Enhancing antibody detection sensitivity in lateral flow immunoassays using endospores of Bacillus subtilis as signal amplifiers.

Antibody detection is the critical first step for tracking the spread of many diseases including COVID-19. Lateral flow immunoassay (LFIA) is the most commonly used method for rapid antibody detection because it is easy-to-use and inexpensive. However, LFIA has limited sensitivity when gold nanoparticles (AuNPs) are used as the signals. In this study, the endospores of Bacillus subtilis were used in combination with AuNP in a LFIA to detect antibodies. The endospores serve as a signal amplifier. The detection limit was about 10-8 M for anti-beta galactosidase antibody detection whereas the detection limit of conventional LFIA is about 10-6 M. Furthermore, the proposed methods have no additional user steps compared with the traditional LFIA. This method, therefore, improved the sensitivity 100-fold without compromising any advantages of LFIA. We believe that the proposed method will be useful for detection of antibodies against HIV, Zika virus, SARS-CoV-2, and so on.

Huaier Polysaccharide Alleviates Dextran Sulphate Sodium Salt-Induced Colitis by Inhibiting Inflammation and Oxidative Stress, Maintaining the Intestinal Barrier, and Modulating Gut Microbiota.

The incidence of ulcerative colitis (UC) is increasing annually, and UC has a serious impact on patients' lives. Polysaccharides have gained attention as potential drug candidates for treating ulcerative colitis (UC) in recent years. Huaier (Trametes robiniophila Murr) is a fungus that has been used clinically for more than 1000 years, and its bioactive polysaccharide components have been reported to possess immunomodulatory effects, antitumour potential, and renoprotective effects. In this study, we aimed to examine the protective effects and mechanisms of Huaier polysaccharide (HP) against UC. Based on the H2O2-induced oxidative stress model in HT-29 cells and the dextran sulphate sodium salt (DSS)-induced UC model, we demonstrated that Huaier polysaccharides significantly alleviated DSS-induced colitis (weight loss, elevated disease activity index (DAI) scores, and colonic shortening). In addition, HP inhibited oxidative stress and inflammation and alleviated DSS-induced intestinal barrier damage. It also significantly promoted the expression of the mucin Muc2. Furthermore, HP reduced the abundance of harmful bacteria Escherichia-Shigella and promoted the abundance of beneficial bacteria Muribaculaceae_unclassified, Anaerotruncus, and Ruminococcaceae_unclassified to regulate the intestinal flora disturbance caused by DSS. Nontargeted metabolomics revealed that HP intervention would modulate metabolism by promoting levels of 3-hydroxybutyric acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE). These results demonstrated that HP had the ability to mitigate DSS-induced UC by suppressing oxidative stress and inflammation, maintaining the intestinal barrier, and modulating the intestinal flora. These findings will expand our knowledge of how HP functions and offer a theoretical foundation for using HP as a potential prebiotic to prevent UC.

Comparison of laser versus cold knife visual internal urethrotomy in the treatment of urethral stricture (stricture length <2 cm): A systematic review and meta-analysis.

PURPOSE: There is still controversy regarding the safety and efficacy of cold knife visual internal urethrotomy and laser incisions for the treatment of urethral stricture. This study aims to compare the results of postoperative long-term and short-term maximum urinary flow rates (Qmax), surgical time, postoperative complications, and 1-year recurrence rates between the cold knife and laser surgery. METHODS: We searched databases including Embase, PubMed, Cochrane, and Clinical Trials.gov to identify relevant literature published in English up to September 2023. We used Stata to compare various parameters. This study is registered in PROSPERO (CRD42023471634). Nine comparative experiments were conducted, involving a total of 659 participants. RESULTS: The laser group showed significantly better results compared to the cold knife group in terms of postoperative 12-month maximum urinary flow rate (mean differences [MD] 2.131; 95% [1.015, 3.249], P < .0001), postoperative bleeding (RR 0.277, 95% [0.079, 0.977], P = .046), and 1-year recurrence rate (RR 0.667, 95% [0.456, 0.976], P = .037). However, there were no significant differences in postoperative 6-month and 3-month Qmax, surgical time, urethral leakage complications, overall complications, and Visual Analog Scale (VAS) scores. CONCLUSION: The current study results suggest that laser urethral incision has greater advantages in the long-term (12 months), 1-year recurrence rate, and bleeding complications compared to cold knife urethral incision in the treatment of urethral stricture (<2 cm). Therefore, laser urethral incision may be a better choice for patients with urethral stricture.

