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Abstract Background The gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in Traumatic brain injury (TBI) patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). P. copri has been shown to have antioxidant effects in various diseases. Meanwhile, guanosine (GUO) is a metabolite of intestinal microbiota that can alleviate oxidative stress after TBI by activating the PI3K/Akt pathway. In this study, we investigated the effect of P. copri transplantation on TBI and its relationship with GUO-PI3K/Akt pathway. Methods In this study, a controlled cortical impact (CCI) model was used to induce TBI in adult male C57BL/6J mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2 h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30 min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16 S rDNA sequencing. Results P. copri abundance was significantly reduced after TBI. P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris’s water maze and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, PI3K inhibitor LY294002 treatment attenuated the observed improvements. Conclusions We demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.

Abstract Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell‐derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non‐small cell lung cancer (NSCLC) cells, a hypoxia‐induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1‐eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1‐targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA‐mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

Abstract Background White matter injury (WMI) is an important pathological process after traumatic brain injury (TBI). The correlation between white matter functions and the myeloid cells expressing triggering receptor‐2 (TREM2) has been convincingly demonstrated. Moreover, a recent study revealed that microglial sterol metabolism is crucial for early remyelination after demyelinating diseases. However, the potential roles of TREM2 expression and microglial sterol metabolism in WMI after TBI have not yet been explored. Methods Controlled cortical injury was induced in both wild‐type (WT) and TREM2 depletion (TREM2 KO) mice to simulate clinical TBI. COG1410 was used to upregulate TREM2, while PLX5622 and GSK2033 were used to deplete microglia and inhibit the liver X receptor (LXR), respectively. Immunofluorescence, Luxol fast blue staining, magnetic resonance imaging, transmission electron microscopy, and oil red O staining were employed to assess WMI after TBI. Neurological behaviour tests and electrophysiological recordings were utilized to evaluate cognitive functions following TBI. Microglial cell sorting and transcriptomic sequencing were utilized to identify alterations in microglial sterol metabolism‐related genes, while western blot was conducted to validate the findings. Results TREM2 expressed highest at 3 days post‐TBI and was predominantly localized to microglial cells within the white matter. Depletion of TREM2 worsened aberrant neurological behaviours, and this phenomenon was mediated by the exacerbation of WMI, reduced renewal of oligodendrocytes, and impaired phagocytosis ability of microglia after TBI. Subsequently, the upregulation of TREM2 alleviated WMI, promoted oligodendrocyte regeneration, and ultimately facilitated the recovery of neurological behaviours after TBI. Finally, the expression of DHCR24 increased in TREM2 KO mice after TBI. Interestingly, TREM2 inhibited DHCR24 and upregulated members of the LXR pathway. Moreover, LXR inhibition could partially reverse the effects of TREM2 upregulation on electrophysiological activities. Conclusions We demonstrate that TREM2 has the potential to alleviate WMI following TBI, possibly through the DHCR24/LXR pathway in microglia.

Abstract The ability of modern detectors to detect small targets is still an unresolved topic compared to their capability of detecting medium and large targets in the field of object detection. Accurately detecting and identifying small objects in the real‐world scenario suffer from sub‐optimal performance due to various factors such as small target size, complex background, variability in illumination, occlusions, and target distortion. Here, a small object detection method for complex traffic scenarios named deformable local and global attention (DLGADet) is proposed, which seamlessly merges the ability of hierarchical attention mechanisms (HAMs) with the versatility of deformable multi‐scale feature fusion, effectively improving recognition and detection performance. First, DLGADet introduces the combination of multi‐scale separable detection and multi‐scale feature fusion mechanism to obtain richer contextual information for feature fusion while solving the misalignment problem of classification and localisation tasks. Second, a deformation feature extraction module (DFEM) is designed to address the deformation of objects. Finally, a HAM combining global and local attention mechanisms is designed to obtain discriminative features from complex backgrounds. Extensive experiments on three datasets demonstrate the effectiveness of the proposed methods. Code is available at https://github.com/ACAMPUS/DLGADet

Macrophages activation and inflammatory response play crucial roles in intracranial aneurysm (IA) formation and progression. The outcome of ruptured IA is considerably poor, and the mechanisms that trigger IA progression and rupture remain to be clarified, thereby developing effective therapy to prevent subarachnoid hemorrhage (SAH) become difficult. Recently, climbing evidences have been expanding our understanding of the macrophages relevant IA pathogenesis, such as immune cells population, inflammatory activation, intra-/inter-cellular signaling transductions and drug administration responses. Crosstalk between macrophages disorder, inflammation and cellular signaling transduction aggravates the devastating consequences of IA. Illustrating the pros and cons mechanisms of macrophages in IA progression are expected to achieve more efficient treatment interventions. In this review, we summarized the current advanced knowledge of macrophages activation, infiltration, polarization and inflammatory responses in IA occurrence and development, as well as the most relevant NF-κB, signal transducer and activator of transcription 1 (STAT1) and Toll-Like Receptor 4 (TLR4) regulatory signaling modulation. The understanding of macrophages regulatory mechanisms is important for IA patients’ clinical outcomes. Gaining insight into the macrophages regulation potentially contributes to more precise IA interventions and will also greatly facilitate the development of novel medical therapy.

