Gradient conducting polymer surfaces with netrin-1-conjugation promote axon guidance and neuron transmission of human iPSC-derived retinal ganglion cells.

Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies.

Risk factors and clinical impact of seroma formation following laparoscopic inguinal hernia repair: a retrospective study.

BACKGROUND: Although laparoscopic inguinal hernia repair (LIHR) has advantages over open surgery, postoperative seroma formation remains an issue. This study aimed to investigate the risk factors and clinical outcomes of seroma formation in patients undergoing LIHR. METHODS: From January 2016 to March 2023, clinical data of patients who underwent LIHR were retrospectively analyzed. Patients who developed seroma and those who did not were classified into the seroma and non-seroma groups, respectively. The demographic and clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed for variables of interest. The receiver operating characteristic curve was used to evaluate the risk factors of the binary logistic model, and the cutoff value for each risk factor was obtained. RESULTS: Data of 128 patients were evaluated. Compared with patients in the non-seroma group, those in the seroma group had a higher body mass index (BMI) (P < 0.001), more direct hernias (P < 0.001), larger hernial orifice size (P < 0.001), more laparoscopic total extraperitoneal hernioplasty (TEP) (P < 0.001), more frequent reduction of hernial sac (P = 0.011), and lower preoperative serum albumin level (PSAL) (P < 0.001). Multivariate logistic regression analyses performed on these variables showed that high BMI (P = 0.005), large hernial orifice (P = 0.001), TEP (P = 0.033), and low PSAL (P = 0.009) were risk factors for seroma formation. Compared with the non-seroma group, the seroma group exhibited a higher numerical rating scale score for postoperative pain (P < 0.001), and longer hospital stays (P = 0.032). CONCLUSIONS: BMI (> 24.5 kg/m2), hernial orifice size (> 2.5 cm), TEP, and PSAL (< 32.5 g/L) were independent risk factors of postoperative seroma formation in patients who underwent LIHR. Although most seromas resolve spontaneously without surgical intervention, seroma formation results in increased patient pain and prolonged hospital stay.

Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages.

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 µM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.

Dual attention based fusion network for MCI Conversion Prediction.

Alzheimer's disease (AD) severely impacts the lives of many patients and their families. Predicting the progression of the disease from the early stage of mild cognitive impairment (MCI) is of substantial value for treatment, medical research and clinical trials. In this paper, we propose a novel dual attention network to classify progressive MCI (pMCI) and stable MCI (sMCI) using both magnetic resonance imaging (MRI) and neurocognitive metadata. A 3D CNN ShuffleNet V2 model is used as the network backbone to extract MRI image features. Then, neurocognitive metadata is used to guide the spatial attention mechanism to steer the model to focus attention on the most discriminative regions of the brain. In contrast to traditional fusion methods, we propose a ViT based self attention fusion mechanism to fuse the neurocognitive metadata with the 3D CNN feature maps. The experimental results show that our proposed model achieves an accuracy, AUC, and sensitivity of 81.34%, 0.874, and 0.85 respectively using 5-fold cross validation evaluation. A comprehensive experimental study shows our proposed approach significantly outperforms all previous methods for MCI progression classification. In addition, an ablation study shows both fusion methods contribute to the high final performance.

Advances in Surgical Treatments of Left Ventricular Aneurysms.

Despite improvements in the early intervention of myocardial infarction (MI) in recent decades, left ventricular aneurysms (LVA) remain a major health concern, particularly in developing nations. The progression of MI can lead to the thinning of the myocardial wall and the formation of a ventricular wall bulge, characteristic of an LVA. Furthermore, cardiac magnetic resonance (CMR) has emerged as the gold standard for LVA diagnosis due to its superior imaging capabilities. Notably, surgical ventricular reconstruction (SVR) is an effective treatment for LVA, aiming to restore the normal volume and structure of the left ventricle, thereby improving cardiac function. However, the criteria for selecting patients for SVR treatment remains a subject of debate. This review focuses on the current understanding of surgical indications, procedures, and prognostic risk factors that influence outcomes in left ventricular reconstruction, highlighting the need for precise patient selection to optimize surgical benefits.

