrospinal fluid (CSF) and PSQI scores. The effect of IGF1 was assessed using the moderation effect and simple slope analysis, with adjustments made for potential confounders. Results: Active smokers exhibited significantly higher global PSQI scores and lower IGF1 levels in CSF compared to non-smokers. A significant negative correlation was observed between IGF1 and PSQI scores (â = -0.28, P < 0.001), with a stronger association in non-smokers (Pearson r = -0.30) compared to smokers (Pearson r = -0.01). Smoking was associated with higher global PSQI scores (â = 0.282, P < 0.001), and this association was moderated by IGF1 levels in CSF (â = 0.145, P < 0.05), with a stronger effect at high IGF1 levels (Bsimple = 0.402, p < 0.001) compared to low IGF1 levels (Bsimple = 0.112, p = 0.268). Four subgroup analysis revealed similar results for sleep disturbances (Bsimple = 0.628, P < 0.001), with a marginal moderation effect observed on subjective sleep quality (Bsimple = 0.150, P = 0.070). However, independent associations rather than moderating effects were observed between IGF1 and sleep efficiency and daytime disturbance. Conclusion: We provided evidence to demonstrate the moderation effect of IGF1 on the relationship between smoking and sleep in CSF among Chinese adult males.

Identification and validation of a prognostic anoikis-related gene signature in papillary thyroid carcinoma by integrated analysis of single-cell and bulk RNA-sequencing.

Papillary thyroid carcinoma (PTC) prognosis may be deteriorated due to the metastases, and anoikis palys an essential role in the tumor metastasis. However, the potential effect of anoikis-related genes on the prognosis of PTC was unclear. The mRNA and clinical information were obtained from the cancer genome atlas database. Hub genes were identified and risk model was constructed using Cox regression analysis. Kaplan-Meier (K-M) curve was applied for the survival analysis. Immune infiltration and immune therapy response were calculated using CIBERSORT and TIDE. The identification of cell types and cell interaction was performed by Seurat, SingleR and CellChat packages. GO, KEGG, and GSVA were applied for the enrichment analysis. Protein-protein interaction network was constructed in STRING and Cytoscape. Drug sensitivity was assessed in GSCA. Based on bulk RNA data, we identified 4 anoikis-related risk signatures, which were oncogenes, and constructed a risk model. The enrichment analysis found high risk group was enriched in some immune-related pathways. High risk group had higher infiltration of Tregs, higher TIDE score and lower levels of monocytes and CD8 T cells. Based on scRNA data, we found that 4 hub genes were mainly expressed in monocytes and macrophages, and they interacted with T cells. Hub genes were significantly related to immune escape-related genes. Drug sensitivity analysis suggested that cyclin dependent kinase inhibitor 2A may be a better chemotherapy target. We constructed a risk model which could effectively and steadily predict the prognosis of PTC. We inferred that the immune escape may be involved in the development of PTC.

Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol.

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

Pre-sliding of the femoral neck system to prevent postoperative shortening of femoral neck fractures.

Objective: The purpose of this study is to evaluate the effect of pre-sliding of the femoral neck system (FNS) in the prevention of postoperative femoral neck shortening in femoral neck fractures. Method: This study was designed to retrospectively analyze data from 109 patients with femoral neck fractures who were admitted to a Level I trauma center between April 2020 and June 2022. Of these patients, 90 were followed up for more than 12 months. The study included 52 males and 38 females, with 35 cases of Garden I and II fractures and 55 cases of Garden III and IV fractures. The Harris Hip Score at 12 months postoperatively were recorded. The patients were divided into two groups based on their surgical records and postoperative radiography: the Pre-sliding group and the No-pre-sliding group. The purpose of this study is to analyze the role of pre-sliding in preventing femoral neck shortening, fracture healing time, degree of postoperative shortening, complications, and Harris Hip Score, and to make a comparison between the two groups. Results: All 90 patients were followed up for over one year after surgery. A statistically significant difference was observed in the preoperative Garden classification (P < 0.05). At 1 year after the operation, the shortening distance was 6.5 ± 6.4 mm in the No-pre-sliding group and 3.9 ± 3.4 mm in the Pre-sliding group. The Harris Hip Score were 88.7 (79.8, 93.5) in the No-pre-sliding group and 94.8 (87.7, 96.9) in the Pre-sliding group, with a statistically significant difference between the two groups (P < 0.05). Shortening was concentrated at 3 months postoperatively and reached a stable state within 6 months, with less persistent shortening occurring after 6 months. There was no statistically significant difference in the preoperative baseline data. Conclusion: Pre-sliding of the FNS prevents postoperative shortening of the femoral neck and improves hip function as measured by the Harris Hip Score.

