Short-term efficiency of plasma exchange in combination with immunosuppressants and/or biologics in the treatment of idiopathic inflammatory myopathy with rapidly progressive interstitial lung disease: a systematic review and meta-analysis.

OBJECTIVE: Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and serious manifestation of idiopathic inflammatory myopathy (IIM) associated with poor outcomes. Plasma exchange (PE) can quickly remove pathogenic substances from the blood. Therefore, PE may be efficacious in IIM patients who have elevated levels of autoantibodies, cytokines and chemokines, fighting for time for immunosuppressive therapy. However, the value of adding PE to immunosuppressants remains unclear. The purpose of this study was to determine the short-term outcomes, including the survival rate at 6 months and change of the laboratory data, of PE in combination with immunosuppressants and/or biologics in the treatment of IIM-RP-ILD. METHODS: We searched PubMed, Embase and Cochrane Library to find reports of interest published from inception to March 4, 2024. STATA 15.1 was used for data analysis. A fixed or random-effects model with inverse-variance weighting was used to estimate the pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS: Two hundred and thirty studies were identified. Eleven studies, including five retrospective cohort studies, four case-control studies and two case series, were included. PE was performed on 114 patients. The survival rate at 6 months was 80% (95%CI = 64%-92%), with moderate heterogeneity (I2=63.45%, p < 0.05). Moreover, the 6-month survival rate was significantly better in the PE group than in the non-PE group (RR, 1.34; 95% CI = 1.05-1.71, I2=30.7%; p = 0.194). ILD-related serum markers, including ferritin, KL-6 and anti-MDA-5 antibody titres, were significantly suppressed by a series of PE treatments (p < 0.05). CONCLUSION: The application of PE therapy plus treatment with corticosteroids, immunosuppressants and/or biologics was effective for patients with IIM-RP-ILD. PE may have additional supportive effect in intractable disease.

Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer.

Oxidative stress is crucial in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA-222-3p (miR-222-3p) can protect against oxidative stress in IECs, which ameliorates colonic injuries in UC mice and prevents the conversion of UC to CAC. In this case, we hope to explore whether moxibustion can alleviate UC and CAC by inhibiting miR-222-3p based on mouse models of UC and CAC. After herb-partitioned moxibustion (HPM) intervention, the disease activity index (DAI) and colon macroscopic damage index (CMDI) were significantly reduced in UC mice, and the number and volume of intestinal tumors were decreased considerably in CAC mice. Meanwhile, we found that HPM suppressed miR-222-3p expression and upregulated the mRNA and protein expression of Brahma-related gene 1 (BRG1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), while inhibiting Kelch-like ECH-associated protein 1 (Keap1) expression in IECs of UC and CAC mice. With changes in reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α), we verified that HPM protects against oxidative stress and inflammation in IECs of UC and CAC mice. The effect of HPM was inhibited in miR-222-3p overexpression mice, further demonstrating that the protective effect of HPM on UC and CAC mice was through inhibiting miR-222-3p. In summary, HPM regulates the BRG1/Nrf2/HO-1 pathway by inhibiting miR-222-3p to attenuate oxidative stress in IECs in UC and CAC.

Air pollutant exposure is associated with visual trajectories and visual impairment in children.

Air pollution is associated with vision loss in children, but the relationship with vision trajectories has not been explored. The study was conducted as a prospective cohort in 16 districts of Shanghai from 2021 to 2023, involving 5612 children with complete survey data. Each child underwent 3-4 eye tests, including unaided visual acuity and computerized refraction. Children's air pollutant exposure levels (PM2.5, PM10, O3, SO2, NO2, and CO) were assessed using school addresses and examination dates. Latent class mixture modeling was used to identify the trajectories of changes in vision-related measurements in children. Multinomial logistic regression and Cox proportional hazards regression were used to examine the association of air pollutant exposure and visual trajectories, as well as visual impairment outcomes. The study identified three trajectory categories for children's unaided visual acuity, spherical equivalent, and four trajectory categories for axial length. Increased levels of PM2.5, PM10, O3, and SO2 exposure are associated with an increased risk of categorizing vision-related measurements into the "poor" category trajectory in children. Increased exposure to PM2.5, O3, and NO2 was associated with an increased risk of visual impairment outcomes in children with normal vision at baseline, and the effect was more significant in female and older children.

