Long-term night shift work, genetic predisposition, and risk of incident asthma: a prospective cohort study.

BACKGROUND: Evidence about a potential link between current and lifetime night shift work and risk of incident asthma is insufficient. AIM: To investigate the association of current and lifetime night shift work with risk of incident asthma, and the modified effect of genetic susceptibility on this association. DESIGN AND METHODS: We included 253,773 individuals with complete night shift work information in the UK biobank. We calculated the standard polygenetic risk score (PRS) for asthma. The Cox proportional hazard models were conducted to estimate hazard ratios (HRs) and 95% CIs. RESULTS: After multivariable adjustments, we found that current night shift work was associated with an increased risk of incident asthma in a dose-response fashion (P for trend<0.001). Compared with day workers, those working usual/permanent night shifts had a 17% (95% CI: 1.04-1.33) higher risk of asthma incidence. In addition, we observed significant dose-dependent relationships of longer lifetime duration or frequency of night shift work with elevated risk of asthma incidence (all P for trend<0.05). Compared with never night shift workers, those with a duration (≥5 years) or frequency (≥8 nights/month) of night shift work exhibited a 20% (95% CI: 1.03-1.39) or 22% (95% CI: 1.03-1.44) higher risk of incident asthma, respectively. Moreover, the elevated risk of incident asthma related to current and lifetime night shift work exposure was strengthened by high PRS, although no significant shift work-PRS interactions were detected. CONCLUSION: Both current and lifetime night shift work may increase the risk of incident asthma, regardless of genetic predisposition to asthma.

Associations of polychlorinated biphenyls exposure, lifestyle, and genetic susceptibility with dyslipidemias: Evidence from a general Chinese population.

Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals that have been associated with various adverse health conditions. Herein we explored the associations of PCBs with dyslipidemia and further assessed the modification effect of genetic susceptibility and lifestyle factors. Six serum PCBs (PCB-28, 101, 118, 138, 153, 180) were determined in 3845 participants from the Wuhan-Zhuhai cohort. Dyslipidemia, including hyper-total cholesterol (HyperTC), hyper-triglyceride (HyperTG), hyper-low density lipoprotein cholesterol (HyperLDL-C), and hypo-high density lipoprotein cholesterol (HypoHDL-C) were determined, and lipid-specific polygenic risk scores (PRS) and healthy lifestyle score were constructed. We found that all six PCB congeners were positively associated with the prevalence of dyslipidemias, and ΣPCB level was associated with HyperTC, HyperTG, and HyperLDL-C in dose-response manners. Compared with the lowest tertiles of ΣPCB, the odds ratios (95% confidence intervals) in the highest tertiles were 1.490 (1.258, 1.765) for HyperTC, 1.957 (1.623, 2.365) for HyperTG, and 1.569 (1.316, 1.873) for HyperLDL-C, respectively. Compared with those with low ΣPCB, healthy lifestyle, and low genetic risk, participants with high ΣPCB, unfavorable lifestyle, and high genetic risk had the highest odds of HyperTC, HyperTG, and HyperLDL-C. Our study provided evidence that high PCB exposure exacerbated the association of genetic risk and unhealthy lifestyle with dyslipidemia.

Associations between long-term night shift work and incidence of chronic obstructive pulmonary disease: a prospective cohort study of 277,059 UK Biobank participants.

BACKGROUND: Little is known about the effects of night shifts and their interactions with genetic factors on chronic obstructive pulmonary disease (COPD). In this study, we aim to investigate relationships between long-term night shift work exposure and COPD risk, and assess modification effects of genetic predisposition. METHODS: A total of 277,059 subjects who were in paid employment or self-employed were included in the UK Biobank. Information on current and lifetime employment was obtained, and a weighted COPD-specific genetic risk score (GRS) was constructed. We used Cox proportional hazard models to investigate associations between night shift work and COPD risk, and their interaction with COPD-specific GRS. RESULTS: The cohort study included 277,059 participants (133,063 men [48.03%]; mean [SD] age, 52.71 [7.08] years). During a median follow-up of 12.87 years, we documented 6558 incidents of COPD. From day work, irregular night shifts to regular night shifts, there was an increased trend in COPD incidence (P for trend < 0.001). Compared with day workers, the hazard ratio (HR) and 95% confidence interval (CI) of COPD was 1.28 (1.20, 1.37) for subjects with rarely/sometimes night shifts and 1.49 (1.35, 1.66) for those with permanent night shifts. Besides, the longer durations (especially in subjects with night shifts ≥ 10 years) and increasing monthly frequency of night shifts (in workers with > 8 nights/month) were associated with a higher COPD risk. Additionally, there was an additive interaction between night shifts and genetic susceptibility on the COPD risk. Subjects with permanent night shifts and high genetic risk had the highest risk of COPD (HR: 1.90 [95% CI: 1.63, 2.22]), with day workers with low genetic risk as a reference. CONCLUSIONS: Long-term night shift exposure is associated with a higher risk of COPD. Our findings suggest that decreasing the frequency and duration of night shifts may offer a promising approach to mitigating respiratory disease incidence in night shift workers, particularly in light of individual susceptibility.