[Inhibition of Autophagy Augments the Anticancer Activity of KPT-330 in Mantle Cell Lymphoma Cells].

OBJECTIVE: To investigate the influence of novel CRM1 inhibitor KPT-330 on the autophagy of mantle cell lymphoma (MCL) cells, and effect of KPT-330 on the prolifiration of MCL cells in the presence or absence of autophagy inhibitor. METHODS: CCK-8 assay was used to detect the effect of KPT-330 on MCL cell lines Z-138， Jeko-1， Granta-519， Rec-1. The effect of KPT-330 on autophagy features were determined by detecting acidic vesicular organelles (AVO) by MDC staining under fluorescence microscope and detecting protein expression of LC3B-II assessed by Western blot. Further combined application of lysosomal inhibitor Chloroquine (CQ) was used to observe its effect on the increase of LC3B-Ⅱ caused by KPT-330. CalcuSyn 2.0 software was used to detected the Combination index (CI) of KPT-330 combined with CQ. RESULTS: The proliferation of MCL cell lines （Z-138, Jeko-1, Grant-519, Rec-1） could be inhibited by KPT-330 in a dose-dependent manner (r =0.930, 0.946, 0.691, 0.968 respectively). The number of acidic vesicular organelles (AVO) and the expression of LC3B-II were increased in KPT-330 treated Jeko-1 and Granta-519 cells in a dose-dependent manner (r Jeko-1=0.993, r Granta-519=0.971). LC3B-II protein amounts still increased upon KPT-330 treatment with the existence of lysosomal inhibitor CQ in Jeko-1 and Granta-519 cells, which was higher than CQ or KPT-330 single drug group. The combination of KPT-330 and CQ produced the synergistic effects on cells proliferation inhibition with CalcuSyn 2.0 analysis. CONCLUSION: KPT-330 can inhibit MCL cell proliferation and induce autophagy. KPT-330 combined with autophagy inhibitor CQ could produce synergistic anti MCL effects, providing experimental basis for clinical combination therapy.

Development of a Human B7-H3-Specific Antibody with Activity against Colorectal Cancer Cells through a Synthetic Nanobody Library.

Nanobodies have emerged as promising tools in biomedicine due to their single-chain structure and inherent stability. They generally have convex paratopes, which potentially prefer different epitope sites in an antigen compared to traditional antibodies. In this study, a synthetic phage display nanobody library was constructed and used to identify nanobodies targeting a tumor-associated antigen, the human B7-H3 protein. Combining next-generation sequencing and single-clone validation, two nanobodies were identified to specifically bind B7-H3 with medium nanomolar affinities. Further characterization revealed that these two clones targeted a different epitope compared to known B7-H3-specific antibodies, which have been explored in clinical trials. Furthermore, one of the clones, dubbed as A6, exhibited potent antibody-dependent cell-mediated cytotoxicity (ADCC) against a colorectal cancer cell line with an EC50 of 0.67 nM, upon conversion to an Fc-enhanced IgG format. These findings underscore a cost-effective strategy that bypasses the lengthy immunization process, offering potential rapid access to nanobodies targeting unexplored antigenic sites.

Deoxynivalenol Inhibits Progenitor Leydig Cell Development by Stimulating Mitochondrial Fission in Rats.