Short-Term Outcomes of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Pure Severe Aortic Regurgitation.

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with pure severe aortic regurgitation (PSAR) who are contraindicated for surgery or have a high surgical risk. However, the therapeutic efficacy and safety of TAVR in low Society of Thoracic Surgeons (STS) score risk patients remain to be clarified. This study aimed to explore the feasibility of TAVR treatment in different STS-risk patients and to compare the adverse events between the groups. In this study, patients with PSAR who underwent TAVR at Zhongshan Hospital, Fudan University, China, during the inclusion period were included and categorized into 3 groups based on STS scores. The baseline data, imaging results, and follow-up data of the patients were documented. Therefore, of 75 TAVR patients, 38 (50.7%) were categorized as low risk (STS <4), and 37 (49.3%) patients were categorized as intermediate and high risk (STS ≥4). Compared with patients at intermediate and high risk, those in the low-risk group were younger, had a lower body mass index, had a lower prevalence of hypertension, chronic obstructive pulmonary disease, and previous percutaneous coronary intervention, and had better cardiac function (p all <0.05). In the hospital and at the 1-month follow-up, the degree of aortic regurgitation and cardiac function were significantly improved. No significant difference was found between the 2 groups in the hospital or during the 30-day follow-up. In conclusion, TAVR for PSAR in low-STS-risk patients is safe and efficient during 30 days of follow-up compared with intermediate- and high-STS-risk groups. TAVR for PSAR should not be limited to inoperable or STS-defined high-risk patients. Long-term follow-up is needed for further investigation.

Wheat peptide alleviates DSS-induced colitis by activating the Keap1-Nrf2 signaling pathway and maintaining the integrity of the gut barrier.

Inflammatory bowel disease (IBD) is difficult to cure, and formulating a dietary plan is an effective means to prevent and treat this disease. Wheat peptide contains a variety of bioactive peptides with anti-inflammatory and antioxidant functions. The results of this study showed that preventive supplementation with wheat peptide (WP) can significantly alleviate the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. WP can increase body weight, alleviate colon shortening, and reduce disease activity index (DAI) scores. In addition, WP improved intestinal microbial disorders in mice with colitis. Based on LC-MS, a total of 313 peptides were identified in WP, 4 of which were predicted to be bioactive peptides. The regulatory effects of WP and four bioactive peptides on the Keap1-Nrf2 signaling pathway were verified in Caco-2 cells. In conclusion, this study demonstrated that WP alleviates DSS-induced colitis by helping maintain gut barrier integrity and targeting the Keap1-Nrf2 axis; these results provided a rationale for adding WP to dietary strategies to prevent IBD.

Association between vitamin B2 intake and prostate-specific antigen in American men: 2003-2010 National Health and Nutrition Examination Survey.

BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.

Scalable Approach to Molecular Motor-Polymer Conjugates for Light-Driven Artificial Muscles.

The integration of molecular machines and motors into materials represents a promising avenue for creating dynamic and functional molecular systems, with potential applications in soft robotics or reconfigurable biomaterials. However, the development of truly scalable and controllable approaches for incorporating molecular motors into polymeric matrices has remained a challenge. Here, it is shown that light-driven molecular motors with sensitive photo-isomerizable double bonds can be converted into initiators for Cu-mediated controlled/living radical polymerization enabling the synthesis of star-shaped motor-polymer conjugates. This approach enables scalability, precise control over the molecular structure, block copolymer structures, and high-end group fidelity. Moreover, it is demonstrated that these materials can be crosslinked to form gels with quasi-ideal network topology, exhibiting light-triggered contraction. The influence of arm length and polymer structure is investigated, and the first molecular dynamics simulation framework to gain deeper insights into the contraction processes is developed. Leveraging this scalable methodology, the creation of bilayer soft robotic devices and cargo-lifting artificial muscles is showcased, highlighting the versatility and potential applications of this advanced polymer chemistry approach. It is anticipated that the integrated experimental and simulation framework will accelerate scalable approaches for active polymer materials based on molecular machines, opening up new horizons in materials science and bioscience.

Mitochondria-associated membranes contribution to exercise-mediated alleviation of hepatic insulin resistance: Contrasting high-intensity interval training with moderate-intensity continuous training in a high-fat diet mouse model.