Rice volatile compound (E)-ß-caryophyllene induced by rice dwarf virus (RDV) attracts the natural enemy Cyrtorhinus lividipennis to prey on RDV insect vectors.

BACKGROUND: Rice dwarf virus (RDV)-induced rice plant volatiles (E)-ß-caryophyllene and 2-heptanol modulate the olfactory behavior of RDV insect vectors that promote viral acquisition and transmission. However, it remains elusive whether these two volatiles could influence the behaviors of the natural enemies of RDV insect vectors. Herein, we determined the effects of these two volatiles on the olfactory and predatory behaviors of Cyrtorhinus lividipennis (Hemiptera: Miridae), an important predator of RDV insect vectors in rice paddies. RESULTS: The results showed that C. lividipennis preferred RDV-infected rice plant odors over RDV-free rice plant odors. C. lividipennis was attracted by (E)-ß-caryophyllene, but showed no behavioral responses to 2-heptanol. The attraction of (E)-ß-caryophyllene towards C. lividipennis was further confirmed using oscas1 rice plants, which do not release (E)-ß-caryophyllene in response to RDV infection, through a series of complementary assays. The oviposition preference of the RDV vector insect Nephotettix cincticeps (Hemiptera: Cicadellidae) showed no significant difference between RDV-infected and RDV-free wild-type plants, nor between oscas1-RDV and oscas1 plants. However, the predation rate of C. lividipennis for N. cincticeps eggs on RDV-infected plants was higher than that on RDV-free plants, whereas there was no significant difference between oscas1-RDV and oscas1 plants. CONCLUSION: (E)-ß-caryophyllene induced by RDV attracted more C. lividipennis to prey on N. cincticeps eggs and played a crucial role in plant-virus-vector-enemy interactions. These novel findings will promote the design of new strategies for disease control by controlling the populations of insect vectors, for example recruiting more natural enemies by virus-induced plant volatiles. © 2023 Society of Chemical Industry.

Screening for Fungicide Efficacy in Controlling Blackleg Disease in Wasabi (Eutrema japonicum).

Blackleg disease is devastating for wasabi (Eutrema japonicum) production, occurring at any time and everywhere within the main production area of the Sichuan Province, China. There have been very few studies on the chemical control of this disease. In this study, we isolated and identified a local popular strain of the pathogen Plenodomus wasabiae. The isolated fungus strain caused typical disease spots on the leaves and rhizomes upon inoculation back to wasabi seedlings. The symptoms of blackleg disease developed very quickly, becaming visible on the second day after exposure to P. wasabiae and leading to death within one week. We then evaluated the efficacy of ten widely used fungicides to screen out effective fungicides. The efficacy of the tested fungicides was determined through mycelial growth inhibition on medium plates. As a result, tebuconazole and pyraclostrobin were able to inhibit the mycelial growth of P. wasabiae, and the most widely used dimethomorph in local production areas produced the lowest inhibition activity (13.8%). Nevertheless, the highest control efficacy of tebuconazole and pyraclostrobin on wasabi seedlings was only 47.48% and 39.03%, respectively. Generally, the control efficacy of spraying the fungicide before inoculation was better than that after inoculation. An increase in the application concentration of the two fungicides did not proportionately result in improved performance. We cloned the full-length sequence of sterol 14-demethylase (CYP51) and cytochrome B (CYTB) of which the mutations may contribute to the possible antifungalresistance. These two genes of the isolated fungus do not possess any reported mutations that lead to fungicide resistance. Previous studies indicate that there is a significant difference between fungicides in terms of the effectiveness of controlling blackleg disease; however, the control efficacy of fungicides is limited in blackleg control. Therefore, field management to prevent wound infection and unfavorable environmental conditions are more important than pesticide management.