Mortality associated with osteoporosis and pathological fractures in the United States (1999-2020): a multiple-cause-of-death study.

BACKGROUND: Osteoporosis with pathological fractures is a significant public health issue, contributing to morbidity, disability, diminished quality of life, and increased mortality. Understanding mortality trends related to this condition is crucial for developing effective interventions to reduce mortality and improve healthcare outcomes. This study aimed to analyze trends and causes of death associated with osteoporosis and pathological fractures in the United States using a multi-cause approach. METHODS: Annual death and age-standardized mortality rate (ASMR) data from 1999 to 2020 were obtained from the Centers for Disease Control and Prevention (CDC) mortality database. Death certificates listing ICD-10 M82 (osteoporosis with pathological fracture) as an underlying or related cause of death were analyzed. Epidemiological data were analyzed, and the ASMR data were calculated for each year, and trends were assessed using the Cochran-Armitage trend test. RESULTS: From 1999 to 2020, there were 40,441 deaths related to osteoporosis with pathological fractures in the United States, with a female-to-male ratio of 5.6:1. Among these, 12,820 deaths (31.7%) listed osteoporosis with pathological fractures as the underlying cause of death (UCD), yielding a female-to-male ASMR ratio of approximately 5.0-7.7:1. When classified as a non-UCD, the ASMR ratio was approximately 4.8-6.2:1. At the same time, we found that the total number of deaths classified as UCD and multiple causes of death (MCD), but the trend ratio of the two groups in different years did not change statistically significant (P > 0.05), and the ASMR of both groups showed a downward trend. The UCD-to-MCD ratio increased between 1999 and 2007, then decreased from 2007 to 2020. As MCD, the number of female deaths was more than that of male, and both showed a decreasing trend, but there was no statistical significance in the change of trend ratio in different years (P > 0.05). Deaths were predominantly concentrated in individuals over 75 years of age, with those over 84 years being the most affected. The number of deaths in different age groups showed a decreasing trend, and the change of trend ratio in different years was statistically significant (P < 0.05). White individuals had the highest number of deaths. The leading causes of death were heart diseases, chronic lower respiratory diseases, and alzheimer's disease. In addition, the number of deaths of patients with prostate cancer and breast cancer showed a significant downward trend, and the change of trend ratio between the two groups in different years was statistically significant (P < 0.05). CONCLUSIONS: Although mortality from osteoporosis with pathological fractures is decreasing, anti-osteoporosis therapy remains essential for elderly patients. Healthcare providers should remain vigilant for potential complications, including malignant neoplasms, and ensure timely diagnosis and treatment to further reduce mortality in this population.

TIMM9 as a prognostic biomarker in multiple cancers and its associated biological processes.

TIMM9 has been identified as a mediator of essential functions in mitochondria, but its association with pan-cancer is poorly understood. We herein employed bioinformatics, computational chemistry techniques and experiments to investigate the role of TIMM9 in pan-cancer. Our analysis revealed that overexpression of TIMM9 was significantly associated with tumorigenesis, pathological stage progression, and metastasis. Missense mutations (particularly the S49L variant), copy number variations (CNV) and methylation alterations in TIMM9 were found to be associated with poor cancer prognosis. Moreover, TIMM9 was positively related with cell cycle progression, mitochondrial and ribosomal function, oxidative phosphorylation, TCA cycle activity, innate and adaptive immunity. Additionally, we discovered that TIMM9 could be regulated by cancer-associated signaling pathways, such as the mTOR pathway. Using molecular simulations, we identified ITFG1 as the protein that has the strongest physical association with TIMM9, which show a promising structural complement.

Complete mitochondrial genome of Agropyron cristatum reveals gene transfer and RNA editing events.