OBJECTIVE: Mitochondria-associated membranes (MAMs) serve pivotal functions in hepatic insulin resistance (IR). Our aim was to explore the potential role of MAMs in mitigating hepatic IR through exercise and to compare the effects of different intensities of exercise on hepatic MAMs formation in high-fat diet (HFD) mice. METHODS: Male C57BL/6J mice were fed an HFD and randomly assigned to undergo supervised high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). IR was evaluated using the serum triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), glucose tolerance test (GTT), and insulin tolerance test (ITT). Hepatic steatosis was observed using hematoxylin-eosin (H&E) and oil red O staining. The phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K-AKT-GSK3ß) signaling pathway was assessed to determine hepatic IR. MAMs were evaluated through immunofluorescence (colocalization of voltage-dependent anion-selective channel 1 [VDAC1] and inositol 1,4,5-triphosphate receptor [IP3R]). RESULTS: After 8 weeks on an HFD, there was notable inhibition of the hepatic PI3K/Akt/GSK3ß signaling pathway, accompanied by a marked reduction in hepatic IP3R-VDAC1 colocalization levels. Both 8-week HIIT and MICT significantly enhanced the hepatic PI3K/Akt/GSK3ß signaling and colocalization levels of IP3R-VDAC1 in HFD mice, with MICT exhibiting a stronger effect on hepatic MAMs formation. Furthermore, the colocalization of hepatic IP3R-VDAC1 positively correlated with the expression levels of phosphorylation of protein kinase B (p-AKT) and phosphorylation of glycogen synthase kinase 3 beta (p-GSK3ß), while displaying a negative correlation with serum triglyceride/high-density lipoprotein cholesterol levels. CONCLUSION: The reduction in hepatic MAMs formation induced by HFD correlates with the development of hepatic IR. Both HIIT and MICT effectively bolster hepatic MAMs formation in HFD mice, with MICT demonstrating superior efficacy. Thus, MAMs might wield a pivotal role in exercise-induced alleviation of hepatic IR.

Altered functional connectivity strength of primary visual cortex in subjects with thyroid-associated ophthalmopathy.

Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ±â€…4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ±â€…5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.

Local Magnesium Sulfate Administration Ameliorates Nociception, Peripheral Inflammation, and Spinal Sensitization in a Rat Model of Incisional Pain.

OBJECTIVE: Postoperative pain remains one of the most common complaints after surgery, and appropriate treatments are limited. METHODS: We therefore investigated the effect of the anti-nociceptive properties of magnesium sulfate (MgSO4), an N-methyl-D-aspartate (NMDA) receptor antagonist, on incision-induced postoperative pain and peripheral and central nervous system inflammation. RESULTS: We found that local MgSO4 administration dose-dependently increases paw withdrawal latency, indicating reduced peripheral postoperative pain. Furthermore, MgSO4 inhibited the expression of interleukin-1ß (IL-1ß) and inducible nitric oxide synthase (iNOS) and phosphorylation of the NMDA receptor NR1 subunit in injured paw tissue and significantly attenuated microglial and astrocytic activation in the ipsilateral lumbar spinal cord dorsal horn. CONCLUSION: Locally administered MgSO4 has potential for development as an adjunctive therapy for preventing central nociceptive sensitization.

Fabrication of amino- and hydroxyl dual-functionalized magnetic microporous organic network for extraction of zearalenone from traditional Chinese medicine prior to the HPLC determination.

Efficient enrichment of trace zearalenone (ZEN) from the complex traditional Chinese medicine (TCM) samples is quite difficult, but of great significance for TCM quality control. Herein, we reported a novel magnetic solid phase extraction (MSPE) strategy for ZEN enrichment using the amino- and hydroxyl dual-functionalized magnetic microporous organic network (Fe3O4@MON-NH2-OH) as an advanced adsorbent combined with the high-performance liquid chromatography (HPLC) determination. Efficient extraction of ZEN was achieved via the possible hydrogen bonding, hydrophobic, and π-π interactions between Fe3O4@MON-NH2-OH and ZEN. The adsorption capacity of Fe3O4@MON-NH2-OH for ZEN was 215.0 mg g-1 at the room temperature, which was much higher than most of the reported adsorbents. Under the optimal condition, the developed Fe3O4@MON-NH2-OH-MSPE-HPLC method exhibited wide linear range (5-2500 µg L-1), low limits of detection (1.4-35 µg L-1), less adsorbent consumption (5 mg), and large enhancement factor (95) for ZEN. The proposed method was successfully applied to detect trace ZEN from 10 kinds of real TCM samples. Conclusively, this work demonstrates the Fe3O4@MON-NH2-OH can effectively extract trace ZEN from the complex TCM matrices, which may open up a new way for the application of MONs in the enrichment and extraction of trace contaminants or active constituents from the complex TCM samples.