BackgroundHyponatremia is a common electrolyte disturbance in patients with neurological disease; however, its predictive role for outcome in patients with supratentorial spontaneous intracerebral hemorrhage (sICH) is controversial. This study aims to explore the association between hyponatremia within 7 days after bleeding and 90-day mortality in patients with supratentorial sICH.MethodsA retrospective analysis was conducted at our institution. Patients with sICH meeting the inclusion criteria were enrolled in this study. Multivariate regression analyses were performed to determine the predictive value of hyponatremia (serum sodium

Abstract Ten-eleven translocation protein 3 (TET3) is one of the key enzymes in DNA demethylation which can be expressed in liver tissues. However, the clinical value of TET3 for diagnosis and treatment of chronic liver disease have not been reported previously. We investigated the diagnostic accuracy of serum TET3 as a non-invasive screening tool for liver fibrosis. 212 patients with chronic liver disease from were enrolled in this study. Enzyme-linked immunosorbent assay was used to measure the serum levels of TET3. Receiver operating characteristics (ROC) were determined to examine the diagnostic accuracy of TET3 and combination model for diagnosis fibrosis. Serum TET3 level in fibrosis cases was significantly higher than that in non-fibrosis and controls, respectively. The areas under the ROC curve of the TET3 and fibrosis-4 index for liver fibrosis were 0.863 and 0.813, and 0.916 and 0.957 for liver cirrhosis. The combination of TET3 and fibrosis-4 index had a highly promising positive predictive value for detecting liver fibrosis and cirrhosis different stages of (93.5% and 100%) as compared with each diagnostic tool alone. TET3 is related to the development of liver fibrosis and cirrhosis. The TET3-fibrosis-4 model enhances discriminatory power and represents a promising non-invasive tool for the diagnosis and screening of liver fibrosis.

In clinical practice, we noticed that triple negative breast cancer (TNBC) patients had higher shear-wave elasticity (SWE) stiffness than non-TNBC patients and a higher α-SMA expression was found in TNBC tissues than the non-TNBC tissues. Moreover, SWE stiffness also shows a clear correlation to neoadjuvant response efficiency. To elaborate this phenomenon, TNBC cell membrane-modified polylactide acid-glycolic acid (PLGA) nanoparticle was fabricated to specifically deliver artesunate to regulate SWE stiffness through inhibiting CAFs functional status. As tested in MDA-MB-231 and E0771 orthotopic tumor models, CAFs functional status inhibited by 231M-ARS@PLGA nanoparticles (231M-AP NPs) had reduced the SWE stiffness as well as attenuated hypoxia of tumor as tumor soil loosening agent which amplified the antitumor effects of paclitaxel and PD1 inhibitor. Single-cell sequencing indicated that the two main CAFs (extracellular matrix and wound healing CAFs) that produces extracellular matrix could influence the tumor SWE stiffness as well as the antitumor effect of drugs. Further, biomimetic nanoparticles inhibited CAFs function could attenuate tumor hypoxia by increasing proportion of inflammatory blood vessels and oxygen transport capacity. Therefore, our finding is fundamental for understanding the role of CAFs on affecting SWE stiffness and drugs antitumor effects, which can be further implied in the potential clinical theranostic predicting in neoadjuvant therapy efficacy through non-invasive analyzing of SWE imaging.

BackgroundThis study aims to utilize Weighted Gene Co-expression Network Analysis (WGCNA) and Support Vector Machine (SVM) algorithm for screening biomarkers and constructing a diagnostic model for Parkinson’s disease.MethodsFirstly, we conducted WGCNA analysis on gene expression data from Parkinson’s disease patients and control group using three GEO datasets (GSE8397, GSE20163, and GSE20164) to identify gene modules associated with Parkinson’s disease. Then, key genes with significantly differential expression from these gene modules were selected as candidate biomarkers and validated using the GSE7621 dataset. Further functional analysis revealed the important roles of these genes in processes such as immune regulation, inflammatory response, and cell apoptosis. Based on these findings, we constructed a diagnostic model by using the expression data of FLT1, ATP6V0E1, ATP6V0E2, and H2BC12 as inputs and training and validating the model using SVM algorithm.ResultsThe prediction model demonstrated an AUC greater than 0.8 in the training, test, and validation sets, thereby validating its performance through SMOTE analysis. These findings provide strong support for early diagnosis of Parkinson’s disease and offer new opportunities for personalized treatment and disease management.ConclusionIn conclusion, the combination of WGCNA and SVM holds potential in biomarker screening and diagnostic model construction for Parkinson’s disease.

Quantitative research on the supply and demand of urban green infrastructure (GI) ecosystem services (ES) can play a crucial role in supporting ecological governance, which is vital for enhancing the health and well-being of residents and promoting sustainable development. However, current supply and demand studies often fail to consider the complexity and diversity of local climates and economic status, leading to suboptimal outcomes in urban greening programs. Therefore, there is an urgent need to incorporate the diversity and variability of demand for ES in decision-making processes for urban GI planning. To address this issue, this study proposes a multi-development scenario-based supply and demand modelling framework that measures the supply and demand of ES. By using the central city of Tianjin, China, as a case study, the resulting GI construction potential zoning and optimization strategies are determined to achieve the multiple environmental-social-economic benefits of GI. The results show that the supply and demand levels of GI in the study area are significantly spatially heterogeneous, with the demand levels of GI varying considerably under different development scenarios. Furthermore, the demand for GI is highest under the ecological priority scenario. Based on the relationship between the supply and demand of ES, the study area is classified into four zones, including a GI supply deficit zone, a supply surplus zone, a low-level balance zone, and a high-level balance zone. The area of each zone decreases in turn, indicating that the study area as a whole is in a state of mismatch between the supply and demand of ES. Finally, the study area is divided into seven GI construction potential zones based on the degree of scarcity and development orientation. The proposed planning scheme helps to achieve dynamic matching goals of ES supply and demand and provides valuable insights for policymakers to coordinate urban resources and promote sustainable development.

