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Abstract Background It is well-established that understanding the mechanism of prostate cancer (PCa)-associated metastasis is paramount for improving its prognosis. Metastasis is known to involve the communication between tumor-associated macrophages (TAMs) and tumor cells. Exosomes are crucial in mediating this intercellular communication within the tumor microenvironment. Nonetheless, the role of exosomal proteins in PCa metastasis is not yet fully understood. Here, we investigated the mechanisms of prostate cancer-derived exosomal PSM-E on regulating macrophage M2 polarization to suppress tumor invasion and metastasis. Methods PSM-E levels in exosomes were detected by transmission electron microscopy and Western blotting analysis. The diagnostic value of urine-derived exosomal PSM-E in PCa were evaluated by LC-MS/MS, correlation analysis, and ROC curves analysis. The mechanisms underlying the inhibitory effect of exosomal PSM-E on the M2 polarization of macrophages was investigated by co-IP, IHC staining, and PCa tumorigenesis model, etc. Results We revealed that exosomal PSM-E is upregulated in exosomes derived from the serum and urine of PCa patients. Clinically, an elevated exosomal PSM-E expression in urine is significantly correlated with an advanced pathological tumor stage and a high Gleason score. Our research also revealed that exosomal PSM-E inhibits prostate cancer cell proliferation, invasion, and metastasis by suppressing macrophage polarization in vitro and in vivo. Furthermore, we provided compelling evidence that exosomal PSM-E inhibits M2 polarization of macrophages by recruiting RACK1 and suppressing the FAK and ERK signaling pathways, consequently suppressing PCa invasion and metastasis. Furthermore, we found that the protease-associated domain of PSM-E and the fourth tryptophan-aspartate repeat of RACK1 are crucial for the interaction between PSM-E and RACK1. Conclusions Notably, exosomes carrying PSM-E from PCa urine could potentially serve as a biomarker for PCa, and targeting exosomal PSM-E may represent a strategy for preventing tumor progression in this patient population.

Abstract Despite the well-established significance of transcription factors (TFs) in pathogenesis, their utilization as pharmacological targets has been limited by the inherent challenges in modulating their protein interactions. The lack of defined small-molecule binding pockets and the nuclear localization of TFs do not favor the use of traditional tools. Aptamers possess large molecular weights, expansive blocking surfaces and efficient cellular internalization, making them compelling tools for modulating TF interactions. Here, we report a structure-guided design strategy called Blocker-SELEX to develop inhibitory aptamers (iAptamers) that selectively block TF interactions. Our approach leads to the discovery of iAptamers that cooperatively disrupt SCAF4/SCAF8-RNAP2 interactions, dysregulating RNAP2-dependent gene expression, which impairs cell proliferation. This approach is further applied to develop iAptamers blocking WDR5-MYC interactions. Overall, our study highlights the potential of iAptamers in disrupting pathogenic TF interactions, implicating their potential utility in studying the biological functions of TF interactions and in nucleic acids drug discovery.

Biofilm reactors, known for utilizing biofilm formation for cell immobilization, offer enhanced biomass concentration and operational stability over traditional planktonic systems. However, the dense nature of biofilms poses challenges for substrate accessibility to cells and the efficient release of products, making mass transfer efficiency a critical issue in these systems. Recent advancements have unveiled the intricate, heterogeneous architecture of biofilms, contradicting the earlier view of them as uniform, porous structures with consistent mass transfer properties. In this review, we explore six biofilm reactor configurations and their potential combinations, emphasizing how the spatial arrangement of biofilms within reactors influences mass transfer efficiency and overall reactor performance. Furthermore, we discuss how to apply artificial intelligence in processing biofilm measurement data and predicting reactor performance. This review highlights the role of biofilm reactors in environmental and energy sectors, paving the way for future innovations in biofilm-based technologies and their broader applications.