BACKGROUND: As an important forage in arid and semi-arid regions, Agropyron cristatum provides livestock with exceptionally high nutritional value. Additionally, A. cristatum exhibits outstanding genetic characteristics to endure drought and disease. Therefore, rich genetic diversity serves as a cornerstone for the improvement of major food crops. The purposes of this study were to systematically describe mitogenome of A.cristatum and preliminarily analyze its internal variations. RESULT: The A. cristatum mitogenome was a single-ring molecular structure of 381,065 bp that comprised 52 genes, including 35 protein-coding, 3 rRNA and 14 tRNA genes. Among these, two pseudoprotein-coding genes and multiple copies of tRNA genes were observed. A total of 320 repetitive sequences was found to cover more than 10% of the mitogenome (105 simple sequences, 185 dispersed and 30 tandem repeats), which led to a large number of fragment rearrangements in the mitogenome of A. cristatum. Leucine was the most frequent amino acid (n = 1087,10.8%) in the protein-coding genes of A. cristatum mitogenome, and the highest usage codon was ATG (initiation codon). The number of A/T changes at the third base of the codon was much higher than that of G/C. Among 23 PCGs, the range of Pi values is from 0.0021 to 0.0539, with an average of 0.013. Additionally, 81 RNA editing sites were predicted, which were considerably fewer than those reported in other plant mitogenomes. Most of the RNA editing site base positions were concentrated at the first and second codon bases, which were C to T transitions. Moreover, we identified 95 sequence fragments (total length of 34, 343 bp) that were transferred from the chloroplast to mitochondria genes, introns, and intergenic regions. The stability of the tRNA genes was maintained during this process. Selection pressure analysis of 23 protein-coding genes shared by 15 Poaceae plants, showed that most genes were subjected to purifying selection during evolution, whereas rps4, cob, mttB, and ccmB underwent positive selection in different plants. Finally, a phylogenetic tree was constructed based on 22 plant mitogenomes, which showed that Agropyron plants have a high degree of independent heritability in Triticeae. CONCLUSION: The findings of this study provide new data for a better understanding of A. cristatum genes, and demonstrate that mitogenomes are suitable for the study of plant classifications, such as those of Agropyron. Moreover, it provides a reference for further exploration of the phylogenetic relationships within Agropyron species, and establishes a theoretical basis for the subsequent development and utilization of A. cristatum plant germplasm resources.

Malic enzyme 2 maintains metabolic state and anti-tumor immunity of CD8+ T cells.

The functional integrity of CD8+ T cells is closely linked to metabolic reprogramming; therefore, understanding the metabolic basis of CD8+ T cell activation and antitumor immunity could provide insights into tumor immunotherapy. Here, we report that ME2 is critical for mouse CD8+ T cell activation and immune response against malignancy. ME2 deficiency suppresses CD8+ T cell activation and anti-tumor immune response in vitro and in vivo. Mechanistically, ME2 depletion blocks the TCA cycle flux, leading to the accumulation of fumarate. Fumarate directly binds to DAPK1 and inhibits its activity by competing with ATP for binding. Notably, pharmacological inhibition of DAPK1 abolishes the anti-tumor function conferred by ME2 to CD8+ T cells. Collectively, these findings demonstrate a role for ME2 in the regulation of CD8+ T cell metabolism and effector functions as well as an unexpected function for fumarate as a metabolic signal in the inhibition of DAPK1.

If CE affects infertile women's outcomes after surgery?

OBJECTIVE: To investigate the prevalence of chronic endometritis (CE) in infertile patients and whether it affects spontaneous pregnancy after reproductive surgery in infertile patients. MATERIALS AND METHODS: In this study, we collected clinical information on infertility patients who underwent reproductive surgery at the Reproductive Medicine Centre of the Second Hospital of Lanzhou University from 2021.1 to 2022.8. All patients underwent laparoscopic and hysteroscopic surgery. Tubal lubrication was performed concurrently with endometrial sample collection and pathological examination. The specimens were immunohistochemically stained with CD38 and CD138, and those who tested positive at the same time were diagnosed with chronic endometritis. As of 2023.9, the patients were followed up by telephone to determine whether chronic endometritis impacted postoperative pregnancy. OUTCOME: A total of 81 patients were finally included in the study. Of these, 25 were in the chronic endometritis group, and 56 were in the non-chronic endometritis group. There were no appreciable differences between the two groups' demographic statistics. Furthermore, neither the bilateral appendages nor the uterus's intraoperative conditions showed a statistically significant difference. Patients in the chronic endometritis group had a longer time to conception from the time of surgery (7 (6.00-11.75) vs. 10 (6.50-16.00), p = 0.467) and a lower rate of spontaneous pregnancies (8/25 = 32.00 % vs. 28/55 = 50.00 %, p = 0.132) than patients with non-chronic endometritis. Among the patients who had successful spontaneous pregnancies after surgery, approximately 77.14 % had live births and 22.86 % had miscarriages, and the live birth rate between the two groups was not significantly different. (21/28 = 75.00 % vs 7/8 = 87.50 %, p = 0.651) CONCLUSION: Chronic endometritis affects approximately 31.82% of infertile patients, and following reproductive surgery, it has no discernible impact on spontaneous pregnancy.