To improve the combustion behavior of potassium perchlorate-based pyrotechnics, this study successfully prepared perovskite LaFeO3 with nitrates as raw materials using the co-precipitation method and characterized perovskite LaFeO3 through X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectrometry (EDS). Moreover, it investigated the catalytic effect of LaFeO3 on the thermal decomposition of potassium perchlorate (KP) through the differential scanning calorimetry (DSC) and thermogravimetric analysis (TG) and explored the thermal reaction behavior of pyrotechnics composed of KP and lactose. The results show that the thermal decomposition temperature of KP was 552 ​°C by adding LaFeO3, reduced by 58 ​°C. The temperature of catalytic decomposition was exactly the extrapolated onset temperature of the endothermic melting peak of KP. The addition of LaFeO3 caused the premature decomposition of the KP not yet molten, thus generating more heat in its thermal decomposition. Moreover, the addition of LaFeO3 reduced the thermal reaction peak temperature of pyrotechnics by 7 ​°C and increased the burning rate to more than two times.

(1) Background: Polygonatum cyrtonema is a medicinal plant, and its polysaccharides are used for immunomodulation and the treatment of hyperglycemia. Investigation of the tissue distribution and pharmacokinetics of P. cyrtonema polysaccharide can further elucidate its pharmacological mechanisms. (2) Methods: A fluorescence-labeling approach using rhodamine B (RhB) as a fluorescent molecular probe was used for the quantitative assessment of the polysaccharide from dried P. cyrtonema (DPC1) samples, and the pharmacokinetics and tissue distribution of DPC1 were evaluated in mice after intraperitoneal or oral administration. (3) Results: DPC1 was successfully labeled with RhB, showing degrees of fluorescence labeling at 0.453% and 0.568% as determined by the ultraviolet and enzyme marker methods, respectively. DPC1-RhB was rapidly absorbed into the bloodstream after oral and intraperitoneal administration. Pharmacokinetic characteristics showed that oral administration and intraperitoneal administration were consistent with the features of a two-compartment model. (4) Conclusion: After administration, DPC1-RhB was primarily distributed in the tissues of the heart, spleen, and lung, indicating that the drug has a targeted effect on these tissues. Overall, the findings provide a comprehensive reference for the in vivo distribution of DPC1, together with a foundation for further elucidation of its pharmacological mechanisms and the development and application of DPC1 formulations.

Abstract Background Neuroinflammation is one of the most important processes in secondary injury after traumatic brain injury (TBI). Triggering receptor expressed on myeloid cells 2 (TREM2) has been proven to exert neuroprotective effects in neurodegenerative diseases and stroke by modulating neuroinflammation, and promoting phagocytosis and cell survival. However, the role of TREM2 in TBI has not yet been elucidated. In this study, we are the first to use COG1410, an agonist of TREM2, to assess the effects of TREM2 activation in a murine TBI model. Methods Adult male wild-type (WT) C57BL/6 mice and adult male TREM2 KO mice were subjected to different treatments. TBI was established by the controlled cortical impact (CCI) method. COG1410 was delivered 1 h after CCI via tail vein injection. Western blot analysis, immunofluorescence, laser speckle contrast imaging (LSCI), neurological behaviour tests, brain electrophysiological monitoring, Evans blue assays, magnetic resonance imaging (MRI), and brain water content measurement were performed in this study. Results The expression of endogenous TREM2 peaked at 3 d after CCI, and it was mainly expressed on microglia and neurons. We found that COG1410 improved neurological functions within 3 d, as well as neurological functions and brain electrophysiological activity at 2 weeks after CCI. COG1410 exerted neuroprotective effects by inhibiting neutrophil infiltration and microglial activation, and suppressing neuroinflammation after CCI. In addition, COG1410 treatment alleviated blood brain barrier (BBB) disruption and brain oedema; furthermore, COG1410 promoted cerebral blood flow (CBF) recovery at traumatic injury sites after CCI. In addition, COG1410 suppressed neural apoptosis at 3 d after CCI. TREM2 activation upregulated p-Akt, p-CREB, BDNF, and Bcl-2 and suppressed TNF-α, IL-1β, Bax, and cleaved caspase-3 at 3 d after CCI. Moreover, TREM2 knockout abolished the effects of COG1410 on vascular phenotypes and microglial states. Finally, the neuroprotective effects of COG1410 were suppressed by TREM2 depletion. Conclusions Altogether, we are the first to demonstrate that TREM2 activation by COG1410 alleviated neural damage through activation of Akt/CREB/BDNF signalling axis in microglia after CCI. Finally, COG1410 treatment improved neurological behaviour and brain electrophysiological activity after CCI. Graphical Abstract

Abstract Background The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5–30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. Methods The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. Results Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. Conclusions The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.

Plant phenolic compounds have attracted considerable attention because of their health benefits. This study aimed to investigate the composition and antioxidant activity of phenol extracts from Polygonatum zanlanscianense Pamp. steam and leaf (PPP). The FTIR, UPLC-Q-Obtrip-MS, and HPLC−DAD methods were used to analyze the composition of PPP, and 20 phenolic compounds were preliminarily identified. Among them, the contents of hyperin, astragalin, and diosmetin levels were the highest. Treatment with PPP can significantly reduce t-BHP-induced cell damage in HepG2 cells, reactive oxygen species (ROS) accumulation, and malondialdehyde (MDA) content. Meanwhile, the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH−Px) activities can be increased. Moreover, PPP enhanced Nrf2 expression, which was consistent with that of heme oxygenase-1 (HO−1), glutamate–cysteine ligase catalytic subunit (GCLC), and NAD(P)H quinone oxidoreductase-1 (NQO1), whereas the expression of Keap1, the Nrf2 inhibitor, was decreased. All findings indicate that PPP can serve as a natural bioactive substance for preventing oxidative stress.