The Proton Exchange Membrane (PEM) water electrolyzer is considered one of the promising energy storing means for harnessing variable renewable energy sources to produce hydrogen. Understanding the internal fluid dynamics, which are often challenging to directly observe experimentally, has prompted the use of numerical models to investigate two-phase flow within PEM water electrolyzers. In this study, we provide a comprehensive review of prior research focusing on two-phase modeling of PEM electrolyzers, encompassing both components at mesoscopic scales and the full electrolyzer at the macroscopic level. We delve into the specifics of various modeling approaches for two-phase flow at different scales and summarize and discuss the current state of the art in the field. Presently, two-phase models for the full electrolyzer predominantly employ a macroscopic homogeneous assumption. However, mesoscopic and microscopic models capable of tracking phase interfaces are limited to components. Challenges persist in integrating various modeling scales into a comprehensive electrolyzer model, particularly in coupling two-phase flow between the channels and porous media. Future efforts should focus on developing multi-scale models and simulating two-phase flow under fluctuating input conditions. Additionally, given the structural similarities between PEM water electrolyzers and PEM fuel cells, we compare and discuss differences in two-phase modeling between the two technologies. This work offers the insights for researchers in the field of modeling of PEM water electrolyzers and even fuel cells.

Recently, Nominal Compound Chain Extraction (NCCE) has been proposed to detect related mentions in a document to improve understanding of the document’s topic. NCCE involves longer span detection and more complicated rules for relation decisions, making it more difficult than previous chain extraction tasks, such as coreference resolution. Current methods achieve certain progress on the NCCE task, but they suffer from insufficient syntax information utilization and incomplete mention relation mining, which are helpful for NCCE. To fill these gaps, we propose a syntax-guided model using a triaffine interaction to improve the performance of the NCCE task. Instead of solely relying on the text information to detect compound mentions, we also utilize the noun-phrase (NP) boundary information in constituency trees to incorporate prior boundary knowledge. In addition, we use biaffine and triaffine operations to mine the mention interactions in the local and global context of a document. To show the effectiveness of our methods, we conduct a series of experiments on a human-annotated NCCE dataset. Experimental results show that our model significantly outperforms the baseline systems. Moreover, in-depth analyses reveal the effect of utilizing syntactic information and mention interactions in the local and global contexts.

Karst landforms are widely distributed in southern China. The terrain and soil properties in karst basins are complex, which results in high spatial heterogeneity of the ecological environment and soil organic matter (SOM) in karst watersheds. To investigate the spatial distribution characteristics of SOM in different land uses in the karst plateau basin, a total of 3,816 soil samples were taken from 568 soil profiles. The soil animals and different soil properties were recorded, and the concentration of SOM was tested using the potassium dichromate method in the laboratory. Then, the changes in the SOM content associated with soil animals and the soil properties associated with the different land use types were analyzed. The results showed a large discrepancy in SOM in the karst plateau basin. The average values of SOM in different soil layers were between 9.23 g kg−1 and 59.39 g kg−1. The SOM decreased in the following order: forestland > grassland > barren land > cultivated land > garden land. The SOM in soil in which soil animals are present is generally greater than that in the absence of soil animals, and the SOM partially increases with soil species diversity. Agrotis segetum is the main soil animal species that positively affects the distribution of organic matter in the surface soil layer. The SOM in soil with the phylum Annelida is much greater than that in soils with other animals, and earthworms are the main contributor. The structure of soil animal species is complex, and the change trend of SOM is stable. The major positive factors affecting soil animal diversity are soil thickness, soil humidity and soil structure, and rock outcrops are the main negative factor. In summary, good land use can increase animal diversity and abundance in soil, which promotes soil organic matter accumulation. Moreover, microtopography is an important factor that influences soil organic matter accumulation in karst basins and further affects the restructuring of the spatial distribution of soil organic matter.

