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Background Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia–reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1 + ) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. Methods Exosomes were enriched from young Sca-1 + or Sca-1 − cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. Results Sca-1 + exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1 − , at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1 + exosomes had higher miR-150-5p levels, compared to Sca-1 − exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1 + exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. Conclusion This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1 + exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.

Issue Title: Continental extension The Baoshan block of the Tethyan Yunnan, southwestern China, is considered as northern part of the Sibumasu microcontinent. Basement of this block that comprises presumably greenschist-facies Neoproterozoic metamorphic rocks is covered by Paleozoic to Mesozoic low-grade metamorphic sedimentary rocks. This study presents zircon ages and Nd-Hf isotopic composition of granites generated from crustal reworking to reveal geochemical feature of the underlying basement. Dating results obtained using the single zircon U-Pb isotopic dilution method show that granites exposed in the study area formed in early Paleozoic (about 470 Ma; Pingdajie granite) and in late Yanshanian (about 78-61 Ma, Late Cretaceous to Early Tertiary; Huataolin granite). The early Paleozoic granite contains Archean to Mesoproterozoic inherited zircons and the late Yanshanian granite contains late Proterozoic to early Paleozoic zircon cores. Both granites have similar geochemical and Nd-Hf isotopic charateristics, indicating similar magma sources. They have whole-rock T ^sub DM^(Nd) values of around 2,000 Ma and zircon T ^sub DM^(Hf) values clustering around 1,900-1,800 and 1,600-1,400 Ma. The Nd-Hf isotopic data imply Paleoproterozoic to Mesoproterozoic crustal material as the major components of the underlying basement, being consistent with a derivation from Archean and Paleoproterozoic terrains of India or NW Australia. Both granites formed in two different tectonic events similarly originated from intra-crustal reworking. Temporally, the late Yanshanian magmatism is probably related to the closure of the Neotethys ocean. The early Paleozoic magmatism traced in the Baoshan block indicates a comparable history of the basements during early Paleozoic between the SE Asia and the western Tethyan belt, such as the basement outcrops in the Alpine belt and probably in the European Variscides that are considered as continental blocks drifting from Gondwana prior to or simultaneously with those of the SE Asia.[PUBLICATION ABSTRACT]

In a karst tunnel, fissures or cracks that are filled with weathered materials are a type of potential water outlet as they are easily triggered and converted into groundwater outlets under the influence of high groundwater pressure. A terrible water inrush caused by potential water outlets can seriously hinder the project construction. Potential water outlets and water sources that surrounding the tunnel must be detected before water inflow can be treated. This paper provides a successful case of the detection and treatment of water inflow in a karst tunnel and proposes a potential water outlet detection (PWOD) method in which heavy rainfall (>50 mm/d) is considered a trigger for a potential water outlet. The Daba tunnel located in Hunan province, China, has been constructed in a karst stratum where the rock mass has been weathered intensely by the influence of two faults. Heavy rain triggered some potential water outlets, causing a serious water inrush. The PWOD method was applied in this project for the treatment of water inflow, and six potential water outlets in total were identified through three heavy rains. Meanwhile, a geophysical prospecting technique was also used to detect water sources. The connections between water outlets and water sources were identified with a 3-D graphic that included all of them. According to the distribution of water outlets and water sources, the detection area was divided into three sections and separately treated by curtain grouting.

Mud inrush in mountain tunnel is an independent geological hazard type different from water inrush, landslide and debris flow. The intrinsic factor of mud inrush is the instability failure of disaster medium. Its essence is that when the cohesion decreases gradually with the increase of void ratio to the point where the movement of soil particles cannot be restricted, soil particles and groundwater form slurry and gush out. Thus, accurate calculation of cohesion with variable void ratios is crucial for analyzing the reliability of disaster medium. In this study, the disaster medium was regarded as graded soil and a structural model was established wherein soil particles were simplified as cubes and the inter-particle pores were represented by the clearance between cubes. On the basis of the structure model of disaster medium, a function between the soil particle distance and void ratio was derived. Cohesion is equivalent to the resultant force between soil particles per unit area; thus, a cohesion function was derived in which the void ratio is the main variable. This function considers the influence of gradation characteristics on cohesion variation and is generally applicable to various types of disaster medium. A series of direct shear tests were carried out to determine the cohesion variation for different types of disaster medium with variable void ratios. By comparing the variation of cohesion obtained through direct shear tests with those deduced by the proposed cohesion function, we verified the validity and general applicability of the cohesion function. It is of great significance because the cohesion function can accurately predict the variation of cohesion by using the void ratio, and effectively evaluate the possibility of mud inrush according to the initial mechanical properties of disaster medium.

