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Background and aim: Hepatic ischemia–reperfusion injury (IRI) is a significant challenge in liver transplantation, trauma, hypovolemic shock, and hepatectomy, with limited effective interventions available. This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA (shRNA) delivered through adeno-associated virus (AAV) vectors. Materials and methods: This study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver. Lect2-knockout and C57BL/6J mice were used. Hepatic IRI was induced by clamping the hepatic pedicle. Treatments included recombinant human LECT2 (rLECT2) and AAV-Lect2-shRNA. LECT2 expression levels and serum biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were measured. Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results: Serum and liver LECT2 levels were elevated during hepatic IRI. Serum LECT2 protein and mRNA levels increased post reperfusion. Lect2-knockout mice had reduced weight loss; hepatic necrosis; and serum ALT, AST, creatinine, and BUN levels. rLECT2 treatment exacerbated weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN). AAV-Lect2-shRNA treatment significantly reduced weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN), indicating therapeutic potential. Conclusions: Elevated LECT2 levels during hepatic IRI increased liver damage. Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage, indicating its therapeutic potential. AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI, offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

With the increasing demand for astronomical observations, telescope systems are becoming increasingly complex. Thus, the observatory control software needs to be more intelligent. It has to control each instrument inside the observatory, finish the observational tasks autonomously, and report the information to users if needed. We developed a distributed autonomous observatory control framework named the Remote Autonomous Control System 2nd (RACS2) to meet these requirements. Rich features are integrated into the RACS2 framework. The RACS2 is a modular framework, in which each device control software and system services are implemented as different components. Furthermore, the RACS2 framework assimilates new techniques, such as a lightweight message and serialization mechanism. RACS2 also has good compatibility with other frameworks or ecosystems such as Python and the EPICS (Experimental Physics and Industrial Control System). The RACS2 framework can communicate with EPICS-based and Python-based software. With the help of these features, key system components like executor, scheduler are developed. The executor component can support sophisticated tasks. Autonomous observation can be achieved by the scheduler component. A set of web-based graphical user interface (GUI) is designed to help control and manage the framework remotely. Based on the RACS2 framework, we have implemented the Dome A Twins (DATs) telescope’s observation system and the space object observation system. The systems have been operated for more than 1 year. The RACS2 framework also has been used in our other projects like camera control system of Wide Field Survey Telescope (WFST) and its observatory control system, and the design can be a useful reference for the development of other frameworks.

Ferritinophagy is a type of autophagy mediated by nuclear receptor activator 4 (NCOA4), which plays a role in inducing ferroptosis by regulating iron homeostasis and producing reactive oxygen species in cells. Under physiological conditions, ferritinophagy maintains the stability of intracellular iron by regulating the release of free iron. Studies have demonstrated that ferritinophagy is necessary to induce ferroptosis; however, under pathological conditions, excessive ferritinophagy results in the release of free iron in large quantities, which leads to lipid peroxidation and iron-dependent cell death, known as ferroptosis. Ferritinophagy has become an area of interest in recent years. We here in review the mechanism of ferritinophagy and its association with ferroptosis and various diseases to provide a reference for future clinical and scientific studies.

Pulmonary fibrosis is a scarring disease of lung tissue, which seriously threatens human health. Treatment options are currently limited, and effective strategies are still lacking. In the present study, 25 compounds were isolated from the deep-sea fungus Trichoderma sp. MCCC 3A01244. Among them, two β-carboline alkaloids, trichocarbolines A (1) and C (4) are new compounds. The chemical structures of these compounds were elucidated based on their HRESIMS, 1D and 2D NMR spectra, optical rotation calculation, and comparisons with data reported in the literature. Trichocarboline B [(+)- and (–)-enantiomers] had previously been synthesized, and this is its first report as a natural product. Their anti-pulmonary fibrosis (PF) activity and cytotoxicity were investigated. Compounds 1, 11, and 13 strongly inhibited TGF-β1-induced total collagen accumulation and showed low cytotoxicity against the HFL1 cell line. Further studies revealed compound 1 inhibited extracellular matrix (ECM) deposition by downregulating the expression of protein fibronectin (FN), proliferating cell nuclear antigen (PCNA), and α-smooth muscle actin (α-SMA). Mechanistic study revealed that compound 1 decreased pulmonary fibrosis by inhibiting the TGF-β/Smad signaling pathway. As a newly identified β-carboline alkaloid, compound 1 may be used as a lead compound for developing more efficient anti-pulmonary fibrosis agents.