China’s coal-fired power plants emit over 5.7 billion tons of CO2 annually. To realize the dual carbon goals in time, it is necessary to reduce the carbon emissions of coal-fired power plants. Microalgae carbon fixation can efficiently absorb CO2 through photosynthesis and convert it into biomass, which is a highly promising technology for carbon reduction in coal-fired power plants. Light guide tubes can flexibly change the light distribution in a photobioreactor, while optical fibers can transmit light centrally with low light loss. Therefore, a microalgae photobioreactor with an optical fiber/light guide tube is proposed to expand the light-receiving area of the microalgae suspension, increase the light-harvesting of microalgal cells, and promote carbon fixation via microalgae photosynthesis. The optical simulation software was used to trace the propagation of light in the optical fiber/light guide tube, and the light intensity distribution of the tube wall was obtained. Microalgae cultivation experiments were conducted in various photobioreactors and under different input light energy conditions. The change trends of biomass yield, carbon sequestration rate, and chlorophyll content were obtained, and the impact of built-in optical fiber /light guide tubes on carbon fixation via microalgae was investigated. Results indicated that the light intensity emitted from the optical fiber terminal decreased precipitously from 30 mm to 140 mm along the side of the light guide tube. Additionally, the tube exhibited a concentrated light-emitting range. Adding a conical reflector to reflect the transmitted light at the tube bottom and designing a stepped optical fiber to emit input light from different steps can optimize the light-emitting effect of the light guide tube and make the light distribution in the microalgae photobioreactor more uniform, so that the microalgal cells far away from the light source area can receive the light energy to photosynthesize and fix carbon. At a light input of 3.3 W/L, the minimum light intensity on the side surface of the light guide comprising a two-stage stepped optical fiber and conical reflector was 47 μmol/(m2·s). The average light intensity was 64 μmol/(m2·s), representing a 2.6-fold increase compared to the light guide tube lacking both the optical fiber and any enhancements beyond its top section. After seven days of cultivation, the microalgae concentration in the stepped fiber photobioreactor (SF-PBR) could reach 1.9 g/L, which was 46.2% higher than that of the photobioreactor inserted with flat-end fiber optic light guide (FF-PBR) and 111.1% higher than that of the photobioreactor with only top-fed light (LG-PBR). When the light input was escalated to 5.0 W/L, a high microalgae concentration of 2.8 g/L was achieved at 7 d. Meanwhile, the average carbon sequestration rate of 608.3 mg/(L·d) was obtained, exhibiting 1.9-fold augmentation compared to the control LG-PBR.

A Scene-Based Nonuniformity Correction (SBNUC) approach is proposed for the correction of fixed-pattern-noise (FPN) in infrared image arrays. This method diverges from conventional neural-network based techniques by eschewing spatial filters for the computation of the desired image. Instead, it harnesses the sparse representation of the estimated irradiance within a hypersphere of adaptive radius, adhering to a distance constraint. The proposed method conceptualizes images as points in a high-dimensional space, with the distance between two images defined by their root mean square difference. The adaptive radius is derived from a sophisticated selection criterion, inversely related to the distance between the noisy input image and the estimated irradiance. This approach ensures edge preservation without excessive blurring while discarding FPN as redundant in the representation coefficients. We propose an adaptive learning rate tailored to the desired image from sparse representation, which contrasts with traditional learning rates that rely on local spatial standard deviation. This new learning rate is determined by the pixel-wise distance between the input image and the desired image, integrating a new motion detection criterion to synchronize the update of correction coefficients across pixels. Our experimental results demonstrate that the method proposed in this paper achieves better removal of fixed-pattern-noise in both simulated and real infrared image sequences compared to the methods used for comparison.

Sea fog detection is a significant and challenging issue in meteorological satellite imagery. Distinguishing between sea fog and low clouds is challenging due to the similar morphology and brightness characteristics of these two phenomena on the imageries. Most of the existing deep learning methods are based on a single imagery feature extraction without the time-related features in imagery sequence. Although the designed temporal models, such as temporal U-Net, expand the available features from a single imagery to the consecutive frames and introduce general temporal information, the learned motion features are not explicit and can only be implicitly learned through a large amount of data. Thus, we introduce motion features obtained from continuous temporal imagery sequences into the sea fog detection task due to the discrepancy between sea fog and other types of clouds. In this article, under the motion features acquired by Horn–Schunck (HS) optical flow method and attention mechanisms, a Motion Attention Network (MoANet) for sea fog detection is proposed, named MoANet. We performed detailed experiments on the Himawaria-8 satellite imagery data set (H-8 Dataset). The Mean Intersection over Union (MIoU) of our method reaches 81.38%, which is 6.49% higher than the single imagery method. The visualization of the results shows that MoANet has more smooth edges, as well as detects more complete area than others. Furthermore, we validate on International Comprehensive Ocean-Atmosphere Data Set (ICOADS) through contrasting visibility value to prove the practicality of the proposed method and the accuracy achieves 90.65%.

Efferocytosis, the process of engulfing and removing apoptotic cells, plays an essential role in preserving tissue health and averting undue inflammation. While macrophages are primarily known for this task, dendritic cells (DCs) also play a significant role. This review delves into the unique contributions of various DC subsets to efferocytosis, highlighting the distinctions in how DCs and macrophages recognize and handle apoptotic cells. It further explores how efferocytosis influences DC maturation, thereby affecting immune tolerance. This underscores the pivotal role of DCs in orchestrating immune responses and sustaining immune equilibrium, providing new insights into their function in immune regulation.