Prevalence and associated factors of sexting among Taiwanese adolescents.

This study utilized a large-scale representative sample to explore the prevalence of sexting and its associated factors among adolescents in Taiwan. A total of 12,954 students in grade 5-12 countrywide were randomly selected to answer the sexting module of an online survey. 13.7% of the respondents reported having ever received sexts on cellphone, and 2.0% had sent sexts to others. The prevalence was higher among older adolescents. Gender differences were also found, in which female students were more likely to receive sexts (15.8% vs. 11.7%), while male students were at higher risk of sending sexts to others (2.9% vs. 1.1%). A series of hierarchical logistic regression were further performed to examine the associations between potential factors and receiving/sending sexts as the outcome variables. Age, gender, and time spending on texting were significantly associated with receiving and ending sexts. Online respect was found positively associated with receiving sexts but negatively associated with sending them. Privacy awareness was found not significantly associated with sexting. As the first national survey on this growing issue in Taiwan, the results of the present study highlighted the existence of sexting among local youth. Practice and policy implications were discussed.

Harnessing the potential of mesenchymal stem cells-derived exosomes in degenerative diseases.

Mesenchymal stem cells (MSCs) have gained attention as a promising therapeutic approach in both preclinical and clinical osteoarthritis (OA) settings. Various joint cell types, such as chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and release extracellular vesicles (EVs), which subsequently influence the biological activities of recipient cells. Recently, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown the potential to modulate various physiological and pathological processes through the modulation of cellular differentiation, immune responses, and tissue repair. This review explores the roles and therapeutic potential of MSC-EVs in OA and rheumatoid arthritis, cardiovascular disease, age-related macular degeneration, Alzheimer's disease, and other degenerative diseases. Notably, we provide a comprehensive summary of exosome biogenesis, microRNA composition, mechanisms of intercellular transfer, and their evolving role in the highlight of exosome-based treatments in both preclinical and clinical avenues.

Mechanism of modified danggui buxue decoction in glucocorticoid-induced osteoporosis: A discussion based on network pharmacology and molecular docking.

Objective: Glucocorticoid-induced osteoporosis (GIOP) represents a major complication arising from the long-term use of glucocorticoids, which are widely prescribed for various inflammatory and autoimmune conditions. Despite its prevalence, the current therapeutic options for GIOP are limited in terms of efficacy, safety profiles, and patient compliance. The Modified Danggui Buxue Decoction (DGBXD), a traditional Chinese herbal formulation, has shown promise in preliminary studies for its potential osteoprotective effects. The present study aimed to explore the mechanistic underpinnings of DGBXD's action on GIOP using network pharmacology and molecular docking approaches, bridging traditional medicine with modern pharmacological insights. Method: Network pharmacology is applied to screen drug-active compounds and potential core target proteins for disease treatment and to explore the drugs' therapeutic mechanisms. Result: Altogether, 78 DGBXD active compounds and 223 DGBXD-related, 146 component-disease common, and 2168 GIOP-associated target genes were obtained. The PPI network had 43 nodes and 462 edges, and a total of 10 core target genes, including TP53, JUN and MAPK3, were identified. The results of the GO enrichment analysis implied that DGBXD might participate in biological activities, including responses to oxidative stress and nutrient levels. The outcomes of the KEGG pathway enrichment analysis showed that DGBXD may treat GIOP through TNF, IL-17, and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathways. Based on to the molecular docking results, biologically active compounds (beta-carotene, formononetin, luteolin, and isorhamnetin) exhibited good binding to AKT1 and ESR1. Conclusion: DGBXD may aid in GIOP treatment by modulating multiple therapeutic targets and signaling pathways.

Development of a Dementia Case Management Information System App: Mixed Methods Study.