As natural products with biological activity, the quality of traditional Chinese medicines (TCM) is the key to their clinical application. Fingerprints based on the types and contents of chemical components in TCM are an internationally recognized quality evaluation method but ignore the correlation between chemical components and efficacy. Through chemometric methods, the fingerprints represented by the chemical components of TCM were correlated with its pharmacodynamic activity results to obtain the spectrum–effect relationships of TCM, which can reveal the pharmacodynamic components information related to the pharmacodynamic activity and solve the limitations of segmentation of chemical components and pharmacodynamic research in TCM. In the 20th anniversary of the proposed spectrum–effect relationships, this paper reviews its research progress in the field of TCM, including the establishment of fingerprints, pharmacodynamic evaluation methods, chemometric methods and their practical applications in the field of TCM. Furthermore, the new strategy of spectrum–effect relationships research in recent years was also discussed, and the application prospects of this technology were discussed.

Abstract Ten new germacrane-type sesquiterpenoids, artemyrianosins A–J (1–10), were isolated from the aerial parts of Artemisia myriantha. Their structures were elucidated by spectral analyses including UV, IR, HRESIMS, 1D and 2D NMR, ECD and the absolute configurations of compounds 1 and 7–9 were characterized using X-ray crystallography. All isolates were tested their cytotoxicity against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1), and compounds 1–3, 7, and 10 showed cytotoxicity with IC50 values ranging from 43.7 to 89.3 μM. Among them, the most active compound 3 exhibited activity against three human hepatoma cell lines with IC50 values of 43.7 μM (HepG2), 47.9 μM (Huh7), and 44.9 μM (SK-Hep-1). Graphical Abstract

Abstract Since the industrialization of single-phase nanomaterial-based devices is still challenging, intensive research focus has been given to complex materials consisting of multiple nanoscale entities, including networks and matrices of nanowires, nanotubes, nanoribbons, or other large molecules; among these complex materials, networks of carbon nanotubes are a typical example. Detailed knowledge of the energy sensitivity and band gap of electronic transport in such a material system is difficult to detect, despite its importance in electronic, energetic and sensing applications. Here, we propose a new methodology to obtain these quantities using the measured Seebeck coefficient at a certain temperature but different Fermi levels. We discover that the network consisting of semiconducting (11,10)-carbon nanotubes actually exhibits metallic transport at room temperature. It is also interesting to verify that intrananotube ballistic transport is dominant over diffusive scattering by long-range disorder, as well as the quantum hopping resistance at the contact points. The transport asymmetry ratio between the holes and electrons (1.75) is similar to the value observed in pristine graphene samples (1.50).

Background: In December 2023, our hospital confirmed a case of systemic lupus erythematosus complicated with Mycobacterium leprae infection. The patient has extensive patchy erythema on the back and face, with obvious itching. There are multiple subcutaneous masses on both hands, some of which are accompanied by tenderness, wave sensation, and other symptoms. The patient's mother has a history of leprosy and close contact with the patient. The patient tested positive for syphilis antibodies 2 years ago and did not receive formal treatment. There is no other history of chronic illness. Methods: Under local anesthesia, the left hand skin lesion was excised, followed by tissue pathological biopsy, acidfast staining, mNGS, and serum Treponema pallidum antibody detection. Results: Pathological biopsy results: A large number of foam-like histiocytes, lymphocytes, and plasma cells were mainly found in the superficial and deep layers of the dermis, as well as around the blood vessels and sweat glands in the subcutaneous fat. Cellulose-like degeneration is seen in some blood vessel walls. Tissue acid-fast staining: positive, tissue mNGS detection: Mycobacterium leprae. Clinical diagnosis: 1. Borderline leprosy, 2. Subacute cutaneous lupus erythematosus. Treat with methylprednisolone 32 mg qd po + aluminum magnesium suspension 15 mL tid po + calcium carbonate D3 tablets 0.6 g qd po + rifampicin 450 mg qd po + dapsone 100 mg qd. After 10 days of treatment, the patient improved and was discharged from the hospital. Conclusions: Mycobacterium leprae infection occurs during SLE treatment and is often difficult to distinguish from skin symptoms caused by SLE. In the clinical treatment of infectious diseases, the effect of conventional antibacterial drugs is not good. The auxiliary examination indicates severe infection and the routine culture is negative. The possibility of special pathogen infection should be considered in combination with the medical history. With the popularity of new detection methods such as mNGS, the importance of traditional smear detection methods cannot be ignored. [ABSTRACT FROM AUTHOR]

Suckling mouse inoculation is an important method that has been used for years to isolate viruses from ticks; however, this method has usually been briefly described in the literature on a case-by-case basis upon successful isolation rather than providing extensive details. This study describes the procedure from preparation of tick homogenates to identification of virus isolation using the suckling mouse inoculation method. The transient and persistent features were characterized and the incidence of manifestations that developed in the suckling mice, especially in mice from which viruses were isolated, is reported. We identified 22 symptoms that developed in mice, including 13 transient symptoms that recovered by the end of the observation period and 7 persistent symptoms that the mice suffered from throughout the observation period. Persistent symptoms (lateral positioning and dead) and transient symptoms (malaise, emaciation, and difficulty turning over) were the main symptoms based on the high overall incidence. Moreover, we showed that mice from which viruses were isolated had a concentrated period and advanced days of disease onset. This study provides detailed information necessary for better use of suckling mouse inoculation to isolate viruses from ticks, which may benefit optimization of this method to identify, discover, and acquire tick-borne viruses.