Pathogenicity characteristics of different subgenotype pseudorabies virus in newborn piglets.

Pseudorabies virus is a major pathogen in the pig industry, causing substantial economic losses. The emergence of pseudorabies virus variant strains in China has led to extensive spread, raising concerns about their potential impact. However, the differences in pathogenicity between the classical strains and the variant strains of genotype II are not well understood. In this study, we isolated three pseudorabies virus strains to evaluate their replication characteristics and to examine the differences in virulence genes among various subgenotypes strains. Additionally, a piglet infection model was utilized to investigate the clinical features of infection, tissue tropism, and the inflammatory responses induced by these strains. Our results showed that the genotype II variant strains (MS, XJ, LS, and CZ) had significantly larger plaque sizes and higher replication capacities than the genotype II classical strain Fa. The animal experiments revealed significant differences in pathogenicity among the pseudorabies virus subgenotype strains, with the variant strains showing higher mortality rates, more severe clinical symptoms, increased nasal virus shedding, and a more robust inflammatory response compared to the genotype II classical strain. There were also notable differences in tissue tropism among the strains. In terms of tissue viral loads, the genotype II variant strains did not exhibit a significant advantage over the genotype I classical strain. Furthermore, our findings indicate that antibodies against the genotype II classical strains have a reduced neutralizing capacity against the genotype II variant strains. On the other hand, antibodies against the genotype II variant strains displayed similar neutralizing abilities against both classical and variant strains. Overall, these findings offer important insights into the distinctions among pseudorabies virus subgenotypes and their implications for the clinical control of pseudorabies virus infections in pig farming.

CLINICOPATHOLOGIC CHANGES OF VITREOMACULAR INTERFACE IN IDIOPATHIC EPIRETINAL MEMBRANE WITH DISORGANIZATION OF RETINAL INNER LAYERS.

PURPOSE: To compare the pathological characteristics of the vitreomacular interface of the idiopathic epiretinal membrane with and without disorganization of retinal inner layers (DRIL) and to correlate with clinical data. METHODS: In this clinicopathologic study, the samples of epiretinal membrane and internal limiting membrane were extracted from DRIL(+) (19 eyes) and DRIL(-) (22 eyes) idiopathic epiretinal membrane eyes. Ultrathin series sectioning for transmission electron microscopy was observed and correlated with surgery status and prognosis. RESULTS: All idiopathic epiretinal membrane eyes presented fibrocellular membranes accompanied by vitreous collagen, glial cells, and myofibroblasts, regardless of association with DRIL. A robust signal indicative of Collagen Type VI was observed in eyes DRIL(-), whereas Collagen Type I was discovered in DRIL eyes. Cell debris and microvascular basement membrane were seen on the retinal side of DRIL eyes and a larger cell count on the vitreous side. These have more intraoperative complications and less surgery benefit. CONCLUSION: Although internal limiting membrane peeling seems important, the histopathologic findings underscore the potential for retinal injury in DRIL(+) idiopathic epiretinal membrane eyes. This suggests that further research is needed to investigate individual preoperative assessment and to modify surgical procedures.

Potential of resveratrol in the treatment of systemic lupus erythematosus (Review).

