Consensus-Agent Deep Reinforcement Learning for Face Aging.

Face aging tasks aim to simulate changes in the appearance of faces over time. However, due to the lack of data on different ages under the same identity, existing models are commonly trained using mapping between age groups. This makes it difficult for most existing aging methods to accurately capture the correspondence between individual identities and aging features, leading to generating faces that do not match the real aging appearance. In this paper, we re-annotate the CACD2000 dataset and propose a consensus-agent deep reinforcement learning method to solve the aforementioned problem. Specifically, we define two agents, the aging process agent and the aging personalization agent, and model the task of matching aging features as a Markov decision process. The aging process agent simulates the aging process of an individual, while the aging personalization agent calculates the difference between the aging appearance of an individual and the average aging appearance. The two agents iteratively adjust the matching degree between the target aging feature and the current identity through a form of synergistic cooperation. Extensive experimental results on four face aging datasets show that our model achieves convincing performance compared to the current state-of-the-art methods.

Laparoscopic orchidopexy for the treatment of cryptorchidism in adults: a description of the technique and outcomes.

BACKGROUND: There are few studies on cryptorchidism in adults, and its treatment is still controversial. METHODS: To summarize the surgical strategy and clinical efficacy of laparoscopic orchidopexy for the treatment of cryptorchidism in adults, 37 adult cryptorchidism patients were retrospectively analyzed between September 2017 and February 2022. All 37 patients underwent laparoscopic orchidopexy, of whom 33 underwent inguinal hernia repair without tension. The intraoperative procedures and surgical techniques were recorded in detail. Preoperative examination and regular postoperative review of color Doppler ultrasound, and reproductive hormone, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase levels were performed. RESULTS: All testes descended successfully into the scrotum, including 25 through the inguinal route and 12 through Hesselbach's triangle route. No intraoperative or postoperative complications were observed. The follow-up time was 38.6 (± 19.4) months, and no evidence of testicular malignancy was found during the follow-up period. After analyzing the reproductive hormone levels at 1 year postoperatively in 28 patients with more than 1 year of follow-up, it was found that the patients had a significant increase in testosterone levels and a decrease in follicle-stimulating hormone levels after surgery. None of the patients showed any significant improvement in semen quality after surgery. CONCLUSION: Our study suggests that laparoscopic orchidopexy is a safe and feasible surgical procedure for the treatment of cryptorchidism in adults, especially high cryptorchidism, which is difficult to treat. After comprehensive consideration, preserving the testis should be preferred for treating cryptorchidism in adults to maximize the protection of the patient's reproductive hormone secretion function.

SurgNet: Self-Supervised Pretraining With Semantic Consistency for Vessel and Instrument Segmentation in Surgical Images.

Blood vessel and surgical instrument segmentation is a fundamental technique for robot-assisted surgical navigation. Despite the significant progress in natural image segmentation, surgical image-based vessel and instrument segmentation are rarely studied. In this work, we propose a novel self-supervised pretraining method (SurgNet) that can effectively learn representative vessel and instrument features from unlabeled surgical images. As a result, it allows for precise and efficient segmentation of vessels and instruments with only a small amount of labeled data. Specifically, we first construct a region adjacency graph (RAG) based on local semantic consistency in unlabeled surgical images and use it as a self-supervision signal for pseudo-mask segmentation. We then use the pseudo-mask to perform guided masked image modeling (GMIM) to learn representations that integrate structural information of intraoperative objectives more effectively. Our pretrained model, paired with various segmentation methods, can be applied to perform vessel and instrument segmentation accurately using limited labeled data for fine-tuning. We build an Intraoperative Vessel and Instrument Segmentation (IVIS) dataset, comprised of ~3 million unlabeled images and over 4,000 labeled images with manual vessel and instrument annotations to evaluate the effectiveness of our self-supervised pretraining method. We also evaluated the generalizability of our method to similar tasks using two public datasets. The results demonstrate that our approach outperforms the current state-of-the-art (SOTA) self-supervised representation learning methods in various surgical image segmentation tasks.

Research trends and hotspots in exercise rehabilitation for coronary heart disease: A bibliometric analysis.