Role and mechanism of WNT5A in benzo(a)pyrene-induced acute lung injury and lung function decline.

Benzo(a)pyrene was sparsely studied for its early respiratory impairment. The non-canonical ligand WNT5A play a role in pneumonopathy, while its function during benzo(a)pyrene-induced adverse effects were largely unexplored. Individual benzo(a)pyrene, plasma WNT5A, and spirometry 24-hour change for 87 residents from Wuhan-Zhuhai cohort were determined to analyze potential role of WNT5A in benzo(a)pyrene-induced lung function alternation. Normal bronchial epithelial cell lines were employed to verify the role of WNT5A after benzo(a)pyrene treatment. RNA sequencing was adopted to screen for benzo(a)pyrene-related circulating microRNAs and differentially expressed microRNAs between benzo(a)pyrene-induced cells and controls. The most potent microRNA was selected for functional experiments and target gene validation, and their mechanistic link with WNT5A-mediated non-canonical Wnt signaling was characterized through rescue assays. We found significant associations between increased benzo(a)pyrene and reduced 24-hour changes of FEF50% and FEF75%, as well as increased WNT5A. The benzo(a)pyrene-induced inflammation and epithelial-mesenchymal transition in BEAS-2B and 16HBE cells were attenuated by WNT5A silencing. hsa-miR-122-5p was significantly and positively associated with benzo(a)pyrene and elevated after benzo(a)pyrene induction, and exerted its effect by downregulating target gene TP53. Functionally, WNT5A participates in benzo(a)pyrene-induced lung epithelial injury via non-canonical Wnt signaling modulated by hsa-miR-122-5p/TP53 axis, showing great potential as a preventive and therapeutic target.

Large-Scale Biomedical Relation Extraction Across Diverse Relation Types: Model Development and Usability Study on COVID-19.

BACKGROUND: Biomedical relation extraction (RE) is of great importance for researchers to conduct systematic biomedical studies. It not only helps knowledge mining, such as knowledge graphs and novel knowledge discovery, but also promotes translational applications, such as clinical diagnosis, decision-making, and precision medicine. However, the relations between biomedical entities are complex and diverse, and comprehensive biomedical RE is not yet well established. OBJECTIVE: We aimed to investigate and improve large-scale RE with diverse relation types and conduct usability studies with application scenarios to optimize biomedical text mining. METHODS: Data sets containing 125 relation types with different entity semantic levels were constructed to evaluate the impact of entity semantic information on RE, and performance analysis was conducted on different model architectures and domain models. This study also proposed a continued pretraining strategy and integrated models with scripts into a tool. Furthermore, this study applied RE to the COVID-19 corpus with article topics and application scenarios of clinical interest to assess and demonstrate its biological interpretability and usability. RESULTS: The performance analysis revealed that RE achieves the best performance when the detailed semantic type is provided. For a single model, PubMedBERT with continued pretraining performed the best, with an F1-score of 0.8998. Usability studies on COVID-19 demonstrated the interpretability and usability of RE, and a relation graph database was constructed, which was used to reveal existing and novel drug paths with edge explanations. The models (including pretrained and fine-tuned models), integrated tool (Docker), and generated data (including the COVID-19 relation graph database and drug paths) have been made publicly available to the biomedical text mining community and clinical researchers. CONCLUSIONS: This study provided a comprehensive analysis of RE with diverse relation types. Optimized RE models and tools for diverse relation types were developed, which can be widely used in biomedical text mining. Our usability studies provided a proof-of-concept demonstration of how large-scale RE can be leveraged to facilitate novel research.

Hierarchical Clustering Algorithm for Multi-Camera Vehicle Trajectories Based on Spatio-Temporal Grouping under Intelligent Transportation and Smart City.