The investigation of genetics-based biopesticides has become a central focus in pesticide studies due to their inherent advantages, including species specificity, environmental safety, and a wide range of target genes. In this study, a mixture of miR-184 agomir and nanomaterial star polycation (SPc) was used to treat the nymphs of the English grain aphid, Sitobion avenae (F.). The life parameters of the aphids at various developmental stages were analyzed using an age–stage two-sex life table to assess the effect of miR-184 agomir on the experimental population. The results indicated that miR-184 agomir had a significant negative effect on four key life parameters, including the intrinsic rate of increase, the finite rate of increase, the net rate of increase, and the mean generation time. The population prediction revealed a substantial reduction (91.81% and 95.88%) in the population size of S. avenae at 60 d after treatment with miR-184 agomir, compared to the control groups. Our findings suggest that the miR-184 agomir has the potential to reduce the survival rate and mean longevity of S. avenae, highlighting its potential as a promising candidate for the development of an effective genetics-based biopesticide.

Introduction: Spontaneous subarachnoid hemorrhage (SAH), is a disorder that may be fatal and is primarily caused by a ruptured brain aneurysm. Despite significant leaps forward in the methods to produce aneurysms, the long-term outcomes did not much improve. Pioglitazone is a medication that has been authorized by the FDA as an agonist for the peroxisome proliferator-activated receptor-gamma (PPARγ). Pioglitazone or PPARγ has neuroprotective benefits in animal experiments both during and after traumatic brain injury (TBI) and SAH. Nevertheless, the treatment impact of Pioglitazone on humans is still unknown at this time. As a result, we will conduct a randomized, double-blind, placebo-controlled trial to explore the impact of pioglitazone on SAH.Methods/Design: This trial will recruit 400 patients with SAH from four Chinese hospitals. These patients will be equally and randomly assigned to Pioglitazone and placebo control groups for up to 30 days. Scores on the modified Rankin scale (mRS) are the primary outcomes. The secondary outcomes are a 30-day all-cause mortality rate, 6 months of Montreal cognitive assessment (Mo-CA), delayed cerebral ischemia, the requirement for intensive care, the incidence of sepsis, etc. All serious adverse events (SAEs) were recorded during the hospital. Every primary and safety analysis was conducted based on the intention-to-treat technique. The participants were given either a matching placebo or 15 mg of pioglitazone, with dose titrated to a target of 45 mg daily. Data on the therapeutic use of pioglitazone after SAH will be provided as a consequence of the findings of this experiment. In addition, this pilot trial is the first to prospectively investigate the effectiveness and safety of pioglitazone in patients with SAH.Ethics and dissemination: Ethics approval was obtained from the Medical Ethics Committee of 904th Hospital of Joint Logistic Support Force of PLA (Wuxi Taihu Hospital, approval No. 20220701). The findings of the trial will be presented at conferences, discussed in relevant patient groups, and published in peer-reviewed journals.Clinical Trial Registration:clinicaltrials.gov, identifier ChiCTR2200062954.

Objective: This study aimed to investigate the infection status of Omicron in the population and the association between COVID-19 vaccination and infection with Omicron. Methods: We conducted a cross-sectional study to openly recruit participants for a survey of SARS-CoV-2 infection by convenience sampling from 1 January to 15 January 2023 after a COVID-19 pandemic swept across China. Additionally, the binary logistic regression model was adopted to evaluate the association between COVID-19 vaccination and the infection outcomes or symptom severity, respectively. Meanwhile, the relations between the vaccination and duration of the symptoms were estimated via ordinal logistic analysis. Results: Of the 2007 participants, the prevalence of infection with Omicron was 82.9%. Compared with unvaccinated individuals, inactivated COVID-19 vaccination could increase the risk of Omicron infection (OR = 1.942, 95% CI: 1.093–3.448), and the receipt of at least one dose of non-inactivated COVID-19 vaccines was a protective factor against infection (OR = 0.428, 95% CI: 0.226–0.812). By contrast, no relations were observed in COVID-19 vaccination with the symptoms of infection and duration of symptoms (p > 0.05). Conclusions: This cross-sectional study concluded that inactivated COVID-19 vaccination might increase the risk of Omicron infection, which should be a concern during COVID-19 vaccination and the treatment of variant infections in the future, and the receipt of at least one dose of non-inactivated COVID-19 vaccine was a protective factor against infection.