Exercise rehabilitation can improve the prognosis of patients with coronary heart disease. However, a bibliometric analysis of the global exercise rehabilitation for coronary heart disease (CHD) research topic is lacking. This study investigated the development trends and research hotspots in the field of coronary heart disease and exercise rehabilitation. CiteSpace software was used to analyze the literature on exercise therapy for CHD in the Web of Science Core Collection database. We analyzed the data of countries/institutions, journals, authors, keywords, and cited references. A total of 3485 peer-reviewed papers were found, and the number of publications on the topic has steadily increased. The most productive country is the USA (1125), followed by China (477) and England (399). The top 3 active academic institutions are Research Libraries UK (RLUK) (236), Harvard University (152), and the University of California System (118). The most commonly cited journals are Circulation (2596), The most commonly cited references are "Exercise-based cardiac rehabilitation for coronary heart disease" (75), Lavie CJ had published the most papers (48). World Health Organization was the most influential author (334 citations). The research frontier trends in this field are body composition, participation, and function. Research on the effects of physical activity or exercise on patients with CHD is a focus of continuous exploration in this field. This study provides a new scientific perspective for exercise rehabilitation and CHD research and gives researchers valuable information for detecting the current research status, hotspots, and emerging trends for further research.

The theoretical model and sinusoidal optimization strategy for oscillating shear valve type continuous waves generator.

Continuous-wave mud generator is widely adopted for real-time downhole data transmission of deep wells in the oil industry. There have been many studies on rotor structure optimization of continuous rotary valve tools but few studies on the different optimization mechanisms of oscillating shear valve tools. In this paper, a theoretical model of pressure wave generation for oscillating shear valve tools was presented, and the reason for the non-sinusoidal waveform was analyzed theoretically for the first time. A series of rotor rotation strategies were proposed to improve the sinusoidal properties of pressure waves without changing the mechanical structure of the rotor. Finally, CFD with different parameters was conducted to verify the feasibility of the optimization scheme. The numerical results give the recommended range of parameters under different control schemes. In addition, the relationship between throttle pressure drop and pressure wave waveform is found through comparison with previous research of the team, which provides a new research idea for the optimization of the pressure wave in the future.

Microvascular Doppler-assisted Microsurgical Left Spermatic-inferior Epigastric Vein Anastomosis for Treating Nutcracker Syndrome-associated Varicocele.

Background: Nutcracker syndrome (NCS) is a rare cause of varicocele and its treatment is still controversial. Objective: To summarize the surgical strategy and outcomes of microvascular Doppler (MVD)-assisted microsurgical left spermatic-inferior epigastric vein anastomosis (MLSIEVA) with microsurgical varicocelectomy (MV) at the same incision for treating NCS-associated varicocele. Design setting and participants: A retrospective analysis of 13 cases of NCS-associated varicocele between July 2018 and January 2022 was performed. Surgical procedure: A small incision in the body projection corresponding to the deep inguinal ring was chosen as the surgical incision. All patients underwent MLSIEVA and MV with the assistance of MVD. Measurements: Patients received real-time Doppler ultrasound (DUS) before and after surgery; urine red blood cells and protein were tested, with a follow-up time of 12-53 mo. Results and limitations: All patients had no intraoperative complications, and all postoperative symptoms of hematuria or proteinuria, scrotal swelling, and low back pain disappeared. Comparing pre- and postoperative DUS, two patients did not show any improvement in their postoperative measurements. However, in the remaining patients, the internal diameter of the renal vein at the hilum portion and at the aortomesenteric angle portion, as well as their ratio, improved significantly compared with preoperative measurements. No complications or recurrence of varicocele was observed during postoperative follow-up. Conclusions: Our study suggests that MVD-assisted MLSIEVA with MV is feasible with no major short-term complication and effective regarding the treatment of varicocele and NCS. Patient summary: We investigated microsurgery mediated by microultrasound for the treatment of varicocele associated with nutcracker syndrome. We found this procedure to be safe and effective with good long-term results.

Semi-Supervised CT Lesion Segmentation Using Uncertainty-Based Data Pairing and SwapMix.

