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Background: Fetal growth restriction (FGR) is a major determinant of perinatal morbidity and mortality. Our study aimed to develop a prediction model for the risk of FGR developing adverse perinatal outcome (APO) and evaluate its performance., Methods: This was a prospective observational cohort study of consecutive singleton gestations meeting the ACOG-endorsed criteria for FGR from January 2022 to June 2023 at Obstetrics and Gynecology Hospital of Fudan University. Clinical information, ultrasound indicators and serum biomarkers were collected. The primary composite APO comprised one or more of: perinatal death, intrauterine demise, intraventricular hemorrhage, periventricular leukomalacia, seizures, necrotizing enterocolitis, neonatal respiratory distress syndrome, sepsis and the length of stay in the neonatal intensive care unit > 7 days. Least absolute shrinkage and selection operator regression was used to screen variables for nomogram model construction. The discrimination, calibration and clinical effectiveness of the nomogram were evaluated using receiver operating characteristic curve, calibration plots and decision curve analysis in training and validation cohorts., Results: A total of 122 pregnancies were enrolled in the final statistical analysis. Five variables were identified to establish a nomogram, including gestational weeks at diagnosis, abnormal umbilical artery Doppler, abnormal uterine artery Doppler, and multiples of the median values of placental growth factor and soluble fms-like tyrosine kinase-1. The area under the receiver-operating-characteristics curve of 0.87 (95% CI, 0.75-0.99) and 0.86 (95% CI, 0.74-0.98) in the training and validation cohort respectively, indicated satisfactory discriminative ability of the nomogram. The calibration plots showed favorable consistency between the nomogram's predictions and actual observations. Decision curve analysis supported its practical value in a clinical setting., Conclusions: A nomogram was developed and validated to possess the promising capacity of predicting APO in FGR-afflicted neonates, and may prove useful in counseling and management of pregnancies complicated by FGR., Competing Interests: Declarations. Ethics approval and consent to participate: The Ethics Committee of the Gynecology and Obstetrics Hospital of Fudan University reviewed and approved all the study procedures (approval number 2022-18). All participants were fully informed of the content and purpose of the study and provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: This study compared the diagnostic performance of standard endoscopic ultrasound (EUS) and submucosal injection of normal saline and epinephrine-enhanced EUS (SINE-EUS) in detecting early colorectal cancer (CRC), emphasizing accuracy, sensitivity, and specificity., Methods: The self-controlled study was conducted with 115 patients diagnosed with early CRC through optical enhancement (OE) magnified endoscopy. Among them, 104 patients underwent sequential diagnostic procedures, starting with standard EUS and followed by SINE-EUS. Pathological findings were used as the reference standard. Statistical analyses assessed the diagnostic metrics and identified factors influencing accuracy., Results: Among 104 patients, 82 were pathologically diagnosed with early CRC (63 cases of Tis/T1a and 19 cases of T1b). Standard EUS showed a sensitivity of 68.3%, specificity of 52.6%, and overall accuracy of 64.6%. In contrast, SINE-EUS significantly improved sensitivity (85.7%), specificity (68.4%), and overall accuracy (81.7%) (P < 0.0167). Risk factors such as ulceration were identified as independent predictors of reduced diagnostic accuracy., Conclusions: SINE-EUS outperforms standard EUS in diagnosing early CRC, particularly in terms of sensitivity and overall accuracy. This technique is reliable for clinical application, although limitations remain in improving specificity for deeper lesions., Competing Interests: Declarations. Ethics approval and consent to participate: This study followed the Declaration of Helsinki and was approved by the Ethics Committee of Zhengzhou University. All participants signed an informed consent form. Consent for publication: All authors have read and consented to the final manuscript for publication. Competing interests: The authors declare no competing interests. No multiple submissions: The submitted manuscript is an original work and has not been published in any form in other journals, conference proceedings, or publications; furthermore, the manuscript has not been simultaneously reviewed in other journals or publications, and there is no duplication., (© 2025. The Author(s).)

Objective: The objective of this study is to investigate the effect after the application of Failure Model and Effect Analysis (FMEA) in nursing care for patients who have undergone endoscopic submucosal dissection (ESD)., Methods: A cohort of 40 patients who underwent ESD between July and September 2023 were selected as the control group, while 42 patients who underwent ESD between October 2023 and June 2024 after implementing FMEA were selected as the observation group. A multidisciplinary team was established based on the FMEA model to analyze and create a nursing flowchart. The 3 primary processes and 13 sub-processes were thoroughly analyzed and assessed to identify potential failure models, possible causes of failure, and consequences for each sub-process. Risk Priority Numbers (RPNs) were calculated to determine priority failure models, including medication and item preparation, specimen collection, equipment/instrument/accessory preparation, and nursing coordination. Corresponding improvement measures were formulated and implemented followed by a subsequent analysis of the effects., Results: After implementing the improvement measures, there was a significant decrease in RPNs in the observation group when compared with the control group. A statistical significance was observed in context of medication and item preparation (P < 0.001), specimen collection (P < 0.001), equipment/instrument/accessory preparation (P < 0.001), and nursing coordination (P < 0.001)., Conclusion: The application of the FMEA model can effectively facilitate early nursing interventions for identified risks in patient who have undergone ESD. By instituting suitable corrective measures for aspects deemed high-risk, this approach significantly diminishes surgical nursing hazards, enhances the quality of nursing care, and guarantees patient safety., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted with approval from the Ethics Committee of Zhengzhou Central Hospital affiliated to Zhengzhou University. This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The adoption of in vivo digital measures in pharmaceutical research and development (R&D) presents an opportunity to enhance the efficiency and effectiveness of discovering and developing new therapeutics. For clinical measures, the Digital Medicine Society's (DiMe) V3 Framework is a comprehensive validation framework that encompasses verification, analytical validation, and clinical validation. This manuscript describes collaborative efforts to adapt this framework to ensure the reliability and relevance of digital measures for a preclinical context. Verification ensures that digital technologies accurately capture and store raw data. Analytical validation assesses the precision and accuracy of algorithms that transform raw data into meaningful biological metrics. Clinical validation confirms that these digital measures accurately reflect the biological or functional states in animal models relevant to their context of use. By widely adopting this structured approach, stakeholders-including researchers, technology developers, and regulators-can enhance the reliability and applicability of digital measures in preclinical research, ultimately supporting more robust and translatable drug discovery and development processes., Competing Interests: Author SWB was employed by VeriSIM Life. Author SEB was employed by AbbVie Inc. Author SG was employed by Tecniplast SpA. Author MvG was employed by Evotec. Author ML was employed by The 3Rs Collaborative. Author C-NL was employed by Pfizer. Author SM was employed by GSK. Author LN was employed by Noldus Information Technology BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Baran, Bolin, Gaburro, van Gaalen, LaFollette, Liu, Maguire, Noldus, Bratcher-Petersen and Berridge.)

Purpose: To examine the effects of different warm-up methods on 50 m breaststroke performance in both breaststroke specialists and individual medley swimmers., Methods: 18 swimmers (breaststroke group: 9, individual medley group: 9) who met the qualification standards for the National Intercollegiate Athletic Games participated in this study. Each participant completed four different warm-up protocols (a conventional 1,400 m warm-up and a 700 m conventional warm-up that integrated tubing-assisted (TA), paddle (PD), or squat (SQ) warm-ups) over four separate days. Following each warm-up protocol, a 50 m breaststroke performance test was conducted with inertial measurement unit (IMU) sensors attached to specific body segments to evaluate and compare stroke performance, stroke length, stroke frequency, and the acceleration of the hands, sacrum, and feet across different warm-up methods., Results: The breaststroke specialists who performed the TA warm-ups recorded significantly less time than those who performed the conventional 1,400 m warm-ups (35.31 ± 1.66 s vs. 35.67 ± 1.83 s, p = 0.006). There was a trend that individual medley specialists who performed the SQ warm-ups recorded less time than those who performed the PD warm-ups (34.52 ± 1.45 s vs. 34.92 ± 1.46 s, p = 0.043). The stroke length of breaststroke specialists following the TA warm-ups was shorter than that following the PD warm-ups, the SQ warm-ups, and the conventional 1,400 m warm-ups. Breaststroke specialists who engaged in the TA warm-ups had higher stroke frequency than those who engaged in the conventional 1,400 m warm-ups, the SQ warm-ups, and the PD warm-ups. During the TA warm-ups, breaststroke specialists exhibited a shorter stroke length and a higher stroke frequency than individual medley specialists. Acceleration data from the center of mass and limb segments, recorded by IMUs, were insufficient to fully explain the variations in stroke frequency, stroke length, and overall performance caused by the different warm-up protocols., Conclusion: Breaststroke specialists exhibited significant improvement in their 50 m breaststroke performance after the TA warm-up. By contrast, individual medley specialists benefited more from the SQ warm-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Lee, Chao, Hsu, Chang, Chen and Tsai.)