Systemic lupus erythematosus (SLE) is a multi­system chronic autoimmune disease with a complex occurrence and development process, associated with immune disorders, uncertain prognosis, and treatment modalities which vary by patient and disease activity. At present, the clinical treatment of SLE mainly focuses on hormones and immunosuppressants. In recent years, the research on new treatment strategies for SLE has been booming, and strong preclinical results and clinical research have promoted the development of numerous drugs (such as rituximab and orencia), but numerous of these drugs have failed to achieve effectiveness in clinical trials, and there are some adverse reactions. Recent evidence suggests that resveratrol (RSV) has the effect of ameliorating immune disorders by inhibiting overactivation of immune cells. In the present review, advances in research on the protective effects and potential mechanisms of RSV against SLE are summarized and the potential potency of RSV and its use as a promising therapeutic option for the treatment of SLE are highlighted.

[Advances in artificial cells based on microfluidic chips].

One of the main goals of synthetic biology is to build artificial cells in a bottom-up manner, which not only facilitates the deep understanding of the origin of life and cell function but also plays a critical role in the research fields such as the development of artificial cell chassis, tissue models, engineering drug delivery systems, and drug screening tools. However, achieving this goal is extremely challenging. The complexity of cell structures and the miniaturization and diversity of basic modules pose high requirements for the construction methods. The microfluidic chip, as an advanced microanalysis system, serves as an effective tool for building artificial cells. It can accurately control the structure and local microenvironment of artificial cells, becoming the preferred approach for the current research on synthetic life. This article reviewed the methods of constructing, manipulating, and analyzed artificial cells based on microfluidic chips, emphasized the importance of the microenvironment for life systems and artificial self-sustaining systems. In addition, this article demonstrated the wide applications of artificial cells in multiple critical biomedical fields. Exploring the advantages, disadvantages, and application performance of different microfluidic methods can enrich our knowledge about artificial cell research. Finally, we made an outlook on the development of artificial cell research based on microfluidics, expecting that this field can achieve greater breakthroughs and progress.

Detection of Cervical Lesion Cell/Clumps Based on Adaptive Feature Extraction.

Automated detection of cervical lesion cell/clumps in cervical cytological images is essential for computer-aided diagnosis. In this task, the shape and size of the lesion cell/clumps appeared to vary considerably, reducing the detection performance of cervical lesion cell/clumps. To address the issue, we propose an adaptive feature extraction network for cervical lesion cell/clumps detection, called AFE-Net. Specifically, we propose the adaptive module to acquire the features of cervical lesion cell/clumps, while introducing the global bias mechanism to acquire the global average information, aiming at combining the adaptive features with the global information to improve the representation of the target features in the model, and thus enhance the detection performance of the model. Furthermore, we analyze the results of the popular bounding box loss on the model and propose the new bounding box loss tendency-IoU (TIoU). Finally, the network achieves the mean Average Precision (mAP) of 64.8% on the CDetector dataset, with 30.7 million parameters. Compared with YOLOv7 of 62.6% and 34.8M, the model improved mAP by 2.2% and reduced the number of parameters by 11.8%.

Predicting risk of the subsequent early pregnancy loss in women with recurrent pregnancy loss based on preconception data.

BACKGROUND: For women who have experienced recurrent pregnancy loss (RPL), it is crucial not only to treat them but also to evaluate the risk of recurrence. The study aimed to develop a risk predictive model to predict the subsequent early pregnancy loss (EPL) in women with RPL based on preconception data. METHODS: A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to December 2022, a total of 1050 non-pregnant women with RPL were participated. By December 2023, 605 women had subsequent pregnancy outcomes and were randomly divided into training and validation group by 3:1 ratio. In the training group, univariable screening was performed on RPL patients with subsequent EPL outcome. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables, respectively. Subsequent EPL prediction model was constructed using generalize linear model (GLM), gradient boosting machine (GBM), random forest (RF), and deep learning (DP). The variables selected by LASSO regression and multivariate logistic regression were then established and compared using the best prediction model. The AUC, calibration curve, and decision curve (DCA) were performed to assess the prediction performances of the best model. The best model was validated using the validation group. Finally, a nomogram was established based on the best predictive features. RESULTS: In the training group, the GBM model achieved the best performance with the highest AUC (0.805). The AUC between the variables screened by the LASSO regression (16-variables) and logistic regression (9-variables) models showed no significant difference (AUC: 0.805 vs. 0.777, P = 0.1498). Meanwhile, the 9-variable model displayed a well discrimination performance in the validation group, with an AUC value of 0.781 (95%CI 0.702, 0.843). The DCA showed the model performed well and was feasible for making beneficial clinical decisions. Calibration curves revealed the goodness of fit between the predicted values by the model and the actual values, the Hosmer-Lemeshow test was 7.427, and P = 0.505. CONCLUSIONS: Predicting subsequent EPL in RPL patients using the GBM model has important clinical implications. Future prospective studies are needed to verify the clinical applicability. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

The TDP-43/TP63 Positive Feedback Circuit Promotes Esophageal Squamous Cell Carcinoma Progression.