Semi-supervised learning (SSL) methods show their powerful performance to deal with the issue of data shortage in the field of medical image segmentation. However, existing SSL methods still suffer from the problem of unreliable predictions on unannotated data due to the lack of manual annotations for them. In this paper, we propose an unreliability-diluted consistency training (UDiCT) mechanism to dilute the unreliability in SSL by assembling reliable annotated data into unreliable unannotated data. Specifically, we first propose an uncertainty-based data pairing module to pair annotated data with unannotated data based on a complementary uncertainty pairing rule, which avoids two hard samples being paired off. Secondly, we develop SwapMix, a mixed sample data augmentation method, to integrate annotated data into unannotated data for training our model in a low-unreliability manner. Finally, UDiCT is trained by minimizing a supervised loss and an unreliability-diluted consistency loss, which makes our model robust to diverse backgrounds. Extensive experiments on three chest CT datasets show the effectiveness of our method for semi-supervised CT lesion segmentation.

[Effect of MiR-424-5p on the Drug Resistance of Diffuse Large B-Cell Lymphoma Cells by Regulating PD-1/PD-L1 Signaling Pathway].

OBJECTIVE: To explore the effect of microRNA-424-5p (miR-424-5p) on the drug resistance of diffuse large B-cell lymphoma (DLBCL) cells by regulating the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway. METHODS: Human DLBCL cell line CRL2631 cells were induced to construct CRL2631-CHOP resistant cell line. RT-qPCR and Western blot were used to detect the expression levels of MiR-424-5p, PD-L1 mRNA and protein, and multidrug resistance gene-1 (MDR-1) protein in CRL2631 cells and CRL2631-CHOP cells, respectively. The target genes of MiR-424-5p was verified by dual luciferase reporter assay. The miRNA simulation/interference technology and thiazole blue (MTT) method were used to detect the resistance of CRL2631 cells and CRL2631-CHOP cells to CHOP. RESULTS: Compared with CRL2631 cells, the drug resistance of CRL2631-CHOP cells to CHOP and the levels of MDR-1 protein (P<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both P<0.001), while the relative level of MiR-424-5p was significantly reduced (P<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of MiR-424-5p (P<0.001). After transfection of MiR-424-5p inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (P<0.01), PD-L1 mRNA and protein also increased significantly (both P<0.01). After transfection of MiR-424-5p mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (P<0.001), PD-L1 mRNA and protein also decreased significantly (both P<0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating MiR-424-5p on PD-L1 (P<0.001). CONCLUSION: Down-regulation of MiR-424-5p enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.

Altered microbiota profile in seminal vesicles of men presenting with refractory hematospermia.

BACKGROUND: Currently, no recognized evidence is known about the bacterial communities found within seminal vesicles (SV) of men presenting with refractory hematospermia. METHODS AND RESULTS: Fifteen male patients with refractory hematospermia or anejaculation were enrolled, and 15 SV-Infection (SV-In) samples from SV with hemorrhage and/or stones, 11 SV-Control (SV-C) samples from SV with non-infection, and 14 Urine (Urine) samples from posterior urethra were obtained via transurethral seminal vesiculoscopy. Then the high-throughput 16 S rRNA gene sequencing method was performed to characterize the microbiota profile. Finally, a total of 1535 operational taxonomic units (OTUs) were found, 1295 OTUs were shared across three groups, 7 OTUs, 45 OTUs, and 48 OTUs were unique to SV-C group, SV-In group, and Urine group, respectively. The 5 top bacterial phyla (mean relative abundance) in all samples were Firmicutes (52.08%), Bacteroidetes (21.69%), Proteobacteria (12.72%), Actinobacteria (9.64%), and Fusobacteria (1.62%), the 5 top bacterial genera in all samples were Bacteroides (9.13%), Lactobacillus (5.38%), Bifidobacterium (5.35%), Faecalibacterium (5.10%), and Allobaculum (3.34%), of which Bifidobacterium had the highest level in SV-C samples and had a significant difference (P < 0.05) across all groups. Differential analysis showed genera Leuconostoc and LachnospiraceaeFCS020group were identified as biomarkers in the SV-In microbiota. CONCLUSION: Altered microbiota composition in seminal vesicles is related to refractory hematospermia in men, and the distribution of genus Leuconostoc or LachnospiraceaeFCS020group within seminal vesicles may interact with hematospermia. This study provides clues for the diagnosis and treatment of this urologic disorder.