With the emergence of intelligent transportation and smart city system, the issue of how to perform an efficient and reasonable clustering analysis of the mass vehicle trajectories on multi-camera monitoring videos through computer vision has become a significant area of research. The traditional trajectory clustering algorithm does not consider camera position and field of view and neglects the hierarchical relation of the video object motion between the camera and the scenario, leading to poor multi-camera video object trajectory clustering. To address this challenge, this paper proposed a hierarchical clustering algorithm for multi-camera vehicle trajectories based on spatio-temporal grouping. First, we supervised clustered vehicle trajectories in the camera group according to the optimal point correspondence rule for unequal-length trajectories. Then, we extracted the starting and ending points of the video object under each group, hierarchized the trajectory according to the number of cross-camera groups, and supervised clustered the subsegment sets of different hierarchies. This method takes into account the spatial relationship between the camera and video scenario, which is not considered by traditional algorithms. The effectiveness of this approach has been proved through experiments comparing silhouette coefficient and CPU time.

MADAv2: Advanced Multi-Anchor Based Active Domain Adaptation Segmentation.

Unsupervised domain adaption has been widely adopted in tasks with scarce annotated data. Unfortunately, mapping the target-domain distribution to the source-domain unconditionally may distort the essential structural information of the target-domain data, leading to inferior performance. To address this issue, we first propose to introduce active sample selection to assist domain adaptation regarding the semantic segmentation task. By innovatively adopting multiple anchors instead of a single centroid, both source and target domains can be better characterized as multimodal distributions, in which way more complementary and informative samples are selected from the target domain. With only a little workload to manually annotate these active samples, the distortion of the target-domain distribution can be effectively alleviated, achieving a large performance gain. In addition, a powerful semi-supervised domain adaptation strategy is proposed to alleviate the long-tail distribution problem and further improve the segmentation performance. Extensive experiments are conducted on public datasets, and the results demonstrate that the proposed approach outperforms state-of-the-art methods by large margins and achieves similar performance to the fully-supervised upperbound, i.e., 71.4% mIoU on GTA5 and 71.8% mIoU on SYNTHIA. The effectiveness of each component is also verified by thorough ablation studies.

A systematic review and meta-analysis of acupuncture in Parkinson's disease with dysphagia.

Objective: The systematic review and meta-analysis aimed to comprehensively evaluate acupuncture's efficacy and safety in treating dysphagia in Parkinson's disease (PD). Methods: We searched PubMed, Cochrane Library, Embase, Web of Science, China Knowledge Infrastructure (CNKI), China Science Journal Database (VIP), Wan-fang Database, and the China Biomedical Literature Service System (CBM) for randomized controlled trials (RCTs) comparing the efficacy of acupuncture alone or in combination with control treatment in improving dysphagia by October 2022. The degree of dysphagia was the primary outcome indicator, with secondary outcomes including serum albumin (ALB) and hemoglobin (Hb) levels, the incidence of pneumonia, and adverse events. Two investigators independently extracted information according to the inclusion and exclusion criteria. Data synthesis was calculated by RevMan (V.5.4.1) software. Results: This study included ten randomized controlled trials with 724 patients. Most RCTs have a high or uncertain risk of bias due to the lack of a blinded design. Meta-analysis showed that acupuncture combined with control treatment was superior to control treatment alone in improving Videofluoroscopic Swallowing Study (VFSS) scores (MD: 1.48; 95% CI: 1.16, 1.81; P < 0.00001) and reducing Standardized Swallowing Assessment (SSA) scores (MD: -3.08; 95% CI: -4.01, -2.15; P < 0.00001). Acupuncture combined with control therapy has a more significant benefit in improving the clinical efficiency of dysphagia in PD (RR: 1.40; 95%CI: 1.25, 1.58; P < 0.00001). Compared to the control group without acupuncture, acupuncture improved the nutritional status of patients and increased their serum ALB (MD: 3.38, 95%CI: 1.83, 4.92, P < 0.00001) and Hb levels (MD: 7.66; 95%CI: 5.57, 9.75; P < 0.00001). Three RCTs reported that the rate of pulmonary infections in the acupuncture group was lower than without acupuncture intervention (RR: 0.29, 95% CI: 0.14, 0.63; P = 0.001). Conclusion: Acupuncture could be recommended as an adjunctive treatment for dysphagia in PD. However, due to the high risk of bias in the included studies, more high-quality evidence is needed to confirm the efficacy and safety of acupuncture for dysphagia in PD. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370221.