Background: Gut microbiome on predicting clinical responses to immune checkpoint inhibitors (ICIs) has been discussed in detail for decades, while microecological features of the lower respiratory tract within advanced non-small-cell lung cancer (NSCLC) are still relatively vague., Methods: During this study, 26 bronchoalveolar lavage fluids (BALF) from advanced NSCLC participants who received immune checkpoint inhibitor monotherapy were performed 16S rRNA sequencing and untargeted metabolome sequencing to identify differentially abundant microbes and metabolic characteristics. Additionally, inflammatory cytokines and chemokines were also launched in paired BALF and serum samples by immunoassays to uncover their underlying correlations. The omics data were separately analyzed and integrated by using multiple correlation coefficients. Multiplex immunohistochemical staining was then used to assess the immune cell infiltration after immune checkpoint blockade therapy., Results: Lower respiratory tract microbiome diversity favoured preferred responses to ICIs. Microbial markers demonstrated microbial diversity overweight a single strain in favoured response to ICI therapy, where Bacillus matters. Sphingomonas and Sediminibacterium were liable to remodulate lipid and essential amino acid degradations to embrace progression after immunotherapies. Microbiome-derived metabolites reshaped the immune microenvironment in the lower respiratory tract by releasing inflammatory cytokines and chemokines, which was partially achieved by metabolite-mediated tumoral inflammatory products and reduction of CD8 + effective T cells and M1 phenotypes macrophages in malignant lesions., Conclusions: This study provided a microecological landscape of the lower respiratory tract with advanced NSCLC to ICI interventions and presented a multidimensional perspective with favoured outcomes that may improve the predictive capacity of the localized microbiome in clinical practices., Highlights: Alterations of the lower respiratory tract microbiome indicate different clinical responses to ICB within advanced NSCLC. Reduced microbial diversity of lower respiratory tracts impairs anti-tumoral performances. Microbe-derived metabolites perform as a dominant regulator to remodify the microecological environment in lower respiratory tracts. Multi-omics sequencings of the lower respiratory tract possess the potential to predict the long-term clinical responses to ICB among advanced NSCLC., (© 2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Softening in fruit adversely impacts their edible quality and commercial value, leading to substantial economic losses during fruit ripening, long-term storage, long-distance transportation, and marketing. As the apple fruit demonstrates climacteric respiration, its firmness decreases with increasing ethylene release rate during fruit ripening and postharvest storage. However, the molecular mechanisms underlying ethylene-mediated regulation of fruit softening in apple remain poorly understood. In this study, we identified a WRKY transcription factor (TF) MdWRKY31, which is repressed by ethylene treatment. Using transgenic approaches, we found that overexpression of MdWRKY31 delays softening by negatively regulating xyloglucan endotransglucosylase/hydrolases 2 (MdXTH2) expression. Yeast one-hybrid (Y1H), electrophoretic mobility shift (EMSA), and dual-luciferase assays further suggested that MdWRKY31 directly binds to the MdXTH2 promoter via a W-box element and represses its transcription. Transient overexpression of ethylene-induced MdNAC7, a NAC TF, in apple fruit promoted softening by decreasing cellulose content and increasing water-soluble pectin content in fruit. MdNAC7 interacted with MdWRKY31 to form a protein complex, and their interaction decreased the transcriptional repression of MdWRKY31 on MdXTH2. Furthermore, MdNAC7 does not directly regulate MdXTH2 expression, but the protein complex formed with MdWRKY31 hinders MdWRKY31 from binding to the promoter of MdXTH2. Our findings underscore the significance of the regulatory complex NAC7-WRKY31 in ethylene-responsive signalling, connecting the ethylene signal to XTH2 expression to promote fruit softening. This sheds light on the intricate mechanisms governing apple fruit firmness and opens avenues for enhancing fruit quality and reducing economic losses associated with softening., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Good piezoelectricity and high resistivity are prerequisites for high-temperature acceleration sensors to function correctly in high-temperature environments. Bismuth layered structure ferroelectrics (BLSFs) are promising candidates for piezoelectric ceramics with excellent piezoelectric performance at high temperatures, high electrical resistivity, and high Curie temperatures ( T c ). In this study, (LiMn) 5+ is substituted for Bi at the A-site, and Ce-doping is performed to replace Ti ions in Na 0.5 Bi 4.5 Ti 4 O 15 , which achieves the desired combination of high piezoelectric coefficients and high resistivity. Herein, we prepared Na 0.5 Bi 3 (LiMn) 0.9 Ti 4-x Ce x O 15 high-temperature piezoelectric ceramics, achieving a high piezoelectric coefficient d 33 of 32.0 pC/N and a high resistivity ρ of 1.2 × 10 8 Ω·cm (at 500 °C), and a high Curie temperature of 648 °C. It is important that the d 33 variation remains within 8% over a wide temperature range from 25 °C to 600 °C, demonstrating excellent thermal stability. Structural characterization and microstructure analysis showed that the excellent piezoelectric coefficient and high resistivity of cerium-doped Na 0.5 Bi 4.5 Ti 4 O 15 -based ceramics are attributable to the synergistic effects of structural characteristics, defect concentration, refined grain size and domain morphology. This study demonstrates that the superior properties of Na 0.5 Bi 3 (LiMn) 0.9 Ti 4-x Ce x O 15 ceramics are crucial for the stable operation of high-temperature accelerometer sensors and for the development of high-temperature devices.

Combining near-earth remote sensing spectral imaging technology with unmanned aerial vehicle (UAV) remote sensing sensing technology, we measured the Ningqi No. 10 goji variety under conditions of health, infestation by psyllids, and infestation by gall mites in Shizuishan City, Ningxia Hui Autonomous Region. The results indicate that the red and near-infrared spectral bands are particularly sensitive for detecting pest and disease conditions in goji. Using UAV-measured data, a remote sensing monitoring model for goji pest and disease was developed and validated using near-earth remote sensing hyperspectral data. A fully connected neural network achieved an accuracy of over 96.82% in classifying gall mite infestations, thereby enhancing the precision of pest and disease monitoring in goji. This demonstrates the reliability of UAV remote sensing. The pest and disease remote sensing monitoring model was used to visually present predictive results on hyperspectral images of goji, achieving data visualization.