Background The optimal red blood cell transfusion (RBCT) strategy for traumatic brain injury (TBI) patients remains a topic of debate. This systematic review and meta-analysis aimed to compare the outcomes of a liberal transfusion strategy versus a restrictive strategy in critically ill patients with TBI. Methods PubMed, Web of Science, Embase, and Cochrane Library were searched from inception to November 17, 2024. We included randomized controlled trials (RCTs) of critically ill adult patients with TBI, reporting data on RBCT strategies. The outcomes included intensive care unit (ICU) mortality, long-term mortality, unfavorable functional outcomes, and the incidence of adverse events, such as transfused acute respiratory distress syndrome (TARDS) and venous thromboembolism. We also performed subgroup analyses comparing the association between disease severity and long-term mortality. This review was submitted to PROSPERO (Registration number: CRD42024558797). Results In the results, our analysis revealed that compared to a restrictive transfusion strategy, a liberal strategy did not significantly reduce the risk of ICU mortality (RR: 0.74; 95% CI 0.28–1.91; P  = 0.53) and long-term mortality (RR: 1.02; 95% CI 0.83–1.25; P = 0.87), but it was able to reduce the risk of unfavorable functional outcomes (RR: 0.90; 95% CI 0.82–0.98; P  = 0.01), although there may be a false positive error. In addition, the liberal transfusion strategy was associated with a higher incidence of Transfused Acute Respiratory Distress Syndrome (TARDS) (RR: 1.78; 95% CI 1.06–2.98; P  = 0.03). Conclusions In critically ill patients with TBI, a liberal RBCT strategy appears to improve functional outcomes but carries the risk of false positive errors. In addition, this strategy does not seem to improve survival and may increase the risk of TARDS. Despite this, there remains insufficient evidence to recommend either strategy in this population.

Background The opportunistic bacterial pathogen Legionella pneumophila uses substrate effectors of Dot/Icm type IVB secretion system (T4BSS) to accomplish survival and replication in amoebae cells and mammalian alveolar macrophages. During the conversion between its highly resistant, infectious dormant form and vigorously growing, uninfectious replicative form, L. pneumophila utilizes a complicated regulatory network in which proteolysis may play a significant role. As a highly conserved core protease, ClpP is involved in various cellular processes as well as virulence in bacteria, and has been proved to be required for the expression of transmission traits and cell division of L. pneumophila . Results The clpP -deficient L. pneumophila strain failed to replicate and was digested in the first 3 h post-infection in mammalian cells J774A.1. Further investigation demonstrates that the clpP deficient mutant strain was unable to escape the endosome-lysosomal pathway in host cells. We also found that the clpP deficient mutant strain still expresses T4BSS components, induces contact-dependent cytotoxicity and translocate effector proteins RalF and LegK2, indicating that its T4BSS was overall functional. Interestingly, we further found that the translocation of several effector proteins is significantly reduced without ClpP. Conclusions The data indicate that ClpP plays an important role in regulating the virulence and effector translocation of Legionella pneumophila.