Early-life tobacco smoke exposure, genetic susceptibility and the risk of type 2 diabetes in adulthood: A large prospective cohort study.

OBJECTIVES: We aimed to assess the relationships between early-life tobacco smoke exposures and the incident risk of type 2 diabetes (T2D) in later life as well as the joint effects and interactions between genetic susceptibility and early-life tobacco exposures. METHODS: We used data on in utero tobacco exposure and the age of smoking initiation to estimate the status of early-life tobacco exposure in the UK Biobank. Cox proportion hazard models were applied to estimate the associations between early-life tobacco exposure and T2D risk and investigate joint effects and interactions of early-life tobacco smoke exposure with genetic susceptibility. RESULTS: Among 407,943 subjects from the UK Biobank, 17,115 incident cases were documented during a median follow-up of 12.80 years. Compared with subjects without prenatal tobacco exposure, those with in utero tobacco exposure had a higher risk of T2D with a hazard ratio (HR) (95 % confidence interval [CI]) of 1.11 (1.08, 1.15). Besides, the HRs (95 % CIs) of incident T2D for smoking initiation in adulthood, adolescence, and childhood (vs. never smokers) were 1.36 (1.31, 1.42), 1.44 (1.38, 1.50), and 1.78 (1.69, 1.88), respectively (P trend <0.001). No interaction between early-life tobacco exposure and genetic susceptibility was observed. In addition, participants with prenatal (HR 4.67 [95 % CI 4.31, 5.06]) or childhood (6.91 [6.18, 7.72]) tobacco exposure combined with high genetic risk showed the highest risk of T2D, compared to low genetic risk subjects without early-life smoke exposure. CONCLUSION: Early-life tobacco exposure was associated with an increased risk of T2D later in life regardless of genetic background. This highlights the significance of education campaigns aimed at reducing smoking among children, adolescents, and pregnant women as an effective measure to combat the T2D epidemic.

A knowledge empowered explainable gene ontology fingerprint approach to improve gene functional explication and prediction.

Functional explication of genes is of great scientific value. However, conventional methods have challenges for those genes that may affect biological processes but are not annotated in public databases. Here, we developed a novel explainable gene ontology fingerprint (XGOF) method to automatically produce knowledge networks on biomedical literature in a given field which quantitatively characterizes the association between genes and ontologies. XGOF provides systematic knowledge for the potential function of genes and ontologically compares similarities and discrepancies in different disease-XGOFs integrating omics data. More importantly, XGOF can not only help to infer major cellular components in a disease microenvironment but also reveal novel gene panels or functions for in-depth experimental research where few explicit connections to diseases have previously been described in the literature. The reliability of XGOF is validated in four application scenarios, indicating a unique perspective of integrating text and data mining, with the potential to accelerate scientific discovery.

Morphological and Molecular Characterization, Including Parasitic and Pathogenic Studies of a New Spherical Cyst Nematode Species, Globodera vulgaris n. sp. (Nematoda: Heteroderidae), Associated with Potatoes in China.

In this study, a new spherical cyst nematode belonging to the genus Globodera, herein described as Globodera vulgaris n. sp., was extracted from the roots and rhizosphere soil of potato and circumjacent weeds belonging to different families in three provinces in southwest China. The new species was characterized by 8 to 24 ridges between the anus and fenestra and an average Granek's ratio of 2.8 to 3.8 in cysts, a head with three to four annules, a dorsal knob anteriorly projected, ventral knobs round or anteriorly projected in second stage juveniles, a head with three to five annules, a short spicule with an average length of less than 30.0 µm, and a developed velum in males. Pathogenicity tests showed that G. vulgaris n. sp. infected potato but did not damage or affect the potato yield compared with the control, and it parasitized tomato with a low reproduction rate (RF < 1) while it did not parasitize tobacco (RF = 0). The new species was closely related to G. rostochiensis, based on molecular diagnostic marker sequences and constructed phylogenetic analysis, based on internal transcribed spacers of ribosomal DNA, large-subunit rDNA, and small-subunit rDNA. However, the new species exhibited differences from G. rostochiensis in terms of morphological characteristics, a wide host preference, lack of damage to hosts, and an egg-hatching rate induced by hatching factors.