Deoxynivalenol (DON) is a common food contaminant that can impair male reproductive function. This study investigated the effects and mechanisms of DON exposure on progenitor Leydig cell (PLC) development in prepubertal male rats. Rats were orally administrated DON (0-4 mg/kg) from postnatal days 21-28. DON increased PLC proliferation but inhibited PLC maturation and function, including reducing testosterone levels and downregulating biomarkers like HSD11B1 and INSL3 at ≥2 mg/kg. DON also stimulated mitochondrial fission via upregulating DRP1 and FIS1 protein levels and increased oxidative stress by reducing antioxidant capacity (including NRF2, SOD1, SOD2, and CAT) in PLCs in vivo. In vitro, DON (2-4 µM) inhibited PLC androgen biosynthesis, increased reactive oxygen species production and protein levels of DRP1, FIS1, MFF, and pAMPK, decreased mitochondrial membrane potential and MFN1 protein levels, and caused mitochondrial fragmentation. The mitochondrial fission inhibitor mdivi-1 attenuated DON-induced impairments in PLCs. DON inhibited PLC steroidogenesis, increased oxidative stress, perturbed mitochondrial homeostasis, and impaired maturation. In conclusion, DON disrupts PLC development in prepubertal rats by stimulating mitochondrial fission.

Carbon-chain length determines the binding affinity and inhibitory strength of per- and polyfluoroalkyl substances on human and rat steroid 5α-reductase 1 activity.

Per- and polyfluoroalkyl substances (PFAS) are widely used synthetic chemicals that persist in the environment and bioaccumulate in animals and humans. There is growing evidence that PFAS exposure adversely impacts neurodevelopment and neurological health. Steroid 5α-reductase 1 (SRD5A1) plays a key role in neurosteroidogenesis by catalyzing the conversion of testosterone or pregnenolone to neuroactive steroids, which influence neural development, cognition, mood, and behavior. This study investigated the inhibitory strength and binding interactions of 18 PFAS on human and rat SRD5A1 activity using enzyme assays, molecular docking, and structure-activity relationship analysis. Results revealed that C9-C14 PFAS carboxylic acid at 100 µM significantly inhibited human SRD5A1, with IC50 values ranged from 10.99 µM (C11) to 105.01 µM (C14), and only one PFAS sulfonic acid (C8S) significantly inhibited human SRD5A1 activity, with IC50 value of 8.15 µM. For rat SRD5A1, C9-C14 PFAS inhibited rat SRD5A1, showing the similar trend, depending on carbon number of the carbon chain. PFAS inhibit human and rat SRD5A1 in a carbon chain length-dependent manner, with optimal inhibition around C11. Kinetic studies indicated PFAS acted through mixed inhibition. Molecular docking revealed PFAS bind to the domain between NADPH and testosterone binding site of both SRD5A1 enzymes. Inhibitory potency correlated with physicochemical properties like carbon number of the carbon chain. These findings suggest PFAS may disrupt neurosteroid synthesis and provide insight into structure-based inhibition of SRD5A1.

Comparison of femoral neck shortening after femoral neck system and cannulated cancellous screw fixation for displaced femoral neck fractures in young adults.

