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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmitted through the respiratory route, but potential extra-respiratory routes of SARS-CoV-2 transmission remain uncertain. Here we inoculated five rhesus macaques with 1 × 10 6 TCID 50 of SARS-CoV-2 conjunctivally (CJ), intratracheally (IT), and intragastrically (IG). Nasal and throat swabs collected from CJ and IT had detectable viral RNA at 1–7 days post-inoculation (dpi). Viral RNA was detected in anal swabs from only the IT group at 1–7 dpi. Viral RNA was undetectable in tested swabs and tissues after intragastric inoculation. The CJ infected animal had a higher viral load in the nasolacrimal system than the IT infected animal but also showed mild interstitial pneumonia, suggesting distinct virus distributions. This study shows that infection via the conjunctival route is possible in non-human primates; further studies are necessary to compare the relative risk and pathogenesis of infection through these different routes in more detail. SARS-CoV-2 mainly transmits via respiratory droplets. Here Deng et al. show that SARS-CoV-2 can infect rhesus macaques via ocular conjunctival inoculation.

Cancer treatment has always been a challenge for humanity. The inadequacies of current technologies underscore the limitations of our efforts against this disease. Nevertheless, the advent of targeted therapy has introduced a promising avenue, furnishing us with more efficacious tools. Consequently, researchers have turned their attention toward epigenetics, offering a novel perspective in this realm. The investigation of epigenetics has brought RNA readers to the forefront, as they play pivotal roles in recognizing and regulating RNA functions. Recently, the development of inhibitors targeting these RNA readers has emerged as a focal point in research and holds promise for further strides in targeted therapy. In this review, we comprehensively summarize various types of inhibitors targeting RNA readers, including non-coding RNA (ncRNA) inhibitors, small-molecule inhibitors, and other potential inhibitors. We systematically elucidate their mechanisms in suppressing cancer progression by inhibiting readers, aiming to present inhibitors of readers at the current stage and provide more insights into the development of anticancer drugs.

Although the innate immune response to induce postischemic inflammation is considered as an essential step in the progression of cerebral ischemia injury, the role of innate immunity mediator NLRP3 in the pathogenesis of ischemic stroke is unknown. In this study, focal ischemia was induced by middle cerebral artery occlusion in NLRP3−/−, NOX2−/−, or wild-type (WT) mice. By magnetic resonance imaging (MRI), Evans blue permeability, and electron microscopic analyses, we found that NLRP3 deficiency ameliorated cerebral injury in mice after ischemic stroke by reducing infarcts and blood–brain barrier (BBB) damage. We further showed that the contribution of NLRP3 to neurovascular damage was associated with an autocrine/paracrine pattern of NLRP3-mediated interleukin-1β (IL-1β) release as evidenced by increased brain microvessel endothelial cell permeability and microglia-mediated neurotoxicity. Finally, we found that NOX2 deficiency improved outcomes after ischemic stroke by mediating NLRP3 signaling. This study for the first time shows the contribution of NLRP3 to neurovascular damage and provides direct evidence that NLRP3 as an important target molecule links NOX2-mediated oxidative stress to neurovascular damage in ischemic stroke. Pharmacological targeting of NLRP3-mediated inflammatory response at multiple levels may help design a new approach to develop therapeutic strategies for prevention of deterioration of cerebral function and for the treatment of stroke.

Apatite is widely used as an indicator mineral to reflect the characteristics and petrogenesis of host magma. In this study, we present apatite geochemical and in-situ Sr–Nd isotopic data of monzogranite, granodiorite and dioritic enclave in the eastern Songnen-Zhangguangcai Range Massif, aiming to fingerprinting their petrogenesis and magmatic evolution processes. Based on apatite textures and geochemistry characteristics, the apatites were categorized into two distinct groups. Group 1 apatites have subhedral-anhedral textures and high Sr content (> 500 ppm). The majority of their ε Nd (t) values are relatively consistent with those of host monzogranites, indicating that they crystallized from crustal-derived material. Conversely, Group 2 magmatic apatites have euhedral-subhedral and core-rim textures, as well as low Sr content (< 500 ppm). This group can further be divided into two subgroups of Group 2A and 2B based on zoned textures and compositions. Group 2A zoned apatites exhibit high Sr/Nd and Sr/Y ratios at the rim and have discontinuous Ba contents, suggesting that they were derived from magma mixing and the granodiorite may be the felsic end-member. The Group 2B apatites are characterized by high Ce and Eu contents with low Y contents and Sm/Nd ratios, indicating that they originated from metaluminous I-type granitoids. The apatites also record the magmatic evolution processes, including fractional crystallization of plagioclase and titanite, as well as fluid exsolution. Combining apatite and whole rock geochemistry, it is shown that the parental magma was related to subduction of Mudanjiang Oceanic crust.