Effects of natural extract interventions in prostate cancer: A systematic review and network meta-analysis.

BACKGROUND: Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. OBJECTIVE: Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. METHODS: Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. RESULTS: Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. CONCLUSION: The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.

Cuproptosis-Related Gene FDX1 Identified as a Potential Target for Human Ovarian Aging.

Cuproptosis is a recently discovered mode of cell death that has garnered attention due to its association with various diseases. However, the intricate genetic relationship between cuproptosis and ovarian aging has remained largely unexplored. This study aimed to bridge this knowledge gap by leveraging data sets related to ovarian aging and cuproptosis. Through comprehensive bioinformatics analyses, facilitated by R software, we uncovered FDX1 as a potential cuproptosis-related gene with relevance to ovarian aging. To gain insights into FDX1's role, we conducted spatial transcriptome analyses in the ovaries of both young and aged female mice. These experiments revealed a significant reduction in FDX1 expression in the aging group compared to the young group. To substantiate these findings at the genetic level, we turned to clinical infertility biopsies. Impressively, we observed consistent results in biopsies from elderly infertile patients, reinforcing the link between FDX1 and ovarian aging. Moreover, we delved into the pharmacogenomics of ovarian cell lines and discovered that FDX1 expression levels were intricately associated with heightened sensitivity to specific small molecule drugs. This observation suggests that modulating FDX1 could potentially be a strategy to influence drug responses in ovarian-related therapies. In sum, this study marks a pioneering effort in identifying FDX1 as a cuproptosis-related gene implicated in ovarian aging. These findings hold substantial promise, not only in shedding light on the underlying mechanisms of ovarian aging but also in positioning FDX1 as a potential diagnostic biomarker and therapeutic target. With further research, FDX1 could play a pivotal role in advancing precision medicine and therapies for ovarian-related conditions.

Marine-derived antimicrobial peptide piscidin-1 triggers extrinsic and intrinsic apoptosis in oral squamous cell carcinoma through reactive oxygen species production and inhibits angiogenesis.

Cancer of the head and neck encompasses a wide range of cancers, including oral and oropharyngeal cancers. Oral cancer is often diagnosed at advanced stages and has a dismal prognosis. Piscidin-1, a marine antimicrobial peptide (AMP) containing approximately 22 amino acids, also exhibits significant anticancer properties. We investigated the possible anti-oral cancer effects of piscidin-1 and clarified the mechanisms underlying these effects. We treated the oral squamous cell carcinoma cell lines OC2 and SCC4 with piscidin-1. Cell viability and the expression of different hallmark apoptotic molecules, including reactive oxygen species (ROS), were tested using the appropriate MTT assay, flow cytometry and western blotting assays, and human umbilical vein endothelial cell (HUVEC) wound healing, migration, and tube formation (angiogenesis) assays. Piscidin-1 increases cleaved caspase 3 levels to induce apoptosis. Piscidin-1 also increases ROS levels and intensifies oxidative stress in the endoplasmic reticulum and mitochondria, causing mitochondrial dysfunction. Additionally, it decreases the oxygen consumption rates and activity of mitochondrial complexes I-V. As expected, the antioxidants MitoTEMPOL and N-acetylcysteine reduce piscidin-1-induced ROS generation and intracellular calcium accumulation. Piscidin-1 also inhibits matrix metalloproteinase (MMP)-2/-9 expression in HUVECs, affecting migration and tube formation angiogenesis. We demonstrated that piscidin-1 can promote apoptosis via both intrinsic and extrinsic apoptotic pathways and findings indicate that piscidin-1 has anti-proliferative and anti-angiogenic properties in oral cancer treatment. Our study on piscidin-1 thus provides a basis for future translational anti-oral cancer drug research and a new theoretical approach for anti-oral cancer clinical research.