BACKGROUND: The purpose of this study was to compare the outcomes of femoral neck shortening between the femoral neck system (FNS) and the cannulated cancellous screws (CCS) for displaced femoral neck fractures in young adults PATIENTS AND METHODS: In this retrospective analysis, 225 patients aged 18-65 years with displaced femoral neck fracture were divided into two groups according to internal fixation: 135 patients in the FNS group and 90 patients in the CCS group. The length of hospital stay, duration of surgery, intraoperative blood loss, quality of reduction, extent of femoral neck shortening, incidence of femoral neck shortening, femoral neck shortening at each follow-up visit, Harris hip score (HHS), reoperation, and complications were compared between the two groups. RESULTS: The median follow-up time was 28.2 (26.0, 31.2) months in the FNS group and 30.2 (26.3, 34.7) months in the CCS group. The follow-up time, age, sex distribution, body mass index (BMI), mechanism of injury, injured side, length of hospital stay, time from injury to surgery, and fracture classification were similar between the groups. Duration of surgery was longer in the FNS group (65.0 (55.0, 87.0) min versus 55.0 (50.0, 65.0) min, P<0.001); intraoperative blood loss was greater in the FNS group (50.0 (20.0, 60.0) ml versus 20.0 (10.0, 35.0) ml, P<0.001). Femoral neck shortening was 2.4 (1.0, 4.5) mm in the FNS group versus 0.6 (0.0, 2.6) mm in the CCS group at 1 month postoperatively (P<0.001); 3.7 (1.8, 6.4) mm in the FNS group versus 1.2 (0.6, 3.8) mm in the CCS group at 3 months (P<0.001); 4.1(2.4, 7.7) mm in the FNS group versus 2.3 (1.1, 4.4) mm in the CCS group at 6 months (P<0.001); 4.2 (2.6, 7.7) mm in the FNS group versus 2.6 (1.3, 4.6) mm in the CCS group at 12 months (P<0.001); and 4.5 (2.8, 8.0) mm in the FNS group versus 2.8 (1.5, 4.8) mm in the CCS group at 18 months (P<0.001). The two groups showed no significant differences in HHS, reoperation, and reduction quality. CONCLUSION: Compared to CCS, FNS is deficient in preventing femoral neck shortening. Future research should focus on improving FNS in terms of preventing femoral neck shortening.

The experimental study of mir-99a-5p negative regulation of TLR8 receptor mediated-mediated innate immune response in rabbit knee cartilage injury.

BACKGROUND: Traumatic cartilage injury is an important cause of osteoarthritis (OA) and limb disability, and toll-like receptors (TLRs) mediated innate immune response has been confirmed to play a crucial role in cartilage injury. In the previous study, we found that the activation of TLR8 molecules in injured articular cartilage was more obvious than other TLRs by establishing an animal model of knee impact injury in rabbits, and the changes of TLR8 molecules could significantly affect the process of articular cartilage injury and repair. OBJECTIVE: To verify how mir-99a-5p regulates TLR8 receptor mediated innate immune response to treat traumatic cartilage injury. METHODS: The impact of a heavy object on the medial condyle of the rabbit's knee joint caused damage to the medial condylar cartilage. Through pathological and imaging analysis, it was demonstrated whether the establishment of an animal model of traumatic cartilage injury was successful. Establishing a cell model by virus transfection of chondrocytes to demonstrate the role of TLR8 in the innate immune response to impact cartilage injury. Through transcriptome sequencing, potential targets of TLR8, mir-99a-5p, were predicted, and basic experiments were conducted to demonstrate how they interact with innate immune responses to impact cartilage damage. RESULTS: TLR8 is a receptor protein of the immune system, which is widely expressed in immune cells. In our study, we found that TLR8 expression is localized in lysosomes and endosomes. Mir-99a-5p can negatively regulate TLR8 to activate PI3K-AKT molecular pathway and aggravate cartilage damage. Inhibiting TLR8 expression can effectively reduce the incidence of articular cartilage damage. CONCLUSION: Based on the results from this study, mir-99a-5p may be an effective molecular marker for predicting traumatic cartilage injury and targeting TLR8 is a novel and promising approach for the prevention or early treatment of cartilage damage.

Changes in serum sodium concentration during hemodialysis is a predictor of mortality and cardio-cerebrovascular event.

BACKGROUND: Previous study consistently showed that lower serum sodium (SNa) was associated with a greater risk of mortality in hemodialysis (HD) patients. However, few studies have focused on the change in SNa (ΔSNa = post-HD SNa - pre-HD SNa) during an HD session. METHODS: In a retrospective cohort of maintenance HD adults, all-cause mortality and cardio-cerebrovascular event (CCVE) were followed up for a medium of 82 months. Baseline pre-HD SNa and ΔSNa were collected; time-averaged pre-HD SNa and ΔSNa were computed as the mean values within 1-year, 2-year and 3-year intervals after enrollment. Cox proportional hazards models were used to evaluate the relationships of pre-HD and ΔSNa with outcomes. RESULTS: Time-averaged pre-HD SNa were associated with all-cause mortality (2-year pre-HD SNa: HR [95% CI] 0.86 [0.74-0.99], p = 0.042) and CCVE (3-year pre-HD SNa: HR [95% CI] 0.83 [0.72-0.96], p = 0.012) with full adjustment. Time-averaged ΔSNa also demonstrated an association with all-cause mortality (3-year ΔSNa: HR [95% CI] 1.26 [1.03-1.55], p = 0.026) as well as with CCVE (3-year ΔSNa: HR [95% CI] 1.51 [1.21-1.88], p = <0.001) when fully adjusted. Baseline pre-HD SNa and ΔSNa didn't exhibit association with both outcomes. CONCLUSIONS: Lower time-averaged pre-HD SNa and higher time-averaged ΔSNa were associated with a greater risk of all-cause mortality and CCVE in HD patients.