Objective To analyze risk factors related to acute ischemic stroke after intracranial aneurysm clipping. Methods From January 2013 to January 2018, 267 cases of intracranial ruptured aneurysm in our hospital were collected retrospectively. All patients were given intracranial aneurysm clipping, ventricular drainage and decompression with bone flap vemova. Univariate and multivariate backward Logistic regression analysis were used to analyze the risk factors for ischemic stroke after intracranial aneurysm clipping. Results There were 62 patients (23.22%) with acute ischemic stroke after intracranial aneurysm clipping. Logistic regression analysis showed that hypertension (OR=1.695,95%CI: 1.247-2.631; P=0.006), bloodglucose (OR=4.206,95%CI:2.771-6.284; P=0.000), Hunt⁃Hessgrade ≥ Ⅲ (OR=1.443,95%CI:1.205-1.872; P=0.017),ventricular hemorrhage (OR=1.947,95%CI:1.465-2.973; P=0.001)and acute hydrocephalus (OR=3.221,95%CI:2.218-4.960; P=0.000) were risk factors for acute ischemic stroke after intracranial aneurysm clipping. Conclusions The hypertension, blood glucose increased on admission, preoperative Hunt ⁃ Hess grade ≥ Ⅲ, ventricular hemorrhage and acute hydrocephalus were risk factors for acute ischemic stroke after clipping of intracranial aneurysm rupture. DOI：10.3969/j.issn.1672⁃6731.2020.09.012

In recent years, more and more countries are focusing on the control of mining sites and the surrounding ecological environment, and the new environmental concept of green mines has been proposed. By investigating the ecological background of a mine site, pollution and ecological imbalances in the mine can be predicted, managed or transformed. This study investigated the effects of rare earth elements on plant growth in the Baotou Bayan Obo Rare Earth Mine and evaluated soil contamination and subsequent remediation through the measured plant height. Using linear regression, BP(Back Propagation) neural networks, GA-BP(Genetic Algorithm- Back Propagation) neural networks, ELM(Extreme Learning Machine) and GA-ELM(Genetic Algorithm- Extreme Learning Machine) model prediction instruments, the different rare earth solution concentrations were set as input values and the heights of Artemisia desertorum, which as the model plant, were set as output values in the prediction. The results showed that the linear regression predicted the standard error of single La(III), Ce(III) solution and compound La(III) + Ce(III) solution for Artemisia desertorum growth stress was on the high side, 7.02%− 8.92%; the efficiency range of each group of models under BP neural network, GA-BP neural network and ELM neural network were 1.15%− 2.53%, 0.85%− 1.28%, 1.76%− 3.53%; while the efficiency range under GA-ELM neural network was 0.59%− 0.68%, with average error values and predicted values close to the true values. Among them, the MAPE of GA-ELM neural network are significantly lower than other models, and the error decreases with increasing concentration of the compound solution. So GA-ELM neural network can be used as an efficient, fast and reasonable optimal model for predicting the growth stress of Artemisia desertorum in Bayan Obo mining area. The experimental results can provide a theoretical basis for assessing the risk of soil rare earth contamination in the area, evaluating the expectation of later remediation, and provide a degree of new ideas for the construction of green mines.