BACKGROUND: Case managers for persons with dementia not only coordinate patient care but also provide family caregivers with educational material and available support services. Taiwan uses a government-based information system for monitoring the provision of health care services. Unfortunately, scheduling patient care and providing information to family caregivers continues to be paper-based, which results in a duplication of patient assessments, complicates scheduling of follow-ups, and hinders communication with caregivers, which limits the ability of case managers to provide cohesive, quality care. OBJECTIVE: This multiphase study aimed to develop an electronic information system for dementia care case managers based on their perceived case management needs and what they would like included in an electronic health care app. METHODS: Case managers were recruited to participate (N=63) by purposive sampling from 28 facilities representing two types of community-based dementia care centers in Taiwan. A dementia case management information system (DCMIS) app was developed in four phases. Phase 1 assessed what should be included in the app by analyzing qualitative face-to-face or internet-based interviews with 33 case managers. Phase 2 formulated a framework for the app to support case managers based on key categories identified in phase 1. During phase 3, a multidisciplinary team of information technology engineers and dementia care experts developed the DCMIS app: hardware and software components were selected, including platforms for messaging, data management, and security. The app was designed to eventually interface with a family caregiver app. Phase 4 involved pilot-testing the DCMIS app with a second group of managers (n=30); feedback was provided via face-to-face interviews about their user experience. RESULTS: Findings from interviews in phase 1 indicated the DCMIS framework should include unified databases for patient reminder follow-up scheduling, support services, a health education module, and shared recordkeeping to facilitate teamwork, networking, and communication. The DCMIS app was built on the LINE (LY Corporation) messaging platform, which is the mobile app most widely used in Taiwan. An open-source database management system allows secure entry and storage of user information and patient data. Case managers had easy access to educational materials on dementia and caregiving for persons living with dementia that could be provided to caregivers. Interviews with case managers following pilot testing indicated that the DCMIS app facilitated the completion of tasks and management responsibilities. Some case managers thought it would be helpful to have a DCMIS desktop computer system rather than a mobile app. CONCLUSIONS: Based on pilot testing, the DCMIS app could reduce the growing challenges of high caseloads faced by case managers of persons with dementia, which could improve continuity of care. These findings will serve as a reference when the system is fully developed and integrated with the electronic health care system in Taiwan.

Management of peripheral neuropathy associated with brentuximab vedotin in the frontline treatment of classical Hodgkin lymphoma.

The ECHELON-1 trial demonstrated the effectiveness of brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment regimen in classical Hodgkin lymphoma. However, peripheral neuropathy (PN) is common with this regimen, occurring in up to two-thirds of patients. While standard prescribing information recommends BV dose modification at the onset of grade 2 PN, management strategies for PN are not well-defined. Most commonly, clinicians dose reduce or discontinue BV, vinblastine, or both. We review evidence-based and practical approaches for managing peripheral neuropathy, emphasizing early detection and dose modification.

Interactive effect between transcranial focused ultrasound and transcranial magnetic stimulation on human motor cortex.

OBJECTIVE: Transcranial focused ultrasound (TUS) can suppress human motor cortical excitability. However, it is unclear whether the TUS may interact with transcranial magnetic stimulation (TMS) when they co-delivered in multiple trials. METHODS: Nineteen subjects received three different TUS-TMS co-stimulation protocols to the motor cortex including concurrent stimulation (TUS-TMS-C), separated stimulation (TUS-TMS-S), and TMS only. In each condition, two runs of 30 stimulation trials were conducted with a five-minute rest between runs. Motor-evoked potentials (MEP) were recorded during stimulation and at 0, 10, 20, and 30 min after stimulation. The MEP amplitudes after intervention were normalized to the mean pre-intervention MEP amplitude and expressed as MEP ratios. An additional test with TUS alone was applied to all participants to assess whether TUS itself can elicit after-effects. RESULTS: There were no significant after-effects of all three interventions on MEP ratios. However, 11 subjects who showed online inhibition (OI + ) during the TUS-TMS-C protocol, defined as having MEP ratio less than 1 during TUS-TMS-C, showed significant MEP suppression at 10, 20 and 30 min after TUS-TMS-C. In 8 subjects did not show online inhibition (OI-), defined as having MEP ratios greater than 1 during TUS-TMS-C, showed no significant inhibitory after-effects. OI + and OI- status did not change in a follow-up repeat TUS-TMS-C test. TUS alone did not generate inhibitory after-effects in either OI + or OI- participants. CONCLUSIONS: Our results showed that co-delivery of TUS and TMS can elicit inhibitory after-effect in subjects who showed online inhibition, suggesting that TUS and TMS may interact with each other to produce plasticity effects. SIGNIFICANCE: TUS and TMS may interact with each other to modulate cortical excitability.