In the process of sepsis, excessive occurrence of pyroptosis, a form of programmed cell death acting as a defense mechanism against pathogens, can disrupt immune responses, thus leading to tissue damage and organ dysfunction. Chitosan oligosaccharide (COS), derived from chitosan degradation, has demonstrated diverse beneficial effects. However, its impact on sepsis-induced pyroptosis remains unexplored. In the present study, ATP/LPS was utilized to induce canonical-pyroptosis in THP-1 cells, while bacterial outer membrane vesicles (OMV) were employed to trigger non-canonical pyroptosis in RAW264.7 cells. Our results revealed a dose-dependent effect of COS on both types of pyroptosis. This was evidenced by a reduction in the expression of pro-inflammatory cytokines, as well as crucial regulatory proteins involved in pyroptosis. In addition, COS inhibited the cleavage of caspase-1 and GSDMD, and reduced ASC oligomerization. The underlying mechanism revealed that COS acts an antioxidant, reducing the release of pyroptosis-induced ROS and malondialdehyde (MDA) by upregulation the expression and promoting the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2), which led to an elevation of glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD). Notably, the actions of COS were completely reversed by the Nrf2 inhibitor. Consequently, COS intervention increased the survival rate of sepsis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The ATP-binding cassette (ABC) superfamily is involved in numerous complex biological processes. However, the understanding of ABCs in plant pathogen defense, particularly against Botryosphaeria dothidea , remains limited. In this study, we identified MdABCI17 that plays a positive role in apple resistance to B. dothidea . Overexpression of MdABCI17 significantly enhanced the resistance of apple calli and fruits to B. dothidea . Our findings revealed that the jasmonic acid (JA) content and the expression of genes associated with JA biosynthesis and signal transduction were higher in stable MdABCI17- overexpressing apple calli than that of wild-type after inoculation with B. dothidea . Similar results were obtained for apple fruits with transient overexpression of MdABCI17 . Our research indicates that MdABCI17 enhances apple resistance to B. dothidea through the JA signaling pathway. We further determined that MdABCI17 plays a crucial role in the apple's response to JA signaling. Moreover, exogenous methyl jasmonate (MeJA) treatment significantly enhanced the effectiveness of MdABCI17 in boosting apple resistance to B. dothidea . We proposed a positive feedback regulatory loop between MdABCI17 -mediated apple resistance to B. dothidea and JA signal. In summary, our study offers new insights into the role of ABC superfamily members in the control of plant disease resistance., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01501-9., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: We used simple variables to construct prognostic prediction ensemble learning models for patients with sudden sensorineural hearing loss (SSNHL)., Study Design: Retrospectively study., Setting: Tertiary medical center., Patients: 1,572 patients with SSNHL., Intervention: Prognostic., Main Outcome Measures: We selected four variables, namely, age, days after onset of hearing loss, vertigo, and type of hearing loss. We also compared the accuracy between different ensemble learning models based on the boosting, bagging, AdaBoost, and stacking algorithms., Results: We enrolled 1,572 patients with SSNHL; 73.5% of them showed improving and 26.5% did not. Significant between-group differences were noted in terms of age ( p = 0.011), days after onset of hearing loss ( p < 0.001), and concurrent vertigo ( p < 0.001), indicating that the patients who showed improving to treatment were younger and had fewer days after onset and fewer vertigo symptoms. Among ensemble learning models, the AdaBoost algorithm, compared with the other algorithms, achieved higher accuracy (82.89%), higher precision (86.66%), a higher F1 score (89.20), and a larger area under the receiver operating characteristics curve (0.79), as indicated by test results of a dataset with 10 independent runs. Furthermore, Gini scores indicated that age and days after onset are two key parameters of the predictive model., Conclusions: The AdaBoost model is an effective model for predicting SSNHL. The use of simple parameters can increase its practicality and applicability in remote medical care. Moreover, age may be a key factor influencing prognosis., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Drought stress is one of the dominating challenges to the growth and productivity in crop plants. Elucidating the molecular mechanisms of plants responses to drought stress is fundamental to improve fruit quality. However, such molecular mechanisms are poorly understood in apple (Malus domestica Borkh.). In this study, we explored that the BTB-BACK-TAZ protein, MdBT2, negatively modulates the drought tolerance of apple plantlets. Moreover, we identified a novel Homeodomain-leucine zipper (HD-Zip) transcription factor, MdHDZ27, using a yeast two-hybrid (Y2H) screen with MdBT2 as the bait. Overexpression of MdHDZ27 in apple plantlets, calli, and tomato plantlets enhanced their drought tolerance by promoting the expression of drought tolerance-related genes [responsive to dehydration 29A (MdRD29A) and MdRD29B]. Biochemical analyses demonstrated that MdHDZ27 directly binds to and activates the promoters of MdRD29A and MdRD29B. Furthermore, in vitro and in vivo assays indicate that MdBT2 interacts with and ubiquitinates MdHDZ27, via the ubiquitin/26S proteasome pathway. This ubiquitination results in the degradation of MdHDZ27 and weakens the transcriptional activation of MdHDZ27 on MdRD29A and MdRD29B. Finally, a series of transgenic analyses in apple plantlets further clarified the role of the relationship between MdBT2 and MdHDZ27, as well as the effect of their interaction on drought resistance in apple plantlets. Collectively, our findings reveal a novel mechanism by which the MdBT2-MdHDZ27 regulatory module controls drought tolerance, which is of great significance for enhancing the drought resistance of apple and other plants., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Introduction: Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation., Methods: For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments., Results: Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland., Conclusion: Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Che, Zhang, Xiong, Shu, Jiang, Li, Guo, Qiao, Li, Li, Chang, Zhang, Zhang, Qiu, Xi, Li, Chen, Ye and Zhang.)

Background: Parathyroid carcinoma (PC) is a difficult-to-diagnose rare disease with low incidence. Relatively accurate preoperative diagnosis is very important in choosing surgical methods and patient prognosis., Case Summary: This study reported the clinical diagnosis and treatment of a rare patient with PC located in the thyroid gland and provided a case reference for the diagnosis and treatment of PC. A case of a 64-year-old male patient who presented to our hospital with systemic muscle and joint pain and palpitations is outlined. Subsequently, the patient was admitted to the Department of Nephrology for the treatment of "multiple myeloma nephropathy pending investigation". The patient was diagnosed with "primary hyperparathyroidism and hypercalcemic crisis" using thyroid color ultrasound., Conclusion: The intraoperative frozen section report considered the parathyroid tumor. Surgical tumor resection was promptly performed, and the diagnosis of PC was confirmed., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Diorhabda rybakowi Weise is one of the dominant pests feeding on Nitraria spp., a pioneer plant used for windbreaking and sand fixation purposes, and poses a threat to local livestock and ecosystems. To clarify the key olfactory genes of D. rybakowi and provide a theoretical basis for attractant and repellent development, the optimal reference genes under two different conditions (tissue and sex) were identified, and the bioinformatics and characterization of the tissue expression profiles of two categories of soluble olfactory proteins (OBPs and CSPs) were investigated. The results showed that the best reference genes were RPL13a and RPS18 for comparison among tissues, and RPL19 and RPS18 for comparison between sexes. Strong expressions of DrybOBP3 , DrybOBP6 , DrybOBP7 , DrybOBP10 , DrybOBP11 , DrybCSP2 , and DrybCSP5 were found in antennae, the most important olfactory organ for D. rybakowi . These findings not only provide a basis for further in-depth research on the olfactory molecular mechanisms of host-specialized pests but also provide a theoretical basis for the future development of new chemical attractants or repellents using volatiles to control D. rybakowi .

Objectives: To investigate the role of normal weight central obesity (NWCO) in the prognosis of sudden sensorineural hearing loss (SSNHL)., Methods: We retrospectively investigated 807 cases of SSNHL from January of 2008 to August of 2019 from the Department of Otorhinolaryngology at Kaohsiung Medical University Hospital in southern Taiwan. We analyzed the association between overweight and obesity, NWCO, and the prognosis of SSNHL. The demographic and clinical characteristics, audiometry results, and outcomes were also reviewed., Results: The nonobese (body mass index [BMI] < 24 kg/m 2 ) and overweight and obese groups (BMI ≥ 24 kg/m 2 ) comprised 343 (42.50%) and 464 (57.50%) patients, respectively. The favorable prognosis rates in the nonobese and the overweight and obese groups were 45.48% and 45.91%, respectively, without a significant difference ( P  = .9048). Multivariate logistic regression revealed that BMI (adjusted odds ratio [aOR] = 1.00, 95% CI = 0.948-1.062, P  = .9165) was not significantly associated with SSNHL recovery. The normal weight noncentral obesity (NWNCO) and NWCO groups comprised 266 (77.55%) and 77 (22.45%) patients, respectively, and had favorable prognosis rates of 48.50% and 35.06%, respectively. The difference between the groups was significant ( P  = .0371). Multivariate logistic regression analysis revealed that NWCO (aOR = 2.51, 95% CI = 1.292-5.019, P  = .0075) was significantly associated with SSNHL recovery., Conclusions: NWCO may significantly affect the prognosis of SSNHL., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

For 15 years, gene therapy has been viewed as a beacon of hope for inherited retinal diseases. Many preclinical investigations have centered around vectors with maximal gene expression capabilities, yet despite efficient gene transfer, minimal physiological improvements have been observed in various ciliopathies. Retinitis pigmentosa-type 28 (RP28) is the consequence of bi-allelic null mutations in the FAM161A, an essential protein for the structure of the photoreceptor connecting cilium (CC). In its absence, cilia become disorganized, leading to outer segment collapses and vision impairment. Within the human retina, FAM161A has two isoforms: the long one with exon 4, and the short one without it. To restore CC in Fam161a-deficient mice shortly after the onset of cilium disorganization, we compared AAV vectors with varying promoter activities, doses, and human isoforms. While all vectors improved cell survival, only the combination of both isoforms using the weak FCBR1-F0.4 promoter enabled precise FAM161A expression in the CC and enhanced retinal function. Our investigation into FAM161A gene replacement for RP28 emphasizes the importance of precise therapeutic gene regulation, appropriate vector dosing, and delivery of both isoforms. This precision is pivotal for secure gene therapy involving structural proteins like FAM161A., (© 2024. The Author(s).)

Though the portfolio of medicines that are extending and improving the lives of patients continues to grow, drug discovery and development remains a challenging business on its best day. Safety liabilities are a significant contributor to development attrition where the costliest liabilities to both drug developers and patients emerge in late development or post-marketing. Animal studies are an important and influential contributor to the current drug discovery and development paradigm intending to provide evidence that a novel drug candidate can be used safely and effectively in human volunteers and patients. However, translational gaps-such as toxicity in patients not predicted by animal studies-have prompted efforts to improve their effectiveness, especially in safety assessment. More holistic monitoring and "digitalization" of animal studies has the potential to enrich study outcomes leading to datasets that are more computationally accessible, translationally relevant, replicable, and technically efficient. Continuous monitoring of animal behavior and physiology enables longitudinal assessment of drug effects, detection of effects during the animal's sleep and wake cycles and the opportunity to detect health or welfare events earlier. Automated measures can also mitigate human biases and reduce subjectivity. Reinventing a conservative, standardized, and traditional paradigm like drug safety assessment requires the collaboration and contributions of a broad and multi-disciplinary stakeholder group. In this perspective, we review the current state of the field and discuss opportunities to improve current approaches by more fully leveraging the power of sensor technologies, artificial intelligence (AI), and animal behavior in a home cage environment., Competing Interests: BB is self-employed as a consultant to TLR Ventures. SB is employed by VeriSIM Life. NB-P and TR are employed by TLR Ventures. C-NL is employed by Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Berridge, Baran, Kumar, Bratcher-Petersen, Ellis, Liu and Robertson.)