Two series of pleuromutilin derivatives were designed and synthesized as inhibitors against Staphylococcus aureus (S. aureus). 6-chloro-4-amino-1-R-1H-pyrazolo[3,4-d]pyrimidine or 4-(6-chloro-1-R-1H-pyrazolo[3,4-d]pyrimidine-4-yl)amino-phenylthiol were connected to pleuromutilin. A diverse array of substituents was introduced at the N-1 position of the pyrazole ring. The in vitro antibacterial activities of these semisynthetic derivatives were evaluated against two standard strains, Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, Staphylococcus aureus (S. aureus), ATCC 29213 and two clinical S. aureus strains (144, AD3) using the broth dilution method. Compounds 12c, 19c and 22c (MIC = 0.25 μg/mL) manifested good in vitro antibacterial ability against MRSA which was similar to that of tiamulin (MIC = 0.5 μg/mL). Among them, compound 22c killed MRSA in a time-dependent manner and performed faster bactericidal kinetics than tiamulin in time–kill curves. In addition, compound 22c exhibited longer PAE than tiamulin, and showed no significant inhibition on the cell viability of RAW 264.7, Caco-2 and 16-HBE cells at high doses (≤8 μg/mL). The neutropenic murine thigh infection model study revealed that compound 22c displayed more effective in vivo bactericidal activity than tiamulin in reducing MRSA load. The molecular docking studies indicated that compound 22c was successfully localized inside the binding pocket of 50S ribosomal, and four hydrogen bonds played important roles in the binding of them.

Autism spectrum disorder (ASD) is a heterogeneous disorder characterized by different levels of repetitive and stereotypic behavior as well as deficits in social interaction and communication. In this current study, we explored the changes in cerebral neural activities in ASD. The purpose of this study is to investigate whether there exists a dysfunction of interactive information processing between the prefrontal cortex and posterior brain regions in ASD. We investigated the atypical connectivity and information flow between the prefrontal cortex and posterior brain regions in ASD utilizing the entropy connectivity (a kind of directional connectivity) method. Eighty-nine patients with ASD and 94 typical developing (TD) teenagers participated in this study. Two-sample t-tests revealed weakened interactive entropy connectivity between the prefrontal cortex and posterior brain regions. This result indicates that there exists interactive prefrontal-posterior underconnectivity in ASD, and this disorder might lead to less prior knowledge being used and updated. Our proposals highlighted that aforementioned atypical change might accelerate the deoptimization of brain networks in ASD.

It remains poorly understood how brain causal connectivity networks change following hearing loss and their effects on cognition. In the current study, we investigated this issue. Twelve patients with long-term bilateral sensorineural hearing loss [mean age, 55.7 ± 2.0; range, 39–63 years; threshold of hearing level (HL): left ear, 49.0 ± 4.1 dB HL, range, 31.25–76.25 dB HL; right ear, 55.1 ± 7.1 dB HL, range, 35–115 dB HL; the duration of hearing loss, 16.67 ± 4.5, range, 3–55 years] and 12 matched normally hearing controls (mean age, 52.3 ± 1.8; range, 42–63 years; threshold of hearing level: left ear, 17.6 ± 1.3 dB HL, range, 11.25–26.25 dB HL; right ear, 19.7 ± 1.3 dB HL, range, 8.75–26.25 dB HL) participated in this experiment. We constructed and analyzed the causal connectivity networks based on functional magnetic resonance imaging data of these participants. Two-sample t-tests revealed significant changes of causal connections and nodal degrees in the right secondary visual cortex, associative visual cortex, right dorsolateral prefrontal cortex, left subgenual cortex, and the left cingulate cortex, as well as the shortest causal connectivity paths from the right secondary visual cortex to Broca’s area in hearing loss patients. Neuropsychological tests indicated that hearing loss patients presented significant cognitive decline. Pearson’s correlation analysis indicated that changes of nodal degrees and the shortest causal connectivity paths were significantly related with poor cognitive performances. We also found a cross-modal reorganization between associative visual cortex and auditory cortex in patients with hearing loss. Additionally, we noted that visual and auditory signals had different effects on neural activities of Broca’s area, respectively. These results suggest that changes in brain causal connectivity network are an important neuroimaging mark of cognitive decline. Our findings provide some implications for rehabilitation of hearing loss patients.