Triglyceride-rich lipoproteins cholesterol, 10-year atherosclerotic cardiovascular disease risk, and risk of myocardial infarction and ischemic stroke.

BACKGROUND: Triglyceride-rich lipoproteins cholesterol (TRLs-C) has been associated with atherosclerotic cardiovascular disease (ASCVD), even among individuals with low-density lipoprotein cholesterol in the targeted range. We assessed whether the associations of TRLs-C with myocardial infarction (MI) and ischemic stroke (IS) vary by the burden of traditional cardiovascular risk factors, as reflected by predicted 10-year risk for ASCVD. MATERIALS AND METHODS: Included were 327,899 participants from the UK Biobank who were free of MI or IS and did not receive lipid-lowering treatment at baseline. Ten-year risk for ASCVD was estimated by the Pooled Cohort Equations and was grouped as low (<7.5%), intermediate (7.5% to <20%), and high risk (≥20%). Multivariable Cox regression models were used to examine the associations of TRLs-C and triglycerides with risk of MI and IS, overall and by the 10-year risk categories. RESULTS: During a median of 12.3 years of follow-up, 8,358 incident MI and 4,400 incident IS cases were identified. Overall, higher TRLs-C was associated with a higher risk of MI (p-trend <.0001) but not IS (p-trend = 0.074). Triglycerides and non-HDL-C levels provide generally similar results. There was evidence for interactions between TRLs-C, triglycerides, non-HDL-C and 10-year ASCVD risk on risk of MI. However, the interaction was only between TRLs-C, triglycerides and10-year ASCVD risk on risk of IS. Hazard ratios (95% CIs) of MI comparing the highest with the lowest quartiles of TRLs-C, triglycerides, non-HDL-C were 2.10 (1.23-1.30), 2.02 (1.80-2.27) and 2.17 (1.93-2.44) in the low-risk group. The corresponding estimates for IS were 1.24 (1.05-1.45) 1.25 (1.06-1.47) and 1.08 (0.92-1.27) respectively. CONCLUSIONS: The associations of TRLs-C with MI and IS were significant in the low-risk group. Triglycerides and non-HDL cholesterol are roughly equivalent to TRLs-C in determining risk. These findings may have implications for more detailed risk stratification and early intervention.

Protocol for establishing and evaluating a cancer cachexia mouse model.

Cancer cachexia mouse models are needed to recapitulate the clinical features of patients with cachexia. Here, we present a protocol for the establishment and evaluation of cancer cachexia mouse models. We delineate the steps in preparing tumor cells for inoculation and surgical procedures. After the establishment of these mouse models, we describe essential techniques to assess cancer cachexia, including grip strength evaluation, tissue collection, and the calculation of cross-sectional areas of muscle tissue. For complete details on the use and execution of this protocol, please refer to Liu et al.,1 Yang et al.,2 Shi et al.,3 and Zhou et al.4.

p53 Abnormal Oral Epithelial Dysplasias are Associated With High Risks of Progression and Local Recurrence-A Retrospective Study in a Longitudinal Cohort.