Silent information regulator 1 (SIRT1) is a NAD + -dependent class III deacetylase that plays important roles in the pathogenesis of numerous diseases, positioning it as a prime candidate for therapeutic intervention. Among its modulators, SRT2104 emerges as the most specific small molecule activator of SIRT1, currently advancing into the clinical translation phase. The primary objective of this review is to evaluate the emerging roles of SRT2104, and to explore its potential as a therapeutic agent in various diseases. In the present review, we systematically summarized the findings from an extensive array of literature sources including the progress of its application in disease treatment and its potential molecular mechanisms by reviewing the literature published in databases such as PubMed, Web of Science, and the World Health Organization International Clinical Trials Registry Platform. We focuses on the strides made in employing SRT2104 for disease treatment, elucidating its potential molecular underpinnings based on preclinical and clinical research data. The findings reveal that SRT2104, as a potent SIRT1 activator, holds considerable therapeutic potential, particularly in modulating metabolic and longevity-related pathways. This review establishes SRT2104 as a leading SIRT1 activator with significant therapeutic promise., (© 2024. The Author(s).)

Adeno-associated virus (AAV)-based vectors are commonly used for delivering transgenes in gene therapy studies, but they are also known to cause dorsal root ganglia (DRG) and peripheral nerve toxicities in animals. However, the functional implications of these pathologic findings and their time course remain unclear. At 2, 4, 6, and 8 weeks following a single dose of an AAV9 vector carrying human frataxin transgene in rats, non-standard functional assessments, including von Frey filament, electrophysiology, and Rotarod tests, were conducted longitudinally to measure allodynia, nerve conduction velocity, and coordination, respectively. Additionally, DRGs, peripheral nerves, brain and spinal cord were evaluated histologically and circulating neurofilament light chain (NfL) was quantified at 1, 2, 4, and 8 weeks, respectively. At 2 and 4 weeks after dosing, minimal-to-moderate nerve fiber degeneration and neuronal degeneration were observed in the DRGs in some of the AAV9 vector-dosed animals. At 8 weeks, nerve fiber degeneration was observed in DRGs, with or without neuronal degeneration, and in sciatic nerves of all AAV9 vector-dosed animals. NfL values were higher in AAV9 vector-treated animals at weeks 4 and 8 compared with controls. However, there were no significant differences in the three functional endpoints evaluated between the AAV9 vector- and vehicle-dosed animals, or in a longitudinal comparison between baseline (predose), 4, and 8 week values in the AAV9 vector-dose animals. These findings demonstrate that there is no detectable functional consequence to the minimal-to-moderate neurodegeneration observed with our AAV9 vector treatment in rats, suggesting a functional tolerance or reserve for loss of DRG neurons after systemic administration of AAV9 vector., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Most membrane proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, shielding potentially large fractions of protein surface. High glycan conformational freedom hinders complete structural elucidation of glycoproteins. Computer simulations may be used to model glycosylated proteins but require hundreds of thousands of computing hours on supercomputers, thus limiting routine use. Here, we describe GlycoSHIELD, a reductionist method that can be implemented on personal computers to graft realistic ensembles of glycan conformers onto static protein structures in minutes. Using molecular dynamics simulation, small-angle X-ray scattering, cryoelectron microscopy, and mass spectrometry, we show that this open-access toolkit provides enhanced models of glycoprotein structures. Focusing on N-cadherin, human coronavirus spike proteins, and gamma-aminobutyric acid receptors, we show that GlycoSHIELD can shed light on the impact of glycans on the conformation and activity of complex glycoproteins., Competing Interests: Declaration of interests S.v.B., G.H., and M.S. have filed a patent application related to this work: European Patent Application No. 22203671.7 (2022). S.-T.D.H., C.H., and M.S. have filed a patent application related to this work: European Patent Application No. 23307151.3 (2023)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

During the COVID-19 pandemic, Taiwan has implemented strict border controls and community spread prevention measures. As part of these efforts, the government also implemented measures for public transportation. In Taiwan, there are two primary public transportation systems: Taiwan Railways (TR) is commonly utilized for local travel, while the Taiwan High-Speed Rail (THSR) is preferred for business trips and long-distance journeys due to its higher speed. In this study, we examined the impact of these disease prevention measures on the number of passengers and duration of stay in two major public transportation systems during the first community outbreak from April 29th to May 29th, 2021. Using data from a local telecommunications company, our study observed an expected decrease in the number of passengers after the cancellation of non-reserved seats at both TR and THSR stations across all 19 cities in the main island of Taiwan. Surprisingly, however, the duration of stay in some of the cities unexpectedly increased, especially at THSR stations. This unanticipated rise in the duration of stay has the potential to elevate contact probability among passengers and, consequently, the transmission rate. Our analysis shows that intervention policies may result in unforeseen outcomes, highlighting the crucial role of human mobility data as a real-time reference for policymakers. It enables them to monitor the impact of disease prevention measures and facilitates informed, data-driven decision-making., (© 2024. The Author(s).)

Objectives: To investigate the etiology and ossicular pathology of traumatic ossicular injury in Taiwan and examine the hearing outcomes and predictive factors between the titanium prosthesis and autologous incus groups., Methods: We retrospectively analyzed patients with traumatic ossicular injury from 2011 to 2020 in Taiwan. Patients were divided into the titanium or autologous group according to the surgical materials used. The audiometric outcomes and predictive factors of ossiculoplasty were analyzed between groups., Results: Twenty patients with ossicular chain discontinuity were enrolled (8 in the titanium group and 12 in the autologous group). The postoperative hearing threshold (26.6 ± 8.9 dB) and air-bone gap (10.3 ± 5.6 dB) improved significantly compared with the preoperative hearing threshold (50.7 ± 13.3 dB) and air-bone gap (29.9 ± 11.0 dB). The improvements in the hearing threshold and air-bone gap were not significantly different between the titanium and autologous groups. Our patients presented an improvement in hearing restoration with 65% closure of the air-bone gap in 0 to 10 dB range and 30% in 11 to 20 dB range, without sensorineural hearing loss during surgery. Univariate regression analysis revealed that vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative factors influencing the air-bone gap gain., Conclusions: Ossiculoplasty with both titanium prosthesis and autologous materials demonstrated favorable hearing recovery in traumatic ossicular injury. Vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative predictive factors of the hearing benefit after surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Human enteroviruses A71 (EV-A71) and D68 (EV-D68) are the suspected causative agents of hand-foot-and-mouth disease, aseptic meningitis, encephalitis, acute flaccid myelitis, and acute flaccid paralysis in children. Until now, no cure nor mucosal vaccine existed for EV-A71 and EV-D68. Novel mucosal bivalent vaccines are highly important for preventing EV-A71 and EV-D68 infections., Methods: In this study, formalin-inactivated EV-A71 and EV-D68 were used as antigens, while PS-G, a polysaccharide from Ganoderma lucidum, was used as an adjuvant. Natural polysaccharides have the characteristics of intrinsic immunomodulation, biocompatibility, low toxicity, and safety. Mice were immunized intranasally with PBS, EV-A71, EV-D68, or EV-A71 + EV-D68, with or without PS-G as an adjuvant., Results: The EV-A71 + EV-D68 bivalent vaccine generated considerable EV-A71- and EV-D68-specific IgG and IgA titres in the sera, nasal washes, saliva, bronchoalveolar lavage fluid, and feces. These antibodies neutralized EV-D68 and EV-A71 infectivity. They also cross-neutralized infections by different EV-D68 and EV-A71 sub-genotypes. Furthermore, compared with the PBS group, EV-A71 + EV-D68 + PS-G-vaccinated mice exhibited an increased number of EV-D68- and EV-A71-specific IgA- and IgG-producing cells. In addition, T-cell proliferative responses, and IFN-γ and IL-17 secretion in the spleen were substantially induced when PS-G was used as an adjuvant with EV-A71 + EV-D68. Finally, in vivo challenge experiments demonstrated that the immune sera induced by EV-A71 + EV-D68 + PS-G conferred protection in neonate mice against lethal EV-A71 and EV-D68 challenges as indicated by the increased survival rate and decreased clinical score and viral RNA tissue expression. Taken together, all EV-A71/EV-D68 + PS-G-immunized mice developed potent specific humoral, mucosal, and cellular immune responses to EV-D68 and EV-A71 and were protected against them., Conclusions: These findings demonstrated that PS-G can be used as a potential adjuvant for EV-A71 and EV-D68 bivalent mucosal vaccines. Our results provide useful information for the further preclinical and clinical development of a mucosal bivalent enterovirus vaccine against both EV-A71 and EV-D68 infections., (© 2023. The Author(s).)