The objective of this work is to investigate the implications of geological influence factors on gas content and geochemical characteristics of deep-buried (> 800 m) coalbed methane (CBM) reservoirs. Results show that bituminous coal accounts for the majority, which exhibits similar maturity but differ in maceral and chemical constituents. CBM reservoirs show low porosity, low permeability and moderate temperature, with thickness of 0.85–4.15 m. In addition, the total gas content is 4.58–12.33 m 3 /t (average of 8.83 m 3 /t). CH 4 is the main component with concentration of 92.83−99.22% (average of 96.68%), and the δ 13 C CH4 and δ 13 D CH4 is − 53.78‰–−44.62‰ (average of − 48.82‰) and − 223.93‰––−4.49‰ (average of − 215.37‰), respectively. All CBM samples are the mixtures of thermogenic gases and secondary biogenic gases with CO 2 reduction. In addition, gas content characteristic at the critical point of burial depth is the result by positive and negative geological effects. CH 4 concentration shows a wide range with the increases of buried depth, while the numerical values of which for the selected samples display complex variation characteristics. Furthermore, the values of δ 13 C CH4 and δ 13 D CH4 become heavier with the increases of buried depth. Besides, the above two geochemical parameters are related to R o, max and reservoir temperature.

Background The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. Methods This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m 2 who were screened from January 2018 to December 2023 at Henan Provincial People’s Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. Results Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69–5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94–3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P  < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > – 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. Conclusion In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.

Accurate estimation of overlying strata subsidence and surface deformation caused by coal extraction is crucial for assessing the impact of mining activities on surface infrastructure. In this study, we investigated the subsidence evolution of overlying strata and ground surface induced by underground mining using finite element simulation and focus on a mining district in the Yu-Heng mining area of the central Ordos Basin and then, the influence of underground longwall mining on the surface roads was evaluated. A three-dimensional geological model of the mining district was constructed, considering the actual stratum structures and the deterioration effect of water on rock mechanical properties. The whole coal mining process was simulated to predict the evolution of the subsidence basin at different mining stages, and the surface deformation characteristics caused by coal mining were calculated. Results showed that the subsidence characteristics by numerical simulation were highly consistent with the records of surface subsidence in the adjacent areas, indicating that the constructed geological model can accurately reflect the actual geological conditions and the deformation behaviors of overlying strata. A comparative study revealed that the mechanical properties of the generalized layers determined by processing the mechanical parameters of dry core samples will be much higher than those of the natural strata under the in situ water-saturated condition, and then the subsidence caused by coal mining will be significantly underestimated. Thus, the water-induced mechanical property deterioration of overlying strata must be fully considered when constructing geological models.

Nanofibers with high specific surface area and chemical stability have broad prospects in the applications of adsorption. However, the adsorption capacity is limited by the scarcity of adsorption groups and storage space. Herein, the activated carbon-hybridized and amine-modified nanofibers are prepared by integrating activated carbon (AC) and polyacrylonitrile (PAN) via electrospinning method and the subsequent amination, which could provide additional storage space and adsorption groups for ultrahigh adsorption capability. Thus, the obtained aminerich porous PAN nanofibers (APAN/AC) readily realized the ultrahigh adsorption capacity for metal ions and dyes in wastewater. Specifically, the adsorption capacity of APAN/AC nanofibers were 284 mg·g−1 for Cr(VI) and 248 mg·g−1 for methyl orange, which were almost 2 and 4 times than that of amine-modified nanofibers (APAN) and carbon-hybridized nanofibers (PAN/AC), respectively. Moreover, the AC inhibited the chain mobility of polymer matrix and thereby endowing APAN/AC nanofibers with excellent recyclability. The adsorption capability retained 80% after nine adsorption-desorption cycles. The adsorption kinetics and corresponding mechanism were further explored. This strategy combines the advantages of polymer nanofibers and AC, opening a new avenue for developing next-generation absorbent materials.