MicroRNAs (miRNA) play a vital role in insects’ growth and development and have significant potential value in pest control. Previously, we identified miR-306 from small RNA libraries within the English grain aphid, Sitobion avenae, a devasting insect pest for wheat. miR-306 not only involves in wing morphogenesis, but also is critically important for aphid survival. Its specific impacts on the life history traits, however, remain unclear. Here, we evaluate the impact of miR-306 perturbation on S. avenae populations using a two-sex life table approach. This comprehensive analysis revealed that miR-306 perturbation significantly prolongs the developmental stages (9.64% and 8.20%) and adult longevity of S. avenae, while decreasing pre-adult survival rate (41.45% and 38.74%) and slightly reducing average fecundity (5.80% and 13.05%). Overall, miR-306 perturbation negatively affects the life table parameters of the aphid population. The population prediction models show a significant decline in the aphid population 60 days post interference, compared to the control groups (98.14% and 97.76%). Our findings highlight the detrimental effects of miR-306 perturbation on S. avenae population growth and suggest potential candidate genes for the development of RNAi-based biopesticides targeted specifically at this pest species.

In this study, polylactic acid/graphene oxide/Dopamine (PLA/GO/DA) porous nanofiber membrane was prepared by electrospinning. L _16 (4 ^3 ) orthogonal experiment was designed to investigate the effects of reaction temperature, reaction time, and DA concentration on the adsorption performance of DA oxidized and self-polymerized on the fiber. Based on the characterization of scanning electron microscopy and the determination of the adsorption performance of the fiber membrane to methylene blue (MB) dye, data visualization analysis, variance analysis, and F-test were conducted to determine the optimal process parameters: reaction temperature of 45 °C, reaction time of 30 h, and DA concentration of 2 mg ml ^−1 . PLA/GO/PDA(Polydopamine) nanofiber was prepared and characterized under the optimal process parameters. The results showed that the average diameter of the PDA-loaded nanofiber increased from 737 nm to 996 nm, and a layer of PDA with a thickness of about 129 nm was loaded on the outer surface of the fiber, making the contact angle of the fiber membrane with 0° and becoming a hydrophilic material. In adsorption performance testing of MB, the PLA/GO/PDA nanofiber membrane prepared based on the PLA/GO/DA fiber membrane with an adsorption rate of 98.81 % in 24 h was superior to the PLA/GO/PDA nanofiber membrane prepared based on the PLA/GO fiber membrane.

Background: Photodynamic therapy (PDT) is a minimally invasive therapy that was gradually established as a first-line treatment for vascular abnormalities. Its action depends on the appropriate wavelength of light and photosensitizer to produce toxic oxygen species and cause cell death. Objective: Several new clinical improvements and trends in PDT have been described in recent years. The aim of this review is to provide an overview of the current data from clinical trials. Methods: In this review, we introduce and generalize the wavelength, duration, dose, strength, and photosensitizer of PDT for the treatment of vascular abnormalities, such as circumscribed choroidal hemangiomas (CCH), choroidal neovascularization (CNV) and capillary malformation (CM). Results: The systematic review findings indicate that the application of PDT is a safe effective method to treat CCH, CNV and CM. However, PDT also has early onset side effects and late onset side effects. Conclusions: Based on the discussion of the effectiveness of PDT, we conclude that PDT has great potential for clinical use, although PDT has possible side effects. [ABSTRACT FROM AUTHOR]

Sodium dual‐ion batteries (Na‐DIBs) have attracted increasing attention due to their high operative voltages and low‐cost raw materials. However, the practical applications of Na‐DIBs are still hindered by the issues, such as low capacity and poor Coulombic efficiency, which is highly correlated with the compatibility between electrode and electrolyte but rarely investigated. Herein, fluoroethylene carbonate (FEC) is introduced into the electrolyte to regulate cation/anion solvation structure and the stability of cathode/anode‐electrolyte interphase of Na‐DIBs. The FEC modulates the environment of PF6− solvation sheath and facilitates the interaction of PF6− on graphite. In addition, the NaF‐rich interphase caused by the preferential decomposition of FEC effectively inhibits side reactions and pulverization of anodes with the electrolyte. Consequently, Sb||graphite full cells in FEC‐containing electrolyte achieve an improved capacity, cycling stability and Coulombic efficiency. This work elucidates the underlying mechanism of bifunctional FEC and provides an alternative strategy of building high‐performance dual ion batteries. [ABSTRACT FROM AUTHOR]