Grading of oral epithelial dysplasia (OED) can be challenging with considerable intraobserver and interobserver variability. Abnormal immunohistochemical staining patterns of the tumor suppressor protein, p53, have been recently shown to be potentially associated with progression in OED. We retrospectively identified 214 oral biopsies from 203 patients recruited in a longitudinal study between 2001 and 2008 with a diagnosis of reactive, nondysplastic lesions, low-grade lesions (mild OED and moderate OED) and high-grade lesions (HGLs; severe OED/carcinoma in situ). Tissue microarrays were constructed from the most representative area of the pathology. Three consecutive sections were sectioned and stained for hematoxylin and eosin, p53 immunohistochemistry, and p16 immunohistochemistry. The staining results were reviewed by 2 pathologists (Y.C.K.K., C.F.P.) blinded to clinical outcome. Samples were categorized into p53 abnormal OED (n = 46), p53 conventional OED (n = 118), and p53 human papillomavirus (HPV) OED (HPV associated) (n = 12) using a previously published pattern-based approach. All cases of p53 HPV OED (HPV associated) were identified in HGLs. In contrast, cases of p53 abnormal OED were observed in mild OED (9.5%), moderate OED (23%), and severe OED/carcinoma in situ (51%). None of the 27 reactive or nondysplastic lesions showed abnormal p53 staining patterns. Among the 135 low-grade lesions, 23 cases (17.0%; 2 mild OEDs and 21 moderate OEDs) progressed to HGL or squamous cell carcinoma, with 11 cases showing progression within the first 3 years. Remarkably, 82% (9/11) of these faster progressors showed abnormal p53 patterns. Survival analysis revealed that p53 abnormal OED had significantly poorer progression-free probability (P < .0001) with hazard ratio of 11.24 (95% CI, 4.26-29.66) compared with p53 conventional OED. Furthermore, p53 abnormal OED had poorer local recurrence-free survival compared with p53 wild-type OED (P = .03). The study supports that OED with p53 abnormal pattern is at high risk for progression and recurrence independent of the dysplasia grade.

Pharmacokinetics, optimal dosages and withdrawal time of amoxicillin in Nile tilapia (Oreochromis niloticus) reared at 25 and 30 °C.

Knowledge of amoxicillin (AMX) pharmacokinetics (PK) and tissue residues in fish, which is necessary for prudent drug use, remains limited. The study aimed to explore the PK characteristics of AMX in Nile tilapia (Oreochromis niloticus) reared at 25 and 30 °C as well as to determine optimal dosages and drug withdrawal time (WDT). In the PK investigation, the fish received a single dose of 40 mg/kg AMX via oral gavage, and the optimal dosage was determined by the pharmacokinetic-pharmacodynamic approach. In the tissue residue study, the fish were orally gavaged with 40 mg/kg/day AMX once daily for 5 days and the WDT was established by the linear regression analysis. The results revealed the temperature-dependent drug elimination; the clearance relative to bioavailability (CL/F) and elimination half-life at 30 °C (0.180 L/kg/h and 6.06 h, respectively) were about twice those at 25 °C (0.090 L/kg/h and 10.49 h, respectively). The optimal dosages at the minimum inhibitory concentration (MIC) of 2 µg/mL were 10.97 (25 °C) and 41.03 (30 °C) mg/kg/day, respectively. Finally, following the multiple oral administration, the muscle/skin residue of AMX on day 1 after the last dosing at 25 and 30 °C were 548 and 264 ng/g, respectively. The average tissue residues were depleted below the maximum residue limits (MRL) of 50 µg/kg on day 5 (25 °C) and 3 (30 °C), respectively, and the WDT were 6 and 4 days when rearing at 25 and 30 °C, respectively. This knowledge serves as a practical guideline for responsible use of AMX in treating bacterial diseases in Nile tilapia aquaculture.

Cloning and expression profiling of voltage-gated sodium channel gene (VGSC) from Spodoptera frugiperda.