Plasma microRNA expression profiles associated with zinc exposure and type 2 diabetes mellitus: Exploring potential role of miR-144-3p in zinc-induced insulin resistance.

Zinc exposure has been linked with disordered glucose metabolism and type 2 diabetes mellitus (T2DM) development. However, the underlying mechanism remains unclear. We conducted population-based studies and in vitro experiments to explore potential role of microRNAs (miRNAs) in zinc-related hyperglycemia and T2DM. In the discovery stage, we identified plasma miRNAs expression profile for zinc exposure based on 87 community residents from the Wuhan-Zhuhai cohort through next-generation sequencing. MiRNAs profiling for T2DM was also performed among 9 pairs newly diagnosed T2DM-healthy controls. In the validating stage, plasma miRNA related to both of zinc exposure and T2DM among the discovery population was measured by qRT-PCR in 161 general individuals derived from the same cohort. Furthermore, zinc treated HepG2 cells with mimic or inhibitor were used to verify the regulating role of miR-144-3p. Based on the discovery and validating populations, we observed that miR-144-3p was positively associated with urinary zinc, hyperglycemia, and risk of T2DM. In vitro experiments confirmed that zinc-induced increase in miR-144-3p expression suppressed the target gene Nrf2 and downstream antioxidant enzymes, and aggravated insulin resistance. Our findings provided a novel clue for mechanism underlying zinc-induced glucose dysmetabolism and T2DM development, emphasizing the important role of miR-144-3p dysregulation.

Neutralization of interleukin-11 attenuates silica particles-induced pulmonary inflammation and fibrosis in vivo.

Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11 (IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines (i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins (i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α (IL-11Rα), Glycoprotein 130 (GP130), and phosphorylated extracellular signal-regulated kinase (p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.

ViMRT: a text-mining tool and search engine for automated virus mutation recognition.

MOTIVATION: Virus mutation is one of the most important research issues which plays a critical role in disease progression and has prompted substantial scientific publications. Mutation extraction from published literature has become an increasingly important task, benefiting many downstream applications such as vaccine design and drug usage. However, most existing approaches have low performances in extracting virus mutation due to both lack of precise virus mutation information and their development based on human gene mutations. RESULTS: We developed ViMRT, a text-mining tool and search engine for automated virus mutation recognition using natural language processing. ViMRT mainly developed 8 optimized rules and 12 regular expressions based on a development dataset comprising 830 papers of 5 human severe disease-related viruses. It achieved higher performance than other tools in a test dataset (1662 papers, 99.17% in F1-score) and has been applied well to two other viruses, influenza virus and severe acute respiratory syndrome coronavirus-2 (212 papers, 96.99% in F1-score). These results indicate that ViMRT is a high-performance method for the extraction of virus mutation from the biomedical literature. Besides, we present a search engine for researchers to quickly find and accurately search virus mutation-related information including virus genes and related diseases. AVAILABILITY AND IMPLEMENTATION: ViMRT software is freely available at http://bmtongji.cn:1225/mutation/index.

The clinical effect of ossotide for injection in the treatment of condylar fracture.

OBJECTIVES: Patients with condylar fractures were treated with osteopeptide injections as an adjuvant therapy to assess pain control and changes in interleukin-1ß (IL-1ß) and bone G-gla protein (BGP) levels. MATERIALS AND METHODS: Eighty-two patients with a condylar neck fracture were randomly assigned to two groups. The control group received conventional surgical treatment, while the experimental group received osteopeptide injections in addition to surgery. Pain level, IL-1ß, and BGP levels were evaluated at 1, 2, and 4 weeks postsurgery. RESULTS: One and two weeks postsurgery, the experimental group had lower Numeric Rating Scale scores compared to the control group. In addition, the IL-1ß level in patients receiving osteopeptide injections was lower than the control group at all three evaluation points (1, 2, and 4 weeks postsurgery) and the BGP level was higher with statistically significant differences (P < 0.05). CONCLUSIONS: The administration of osteopeptide injections as an adjuvant therapy for patients with condylar fractures can effectively reduce pain and facilitate faster initiation of muscle function training. In addition, the reduction of inflammatory factors and promotion of active osteogenesis leads to quicker wound healing.

The emerging role of epigenetic regulation in the progression of silicosis.