Calculation of the Paternity Index for the Alleged Father Related to the Child's Mother / 法医学杂志

OBJECTIVES@#To derive the paternity index (PI) calculation formula of the alleged father (AF) when the AF is a relative (parent/child, siblings, grandparent/grandchild, uncle/nephew, first cousins) of the child's biological mother.@*METHODS@#For the case when the AF is related to the child's biological mother, the existence of the relationship in the numerator and denominator hypothesis of PI was considered. The genotype frequency of the AF was calculated by using the frequency formula in which the mother's genotype was considered, while the random male in the denominator was substituted as another relative of the mother's same rank. The PI calculation formula was derived to eliminate the effect of the relationship between AF and the child's biological mother.@*RESULTS@#When the AF and the biological mother have first, second and tertiary kinship, a more conservative PI was obtained from the PI calculation formula derived in this study compared with the PI calculation method which did not consider kinship.@*CONCLUSIONS@#The calculation method provided in this study can eliminate the effect of the relation of the AF and mother on the PI in incest cases, to obtain more accurate and conservative identification conclusions.

Application of Rat Model of Neurotic Erectile Dysfunction in Experiment / 中国医学科学院学报

Erectile dysfunction (ED) refers to the persistent inability to achieve and/or maintain a sufficient erection of the penis to obtain a satisfactory sexual life,which affects the quality of life of the patients and their sexual partners.To decipher the pathophysiological mechanism of ED,researchers have established a variety of animal models and achieved a series of progress.The cavernous nerve (CN) of rodents,anatomically similar to that of humans,is cost-effective,thick,and easy to be identified,which has gradually become the mainstream of animal models.In this paper,we reviewed the modeling methods of the neurological ED caused by bilateral CN injury in rats in recent years,summarized the model evaluation indicators,and discussed the application and progress of ED models in basic experimental research.

An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice / 神经科学通报·英文版

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.

Influencing factors and population attributable risk percent of low back pain in automobile assemblers / 中国职业医学

Objective: To investigate the influencing factors and population attributable risk percent (PAR%) of low back pain in automobile assemblers. Methods: A total of 634 assemblers from 11 automobile manufacturers in Shiyan City, Hubei Province were chosen as research subjects using judgment sampling method. The prevalence of low back pain in the past one year was investigated using Musculoskeletal Disorders Questionnaire. PAR% was used to analyze the contribution of influencing factors to low back pain. Results: The annual prevalence of low back pain was 68.8%. The results of multivariate logistics regression showed that length of service>15 years, high school or secondary college education or above, standing most of the time, sitting most of the time, the proportion of cumulative time of poor posture in work shift time ≥1/8, and bending for insufficient height of working space were the risk factors for low back pain (all P<0.05). The PAR% of the proportion of cumulative time of poor posture in work shift time ≥1/8 was 43.0%, 37.8% for standing most of the time, and 12.8% for bending for insufficient height of working space. Conclusion: The annual prevalence of low back pain was higher in automobile assemblers. The influencing factors included individual factors and occupational factors. The proportion of cumulative time of poor posture in work shift time ≥1/8, standing most of the time and bending for insufficient height of working space should be taken as the priority intervention factors to reduce the prevalence of low back pain among assemblers in this enterprise.

Investigation of patient dose during digital mammography in Zigong, China, 2022 / 中国辐射卫生

Objective To investigate the average glandular dose of digital mammography in Zigong, China, and to explore the methods of reducing average glandular dose. Methods A total of 260 patients who underwent digital mammography at six hospitals located in Zigong during the year 2022 were included in this study. Their personal information, photography position, breast compression thickness, exposure parameters, and average glandular dose were collected. Analysis of variance and correlation analysis were performed for data analysis. Results Among the 260 patients who underwent digital mammography, the average breast compression thickness was 46.3 mm and the average glandular dose was 1.70 mGy. There was a significant difference in average glandular dose between patients with different breast compression thickness(P <0.05), and average glandular dose was positively correlated with breast compression thickness. There were no significant differences in average glandular dose between patients with different photography positions and patients with different ages (P>0.05). Conclusion The average glandular dose of patients undergoing digital mammography is at an acceptable level in Zigong. The average glandular dose is impacted by the breast compression thickness, target/filter, and exposure parameters. These factors should be optimized to reduce glandular dose during digital mammography.