The closure timing of the Paleo-Asian Ocean and the terminal stage of the Central Asian Orogenic Belt have been widely debated in the geological community. It’s known that the gradual scissor-like closure of the Paleo-Asian Ocean occurred from west to east during the Paleozoic period. However, it was not until the Triassic period that the complete closure of the ocean occurred at the northeastern margin of the North China Craton. Nevertheless, there is still much uncertainty regarding the Late Triassic tectonic setting in Northeast China. In this study, we focused on the Upper Triassic Dajianggang Formation, located in the Shuangyang area of central Jilin Province, which is situated on the northeastern margin of the North China Plate. Our aim was to determine the formation age of the Dajianggang Formation by analyzing the detrital particle composition, petrogeochemistry, detrital zircon U-Pb isotope dating, and apatite fission track thermochronology. Our results indicated that the primary sandstone provenance area of the Dajianggang Formation in the Shuangyang area is the island arc orogenic belt. The tectonic background of the sandstone provenance area is mainly a continental island arc environment. The provenance area is mostly composed of felsic rocks with sedimentary tendencies, and some of its material may have originated from the northern margin of the North China Craton or the eroded recycle orogenic belt. LA-ICP-MS U-Pb dating of detrital zircons shows that the Dajianggang Formation formed after 226.8 ± 5 Ma. Moreover, analysis of the thermal evolution history modelling shows that the Dajianggang Formation in the Shuangyang area continued to be deposited and heated in the early stage, and then experienced rapid exhumation around 30 Ma. This suggests that the study area underwent an orogenic process during the early stage of formation, but then transitioned into a post-orogenic extension period, which constrained the final closure of the Paleo-Asian Ocean prior to the Late Triassic period. In addition, our study indicates that the remote effect of the Pacific subduction did not reach the study area until 30 Ma. The central age of the detrital apatite fission track of sample 19DJ-1 is 94.2 ± 8.3 Ma, which is younger than its corresponding stratigraphic age. The two peak ages of the fission track analysis are 62.9 ± 5.4 Ma and 126 ± 11 Ma. These findings provide new evidence for the tectonic evolution of Northeast China and shed light on the Late Triassic tectonic setting, as well as the influence time of subsequent tectonic domains in the southern part of Northeast China.

We report the isolation of Tamdy virus from Hyalomma asiaticum ticks in northwest China and serologic evidence of human Tamdy virus infection in the same region. These findings highlight the need to further investigate a potential causal relationship between Tamdy virus and febrile illnesses of unknown etiology in that region.

Zirconia is a superior implant material owing to its high mechanical strength, durable corrosion resistance, superior aesthetic effect and excellent biocompatibility. However, the bioactivity of zirconia surfaces remains a great challenge for implant osseointegration. A titania (TiO2) coating was innovatively synthesized on the surface of zirconia by infiltration in a suspension of zirconium oxychloride and titania for dense sintering. Subsequently, the coating was subjected to ultraviolet (UV) light to enhance the biological inertness of zirconia. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and contact angle analysis were conducted to confirm the surface characteristics. Afterwards, in vitro assessments of cell adhesion, proliferation and osteogenic differentiation of MC3T3-E1 cells were performed. Zirconia samples were implanted into rat femurs to assess biocompatibility and host tissue response in vivo. Micro-CT evaluation and histological testing were conducted. After UV irradiation, the content of hydroxyl groups and hydrophilicity of TiO2-modified zirconia were significantly increased. The results of in vitro experiments showed that TiO2-modified zirconia subjected to UV light could promote cell proliferation and spreading, enhance ALP activity and the degree of mineralization, and upregulate osteogenesis-related genes. Furthermore, in vivo assessments confirmed that UV-irradiated TiO2-modified zirconia implants maximized the promotion of osseointegration. TiO2-modified zirconia after UV treatment will have broad clinical application prospects in improving the osseointegration of zirconia implants.

Leading by cytotoxicity against HepG2 cells, bioactivity-guided fractionation of the EtOAc fraction from Artemisia atrovirens led to the isolation of 18 new guaianolide dimers, artematrolides A–R and lavandiolides A, B, C, H, and J. Eight compounds (1, 4, 10, 12, 13, and 19–21) were unambiguously confirmed by the single-crystal X-ray diffraction analyses, and the others were elucidated based on IR, UV, HRESIMS, 1D and 2D NMR experiments, and comparison of the experimental and calculated ECD data. Structurally, all of them were [4 + 2] Diels–Alder adducts of two monomeric guaianolides. The isolates were evaluated for their cytotoxicity against three human hepatoma cell lines, and 19 compounds demonstrated cytotoxicity against HepG2, SMMC-7721, and Huh7 cell lines. Especially, compounds 1, 12, 14, and 15 exhibited cytotoxicity with IC50 values of 4.4, 3.8, 7.6, and 6.7 μmol/L (HepG2), 9.6, 4.6, 6.6, and 6.0 μmol/L (SMMC-7721), and 7.6, 4.5, 6.9, and 5.6 μmol/L (Huh7), respectively. Notably, compound 12 showed the most promising activity against three human hepatoma cell lines and dose-dependently inhibited cell migration and invasion, induced G2/M cell cycle arrest and cell apoptosis in HepG2 cells, down-regulated the expression of BCL-2 and PARP-1, and activated PARP-1 to up-regulate the expression of cleaved-PARP-1.