Background: Evidence for the effects of immunotherapy in non-small cell lung cancer (NSCLC) patients with distant organ metastasis is insufficient, and the predictive efficacy of established markers in tissue and blood is elusive. Our study aimed to determine the prognostic factors and develop a survival prognosis model for these patients., Methods: A total of 100 advanced NSCLC patients with distant organ metastases, who received single or combination immune checkpoint inhibitors (ICIs) in Xijing Hospital between June 2018 and June 2021, were enrolled for retrospective analysis. The major clinicopathological parameters were collected, and associated survival outcomes were followed up by telephone or inpatient follow-up for nearly 3 years to assess prognoses. The survival prognosis model was established based on univariate and multivariate Cox regression analyses to determine the candidate prognostic factors., Results: From the start of immunotherapy to the last follow-up, 77 patients progressed and 42 patients died, with a median follow-up of 18 months [95% confidence interval (CI): 15-19.9]. The median progression-free survival (PFS) and overall survival (OS) were 8 months (95% CI: 5.6-10.4) and 21 months (95% CI: 8.9-33.1), respectively. Multivariate Cox proportional hazards analysis showed Eastern Cooperative Oncology Group performance status (ECOG PS), body mass index (BMI), age-adjusted Charlson comorbidity index (ACCI), lactate dehydrogenase (LDH), and absolute neutrophil count (ANC) were correlated significantly with OS. Based on these five predictive factors, a nomogram and corresponding dynamic web page were constructed with a concordance index (C-index) of 0.81 and a 95% CI of 0.778-0.842. Additionally, the calibration plot and time-receiver operating characteristic (ROC) curve validated the precision of the model at 6-, 12-, and 18-month area under the curves (AUCs) reached 0.934, 0.829, and 0.846, respectively. According to the critical point of the model, patients were further divided into a high-risk total point score (TPS) >258, middle-risk (204< TPS ≤258), and low-risk group (TPS ≤204), and significant OS differences were observed among the three subgroups (median OS: 4.8 vs. 13.0 vs. 32.9 months)., Conclusions: A feasible and practical model based on clinical characteristics has been developed to predict the prognosis of NSCLC patients with distant organ metastasis undergoing immunotherapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-480/coif). The authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

PPCPs (pharmaceuticals and personal care products) are widely found in the environment and can be a risk to human and ecosystem health. In this study, spatiotemporal distribution, critical risk source identification and potential risks of 14 PPCPs found in water collected from sampling points in Luoma Lake and its inflowing rivers in two seasons in 2019 and 2020 were investigated. The PPCPs concentrations ranged from 27.64 ng·L -1 to 613.08 ng·L -1 in December 2019, and from 16.67 ng·L -1 to 3287.41 ng·L -1 in April 2020. Ketoprofen (KPF) dominated the PPCPs with mean concentrations of 125.85 ng·L -1 and 640.26 ng·L -1 , respectively. Analysis of sources showed that the pollution in Luoma Lake mostly originated from sewage treatment plant effluents, inflowing rivers and domestic wastewater. Among them, the inflowing rivers contributed the most (82.95%) to the concentration of total PPCPs. The results of ecological risk assessment showed that there was a moderate risk (0.1 < RQs < 1) from carbamazepine (CBZ) in December 2019 and a high risk (RQs > 1) from naproxen (NPX) in April 2020. The results of human risk assessment found that NPX posed a high risk to infant health, and we found that NPX was associated with 83 diseases according to Comparative Toxicogenomics Database. NPX was identified as a substance requiring major attention. The results provide an understanding of the concentrations and ecological risks of PPCPs in Luoma Lake. We believe the data will support environmental departments to develop management strategies and prevent PPCPs pollution., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The lower respiratory tract microbiome is widely studied to pinpoint microbial dysbiosis of diversity or abundance that is linked to a number of chronic respiratory illnesses. However, it is vital to clarify how the microbiome, through the release of microbial metabolites, impacts lung health and oncogenesis., Methods: In order to discover the powerful correlations between microbial metabolites and disease, we collected, under electronic bronchoscopy examinations, samples of paired bronchoalveolar lavage fluids (BALFs) from tumor-burden lung segments and ipsilateral non-tumor sites from 28 lung cancer participants, further performing metagenomic sequencing, short-chain fatty acid (SCFA) metabolomics, and multiomics analysis to uncover the potential correlations of the microbiome and SCFAs in lung cancer., Results: In comparison to BALFs from normal lung segments of the same participant, those from lung cancer burden lung segments had slightly decreased microbial diversity in the lower respiratory tract. With 18 differentially prevalent microbial species, including the well-known carcinogens Campylobacter jejuni and Nesseria polysaccharea , the relative species abundance in the lower respiratory tract microbiome did not significantly differ between the two groups. Additionally, a collection of commonly recognized probiotic metabolites called short-chain fatty acids showed little significance in either group independently but revealed a strong predictive value when using an integrated model by machine learning. Multiomics also discovered particular species related to SCFAs, showing a positive correlation with Brachyspira hydrosenteriae and a negative one with Pseudomonas at the genus level, despite limited detection in lower airways. Of note, these distinct microbiota and metabolites corresponded with clinical traits that still required confirmation., Conclusions: Further analysis of metagenome functional capacity revealed that genes encoding environmental information processing and metabolism pathways were enriched in the lower respiratory tract metagenomes of lung cancer patients, further supporting the oncogenesis function of various microbial species by different metabolites. These findings point to a potent relationship between particular components of the integrated microbiota-metabolites network and lung cancer, with implications for screening and diagnosis in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Chen, Wang, Li, Ju, Zhang, Xi, Wang, Qiu, Liu, Chang, Zhang, Zhang, Wang, Li and Zhang.)

Photoreceptor cell degeneration and death is the major hallmark of a wide group of human blinding diseases including age-related macular degeneration and inherited retinal diseases such as retinitis pigmentosa. In recent years, inherited retinal diseases have become the "testing ground" for novel therapeutic modalities, including gene and cell-based therapies. Currently there is no available treatment for retinitis pigmentosa caused by FAM161A biallelic pathogenic variants. In this study, we injected an adeno-associated virus encoding for the longer transcript of mFam161a into the subretinal space of P24-P29 Fam161a knockout mice to characterize the safety and efficacy of gene augmentation therapy. Serial in vivo assessment of retinal function and structure at 3, 6, and 8 months of age using the optomotor response test, full-field electroretinography, fundus autofluorescence, and optical coherence tomography imaging as well as ex vivo quantitative histology and immunohistochemical studies revealed a significant structural and functional rescue effect in treated eyes accompanied by expression of the FAM161A protein in photoreceptors. The results of this study may serve as an important step toward future application of gene augmentation therapy in FAM161A-deficient patients by identifying a promising isoform to rescue photoreceptors and their function., Competing Interests: Declaration of interests Y.A., C.K., N.C., D.S., and E.B. have filed a provisional application for FAM161A gene therapy on behalf of The Fondation Asile des aveugles, the Hebrew University, and the University of Lausanne., (Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Complete coverage of all N-glycosylation sites on the SARS-CoV2 spike protein would require the use of multiple proteases in addition to trypsin. Subsequent identification of the resulting glycopeptides by searching against database often introduces assignment errors due to similar mass differences between different permutations of amino acids and glycosyl residues. By manually interpreting the individual MS 2 spectra, we report here the common sources of errors in assignment, especially those introduced by the use of chymotrypsin. We show that by applying a stringent threshold of acceptance, erroneous assignment by the commonly used Byonic software can be controlled within 15%, which can be reduced further if only those also confidently identified by a different search engine, pGlyco3, were considered. A representative site-specific N-glycosylation pattern could be constructed based on quantifying only the overlapping subset of N-glycopeptides identified at higher confidence. Applying the two complimentary glycoproteomic software in a concerted data analysis workflow, we found and confirmed that glycosylation at several sites of an unstable Omicron spike protein differed significantly from those of the stable trimeric product of the parental D614G variant., (© 2023 Wiley-VCH GmbH.)