Patterns of social participation and impacts on memory among the older people.

This study employs latent class analysis to analyze the social participation patterns of elderly Chinese, as well as the impact of different social participation patterns on memory. According to the results, older persons exhibit four distinct social participation patterns. and senior citizens with a strong emphasis on entertainment had a better memory than those with a low participation level. Although there was no difference in urban elders' memory across the four social engagement patterns, the connection varied significantly between urban and rural seniors. As a result, it is suggested that the elderly's memory be improved by protecting their right to social involvement, enriching the style and content of social participation, and assuring the continuity of their social obligations.

Case report: Two cases of primary paratesticular liposarcoma.

Paratesticular liposarcoma is a sporadic urological tumor. We report the clinical presentation, treatment course, and prognosis of 2 cases of primary paratesticular liposarcoma with different pathological types, with the aim of further understanding the diagnosis and treatment of this rare disease. Case 1 was a 53-years-old male patient who presented with left scrotal enlargement with swelling 3 years ago and was considered to have a testicular malignancy on preoperative CT scan and enhanced MRI. The patient underwent resection of the left scrotal mass and left orchiectomy under general anaesthesia. Histopathological study confirmed the diagnosis of dedifferentiated liposarcoma. At the 4-months follow-up, no local recurrence or distant metastasis was observed. Case 2 is a 42-years-old male patient with a left scrotal mass which was discovered six months ago. Preoperatively, he underwent CT plain and enhanced MRI examinations suggesting an intra-scrotal occupancy. The patient underwent scrotoscopic excision of the left scrotal mass under general anesthesia. Histopathological studies confirmed the diagnosis of highly differentiated liposarcoma. At the 10-months follow-up, no local recurrence or distant metastasis was observed. Preoperative differential diagnosis of paratesticular liposarcoma should be noted with testicular tumor and extra-abdominal hernia. Extensive local excision and, if necessary, concomitant radical testicular resection is the treatment of choice. If the tumor in the scrotum spreads to the inguinal region, surgical removal with the aid of a scrotoscope may be attempted. This procedure avoids the formation of a large incision in the inguinal region compared to traditional open surgery. Patients commonly experience local recurrence and less distant metastases after surgery, so long-term follow-up is recommended.

The value of NSE to predict ICU mortality in patients with septic shock: A prospective observational study.

To investigate the predictive value of neuron-specific enolase (NSE) on intensive care unit (ICU) mortality in patients with septic shock. Seventy-five patients with septic shock hospitalized in the emergency intensive care unit (EICU) of Hebei General Hospital from March 2020 to September 2021 were included, and the patients' baseline characteristics and laboratory findings were collected. NSE levels on the first and fourth days after admission were retrieved. NSE% [(NSEday1 - NSEday4)/NSEday1 × 100%] and δNSE (NSEday1 - NSEday4) were calculated. The outcome indicator was ICU mortality. The patients were divided into the survivors group (n = 57) and the nonsurvivors group (n = 18). Multivariate analysis was performed to assess the relationship between NSE and ICU mortality. The predictive value of NSE was evaluated using receiver operating characteristic (ROC) curve. There were no significant differences in age, gender, systolic blood pressure (SBP), heart rate (HR), acute physiology and chronic health evaluation II score (APACHE II score), source of infection, and comorbidities between the 2 groups (all P > .05). Interleukin-6 (IL-6), NSE (day1), and NSE (day4) were significantly higher in patients in the nonsurvivors group (all P < .05), and there were no statistical differences in other laboratory tests between the 2 groups (all P > .05). APACHE II score, IL-6, lactate (Lac), total bilirubin (TBil), NSE (day1), and NSE (day4) showed a weak positive correlation with ICU mortality in patients with septic shock (all P < .05). Multivariate logistic regression analysis demonstrated that APACHE II score (odds ratio [OR] = 1.166, 95% confidence interval [95% confidence interval [CI]] 1.005-1.352, P = .042), IL-6 (OR = 1.001, 95% CI 1.000-1.001, P = .003) and NSE (day4) (OR = 1.099, 95% CI 1.027-1.176, P = .006) were independently associated with the ICU mortality of sepsis shock patients. The area under the curve (AUCs) of APACHE II score, IL-6, NSE (day1), and NSE (day4) for predicting prognosis were 0.650, 0.694, 0.758 and 0.770, respectively (all P < .05). NSE(day4) displayed good sensitivity and specificity (Sn = 61.11%, Sp = 91.23%) for predicting ICU mortality with a cutoff value of 25.94 ug/L. High-level NSE (day4) is an independent predictor of ICU mortality in sepsis shock patients, which may become a good alternate option for evaluating sepsis severity. More extensive studies are needed in the future to demonstrate the prognosis value of NSE.