Despite few human cases of tick-borne encephalitis virus (TBEV), high rates of TBEV seroprevalence were reported among humans and animals in Xinjiang Uygur Autonomous Region in Northwestern China. In this study, the Karshi virus (KSIV) was identified and isolated from Hyalomma asiaticum ticks in Xinjiang. It belongs to the genus Flavivirus of the family Flaviviridae and is closely related to TBEV. KSIV infects cell lines from humans, other mammals and ticks, and causes encephalitis in suckling mice. High minimum infection rates (4.96%) with KSIV were detected among tick groups. KSIV infections have occurred in sheep and marmots, resulting in antibody-positive rates of 2.43 and 2.56%, respectively. We further found that, of the KSIV antibody-positive serum samples from animals, 13.9% had TBEV exposure showing cross-reaction to KSIV, and 11.1% had KSIV infection resulting in cross-reaction to TBEV; 8.3% were likely to have co-exposure to both viruses (or may be infected with one of them and present cross-reactivity with the other). The results revealed a substantial KSIV prevalence among ticks in Xinjiang, indicating exposure of animals to KSIV and TBEV. The findings implied misinterpretation of the high rates of TBEV seroprevalence among humans and animals in previous studies. There is a need to develop detection methods to distinguish KSIV from TBEV and to perform an in-depth investigation of KSIV and TBEV prevalence and incidence in Northwestern China, which would enhance our preparation to provide medical treatment of emerging diseases caused by tick-borne viral pathogens such as KSIV.

Avian leukosis virus (ALV) causes various diseases associated with tumor formation and decreased fertility. Moreover, ALV induces severe immunosuppression, increasing susceptibility to other microbial infections and the risk of failure in subsequent vaccination against other diseases. There is growing evidence showing the interaction between ALV and the host. In this review, we will survey the present knowledge of the involvement of host factors in the important molecular events during ALV infection and discuss the futuristic perspectives from this angle.

Tick-borne viruses (TBVs) capable of transmitting between ticks and hosts have been increasingly recognized as a global public health concern. In this study, Hyalomma ticks and serum samples from camels were collected using recorded sampling correlations in eastern Kenya. Viromes of pooled ticks were profiled by metagenomic sequencing, revealing a diverse community of viruses related to at least 11 families. Five highly abundant viruses, including three novel viruses (Iftin tick virus, Mbalambala tick virus [MATV], and Bangali torovirus [BanToV]) and new strains of previously identified viruses (Bole tick virus 4 [BLTV4] and Liman tick virus [LMTV]), were characterized in terms of genome sequences, organizations, and phylogeny, and their molecular prevalence was investigated in individual ticks. Moreover, viremia and antibody responses to these viruses have been investigated in camels. MATV, BLTV4, LMTV, and BanToV were identified as viral pathogens that can potentially cause zoonotic diseases. The transmission patterns of these viruses were summarized, suggesting three different types according to the sampling relationships between viral RNA-positive ticks and camels positive for viral RNA and/or antibodies. They also revealed the frequent transmission of BanToV and limited but effective transmission of other viruses between ticks and camels. Furthermore, follow-up surveys on TBVs from tick, animal, and human samples with definite sampling relationships are suggested. The findings revealed substantial threats from the emerging TBVs and may guide the prevention and control of TBV-related zoonotic diseases in Kenya and in other African countries.

Ship lock as a typical hydraulic structure has become an important node in waterway transportation. Due to the long operating life and high demand of throughput, many locks are under the overloaded operation situation. However, the service condition assessment of ship locks has rarely been directly studied, and there is a lack of an efficient and standardized method owing to the complex structure of the ship lock system. In this paper, a multi-level hierarchical system including 36 indexes was constructed based on the engineering breakdown structure theory. The synthetic weights of indexes were determined by the order relation method and entropy weight method combining subjectivity and objectivity. The extension cloud model combining the extension theory and cloud model was put forward, aiming to deal with the uncertainty of fuzziness and randomness in the evaluation process. Then, two typical locks were investigated, and the numerical scores indicated that their states belong to Level III and Level IV, respectively. The proposed method reveals the structural condition and provides theoretical reference for the maintenance of ship locks, which can be applied with generalizability and operability.

Infectious diseases caused by arboviruses are a public health concern in Pakistan. However, studies on data prevalence and threats posed by arboviruses are limited. This study investigated the seroprevalence of arboviruses in a healthy population in Pakistan, including severe fever with thrombocytopenia syndrome virus (SFTSV), Crimean-Congo hemorrhagic fever virus (CCHFV), Tamdy virus (TAMV), and Karshi virus (KSIV) based on a newly established luciferase immunoprecipitation system (LIPS) assays, and Zika virus (ZIKV) by enzyme-linked immunosorbent assays (ELISA). Neutralizing activities against these arboviruses were further examined from the antibody positive samples. The results showed that the seroprevalence of SFTSV, CCHFV, TAMV, KSIV, and ZIKV was 17.37%, 7.58%, 4.41%, 1.10%, and 6.48%, respectively, and neutralizing to SFTSV (1.79%), CCHFV (2.62%), and ZIKV (0.69%) were identified, as well as to the SFTSV-related Guertu virus (GTV, 0.83%). Risk factors associated with the incidence of exposure and levels of antibody response were analyzed. Moreover, co-exposure to different arboviruses was demonstrated, as thirty-seven individuals were having antibodies against multiple viruses and thirteen showed neutralizing activity. Males, individuals aged >40 years, and outdoor workers had a high risk of exposure to arboviruses. All these results reveal the substantial risks of infection with arboviruses in Pakistan, and indicate the threat from co-exposure to multiple arboviruses. The findings raise the need for further epidemiologic investigation in expanded regions and populations and the necessity to improve health surveillance in Pakistan. [ABSTRACT FROM AUTHOR]