Abstract Background Both interpregnancy intervals (IPI) and environmental factors might contribute to low birth weight (LBW). However, the extent to which air pollution influences the effect of IPIs on LBW remains unclear. We aimed to investigate whether IPI and air pollution jointly affect LBW. Methods A retrospective cohort study was designed in this study. The data of birth records was collected from the Jiangsu Maternal Child Information System, covering January 2020 to June 2021 in Nantong city, China. IPI was defined as the duration between the delivery date for last live birth and date of LMP for the subsequent birth. The maternal exposure to ambient air pollutants during pregnancy—including particulate matter (PM) with an aerodynamic diameter of ≤ 2.5 μm (PM2.5), PM10, ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)—was estimated using a hybrid kriging-LUR-RF model. A novel air pollution score was proposed, assessing combined exposure to five pollutants (excluding CO) by summing their concentrations, weighted by LBW regression coefficients. Multivariate logistic regression models were used to estimate the effects of IPI, air pollution and their interactions on LBW. Relative excess risk due to interaction (RERI), attributable proportion of interaction (AP) and synergy index (S) were utilized to assess the additive interaction. Results Among 10, 512 singleton live births, the LBW rate was 3.7%. The IPI-LBW risk curve exhibited an L-shaped pattern. The odds ratios (ORs) for LBW for each interquartile range increase in PM2.5, PM10, O3 and the air pollution score were 1.16 (95% CI: 1.01–1.32), 1.30 (1.06–1.59), 1.22 (1.06–1.41), and 1.32 (1.10–1.60) during the entire pregnancy, respectively. An additive interaction between IPI and PM2.5 was noted during the first trimester. Compared to records with normal IPI and low PM2.5 exposure, those with short IPI and high PM2.5 exposure had the highest risk of LBW (relative risk = 3.53, 95% CI: 1.85–6.49, first trimester). Conclusion The study demonstrates a synergistic effect of interpregnancy interval and air pollution on LBW, indicating that rational birth spacing and air pollution control can jointly improve LBW outcomes.

Introduction Tuberculosis (TB) is a major global health issue, particularly, in India and South Africa. We aim to evaluate the potential of the new TB vaccine, Vaccae, to enhance TB control by integrating with active case finding (ACF) strategies in these regions.Methods Using age-structured dynamic models, we projected the epidemiological and economic outcomes of combining Vaccae vaccination with ACF over 27 years. In India, four age-targeted strategies were analysed: (1) adolescent (15 years), (2) adolescent and young adult (AYA, 15–34 years), (3) adult (18–55 years) and (4) elderly (60+ years). In South Africa, strategies were based on HIV status: (1) HIV-targeted, (2) non-HIV and (3) general population. The vaccine efficacy of Vaccae was set at 54.7%, priced at US$120 per course. Outcomes measured included reductions in TB incidence and mortality, prioritised based on budget, incremental cost-effectiveness ratios (ICER) and benefit-cost ratios (BCR).Results In India, the adult strategy could prevent 8.70 (95% UI: 6.86–11.13) million TB cases and 0.61 (0.39–0.91) million deaths, reducing incidence and mortality by 20.1% (18.7%–23.5%) and 19.0% (17.5%–22.5%), respectively. In South Africa, the general population strategy could avert 0.67 (0.45–0.99) million TB cases and 0.21 (0.15–0.28) million deaths, reducing incidence by 28.1% (26.1%–30.3%) and mortality by 27.0% (23.5%–30.0%). The vaccination budgets for the AYA strategy in India and the HIV-targeted strategy in South Africa were US$14.0 (10.14–23.29) billion and US$0.09 (0.06–0.15) billion, respectively. The ICERs were US$1082 (927–1426) and US$70 (53–123) per disability-adjusted life year averted, and the BCRs were 2.0 (1.6–2.4) and 176 (83.4–255.3), respectively. Thus, the AYA strategy in India and the HIV-targeted strategy in South Africa were the most favourable.Conclusion Integrating Vaccae vaccination with ACF could significantly enhance TB control in high-burden countries. Policymakers should consider these strategies, with further research needed to confirm the findings.