Elastography and contrast-enhanced ultrasound to assess the effect of varicocelectomy: A case-controlled study.

To evaluate the changes in testicular stiffness and microcirculation caused by spermatic vein ligation in patients with varicocele, we conducted a case-controlled study. A total of 27 grade III left varicocele cases were enrolled. Testicular stiffness and perfusion were evaluated by shear wave elastography and contrast-enhanced ultrasound during subinguinal microscopic varicocelectomy. The external and the internal parenchyma of bilateral testes were selected to compare the shear wave velocity of bilateral testes during the spermatic vein ligation. We mapped and compared the intensity-time curves following bolus contrast injection three times in the same region of interest. Initially, the shear wave velocity of the left internal parenchyma was higher than the right side (1.10 ± 0.06 m/s vs. 1.00 ± 0.03 m/s). It decreased (1.09 ± 0.06 m/s) (p < 0.05) after ligation. Meanwhile, the left epididymis had the higher agent peak intensity (0.90 × 10E-5 AU), the largest area under the curve (80.20 × 10E-5 AU s), and the longest washout area (54.35 × 10E-5 AU s). In addition, the left internal parenchyma presented a sharper slope (0.18 × 10E-5 AU/s) (p < 0.05). In conclusion, the spermatic vein ligation improved the perfusion of the internal testicular parenchyma, but it could temporally deteriorate the stasis of the epididymis. These changes caused softer testicular parenchyma.

Development and application of an uncapped mRNA platform

A novel uncapped mRNA platform was developed. Five lipid nanoparticle (LNP)-encapsulated mRNA constructs were made to evaluate several aspects of our platform, including transfection efficiency and durability in vitro and in vivo and the activation of humoral and cellular immunity in several animal models. The constructs were eGFP-mRNA-LNP (for enhanced green fluorescence mRNA), Fluc-mRNA-LNP (for firefly luciferase mRNA), S{delta}T-mRNA-LNP (for Delta strain SARS-CoV-2 spike protein trimer mRNA), gDED-mRNA-LNP (for truncated glycoprotein D mRNA coding ectodomain from herpes simplex virus type 2 (HSV2)) and gDFR-mRNA-LNP (for truncated HSV2 glycoprotein D mRNA coding amino acids 1~400). Quantifiable target protein expression was achieved in vitro and in vivo with eGFP- and Fluc-mRNA-LNP. S{delta}T-mRNA-LNP, gDED-mRNA-LNP and gDFR-mRNA-LNP induced both humoral and cellular immune responses comparable to those obtained by previously reported capped mRNA-LNP constructs. Notably, 25, 50 and 100 g of S{delta}T-mRNA-LNP all elicited neutralizing antibodies in hamsters against the Omicron and Delta strains. Additionally, gDED-mRNA-LNP and gDFR-mRNA-LNP induced potent neutralizing antibodies in rabbits and mice. The mRNA constructs with uridine triphosphate (UTP) outperformed those with N1-methylpseudouridine triphosphate (N1m{psi}TP) in the in vivo expression of luciferase and the induction of antibodies via S{delta}T-mRNA-LNP. Our uncapped, process-simplified, and economical mRNA platform may have broad utility in vaccines and protein replacement drugs.

NecroX-5 ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3-mediated epithelial-mesenchymal transition.

BACKGROUND: Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis. RESULTS: We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial-mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-ß1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM. CONCLUSIONS: Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.