Haemaphysalis longicornis ticks, commonly found in East Asia, can transmit various pathogenic viruses, including the severe fever with thrombocytopenia syndrome virus (SFTSV) that has caused febrile diseases among humans in Hubei Province. However, understanding of the viromes of H. longicornis was limited, and the prevalence of viruses among H. longicornis ticks in Hubei was not well clarified. This study investigates the viromes of both engorged (fed) and free (unfed) H. longicornis ticks across three mountainous regions in Hubei Province from 2019 to 2020. RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging to unclassified viruses and seven RNA viral families, namely Chuviridae, Nairoviridae, Orthomyxoviridae, Parvoviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae. Viral abundance and diversity in these ticks were analysed, and phylogenetic characteristics of the Henan tick virus (HNTV), Dabieshan tick virus (DBSTV), Okutama tick virus (OKTV), and Jingmen tick virus (JMTV) were elucidated based on their full genomic sequences. Prevalence analysis demonstrated that DBSTV was the most common virus found in individual H. longicornis ticks (12.59%), followed by HNTV (0.35%), whereas JMTV and OKTV were not detected. These results improve our understanding of H. longicornis tick viromes in central China and highlight the role of tick feeding status and geography in shaping the viral community. The findings of new viral strains and their potential impact on public health raise the need to strengthen surveillance efforts for comprehensively assessing their spillover potentials. [ABSTRACT FROM AUTHOR]

High-pressure (HP) rocks exhumed from subduction zones usually record much warmer geotherms than numerical modelling results, as their peak mineral assemblages are always modified during the exhumation process. The decompressional metamorphic evolution of HP rocks should be considered carefully if using their P–T records to constrain the thermal structure of a subduction zone. The Ondor Sum Group, known as mélanges containing various high P/T metamorphic rocks in central Inner Mongolia, represents a fragment of subducted oceanic crust in the Early Paleozoic, However, the thermal structure of the subduction zone is unavailable due to an absence of exhumed HP rocks with P–T estimates. In this study, the HP schists were newly discovered in the Ondor Sum Group at Airgin Sum in the central Inner Mongolia. The HP schists include a garnet–phengite schist (sample EL01) and a garnet–amphibole schist (sample EL08). The petrography of these rocks and phase equilibrium modelling using THERMOCALC suggest two phases of metamorphism, both of which are characterized by clockwise P–T evolutions involving pre-peak prograde stage, peak-stage, and post-peak decompression stage. The peak P–T conditions of the early-phase metamorphism are constrained by P–T pseudosections to be ∼18 kbar/∼535°C for sample EL01 and 18 kbar/∼500°C for sample EL08. The peak P–T conditions of the late-phase metamorphism are constrained by P–T pseudosections to be ∼8 kbar/532°C in EL01 and ∼7.0 kbar/495°C in EL08. Available U–Pb data of zircons from the HP schists and a granodiorite vein using LA–ICP–MS constrain the timing of early-phase HP metamorphism in the early Paleozoic and the late-phase metamorphism supposed to be in the Devonian based on the previous reported ages. The peak P–T conditions for the early-phase metamorphism were high-P/T conditions with a thermal gradient of ∼8°C/km, pointing to a warm oceanic subduction. The overprinting late-phase metamorphism represents medium-P/T conditions with a geothermal gradient of 22–25°C/km, which we attribute to a collisional thickening process. As a result, we suggest that the HP schists in the Ondor Sum Group represent the terminal stage of subduction of the Paleo-Asian oceanic plate, and that the schists were involved in the continental collision after the closure of the Paleo-Asian Ocean in the Devonian.

ABSTRACT: Infectious bursal disease virus (IBDV) caused an acute and highly contagious infectious disease, resulting in considerable economic losses in the world poultry industry. Although this disease was well-controlled under the widely use of commercial vaccines, the novel variant IBDV strain emerged due to the highly immunized-selection pressure in the field, posting new threats to poultry industry. Here, we reported the epidemic and pathogenicity of IBDV in Hubei Province from May to August 2020. We isolated 12 IBDV strains from the broiler flocks, including 9 novel variants, 2 very virulent strains and 1 medium virulent strain. Interestingly, we identified a series of changes of amino acid sites in the VP2. Further analysis indicated that the novel variant IBDV strains caused damage to bursa of fabricius and spleen, leading to immunosuppression. Our findings underscore the importance of IBDV surveillance, and provide evidence for understanding the evolution of IBDV.

Abstract Two new sesquiterpenoids, artemlavanins A (1) and B (3), together with fifteen known compounds (2 and 4−17) were isolated from the EtOH extract of Artemisia lavandulaefolia. The structures of new compounds were elucidated by extensive spectroscopic analyses (HRESIMS, 1D and 2D NMR) and ECD calculations. Compound 1 was a sesquiterpenoid lactone possessing a rearranged eudesmane skeleton; compounds 2–5, 6–8, 9 and 10–12 belonged to the eudesmane, guaiane, oppositane and farnesane sesquiterpenoids, respectively; compounds 13–17 were the phenyl derivatives with a 4-hydroxyacetophenone moiety. Twelve compounds (1–3, 5–7, 10–12, 14, 15 and 17) displayed cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values ranging from 35.1 to 370.3 μM. Compounds 2, 7, 10–12 and 17 exhibited the stronger cytotoxicity than silybin (IC50, 169.6 μM) with IC50 values of 82.1, 35.1, 95.0, 83.8, 81.6 and 90.1 μM. Compound 7 as the most active one showed significant inhibition on the deposition of human collagen type I (Col I), human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 10.7, 24.5 and 13.3 μM. Graphic Abstract

Abstract Four new sesquiterpenoids, artemyrianins A–D (1–4), and three new norlignans, artemyrianins E–G (5–7), together with five known compounds (8–12), were isolated from the aerial parts of Artemisia myriantha (Asteraceae). The new compounds were established by spectroscopic data analyses (HRMS, IR, 1D and 2D NMR), and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations. The isolates showed cytotoxicity against HepG2 cells with IC50 values ranging from 33.3 to 145.2 μM. Graphic Abstract