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent malignancies with a 5-year survival rate of only 15% in patients with advanced diseases. Tumor protein 63 (TP63), a master transcription factor (TF) in ESCC, cooperates with other TFs to regulate enhancers and/or promoters of target oncogenes, which in turn promotes tumorigenesis. TAR-DNA-binding protein-43 (TDP-43) is an RNA/DNA binding protein with elevated expression in several neoplasms. However, it remains unclear how TDP-43 contributes to ESCC progression. In this study, TDP-43 is identified as a novel oncogene with markedly upregulated expression in ESCC tissues through profiling expression levels of one hundred and fifty canonical RNA binding protein (RBP) genes in multiple ESCC patient cohorts. Importantly, TDP-43 boosted TP63 expression via post-transcriptionally stabilizing TP63 mRNAs as a RBP and promoting TP63 transcription as a TF binding to the TP63 promoter in ESCC cells. In contrast, the master TF TP63 also bound to the TDP-43 promoter, accelerated TDP-43 transcription, and caused a noticeable increase in TDP-43 expression in ESCC cells. The findings highlight TDP-43 as a viable therapeutic target for ESCC and uncover a hitherto unrecognized TDP-43/TP63 circuit in cancer.

SntB Affects Growth to Regulate Infecting Potential in Penicillium italicum.

Penicillium italicum, a major postharvest pathogen, causes blue mold rot in citrus fruits through the deployment of various virulence factors. Recent studies highlight the role of the epigenetic reader, SntB, in modulating the pathogenicity of phytopathogenic fungi. Our research revealed that the deletion of the SntB gene in P. italicum led to significant phenotypic alterations, including delayed mycelial growth, reduced spore production, and decreased utilization of sucrose. Additionally, the mutant strain exhibited increased sensitivity to pH fluctuations and elevated iron and calcium ion stress, culminating in reduced virulence on Gannan Novel oranges. Ultrastructural analyses disclosed notable disruptions in cell membrane integrity, disorganization within the cellular matrix, and signs of autophagy. Transcriptomic data further indicated a pronounced upregulation of hydrolytic enzymes, oxidoreductases, and transport proteins, suggesting a heightened energy demand. The observed phenomena were consistent with a carbon starvation response potentially triggering apoptotic pathways, including iron-dependent cell death. These findings collectively underscored the pivotal role of SntB in maintaining the pathogenic traits of P. italicum, proposing that targeting PiSntB could offer a new avenue for controlling citrus fungal infections and subsequent fruit decay.

Characterization and Comparative Analysis of Complete Chloroplast Genomes of Four Bromus (Poaceae, Bromeae) Species.

Bromus (Poaceae Bromeae) is a forage grass with high adaptability and ecological and economic value. Here, we sequenced Bromus ciliatus, Bromus benekenii, Bromus riparius, and Bromus rubens chloroplast genomes and compared them with four previously described species. The genome sizes of Bromus species ranged from 136,934 bp (Bromus vulgaris) to 137,189 bp (Bromus ciliates, Bromus biebersteinii), with a typical quadripartite structure. The studied species had 129 genes, consisting of 83 protein-coding, 38 tRNA-coding, and 8 rRNA-coding genes. The highest GC content was found in the inverted repeat (IR) region (43.85-44.15%), followed by the large single-copy (LSC) region (36.25-36.65%) and the small single-copy (SSC) region (32.21-32.46%). There were 33 high-frequency codons, with those ending in A/U accounting for 90.91%. A total of 350 simple sequence repeats (SSRs) were identified, with single-nucleotide repeats being the most common (61.43%). A total of 228 forward and 141 palindromic repeats were identified. No reverse or complementary repeats were detected. The sequence identities of all sequences were very similar, especially with respect to the protein-coding and inverted repeat regions. Seven highly variable regions were detected, which could be used for molecular marker development. The constructed phylogenetic tree indicates that Bromus is a monophyletic taxon closely related to Triticum. This comparative analysis of the chloroplast genome of Bromus provides a scientific basis for species identification and phylogenetic studies.