Abstract Background Pneumoconiosis, a chronic disease stemming from prolonged inhalation of dust particles, stands as a significant global burden of occupational diseases. This study aims to investigate the survival outcomes of pneumoconiosis patients in Huangshi city, China, while also evaluating the disease burden on afflicted patients. Methods Data for this study were sourced from the Huangshi Center for Disease Control and Prevention. Survival analyses of pneumoconiosis patients were conducted employing life tables and the Kaplan-Meier method. The Cox proportional hazards models were deployed to identify factors influencing pneumoconiosis patients’ survival duration. Competing risks models were employed to confirm the validity of the model outcomes. Additionally, in the disease burden assessment, disability-adjusted life years (DALYs) were computed for various demographic groups and time frames. Results A total of 5,641 pneumoconiosis cases, diagnosed in Huangshi City, Hubei Province between 1958 and 2021, were incorporated into the cohort analysis. The probability of mortality and the risk ratio increased with advancing age. Notably, the median survival time of stage III pneumoconiosis patients was significantly shorter compared with those in stages I and II. The Cox proportional hazards model and competing risks analyses underscored several significant factors influencing survival time, including dust exposure duration (HR = 1.197, 95% CI: 1.104–1.298), age at first diagnosis (HR = 3.149, 95% CI: 2.961–3.349), presence of silicosis (HR = 1.378, 95% CI: 1.254–1.515), and stage II-III pneumoconiosis (HR = 1.456, 95% CI: 1.148–1.848). Cumulatively, DALYs amounted to 7,974.35 person-years, with an average of 1.41 person-years. The period between 2000 and 2019 witnessed the highest disease burden. Conclusion Our findings highlight the urgent need for improved prevention, earlier detection, and more effective management strategies for the occupational pneumoconiosis population. This study not only underscores the persistent issue of pneumoconiosis in industrial environments but also serves as a crucial call to action for policymakers and healthcare providers.

Background While global newborn hearing screening programmes (NHSP) are far from the optimal level, the combined hearing and genetic screening has emerged as an innovative approach of early healthcare interventions. There is a clear need for economic evaluation to establish whether newborn deafness gene screening (NDGS), currently mandated by many cities in China, is a good investment.Methods A decision-tree model was constructed to simulate a hypothetical 10-million Chinese newborn cohort over a lifetime with three strategies: (1) no screening, (2) NHSP (standard screening) and (3) NHSP+NDGS (combined screening). The presence of permanent congenital hearing loss (PCHL) and genetic mutation were assigned at birth and held constant for all strategies. Input parameters were obtained from the Cohort of Deafness-gene Screening study and literature review. The government contract price for genetic screening was US$77/child. Outcomes of interest included the number of early diagnosed PCHL, prelingual deafness, total deafness, special education referral, incremental cost-effectiveness ratio (ICER) and benefit–cost ratio (BCR).Results Both standard and combined screening strategies were more effective and more costly than ‘no screening’. Compared with standard screening, combined screening led to 9112 (28.0%) more PCHL cases early detected, avoiding 4071 (66.9%) prelingual deafness cases and 3977 (15.6%) special education referrals. The ICER and BCR for combined screening were US$ 4995/disability-adjusted life-year (95% uncertainty interval, 2963 to 9265) and 1.78 (1.19 to 2.39), from healthcare sector perspective. Combined screening would dominate standard screening from societal perspective. Moreover, it remained cost-effective even in pessimistic scenarios.Conclusions Our findings have particular implication for the ‘scale-up’ of genetic screening at the national level in China. The model may serve as a feasible example for hearing screening strategies in other countries, as well as genetic screening for other diseases.