Histone deacetylases (HDACs) has been implicated in cardiac diseases, while the role of HDAC6 in dilated cardiomyopathy (DCM) remains obscure. The in silico analyses predicted potential association of HDAC6 with autophagy-related genes and DCM. Thus, we evaluated the functional relevance of HDAC6 in DCM in vivo and in vitro. We developed a rat model in vivo and a cell model in vitro by doxorubicin (DOX) induction to simulate DCM. HDAC6 expression was determined in myocardial tissues of DCM rats. DCM rats exhibited elevated HDAC6 mRNA and protein expression as compared to sham-operated rats. We knocked HDAC6 down and/or overexpressed NLRP3 in vivo and in vitro to characterize their roles in cardiomyocyte autophagy. It was established that shRNA-mediated HDAC6 silencing augmented cardiomyocyte autophagy and suppressed NLRP3 inflammasome activation, thus ameliorating cardiac injury in myocardial tissues of DCM rats. Besides, in DOX-injured cardiomyocytes, HDAC6 silencing also diminished NLRP3 inflammasome activation and cell apoptosis but enhanced cell autophagy, whereas ectopic NLRP3 expression negated the effects of HDAC6 silencing. Since HDAC6 knockdown correlates with enhanced cardiomyocyte autophagy and suppressed NLRP3 inflammasome activation through an interplay with NLRP3, it is expected to be a potential biomarker and therapeutic target for DCM. 1. HDAC6 was up-regulated in DCM rats. 2. HDAC6 knockdown promoted cardiomyocyte autophagy to relieve cardiac dysfunction. 3. HDAC6 knockdown inhibited NLRP3 inflammasome and promoted cardiomyocyte autophagy. 4. Silencing HDAC6 promoted autophagy and repressed apoptosis in cardiomyocytes. 5. This study provides novel therapeutic targets for DCM., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Blastocystis is a common zoonotic intestinal protozoan and causes a series of gastrointestinal symptoms in humans and animals via the fecal-oral route, causing economic losses and posing public health problems. At present, the prevalence and genetic structure of Blastocystis in sheep and pigs in Shanxi province remains unknown. Thus, the present study collected 492 sheep fecal samples and 362 pig fecal samples from three representative counties in northern, central and southern Shanxi province for the detection of Blastocystis based on its SSU rRNA gene. The results showed that the overall prevalence of Blastocystis in the examined sheep and pigs were 16.26% and 14.09%, respectively. Sequences analyses showed that four known subtypes (ST5, ST10, ST14 and ST30) in sheep and two subtypes (ST1 and ST5) in pigs were detected in this study, with ST5 being the predominate subtype among the study areas. Phylogenetic analysis showed that the same subtypes were clustered into the same branch. This study reveals that sheep and pigs in Shanxi province are hosts for multiple Blastocystis subtypes, including the zoonotic subtypes (ST1 and ST5), posing a risk to public health. Baseline epidemiological data are provided that help in improving our understanding of the role of zoonotic subtypes in Blastocystis transmission.

Asthma, a prevalent disease characterized by innate and adaptive immune responses, has been associated with several risk factors including miR-146a. To better understand the potential impact of miR-146a SNPs on asthma susceptibility and clinical features in Southern Chinese Han population, we conducted a case-control to analyze two functional SNPs (rs2910164 and rs57095329) of the miR-146a (394 patients with asthma and 395 healthy controls). Our findings suggest that the rs2910164 C/G genotype may increase the risk for asthma in females, while the rs57095329 G/G genotype may be involved in the regulation of clinical characteristics of males with asthma. In addition, we demonstrated that the SNPs rs2910164 C/G and rs57095329 A/G variations functionally affected the miR-146a levels in patients with asthma, and may alter structure of miR-146a. Our data are the first to suggest that miR-146a SNPs may be significantly associated with onset asthma in Southern Chinese Han population. Our studies may provide new insight into the potential significance of miR-146a SNPs in asthma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by systemic inflammation of the joints and extra-articular tissues. The incidence of cardiovascular disease (CVD) remains the main cause of morbidity and mortality in patients with RA. Despite the development of new therapeutics targeting the articular manifestations, the relief of the cardiovascular burden is still an unmet medical need during the management of RA. So, the early prognosis of RA-associated CVD plays a crucial role in improving the clinical outcomes of RA patients. Recently, circulating dimethylarginines have gained attention as potential biomarkers for CVDs. Here, we present the development and validation of a high-throughput liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for simultaneous quantification of creatinine, arginine, and dimethylarginines in human serum within 2 mins by isotope dilution mass spectrometry. This method employed a protein precipitation method for rapid sample preparation, trichloroacetic acid (TCA)-based ion pairing chromatography for fast analyte separation, and multiple reaction monitoring (MRM) with stable isotope-labeled internal standards (ISs) for simultaneous quantitation. To assure the quality, our method was validated against the FDA guidelines for lower limit of quantitation (0.2 µM), linearity (square of coefficient correlation>0.99), precision (intra-&inter-assay imprecision < 10 %), accuracy (intra-&inter-assay inaccuracy < 10 %), sample preparation recovery (recovery ≥ 90 %), stability (instability < 10 %), matrix effect (signal suppression < 55 %), and carryover ( < 0.01 %). Afterward, we applied the validated method to a retrospective cross-sectional study. We aimed to evaluate the utility of serological dimethylarginines as potential cardiovascular biomarkers in the development of RA-associated CVD. Our results revealed that the serological ratio of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), an indicator of physiological arginine methylation status, was significantly elevated in patients with RA. This finding might provide value in detecting CVD to improve clinical outcomes in RA management., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Qianyang Huang, Fujian Jia, Chunchao Pu, Dandan Ma, Lei Xu, Hua Zhang, Xin Liu, Kang Liu reports financial support was provided by Shenzhen Kanghua Juntai Biotech Co. Ltd. Qianyang Huang, Fujian Jia, Chunchao Pu, Dandan Ma, Lei Xu, Hua Zhang, Xin Liu, Kang Liu reports a relationship with Shenzhen Kanghua Juntai Biotech Co. Ltd. that includes: employment. Conflict of interest The authors Q.H., F.J., C.P., D.M., L.X., H.Z., X.L. and K.L.are current employees of Shenzhen Kanghua Juntai Biotech Co. Ltd. All other authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disorder with a dismal prognosis. The dysregulation of histone acetylation is of great significance in the pathogenesis and progression of B-ALL. Regarded as a fundamental acetyltransferase gene, the role of HBO1 (lysine acetyltransferase 7/KAT7) in B-ALL has not been investigated. Herein, we found that HBO1 expression was elevated in human B-ALL cells and associated with poor disease-free survival. Strikingly, HBO1 knockdown inhibited viability, proliferation, and G1-S cycle progression in B-ALL cells, while provoking apoptosis. In contrast, ectopic overexpression of HBO1 enhanced cell viability and proliferation but inhibited apoptotic activation. The results of in vivo experiments also certificated the inhibitory effect of HBO1 knockdown on tumor growth. Mechanistically, HBO1 acetylated histone H3K14, H4K8, and H4K12, followed by upregulating CTNNB1 expression, resulting in activation of the Wnt/β-catenin signaling pathway. Moreover, a novel small molecule inhibitor of HBO1, WM-3835, potently inhibited the progression of B-ALL. Our data identified HBO1 as an efficacious regulator of CTNNB1 with therapeutic potential in B-ALL., (© 2023. The Author(s).)

Background: The use of anti-PD-1 or PD-L1 inhibitors in combination with other anti-cancer agents was a priority for treating advanced non-small cell lung cancer (NSCLC) patients with considerable PD-L1 expression. However, studies seldom show the progression of liver metastases after using immune checkpoint inhibitors (ICIs)., Methods: Data were obtained from the Department of Pulmonary and Critical Care of Medicine, the First Affiliated Hospital of the Air Force Military Medical University. In the present study, we analyzed five non-small cell lung cancer (NSCLC) patients who had liver metastases after they were treated with pembrolizumab between 2019 and 2021. All of them had both stable primary lesions and liver progression with pembrolizumab intervention. Blood laboratory tests and imaging examinations were performed regularly during the treatment to assess the tumor responses of patients., Results: All patients displayed reduction or stability in the initial lesions as a result, but they also experienced the emergence of metastatic liver locations, which were regularly detected throughout immunotherapy. Additionally, the appearance of liver metastasis weakened their liver function gradually with the escalation of carcinoembryonic antigen, regarded as a predictor for evaluating the progression of tumors. These individuals were highly distinctive with hyper-progressive diseases associated with immunotherapy. We drew individualized intervention schemes for metastatic lesions in each patient and found that their life expectancy shared no significance given the restricting subjected population., Conclusions: Our study indicated a clinical phenomenon after using immune checkpoint inhibitors and presented a necessity for implementing large scales clinical studies to manage NSCLC-oriented liver metastasis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The recent discovery of the head-direction (HD) system in fruit flies has provided unprecedented insights into the neural mechanisms of spatial orientation. Despite the progress, the neural substance of global inhibition, an essential component of the HD circuits, remains controversial. Some studies suggested that the ring neurons provide global inhibition, while others suggested the Δ7 neurons. In the present study, we provide evaluations from the theoretical perspective by performing systematic analyses on the computational models based on the ring-neuron (R models) and Δ7-neurons (Delta models) hypotheses with modifications according to the latest connectomic data. We conducted four tests: robustness, persistency, speed, and dynamical characteristics. We discovered that the two models led to a comparable performance in general, but each excelled in different tests. The R Models were more robust, while the Delta models were better in the persistency test. We also tested a hybrid model that combines both inhibitory mechanisms. While the performances of the R and Delta models in each test are highly parameter-dependent, the Hybrid model performed well in all tests with the same set of parameters. Our results suggest the possibility of combined inhibitory mechanisms in the HD circuits of fruit flies., (© 2023. The Author(s).)