Red blood cells play an essential role in the immune system. Moreover, red blood cell count (RBC) is an important clinical indicator of various diseases, including anemia, type 2 diabetes and the metabolic syndrome. Thus, it is necessary to reveal the genetic mechanism of RBC for animal disease resistance breeding. However, quite a few studies had focused on porcine RBC, especially at different stages. Thus, studies on porcine RBC at different stages are needed for disease resistant breeding. In this study, the porcine RBC of 20-, 33-, and 80-day old were measured, and genetic parameter estimation and genome-wide association study (GWAS) were both performed. As a result, the heritability was about 0.6 at the early stages, much higher than that at 80 days. Nine novel genome wide significant single nucleotide polymorphisms (SNPs), located at Sus scrofa chromosome (SSC)3, 4, 8, 9, 10 and 15, respectively, were identified. Further, TGFβ2, TMCC2 and PPP1R15B genes were identified as important candidate genes of porcine red blood cell count. So different SNPs and candidate genes were found significantly associated with porcine RBC at different stages, suggesting that different genes might play key roles on porcine RBC at different stages. Overall, new evidences were offered in this study for the genetic bases of animal RBC, and that the SNPs and candidate genes would be useful for disease resistant breeding of pig.

Synthetic immunosuppressive glucocorticoids (GCs) are widely used to control inflammatory bowel disease (IBD). However, the impact of GC signaling on intestinal tumorigenesis remains controversial. Here, we report that intestinal epithelial GC receptor (GR), but not whole intestinal tissue GR, promoted chronic intestinal inflammation-associated colorectal cancer in both humans and mice. In patients with colorectal cancer, GR was enriched in intestinal epithelial cells and high epithelial cell GR levels were associated with poor prognosis. Consistently, intestinal epithelium–specific deletion of GR (GR iKO) in mice increased macrophage infiltration, improved tissue recovery, and enhanced antitumor response in a chronic inflammation–associated colorectal cancer model. Consequently, GR iKO mice developed fewer and less advanced tumors than control mice. Furthermore, oral GC administration in the early phase of tissue injury delayed recovery and accelerated the formation of aggressive colorectal cancers. Our study reveals that intestinal epithelial GR signaling repressed acute colitis but promoted chronic inflammation–associated colorectal cancer. Our study suggests that colorectal epithelial GR could serve as a predictive marker for colorectal cancer risk and prognosis. Our findings further suggest that, although synthetic GC treatment for IBD should be used with caution, there is a therapeutic window for GC therapy during colorectal cancer development in immunocompetent patients.

Molecular skeleton modification has become a recognized method that can effectively improve the photocatalytic performance of g-C3N4 because it not only effectively promotes charge separation, but also tunes the conjugated system of g-C3N4 to make it more conducive to photocatalytic reaction. Herein, thiophene-amide embedded g-C3N4 (TA-CN-x) was successfully prepared by simple one-step thermal polycondensation using urea as a precursor and ethyl-2-amino-4-phenylthiophene-3-carboxylate (EAPC) as an additive. After embedding with thiophene-amide, the induction and delocalization effects are formed in TA-CN-x, which significantly improves the migration efficiency of photogenerated charge carriers. Meanwhile, the conjugate structure is changed due to structural modification, resulting in significant enhancement of visible light absorption compared to the pure g-C3N4 (CN). Specifically, the optimized photocatalytic H2 evolution rate of TA-CN-2 reaches 245.4 μmol·h−1, which is 8.4 times that of CN (with Pt nanoparticles as a co-catalyst), and the apparent quantum efficiency (AQY) at 450 nm is 13.6%. This work opens up a new modification process for fully tapping the photocatalytic hydrogen absorption potential of g-C3N4-based materials.

Container seaport congestion is a challenging problem in improving the service level and optimizing evacuating container vessels after congestion. There is a lack of research on container vessel evacuation strategies for continuous terminals. In this article, the weight of the objective function is regarded as the index for the service priority of vessels. The effects of the service priority on the continuous terminal are analyzed by establishing a mixed integer programming model. The model minimizes the total weighted delay departure time of vessels. Two sets of weight values are adopted, including handling volume of each ship and the squared handling volume, then the optimization results are compared with the unweighted scenario. The model is solved using a genetic algorithm. Lianyungang Port is selected as a case study. The results show that the method using the square of handled container volume is more conducive to ensuring the shipping period of large vessels after congestion. Besides, the quay crane number of large vessels affecting the scheduling strategy is discussed. The method proposed in this article provides a new idea for arranging scheduling strategies in other ports under congestion situations, which can better ensure the planned shipping period of large vessels.

Sphingolipids are important structural components of cell membranes and prominent signaling molecules controlling cell growth, differentiation, and apoptosis. Sphingolipids are particularly abundant in the brain, and defects in sphingolipid degradation are associated with several human neurodegenerative diseases. However, molecular mechanisms governing sphingolipid metabolism remain unclear. Here, we report that sphingolipid degradation is under transcriptional control of SIRT1, a highly conserved mammalian NAD+-dependent protein deacetylase, in mouse embryonic stem cells (mESCs). Deletion of SIRT1 results in accumulation of sphingomyelin in mESCs, primarily due to reduction of SMPDL3B, a GPI-anchored plasma membrane bound sphingomyelin phosphodiesterase. Mechanistically, SIRT1 regulates transcription of Smpdl3b through c-Myc. Functionally, SIRT1 deficiency-induced accumulation of sphingomyelin increases membrane fluidity and impairs neural differentiation in vitro and in vivo. Our findings discover a key regulatory mechanism for sphingolipid homeostasis and neural differentiation, further imply that pharmacological manipulation of SIRT1-mediated sphingomyelin degradation might be beneficial for treatment of human neurological diseases.