Silicosis is one of the most severe occupational diseases worldwide and is characterized by silicon nodules and diffuse pulmonary fibrosis. However, specific treatments for silicosis are still lacking at present. Therefore, elucidating the pathogenesis of silicosis plays a significant guiding role for its treatment and prevention. The occurrence and development of silicosis are accompanied by many regulatory mechanisms, including epigenetic regulation. The main epigenetic regulatory mechanisms of silicosis include DNA methylation, non-coding RNA (ncRNA), and histone modifications. In recent years, the expression and regulation of genes related to silicosis have been explored at epigenetic level to reveal its pathogenesis further, and the identification of aberrant epigenetic markers provides new biomarkers for prediction and diagnosis of silicosis. Here, we summarize the studies on the role of epigenetic changes in the pathogenesis of silicosis to give some clues for finding specific therapeutic targets for silicosis.

Characteristics of Diagnosed and Death Cases of Pneumoconiosis in Hubei Province, China, 1949-2019.

OBJECTIVE: This study aims to summarize the characteristics of diagnosed pneumoconiosis and pneumoconiosis death in the Hubei Province of China, between the years 1949 and 2019, and provide clues for the scientific prevention of pneumoconiosis. METHODS: We recruited 23,069 pneumoconiosis cases in Hubei Province, China, from 1949 to 2019. Basic information and occupational surveillance information were obtained from the Hubei Occupational Diseases and Health Risk Factors Information Surveillance System. RESULTS: The annually diagnosed pneumoconiosis cases showed an overall increasing trend from 1949 to 2019 in Hubei Province. The major types of pneumoconiosis were coal workers' pneumoconiosis (CWP, 49.91%) and silicosis (43.39%). Pneumoconiosis cases were mainly engaged in mining (75.32%) and manufacturing (12.72%), and were distributed in Huangshi (35.48%), Yichang (16.16%), and Jingzhou (7.97%). CWP (47.50%) and silicosis (44.65%) accounted for most of the deaths. CONCLUSIONS: The number of pneumoconiosis cases and deaths in Hubei increased in the period of 1949 to 2019. Silicosis and CWP contributed to the predominant types of pneumoconiosis. Prevention and control measures should continue to be taken to reduce the morbidity and mortality of pneumoconiosis.

Insights into the mechanism underlying crystalline silica-induced pulmonary fibrosis via transcriptome-wide m6A methylation profile.

Silicosis is one of the most severe interstitial lung fibrosis diseases worldwide, caused by crystalline silica exposure. While the mechanisms and pathogenesis underlying silicosis remained unknown. N6-methyladenosine (m6A) methylation has received significant attention in a variety of human diseases. However, whether m6A methylation is involved in silicosis has not been clarified. In this study, we conducted methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and transcriptome sequencing (RNA-Seq) to profile the m6A modification in normal and silicosis mouse models (n = 3 pairs). The global levels of m6A methylation were further assessed by m6A RNA methylation quantification kits, and the major regulators of m6A RNA methylation were verified by qRT-PCR. Our results showed that long-term exposure to crystalline silica led to silicosis, accompanied by increasing levels of m6A methylation. Upregulation of METTL3 and downregulation of ALKBH5, FTO, YTHDF1, and YTHDF3 might contribute to aberrant m6A modification. Compared with controls, 359 genes showed differential m6A methylation peaks in silicosis (P < 0.05 and FC ≥ 2). Among them, 307 genes were hypermethylated, and 52 genes were hypomethylated. RNA-Seq analysis revealed 1091 differentially expressed genes between the two groups, 789 genes were upregulated and 302 genes were downregulated in the lungs of silicosis mice (P < 0.05 and FC ≥ 2). In the conjoint analysis of MeRIP-Seq and RNA-Seq, we identified that 18 genes showed significant changes in both m6A modification and mRNA expression. The functional analysis further noted that these 18 m6A-mediated mRNAs regulated pathways that were closely related to "phagosome", "antigen processing and presentation", and "apoptosis". All findings suggested that m6A methylation played an essential role in the formation of silicosis. Our discovery with multi-omics approaches not only gives clues for the epigenetic mechanisms underlying the pathogenesis of silicosis but also provides novel and viable strategies for the prevention and treatment of silicosis.