Background: Many factors are thought to be associated with the development of cholesteatoma, while the mechanisms of its formation remain unclear. This study aimed to identify the potential mechanisms of the proliferation and growth of cholesteatoma by analysis of the differential expressions of proteins in cholesteatoma and retroauricular skin tissue collected from the same patients., Methods: The present study is a retrospective study performed in an academic medical center. Comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), in addition to immunohistochemical analysis, were conducted to identify differentially-expressed proteins in cholesteatoma tissue as compared with retroauricular skin tissue. Western blotting was also employed to verify the expression patterns of the specific proteins identified by 2-DE and to measure the changes in potential modulators related to cholesteatoma proliferation and growth., Results: Calreticulin (CRT) and annexin A2 (AnxA2) were identified as being differentially-expressed in cholesteatoma by 2-DE and LC-MS/MS, the results of which were in agreement with the results of immunohistochemical analysis and western blotting. Downregulation of CRT and AnxA2 were observed in cholesteatoma., Conclusion: Our data suggests that CRT and AnxA2 downregulation are seen in cholesteatoma compared to retroauricular skin. We speculate that the reduced expression of CRT and the persistent inflammatory response play important roles in the epithelial proliferation of cholesteatoma.

Introduction: Wistar Han rats are a preferred strain of rodents for general toxicology and safety pharmacology studies in drug development. In some of these studies, visual functional tests that assess for retinal toxicity are included as an additional endpoint. Although the influence of gender on human retinal function has been documented for more than 6 decades, preclinically it is still uncertain if there are differences in retinal function between naïve male and female Wistar Han rats. Methods: In this study, sex-related differences in the retinal function were quantified by analyzing electroretinography (ERG) in 7-9-week-old ( n = 52 males and 51 females) and 21-23-week-old Wistar Han rats ( n = 48 males and 51 females). Optokinetic tracking response, brainstem auditory evoked potential, ultrasonic vocalization and histology were tested and evaluated in a subset of animals to investigate the potential compensation mechanisms of spontaneous blindness. Results/Discussion: Absence of scotopic and photopic ERG responses was found in 13% of 7-9-week-old (7/52) and 19% of 21-23-week-old males (9/48), but none of female rats (0/51). The averaged amplitudes of rod- and cone-mediated ERG b -wave responses obtained from males were significantly smaller than the amplitudes of the same responses from age-matched females (-43% and -26%, respectively) at 7-9 weeks of age. There was no difference in the retinal and brain morphology, brainstem auditory responses, or ultrasonic vocalizations between the animals with normal and abnormal ERGs at 21-23 weeks of age. In summary, male Wistar Han rats had altered retinal responses, including a complete lack of responses to test flash stimuli (i.e., blindness), when compared with female rats at 7-9 and 21-23 weeks of age. Therefore, sex differences should be considered when using Wistar Han rats in toxicity and safety pharmacology studies with regards to data interpretation of retinal functional assessments., Competing Interests: All authors were employed by Pfizer at the time of the study., (Copyright © 2023 Tyszkiewicz, Hwang, Manickam, Jakubczak, Walters, Bolt, Santos and Liu.)

Purpose: To analyze the prevalence and associations of facial canal dehiscence (FCD), dural exposure, and labyrinthine fistula in chronic otitis media (COM) with and without cholesteatoma., Methods: This was a retrospective study performed in an academic medical center. Patients who received tympanoplasty with mastoidectomy for COM with and without cholesteatoma were included. The prevalence of FCD, dural exposure, and labyrinthine fistula in COM with and without cholesteatoma (mastoiditis) and their relationships were analyzed., Results: A total of 189 patients, including 107 (56.6%) females and 82 (43.4%) males, with 191 ears were included. There were 149 cases (78.0%) of cholesteatoma and 42 patients (22.0%) with mastoiditis. FCD was noted in 27.5% of patients with cholesteatoma and 9.5% of patients with mastoiditis. Dural exposure was found in 21 patients (14.1%) with cholesteatoma and 4 patients (9.5%) with mastoiditis. Eleven patients (7.4%) with cholesteatoma and 1 patient (2.4%) with mastoiditis had labyrinthine fistula. Patients with a labyrinthine fistula had nearly a fivefold greater chance (OR = 4.924, 95% CI = 1.355-17.896, p = 0.015) of having FCD than those without a fistula. There was a positive correlation between dural exposure and labyrinthine fistula (P = 0.011, Fisher's exact test)., Conclusion: FCD, dural exposure, and labyrinthine fistula are common complications in COM. These complications are more frequently observed in patients with cholesteatoma than in patients with mastoiditis. Surgeons should pay more attention to the treatment of COM., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Myocyte enhancer factor 2D (MEF2D) is involved in the progression of various malignant tumors. However, its impact on B-cell acute lymphoblastic leukemia (B-ALL) has not been elucidated., Methods: In this study, the expression level of MEF2D in B-ALL patients was validated through the Gene Expression Omnibus (GEO) database and clinical specimens. MEF2D-knockdown B-ALL cell lines were constructed by lentivirus transfection, and the effects of MEF2D on the viability, apoptosis, cycle progression, and drug sensitivity of B-ALL cells were verified by Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM). The effect of MEF2D on the proliferation of B-ALL cells in vivo was verified via the construction of a xenograft mouse model. The mechanism of MEF2D regulating B-ALL cells was explored by RNA sequencing analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemical (IHC)., Results: In this study, overexpression of MEF2D was observed in B-ALL patients and was remarkably correlated to disease progression in ALL patients. The knockdown of MEF2D expression suppressed cell viability, induced cell apoptosis, blockaded cell cycle progression, enhanced drug sensitivity of B-ALL cells in vitro , and reduced the tumor load in vivo . Furthermore, mechanistic studies revealed that MEF2D knockdown downregulated the expression of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway., Conclusions: Our research demonstrated that MEF2D was markedly expressed in B-ALL. MEF2D knockdown inhibited cancer progression of B-ALL both in vitro and in vivo , which may be related to the downregulation of the PI3K-AKT signaling pathway. The data suggest that MEF2D plays a vital role in the process of tumorigenesis and may be a potential novel target for B-ALL therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-1778/coif). All authors report that this work was supported by the Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (No. 2018GZR110105014) and the Science and Technology Planning Project of Guangdong Province, China (No. 2018B030311042). The authors have no other conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

Background: The glucocorticoid receptor gene (NR3C1) encodes the receptor to which cortisol and other glucocorticoids bind. Steroids in either oral, intratympanic, or intravascular forms are the treatment of choice for sudden sensorineural hearing loss (SSNHL), but the outcome varies. The outcomes of SSNHL have been investigated for related factors, including age, initial hearing loss severity and pattern, vertigo, genetic variations, and the time between onset and treatment. The objective of the present study was to analyze the association of genetic polymorphisms of NR3C1 with the outcomes of SSNHL., Materials and Methods: We conducted a comparison study of 93 cases with a poor outcome (control) and 100 cases with a good outcome (case) in SSNHL patients. Six single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology., Results: The heterozygous AT genotype of rs17100289 was associated with a poor outcome in comparison with the major homozygous AA genotype after adjustments for age and sex (OR = 0.50; 95% CI 0.26-0.95; P = 0.035) in SSNHL patients. The CT genotype of rs4912912 was also associated with a poor outcome compared with the major homozygous TT genotype after the adjustments (OR = 0.47; 95% CI 0.24-0.92; P = 0.026)., Conclusion: These results suggest that NR3C1 genetic polymorphisms may influence the outcomes of SSNHL., (© 2023. The Author(s).)