Low expression of NR1D1 and NR2E3 is associated with advanced features of retinoblastoma.

PURPOSE: To investigate the expression of nuclear receptor subfamily 1 group D member 1 (NR1D1) and nuclear receptor subfamily 2 group E Member 3 (NR2E3) in retinoblastoma (RB) and their correlation with the clinical and pathological features of RB. METHODS: Immunohistochemical (IHC) assays were performed to detect and evaluate the expression levels of NR1D1 and NR2E3 in paraffin-embedded tissue samples. The relationship between the expression levels and clinicopathological characteristics of RB patients was analyzed using the χ2 test or Fisher exact test. RESULTS: A total of 51 RB patients were involved in this research. The expression levels of NR1D1 (P = 0.004) and NR2E3 (P = 0.024) were significantly lower in RB tumor tissues than in normal retina. The expression levels of NR1D1 and NR2E3 were less positive in RB patients with advanced stages (P = 0.007, P = 0.015), choroidal infiltration (P = 0.003, P = 0.029), and optic nerve infiltration (P = 0.036, P = 0.003). In addition, a low expression level of NR2E3 was associated with high-risk pathology (P = 0.025) and necrosis (P = 0.035) of RB tissues. CONCLUSION: The expression levels of NR1D1 and NR2E3 were decreased in RB and closely associated with the clinical stage and high invasion of the disease. These findings provide new insights into the mechanism of RB progression and suggest that NR1D1 and NR2E3 could be potential targets for treatment strategies.

Resistance Mechanism of Plutella xylostella (L.) Associated with Amino Acid Substitutions in Acetylcholinesterase-1: Insights from Homology Modeling, Docking and Molecular Dynamic Simulation.

Plutella xylostella, a destructive crucifer pest, can rapidly develop resistance to most classes of pesticides. This study investigated the molecular resistance mechanisms to chlorpyrifos, an organophosphate pesticide. Two P. xylostella genes, ace1 and ace2, were described. The nucleotide sequence results revealed no variation in ace2, while the resistant strain (Kar-R) had four amino acid alterations in ace1, two of which (A298S and G324A) were previously shown to confer organophosphate resistance in P. xylostella. In the present study, the 3D model structures of both the wild-type (Gu-S) and mutant (Kar-R) of P. xylostella ace1 strains were studied through molecular dynamics (MDs) simulations and molecular docking. Molecular dynamics simulations of RMSD revealed less structural deviation in the ace1 mutant than in its wild-type counterpart. Higher flexibility in the 425-440 amino acid region in the mutant active site (Glu422 and Acyl pocket) increased the active site's entropy, reducing the enzyme's affinity for the inhibitors. Gene expression analysis revealed that the relative transcription levels of ace1 were significantly different in the Kar-R strain compared with the Gu-S strain. This study enhances the understanding of the mechanisms governing ace1's resistance to insecticide and provides essential insights for new insecticides as well as valuable insights into environmentally conscious pest management techniques.

Renal damage and old age: risk factors for thrombosis in patients with ANCA-associated vasculitis.