Moxibustion ameliorates chronic inflammatory visceral pain via spinal circRNA-miRNA-mRNA networks: a central mechanism study.

This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion's analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.

Screening for thalassemia carriers among the Han population of childbearing age in Southwestern of China.

Purpose: Thalassemia is a severe hereditary blood disorder that poses a significant threat to human health and leads to mortality and disability. It is one of the most prevalent monogenic diseases worldwide. The aim of this study was to analyze the molecular epidemiological data of individuals of childbearing age from the Han ethnic group with thalassemia in Southwest China and to explore the application of next-generation sequencing (NGS) technology in screening thalassemia carriers. Methods: The participants were Han males and females of childbearing age who sought medical advice at the West China Second University Hospital, Sichuan University from June 2022 to June 2023. We detected α- and ß-thalassemia mutations using full-length capture of the thalassemia genes and NGS technology. Results: In a cohort of 1,093 participants, 130 thalassemia carriers were identified, with an overall detection rate of 11.89% (130/1,093). Among these, 0.91% (10/1,093) had mutations that could not be detected using traditional PCR techniques. The proportions of carriers with α-, ß-, and α-complexed ß-thalassemia gene mutations were 7.68% (84/1,093), 3.93% (43/1,093), and 0.27% (3/1,093), respectively. We identified a novel HBA2 c.166del variant that has not been previously reported. Conclusion: Using NGS technology, we found that the mutation-carrying rate of thalassemia genes was 11.89% in the Han population of childbearing age in Southwest China. Compared with the results of traditional PCR techniques, NGS detected an additional 0.91% (10/1,093) rare genetic variants. NGS technology should be utilized as the primary screening method for thalassemia carriers among Han nationality people of childbearing age in Southwest China.

Construction of recombinant pseudorabies virus expressing PCV2 Cap, PCV3 Cap, and IL-4: investigation of their biological characteristics and immunogenicity.

Background: Porcine circovirus type 2 (PCV2) is a globally prevalent and recurrent pathogen that primarily causes slow growth and immunosuppression in pigs. Porcine circovirus type 3 (PCV3), a recently discovered virus, commonly leads to reproductive disorders in pigs and has been extensively disseminated worldwide. Infection with a single PCV subtype alone does not induce severe porcine circovirus-associated diseases (PCVD), whereas concurrent co-infection with PCV2 and PCV3 exacerbates the clinical manifestations. Pseudorabies (PR), a highly contagious disease in pigs, pose a significant threat to the swine industry in China. Methods: In this study, recombinant strains named rPRV-2Cap/3Cap and rPRV-2Cap/3Cap/IL4 was constructed by using a variant strain XJ of pseudorabies virus (PRV) as the parental strain, with the TK/gE/gI genes deleted and simultaneous expression of PCV2 Cap, PCV3 Cap, and IL-4. The two recombinant strains obtained by CRISPR/Cas gE gene editing technology and homologous recombination technology has genetic stability in baby hamster Syrian kidney-21 (BHK-21) cells and is safe to mice. Results: rPRV-2Cap/3Cap and rPRV-2Cap/3Cap/IL4 exhibited good safety and immunogenicity in mice, inducing high levels of antibodies, demonstrated 100% protection against the PRV challenge in mice, reduced viral loads and mitigated pathological changes in the heart, lungs, spleen, and lymph nodes during PCV2 challenge. Moreover, the recombinant viruses with the addition of IL-4 as a molecular adjuvant outperformed the non-addition group in most indicators. Conclusion: rPRV-2Cap/3Cap and rPRV-2Cap/3Cap/IL4 hold promise as recombinant vaccines for the simultaneous prevention of PCV2, PCV3, and PRV, while IL-4, as a vaccine molecular adjuvant, effectively enhances the immune response of the vaccine.