Spodoptera frugiperda is a long-distance migratory pest with strong dispersal ability, fast reproduction speed and destructive feeding, so it is difficult to prevent and control. Pyrethroid insecticides are commonly used in pest insects control, And since the voltage-gated sodium channel (VGSC) serves as a major target of pyrethroids, it is important to study this gene for pest control. VGSC is an integral transmembrane protein consisting of approximately 2,000 amino acid residues found in neurons, myocytes, endocrine cells, and ovarian cells and involved in the initiation and propagation of excitable cellular action potentials. In this study, the cDNA sequence of the VGSC was identified from S. frugiperda by rapid amplification of cDNA ends (RACE) which contained an open reading frame of 6,261 bp encoding a protein of 2,086 amino acids. The molecular weight of this protein was predicted to be 236 kDa, and the theoretical isoelectric point was 5.21. A phylogenetic tree constructed based on lepidopteran insects showed that the VGSC of S. frugiperda was most closely relative to that of Spodoptera litura. VGSC is a highly conserved protein with Ion channel conserved structural domains of transmembrane proteins. qPCR showed that the VGSC gene was highly expressed in the epidermis of 2nd instar larvae, and its expression level was low in other tissues, such as the foregut and Malpighian tubules. In addition, VGSC was also detected in the prepupal stage, then gradually increased in abundance after entering the adult stage, peaked at the adult males on the 4th day of pupal stage, and decreased afterwards. The recombinant plasmid of pSumo-mut-VGSC was constructed and induced to express a His tag fused VGSC protein. Polyclonal antibodies were prepared from purified recombinant VGSC protein. The antibody was ELISA-titered, and the western blotting results showed that it specifically recognized VGSC, whether it was recombinant or endogenous protein. These results have laid the foundation for future studies on the physiological function of this gene in the growth and development of S. frugiperda.

RAGE participates in the intracellular transport of Campylobacter jejuni cytolethal distending toxin.

BACKGROUND: Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to Campylobacter jejuni-associated gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP) signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT intoxication remain to be elucidated. METHODS: Recombinant CDT subunits (CdtA, CdtB, and CdtC) were purified, and their activity was characterized in gastrointestinal cells. Molecular approaches and image tracking were employed to analyze the delivery of CDT in host cells. RESULTS: In this study, we found that CDT interacts with the receptor of advanced glycation end products (RAGE) and high mobility group box 1 (HMGB1) to enter the cells. Our results further showed that CdtB transport in cells through the dynamin-dependent endocytic pathway and lysosome is involved in this process. Conversely, blockage of RAGE signaling resulted in a reduction in CDT-arrested cell cycles, indicating that RAGE is involved in CDT intracellular transport and its subsequent pathogenesis. CONCLUSION: Our results demonstrate that RAGE is important for CDT trafficking in the cells. These findings expand our understanding of important issues related to host cell intoxication by C. jejuni CDT.

Single-cell RNA sequencing and cell-cell communication analysis reveal tumor microenvironment associated with chemotherapy responsiveness in ovarian cancer.

BACKGROUND: To investigate the impact of the tumor microenvironment (TME) on the responsiveness to chemotherapy in ovarian cancer (OV). METHODS: We integrated single cell RNA-seq datasets of OV containing chemo-response information, and characterize their clusters based on different TME sections. We focus on analyzing cell-cell communication to elaborate on the mechanisms by which different components of the TME directly influence the chemo-response of tumor cells. RESULTS: scRNA-seq datasets were annotated according to specific markers for different cell types. Differential analysis of malignant epithelial cells revealed that chemoresistance was associated with the TME. Notably, distinct TME components exhibited varying effects on chemoresistance. Enriched SPP1+ tumor-associated macrophages in chemo-resistant patients could promote chemoresistance through SPP1 binding to CD44 on tumor cells. Additionally, the overexpression of THBS2 in stromal cells could promote chemoresistance through binding with CD47 on tumor cells. In contrast, GZMA in the lymphocytes could downregulate the expression of PARD3 through direct interaction with PARD3, thereby attenuating chemoresistance in tumor cells. CONCLUSION: Our study indicates that the non-tumor cell components of the TME (e.g. SPP1+ TAMs, stromal cells and lymphocytes) can directly impact the chemo-response of OV and targeting the TME was potentially crucial in chemotherapy of OV.