Context.—Phosphatase of regenerating liver (PRL) 3 messenger RNA (mRNA) was reported to express in human colorectal, gastric, ovarian, breast, and hepatic cancers. Objective.—To examine the expression of PRL-1 and PRL-3 mRNAs in human esophageal squamous cell carcinoma (ESCC). Design.—Expression of PRL-1 and PRL-3 mRNA was examined with reverse transcriptase–polymerase chain reaction in fresh tissue collected from 40 cases of ESCC with matched lymph node metastasis in 21 cases. The association of expression of PRL-1 and PRL-3 mRNAs with clinicopathologic parameters was analyzed. Results.—The frequencies of PRL-1 and PRL-3 mRNA expression were significantly higher in ESCC than in normal esophageal tissue (P = .001; P = .01) and also significantly higher in ESCC with lymph node metastasis than in those without lymph node metastasis (P = .01; P = .03). The levels of PRL-1 and PRL-3 mRNA expression were significantly higher in ESCC with lymph node metastasis than in those without lymph node metastasis (P = .04; P = .04). The frequencies and levels of PRL-1 and PRL-3 mRNA expression were correlated with the later stages but not with tumor differentiation, tumor location in the esophagus, patient's sex, and age. Conclusions.—PRL-1 and PRL-3 mRNAs may be involved in and used to predict the metastasis of ESCC. The possibility of using PRL-1 and PRL-3 as the therapeutical target is also discussed.

Aim： MgFe2O4 magnetic nanoparticle composed of As2O3 （As2O3-MNPs） were prepared and their in vitro and in vivo characteristics were studied. Methods： The solvent-displacement method was applied for preparation of the nanoparticle using Poly-D,L-lactic-co-glycolic acid（PLGA）. The characteristics studies of the products included magnetic response, morphology （transmission electron microscopy and scanning electron microscopy）, entrapment efficiency, drug loading, particle sizes, zeta potential, in vitro drug release and tissue magnetic targeting. Nanoparticle cytotoxicity to Saos-2 cells was investigated using the MTT assay. To guide the external magnetic field in the liver, the concentration of As2O3 in the liver and kidney was measured using an atomic fluorescence spectrometer after injecting As2O3-MNPs into the caudal veins of mice. Results： The As2O3-MNPs were approximately spherical. The average diameter, drug loading, entrapment efficiency and zeta potential of As2O3-MNPs were 109.9 nm, 10.08%, 82.16%, and -14.33 mV, respectively. The specific saturation magnetism was 8.65 emu/g. In vivo, the concentration of As2O3 in the liver was significantly higher than that in the non-magnetic group. While the concentration of As2O3 in the kidney was lower than that in the non-magnetic group. The Cmax in liver tissue in the magnetic group was 30.65 μg/g, which was 4.17 times the drug concentration in the same group in kidney tissue （7.35 μg/g） and 2.88 times the concentration of drug （10.66 μg/g） in the liver tissue of the non-magnetic group. Conclusion： The PLGA polymer-loaded magnetic nanoparticle composed of arsenic trioxide can be magnetically targeted well and applied in biomedicine.

Background: Allergen-specific sublingual immunotherapy is a potential treatment for allergic diseases. Its effective dose and underlying mechanism are still to be explored. Here, we investigated the efficacy and mechanism of sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine asthma model. Methods: BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by sublingual treatment with Der f vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week. We analyzed their clinical symptoms, antibody levels, cytokine levels, T-cell proliferation and the regulatory T-cell numbers. Results: Mice treated with high-dose Der f sublingual vaccine prior to challenge displayed alleviated symptoms such as airway hyperreactivity, lung inflammation and mucus production, as well as less eosinophilic cells in bronchoalveolar lavage fluid. Interestingly, reduced responses of Der-f-specific IgE and increased responses of Der-f-specific IgA and IgG1 were aroused in the high-dose Der f sublingual vaccine group. We also observed that interleukin-4 was reduced and interferon-γ and interleukin-10 were increased among splenocytes and in bronchoalveolar lavage fluid, which inhibited Der-f-specific T-cell proliferation of the spleen and increased CD4+CD25+Foxp3+regulatory T cells in the spleen. However, mice treated with low-dose Der f sublingual vaccine developed allergic asthma. Conclusion: Our results illustrate that high-doseDer f sublingual vaccine may play a role in immunologic protection in murine allergic asthma, possibly by inducing regulatory T cells and Th1 reaction.