Daurisoline suppress glioma progression by inhibiting autophagy through PI3K/AKT/mTOR pathway and increases TMZ sensitivity.

Glioma is one of the most common primary malignant tumors of the central nervous system. Temozolomide (TMZ) is the only effective chemotherapeutic agent, but it easily develops resistance and has unsatisfactory efficacy. Consequently, there is an urgent need to develop safe and effective compounds for glioma treatment. The cytotoxicity of 30 candidate compounds to glioma cells was detected by the CCK-8 assay. Daurisoline (DAS) was selected for further investigation due to its potent anti-glioma effects. Our study revealed that DAS induced glioma cell apoptosis through increasing caspase-3/6/9 activity. DAS significantly inhibited the proliferation of glioma cells by inducing G1-phase cell cycle arrest. Meanwhile, DAS remarkably suppressed the migration and invasion of glioma cells by regulating epithelial-mesenchymal transition. Mechanistically, our results revealed that DAS impaired the autophagic flux of glioma cells at a late stage by mediating the PI3K/AKT/mTOR pathway. DAS could inhibit TMZ-induced autophagy and then significantly promote TMZ chemosensitivity. Nude mice xenograft model revealed that DAS could restrain glioma proliferation and promote TMZ chemosensitivity. Thus, DAS is a potential anti-glioma drug that can improve glioma sensitivity to TMZ and provide a new therapeutic strategy for glioma in chemoresistance.

Cervical spinal cord hemisection impacts sigh and the respiratory reset in male rats.

Cervical spinal cord injury impacts ventilatory and non-ventilatory functions of the diaphragm muscle (DIAm) and contributes to clinical morbidity and mortality in the afflicted population. Periodically, integrated brainstem neural circuit activity drives the DIAm to generate a markedly augmented effort or sigh-which plays an important role in preventing atelectasis and thus maintaining lung function. Across species, the general pattern of DIAm efforts during a normal sigh is variable in amplitude and the extent of post-sigh "apnea" (i.e., the post-sigh inter-breath interval). This post-sigh inter-breath interval acts as a respiratory reset, following the interruption of regular respiratory rhythm by sigh. We examined the impact of upper cervical (C2 ) spinal cord hemisection (C2 SH) on the transdiaphragmatic pressure (Pdi ) generated during sighs and the post-sigh respiratory reset in rats. Sighs were identified in Pdi traces by their characteristic biphasic pattern. We found that C2 SH results in a reduction of Pdi during both eupnea and sighs, and a decrease in the immediate post-sigh breath interval. These results are consistent with partial removal of descending excitatory synaptic inputs to phrenic motor neurons that results from C2 SH. Following cervical spinal cord injury, a reduction in the amplitude of Pdi during sighs may compromise the maintenance of normal lung function.

Construction and validation of classification models for predicting the response to concurrent chemo-radiotherapy of patients with esophageal squamous cell carcinoma based on multi-omics data.

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the preferred non-surgical treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Unfortunately, some patients respond poorly, which leads to inappropriate or excessive treatment and affects patient survival. To accurately predict the response of ESCC patients to CCRT, we developed classification models based on the clinical, serum proteomic and radiomic data. METHODS: A total of 138 ESCC patients receiving CCRT were enrolled in this study and randomly split into a training cohort (n = 92) and a test cohort (n = 46). All patients were classified into either complete response (CR) or incomplete response (non-CR) groups according to RECIST1.1. Radiomic features were extracted by 3Dslicer. Serum proteomic data was obtained by Olink proximity extension assay. The logistic regression model with elastic-net penalty and the R-package "rms" v6.2-0 were applied to construct classification and nomogram models, respectively. The area under the receiver operating characteristic curves (AUC) was used to evaluate the predictive performance of the models. RESULTS: Seven classification models based on multi-omics data were constructed, of which Model-COR, which integrates five clinical, five serum proteomic, and seven radiomic features, achieved the best predictive performance on the test cohort (AUC = 0.8357, 95 % CI: 0.7158-0.9556). Meanwhile, patients predicted to be CR by Model-COR showed significantly longer overall survival than those predicted to be non-CR in both cohorts (Log-rank P = 0.0014 and 0.027, respectively). Furthermore, two nomogram models based on multi-omics data also performed well in predicting response to CCRT (AUC = 0.8398 and 0.8483, respectively). CONCLUSION: We developed and validated a multi-omics based classification model and two nomogram models for predicting the response of ESCC patients to CCRT, which achieved the best prediction performance by integrating clinical, serum Olink proteomic, and radiomic data. These models could be useful for personalized treatment decisions and more precise clinical radiotherapy and chemotherapy for ESCC patients.