Abstract Metastatic colorectal cancer continues to have a high fatality rate, with approximately only 14% of patients surviving more than 5 years. To improve the survival rate of these patients, the development of new therapeutic drugs is a priority. In this study, we investigated the effects of Oroxylin A on the metastasis of human colorectal cancer cells and its potential molecular mechanism. This study utilised CCK8 assay, transwell assay, flow cytometry, western blot analysis, molecular docking, HE staining, immunofluorescence staining, and xenograft models. The proliferation, migration, and invasion of colon cancer cells were effectively suppressed by Oroxylin A in a dose-dependent manner. Oroxylin A has the potential to inhibit the process of epithelial‒mesenchymal transition (EMT) by upregulating the expression of E-cadherin, a marker associated with epithelial cells, while downregulating the levels of N-cadherin, Snail, vimentin, and slug, which are markers associated with mesenchymal cells. In addition, 200 mg/kg of Oroxylin A inhibited the growth of colorectal tumours. Molecular docking technology revealed that Oroxylin A can bind to TGFβ and inhibit the activation of the TGFβ-smad signalling pathway. The overexpression of TGFβ weakened the inhibitory effect of Oroxylin A on the proliferation, migration, and invasion of human colorectal cancer cells, as well as the promoting effect on apoptosis. Oroxylin A inhibited the activation of the TGF-smad signalling pathway and the EMT process, thereby suppressing the migration and invasion of human colorectal cancer cells.

Abstract In China, there has been a persistent upward trend in the incidence and mortality rates of colorectal cancer (CRC), with CRC ranking second in incidence and fifth in mortality among all malignant tumors. Although circular RNAs (circRNAs) have been implicated in the progression of various cancers, their specific role in CRC progression remains largely unexplored. The objective of this study was to elucidate the role and underlying mechanisms of circXRN2 in CRC. Differential expression of circXRN2 was identified through whole transcriptome sequencing. The expression levels of circXRN2 and miR-149-5p were quantified in CRC tissues, corresponding adjacent normal tissues, and CRC cell lines using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The stability of circXRN2 was confirmed through RNase R and actinomycin D experiments. The binding interaction between circXRN2 and miR-149-5p was validated through RNA pull-down, RNA immunoprecipitation, and dual-luciferase assays. The biological functions of circXRN2 were assessed through a battery of in vitro experiments, including the CCK-8 assay, EdU assay, scratch assay, Transwell assay, and flow cytometry assay. Additionally, in vivo experiments involving a tumor transplantation model and a liver-lung metastasis model were conducted. The influence of circXRN2 on the expression of epithelial–mesenchymal transition (EMT)-related genes was determined via Western blotting analysis. In CRC tissues and cells, there was an upregulation in the expression levels of both circXRN2 and ENC1, while miR-149-5p exhibited a downregulation in its expression. The overexpression of circXRN2 was found to enhance tumor proliferation and metastasis, as evidenced by results from both in vitro and in vivo experiments. Functionally, circXRN2 exerted its antitumor effect by suppressing cell proliferation, migration, and invasion while also promoting apoptosis. Mechanistically, the dysregulated expression of circXRN2 had an impact on the expression of proteins within the EMT signaling pathway. Our results demonstrated that circXRN2 promoted the proliferation and metastasis of CRC cells through the miR-149-5p/ENC1/EMT axis, suggesting that circXRN2 might serve as a potential therapeutic target and novel biomarker in the progression of CRC.

Abstract Breast cancer (BC) is one of the most common malignancies in women and the leading cause of cancer-related death in women. The newly emerged non-coding RNAs tsRNAs (tRNA-derived small RNAs) play an important role in the occurrence and development of BC. The purpose of this study was to comprehensively evaluate the prognostic, diagnostic and clinicopathological roles of tsRNAs in BC. Through literature screening, a total of 13 BC-related tsRNA studies were included in this meta-analysis, all of which passed quality assessment. Prognostic studies showed upregulated tsRNAs to be associated with poor survival outcomes (HR = 1.64, 95%CI 1.51–1.77) and downregulated tsRNAs to be associated with better outcomes (HR = 0.58, 95%CI 0.50–0.68). Results of diagnostic studies showed a combined sensitivity of 72% (95%CI 68–76%) and combined specificity of 64% (95%CI 61–67%); the AUC was 0.72 (95%CI 0.68–0.75) and the DOR 4.62 (95%CI 3.76–5.68). Finally, correlation analysis of clinicopathological features showed that downregulation of tsRNAs correlated significantly with age, TNM stage and lymphatic metastasis. Sensitivity analysis and publication bias showed no significant difference. In conclusion, BC-associated tsRNAs are closely related to the prognosis and clinicopathological features of patients with this disease and can be used to assist in early diagnosis of BC. Therefore, tsRNAs are potential targets for the diagnosis and treatment of BC.