INTRODUCTION: Thrombosis in ANCA-associated vasculitis (AAV) was prevalent and has been neglected in Chinese patients. This study tried to describe the clinical characteristics, identify the risk factors, and investigate the causal relationship between AAV and venous thromboembolism (VTE) by two-sample Mendelian randomization (MR) analysis. METHODS: In this retrospective, observational study, we included all hospitalized AAV patients from Jan 2013 to Apr 2022 in Peking Union Medical College Hospital. We collected their clinical data for multivariate regression analysis to determine the risk factors for thrombosis. The nomogram was constructed by applying these risk factors to predict thrombosis in AAV patients. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies and extracted the outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) from the UK biobank. RESULTS: 1203 primary AAV patients were enrolled, and thrombosis occurred in 11.3%. Multivariate regression suggested that older than 65 years, EGPA, neurological involvement, lung involvement, significantly elevated serum creatinine (> 500µmol/L), and elevated D-dimer were associated with thrombosis in AAV patients. The model demonstrated satisfied discrimination with an AUC of 0.769 (95% CI, 0.726-0.812). MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035-1.0041, P = 0.009). CONCLUSION: Thrombosis was not rare in Chinese patients with AAV. Renal damage and old age emerged as critical risk factors for thrombosis. EGPA might have a potential causal relationship with DVT and PE.

[Comparison of effectiveness between unilateral biportal endoscopic and uniportal interlaminar endoscopic decompression in the treatment of lumbar spinal stenosis].

Objective: To compare the effectiveness between unilateral laminotomy and bilateral decompression (ULBD) with unilateral biportal endoscopy (UBE) and uniportal interlaminar endoscopy (UIE) in the treatment of lumbar spinal stenosis. Methods: A clinical data of 52 patients with lumbar spinal stenosis, who met the selection criteria and treated with ULBD between March 2021 and November 2022, was retrospectively analyzed. The patients were allocated into UBE group (23 cases) and UIE group (29 cases) according to the surgical methods. There was no significant difference ( P>0.05) in age, gender, body mass index, surgical segment, type of lumbar stenosis, and preoperative visual analogue scale (VAS) score of low back pain, VAS score of leg pain, Oswestry disability index (ODI), disc height, and dural sac area between the two groups. Perioperative indexes (incision length, operation time, hospital stay, and surgical complications), clinical indicators (VAS score of low back pain, VAS score of leg pain, and ODI before operation and at 3 days, 1 month, 6 months, and 12 months after operation), and imaging indicators (disc height and dural sac area before operation and at 1, 12 months after operation, and dural sac expansion area) were recorded and compared between the two group. Results: All operations in both groups were successfully completed. Compared with the UIE group, the UBE group had shorter operation time and longer incision length, with significant differences ( P<0.05). But there was no significant difference in hospital stay and incidence of complications between the two groups ( P>0.05). All patients were followed up 12-20 months (mean, 14 months). The VAS scores of low back pain and leg pain and ODI after operation significantly improved when compared with preoperative values ( P<0.05), and there was no significant difference in the above indicators between different time points after operation ( P>0.05). There was no significant difference between the two groups at different time points ( P>0.05). Imaging examination showed that there was no significant difference in disc height between the two groups at different time points after operation ( P>0.05). However, the dural sac area and dural sac expansion area were significantly larger in the UBE group than in the UIE group ( P<0.05). Conclusion: ULBD with UBE and UIE can achieve satisfactory effectiveness in the treatment of lumbar spinal stenosis. But the former has more thorough decompression and better dural sac expansion than the latter.

Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma.

Two APOBEC (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-like) DNA cytosine deaminase enzymes (APOBEC3A and APOBEC3B) generate somatic mutations in cancer, driving tumour development and drug resistance. Here we used single cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires Grainyhead-like transcription factor 3 (GRHL3). Thus, in normal tissue, neither deaminase appears to be expressed at high levels during DNA replication, the cell cycle stage associated with APOBEC-mediated mutagenesis. In contrast, we show that in squamous cell carcinoma tissues, there is expansion of GRHL3 expression and activity to a subset of cells undergoing DNA replication and concomitant extension of APOBEC3A expression to proliferating cells. These findings indicate a mechanism for acquisition of APOBEC3A mutagenic activity in tumours.