Circular RNAs (circRNAs), a type of covalently closed endogenous single-stranded RNA, have been regarded as the byproducts of the aberrant splicing of genes without any biological functions. Recently, with the development of high-throughput sequencing and bioinformatics, thousands of circRNAs and their differential biological functions have been identified. Except for the great advances in identifying circRNA roles in tumor progression, diagnosis, and treatment, accumulated evidence shows that circRNAs are enriched in the brain, especially in the synapse, and dynamically change with the development or aging of organisms. Because of the specific roles of synapses in higher-order cognitive functions, circRNAs may not only participate in cognitive functions in normal physiological conditions but also lead to cognition-related diseases after abnormal regulation of their expression or location. Thus, in this review, we summarized the progress of studies looking at the role of circRNA in cognitive function, as well as their involvement in the occurrence, development, prognosis, and treatment of cognitive-related diseases, including autism, depression, and Alzheimer's diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Liu, Chang, Fu, Guo and Wang.)

Plasmonic tweezers are an emerging research topic because of their low input power and wide operating range from homogeneous particles to complex biological objects. But it is still challenging for plasmonic tweezers to trap or manipulate objects of tens of microns, especially in biological science. This study introduces a new 3D biocompatible plasmonic tweezer for single living cell manipulation in solution. The key design is a tapered tip whose three-layer surface structure consists of nanoprobe, gold nanofilm, and thermosensitive hydrogel, thiolated poly(N-isopropylacrylamide). Incident light excites the surface plasmon polaritons on gold film and generates heat to induce thermally driven phase transition of the thermosensitive hydrogel, which enables reversible binding between functionalized surface and cell membrane and avoids both thermal and mechanical stresses in the meanwhile. The 3D biocompatible plasmonic tweezer realizes selective capture, 3D pathway free transport, and position-controlled release of target cells, and it displays excellent biocompatibility, low energy consumption, and high operational flexibility., (© 2023 Wiley-VCH GmbH.)

Excessive use of nitrogen (N) fertilizer for sugarcane cultivation is a significant cause of greenhouse gas emission. N use-efficiency (NUE) of sugarcane is relatively low, and considerable effort is now directed to exploit biological nitrogen fixation (BNF) in sugarcane. We hypothesize that genetic base-broadening of sugarcane using high-BNF Saccharum spontaneum , a wild progenitor of sugarcane, will help develop N-efficient varieties. We found remarkable genetic variation for BNF and growth in S. spontaneum accessions, and BNF in some accessions remained highly resilient to inorganic N application. Physiological and molecular analyses of two S. spontaneum accessions with high-BNF capacity and growth, namely G152 and G3, grown under N replete and low N conditions showed considerable similarity for total N, NH 4 -N, soluble sugar, indoleacetic acid, gibberellic acid, zeatin and abscisic acid content; yet, they were strikingly different at molecular level. Global gene expression analysis of G152 and G3 grown under contrasting N supply showed genotype effect explaining much of the gene expression variation observed. Differential gene expression analysis found an over-representation of carbohydrate and amino acid metabolism and transmembrane transport genes in G152 and an enrichment of lipid metabolism and single-organism processes genes in G3, suggesting that distinctly divergent metabolic strategies are driving N-related processes in these accessions. This was attested by the remarkable variation in carbon, N, amino acid and hormone metabolism-related gene expression in G152 and G3 under high- and low-N supply. We conclude that both accessions may be achieving similar BNF and growth phenotypes through overlapping but distinctly different biochemical and molecular mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luo, Li, Yan, Huang, Li, Liu and Lakshmanan.)

Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling. Most asthmatic patients are well-established using standard treatment strategies and advanced biologicals. However, a small group of patients who do not respond to biological treatments or are not effectively controlled by available treatment strategies remain a clinical challenge. Therefore, new therapies are urgently needed for poorly controlled asthma. Mesenchymal stem/stromal cells (MSCs) have shown therapeutic potential in relieving airway inflammation and repairing impaired immune balance in preclinical trials owing to their immunomodulatory abilities. Noteworthy, MSCs exerted a therapeutic effect on steroid-resistant asthma with rare side effects in asthmatic models. Nevertheless, adverse factors such as limited obtained number, nutrient and oxygen deprivation in vitro , and cell senescence or apoptosis affected the survival rate and homing efficiency of MSCs, thus limiting the efficacy of MSCs in asthma. In this review, we elaborate on the roles and underlying mechanisms of MSCs in the treatment of asthma from the perspective of their source, immunogenicity, homing, differentiation, and immunomodulatory capacity and summarize strategies to improve their therapeutic effect.

Two-dimensional layered materials have attracted tremendous attention as photodetectors due to their fascinating features, including comprehensive coverage of band gaps, high potential in new-generation electronic devices, mechanical flexibility, and sensitive light-mass interaction. Currently, graphene and transition-metal dichalcogenides (TMDCs) are the most attractive active materials for constructing photodetectors. A growing number of emerging TMDCs applied in photodetectors bring up opportunities in the direct band gap independence with thickness. This study demonstrated for the first time a photodetector based on a few-layer Re x Mo 1- x S 2 , which was grown by chemical vapor deposition (CVD) under atmospheric pressure. The detailed material characterizations were performed using Raman spectroscopy, photoluminescence, and X-ray photoelectron spectroscopy (XPS) on an as-grown few-layer Re x Mo 1- x S 2 . The results show that both MoS 2 and ReS 2 peaks appear in the Re x Mo 1- x S 2 Raman diagram. Re x Mo 1- x S 2 is observed to emit light at a wavelength of 716.8 nm. The electronic band structure of the few layers of Re x Mo 1- x S 2 calculated using the first-principles theory suggests that the band gap of Re x Mo 1- x S 2 is larger than that of ReS 2 and smaller than that of MoS 2 , which is consistent with the photoluminescence results. The thermal stability of the few layers of Re x Mo 1- x S 2 was evaluated using Raman temperature measurements. It is found that the thermal stability of Re x Mo 1- x S 2 is close to those of pure ReS 2 and MoS 2 . The fabricated Re x Mo 1- x S 2 photodetector shows a high response rate of 7.46 A W -1 under 365 nm illumination, offering a competitive performance to the devices based on TMDCs and graphenes. This study unambiguously distinguishes Re x Mo 1- x S 2 as a future candidate in electronics and optoelectronics., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: The crosstalk between the ubiquitin-proteasome and the immune system plays an important role in the health and pathogenesis of viral infection. However, there have been few studies of ubiquitin activation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Methods: We investigated the effect of ubiquitination on SARS-CoV-2 infection and patient prognosis by integrating published coronavirus disease 2019 (COVID-19) multi-transcriptome data and bioinformatics methods., Results: The differential expression of COVID-19 samples revealed changed ubiquitination in most solid and hollow organs, and it was activated in lymphatic and other immune tissues. In addition, in the respiratory system of COVID-19 patients, the immune response was mainly focused on the alveoli, and the expression of ubiquitination reflected increasing immune infiltration. Ubiquitination stratification could significantly differentiate patients' prognosis and inflammation levels through the general transcriptional analysis of the peripheral blood of patients with COVID-19. Moreover, high ubiquitination levels were associated with a favourable prognosis, low inflammatory response, and reduced mechanical ventilation and intensive care unit. Moreover, high ubiquitination promoted a beneficial immune response while inhibiting immune damage. Finally, prognostic stratification and biomarker screening based on ubiquitination traits played an important role in clinical management and drug development., Conclusion: Ubiquitination characteristics provides new ideas for clinical intervention and prognostic guidance for COVID-19 patients., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Rodents emit ultrasonic vocalizations (USVs) above the human hearing threshold of ~ 20 kHz to communicate emotional states and to coordinate their social interactive behavior. Twenty-two kHz USVs emitted by adult rats have been reported in a variety of aversive social and behavioral situations. They occur not only under painful or restraining conditions but can also be evoked by gentle cutaneous touch or airflow. This study aimed to test if placement of a human hand in a cage can evoke 22-kHz USVs. It was found that 36% of the adult male Sprague-Dawley and 13% of the adult male Wistar Han rats emitted 22-kHz USVs when a gloved hand was introduced into the cages. Average vocalization onset latencies were 5.0 ± 4.4 s (Sprague-Dawley) and 7.4 ± 4.0 s (Wistar Han) and the USVs had a stable frequency (22 kHz) across the calls, ranging from 0.1 to 2.3 seconds in duration. Surprisingly, no 22-kHz USVs were found in any female Wistar Han rats tested. To further explore the mechanisms underlying this observation, we compared retinal function, basal serum corticosterone, and testosterone levels between the 22-kHz USV responders and non-responders. None of these parameters or endpoints showed any significant differences between the two cohorts. The results suggest that the introduction of a gloved-hand inside the cage can trigger adult male albino rats to emit 22-kHz ultrasonic vocalizations. This response should be considered in USV studies and animal welfare., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Hwang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)