A Comparative Study of Two Radiomics-Based Blood Flow Modes with Thyroid Imaging Reporting and Data System in Predicting Malignancy of Thyroid Nodules and Reducing Unnecessary Fine-Needle Aspiration Rate.

RATIONALE AND OBJECTIVES: We aimed to compare superb microvascular imaging (SMI)-based radiomics methods, and contrast-enhanced ultrasound (CEUS)-based radiomics methods to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for classifying thyroid nodules (TNs) and reducing unnecessary fine-needle aspiration biopsy (FNAB) rate. MATERIALS AND METHODS: This retrospective study enrolled a dataset of 472 pathologically confirmed TNs. Radiomics characteristics were extracted from B-mode ultrasound (BMUS), SMI, and CEUS images, respectively. After eliminating redundant features, four radiomics scores (Rad-scores) were constructed. Using multivariable logistic regression analysis, four radiomics prediction models incorporating Rad-score and corresponding US features were constructed and validated in terms of discrimination, calibration, decision curve analysis, and unnecessary FNAB rate. RESULTS: The diagnostic performance of the BMUS + SMI radiomics method was better than ACR TI-RADS (area under the curve [AUC]: 0.875 vs. 0.689 for the training cohort, 0.879 vs. 0.728 for the validation cohort) (P < 0.05), and comparable with BMUS + CEUS radiomics method (AUC: 0.875 vs. 0.878 for the training cohort, 0.879 vs. 0.865 for the validation cohort) (P > 0.05). Decision curve analysis showed that the BMUS+SMI radiomics method could achieve higher net benefits than the BMUS radiomics method and ACR TI-RADS when the threshold probability was between 0.13 and 0.88 in the entire cohort. When applying the BMUS+SMI radiomics method, the unnecessary FNAB rate reduced from 43.4% to 13.9% in the training cohort and from 45.6% to 18.0% in the validation cohorts in comparison to ACR TI-RADS. CONCLUSION: The dual-modal SMI-based radiomics method is convenient and economical and can be an alternative to the dual-modal CEUS-based radiomics method in helping radiologists select the optimal clinical strategy for TN management.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

Postnatal survival of phrenic motor neurons is promoted by BDNF/TrkB.FL signaling.

The number of motor neurons (MNs) declines precipitously during the final trimester before birth. Thereafter, the number of MNs remains relatively stable, with their connections to skeletal muscle dependent on neurotrophins, including brain-derived neurotrophic factor (BDNF) signaling through its high-affinity full-length tropomyosin-related kinase receptor subtype B (TrkB.FL) receptor. As a genetic knockout of BDNF leads to extensive MN loss and postnatal death within 1-2 days after birth, we tested the hypothesis that postnatal inhibition of BDNF/TrkB.FL signaling is important for postnatal phrenic MN (PhMN) survival. In the present study, we used a 1NMPP1-sensitive TrkBF616A mutant mouse to evaluate the effects of inhibition of TrkB kinase activity on phrenic MN (PhMN) numbers and diaphragm muscle (DIAm) fiber cross-sectional area (CSA). Pups were exposed to 1NMPP1 or vehicle (DMSO) from birth to 21 days old (weaning) via the mother's ingestion in the drinking water. Following weaning, the right phrenic nerve was exposed in the neck and the proximal end dipped in a rhodamine solution to retrogradely label PhMNs. After 24 h, the cervical spinal cord and DIAm were excised. Labeled PhMNs were imaged using confocal microscopy, whereas DIAm strips were frozen at ∼1.5× resting length, cryosectioned, and stained with hematoxylin and eosin to assess CSA. We observed an ∼34% reduction in PhMN numbers and increased primary dendrite numbers in 1NMPP1-treated TrkBF616A mice. The distribution of PhMN size (somal surface area) DIAm fiber cross-sectional areas did not differ. We conclude that survival of PhMNs during early postnatal development is sensitive to BDNF/TrkB.FL signaling.NEW & NOTEWORTHY During early postnatal development, BDNF/TrkB signaling promotes PhMN survival. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact PhMN size. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact the number or CSA of DIAm fibers.