This study aimed to evaluate the association between dietary carotenoid intake and periodontitis in diabetic patients. Data on diabetic patients were collected from the National Health and Nutrition Examination Survey (NHANES) 2009–2014 for this cross-sectional study. Dietary intake of carotenoids was assessed through the first 24-hour dietary recall interview. Full-mouth periodontal examinations were conducted by trained dental examiners. Subgroup analysis was conducted in terms of age, gender, the number of missing teeth, cardiovascular disease, smoking, and anti-diabetic drugs. Totally 1914 diabetic patients were included, with 1281 (66.93%) in the periodontitis group. After adjusting for age, gender, race, education, smoking, dental implants, hepatitis, and the number of missing teeth, α-carotene intake ≥55.82 mcg was associated with lower odds of periodontitis than α-carotene intake <55.82 mcg [OR = 0.70, 95% CI: 0.53–0.91, P = 0.010]; lutein and zeaxanthin intake ≥795.95 mcg was associated with decreased odds of periodontitis than lutein and zeaxanthin intake <795.95 mcg (OR = 0.75, 95%CI: 0.57–0.98, P = 0.039). The association between carotenoid intake and periodontitis varied across different subpopulations. In diabetes, dietary intake of α-carotene and lutein and zeaxanthin was inversely associated with the odds of periodontitis, which may facilitate clinical periodontitis management.

Current genetic risk stratification systems for acute myeloid leukemia (AML), including the 2017 European Leukemia Network (ELN), 2022 ELN, and 2023 China (CN) stratifications, inconsistently categorize key genetic variants such as and . These systems also demonstrate limited applicability to Chinese patients, complicating clinical decision-making. This study optimized genetic stratification for Chinese AML patients and developed a multi-omics prognostic model by integrating immunophenotypic and clinical characteristics to enhance outcome prediction. We retrospectively enrolled 378 Chinese AML patients (298 for training, 80 for external validation) and compared the prognostic performance of the 2017/2022 ELN and 2023 CN systems (both integrating molecular genomic and cytogenetic data). Controversial genetic variants were re-evaluated to establish a novel 2023 CN (n-2023 CN) classification. A multi-omics model was constructed by combining n-2023 CN classification with CD15 positivity (leukemic immunophenotype), del(7q) (cytogenetic abnormality), and age ≥ 60 years (clinical factor). The model underwent external validation, was assessed for use in guiding hematopoietic stem cell transplantation (HSCT), and was compared with a published model. The 2023 CN demonstrated superior efficacy in predicting AML relapse and 3-year relapse-free survival compared to 2017/2022 ELN systems. The n-2023 CN reclassified as favorable-risk, t(8;21)/inv(16) with / as intermediate-risk, and as adverse-risk among patients not receiving inhibitors (regardless of co-mutation). CD15 positivity, del(7q), and age ≥ 60 years were independent adverse prognostic factors for overall survival (OS). The model stratified patients into three risk groups with significantly distinct complete remission (CR) rates (93.2%, 71.2%, 35.7%) and OS ( < 0.001), with a concordance index of 0.729 (internal) and 3-year OS AUC of 0.752 (external). High-risk patients receiving HSCT exhibited longer OS. The model outperformed a published comparator in predicting CR and 1- and 3-year OS (all ≤ 0.001). The n-2023 CN resolves uncertainty in genetic risk stratification for Chinese AML patients. The novel multi-omics model incorporates immunophenomics and clinical and cytogenetic factors, captures comprehensive AML characteristics, enhances prognostic precision, and provides reliable guidance for personalized treatment, including HSCT selection.