The α7 nicotinic acetylcholine receptor (α7nAChR) belongs to the superfamily of cys loop cationic ligand-gated channels, which consists of homogeneous α7 subunits. Although our lab found that activation of α7nAChR could alleviate ischemic stroke, the mechanism is still unknown. Herein, we explored whether autophagy is involved in the neuroprotective effect mediated by α7nAChR in ischemic stroke. Transient middle cerebral artery occlusion (tMCAO) and oxygen and glucose deprivation (OGD/R) exposure were applied to in vivo and in vitro models of ischemic stroke, respectively. Neurological deficit score and infarct volume were used to evaluate outcomes of tMCAO in the in vivo study. Autophagy-related proteins were detected by Western blot, and autophagy flux was detected by using tandem fluorescent mRFP-GFP-LC3 lentivirus. At 24 h after tMCAO, α7nAChR knockout mice showed worse neurological function and larger infarct volume than wild-type mice. PNU282987, an α7nAChR agonist, protected against OGD/R-induced neuronal injury, enhanced autophagy, and promoted autophagy flux. However, the beneficial effects of PNU282987 were eliminated by 3-methyladenine (3-MA), an autophagy inhibitor. Moreover, we found that PNU282987 treatment could activate the AMPK-mTOR-p70S6K signaling pathway in the in vitro study, while the effect was attenuated by compound C, an AMPK inhibitor. Our results demonstrated that the beneficial effect on neuronal survival via activation of α7nAChR was associated with enhanced autophagy, and the AMPK-mTOR-p70S6K signaling pathway was involved in α7nAChR activation–mediated neuroprotection.

A new compound, exophilone (1), together with nine known compounds (2–10), were isolated from a deep-sea-derived fungus, Exophiala oligosperma. Their chemical structures, including the absolute configuration of 1, were elucidated using nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectroscopy (HRESIMS), and electronic circular dichroism (ECD) calculation. Compounds were preliminarily screened for their ability to inhibit collagen accumulation. Compounds 1, 4, and 7 showed weaker inhibition of TGF-β1-induced total collagen accumulation in compared with pirfenidone (73.14% inhibition rate). However, pirfenidone exhibited cytotoxicity (77.57% survival rate), while compounds 1, 4, and 7 showed low cytotoxicity against the HFL1 cell line. Particularly, exophilone (1) showed moderate collagen deposition inhibition effect (60.44% inhibition rate) and low toxicity in HFL1 cells (98.14% survival rate) at a concentration of 10 μM. A molecular docking study suggests that exophilone (1) binds to both TGF-β1 and its receptor through hydrogen bonding interactions. Thus, exophilone (1) was identified as a promising anti-pulmonary fibrosis agent. It has the potential to be developed as a drug candidate for pulmonary fibrosis.

The centrality of actors has been a key issue in undirected fuzzy social network (UFSN) analysis. For undirected fuzzy social networks (UFSNs) where edges are just a present or absent undirected fuzzy relation with no more information attached. There has been a growing need to design centrality measures for directed fuzzy social networks (DFSNs), because DFSNs where edges are attached with directed fuzzy relation would contain rich information. In this paper, we propose some new centrality measure called fuzzy in-degree centrality, fuzzy out-degree centrality, fuzzy in-closeness centrality and fuzzy out-closeness centrality which are applicable to the DFSNs. It unveils more structural information about directed fuzzy relation and connectivity of DFSNs. Furthermore, by investigating the validness and robustness of this new centrality measure by illustrating this method to some cases and we obtain reliable results, which provide strong evidences of the new measures’ utility.

MicroRNA-9 (miR-9) has been shown to promote the differentiation of bone marrow mesenchymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study confirmed that increased autophagic activity improved the efficiency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3)-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Results showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron specific enolase and microtubule-associated protein 2 increased in the miR-9 + group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.

Background: Glioblastoma multiforme (GBM) is the most aggressive and deadly primary brain cancer that arises from astrocytes and classified as grade IV. Recently, exosomes have been reported as an essential mediator in diverse cancer carcinogenesis and metastasis. However, their role in GBM is still unclear. In this study, we aimed to investigate whether blood exosomes can be potential clinical diagnostic markers for GBM. Methods: We used a xenograft orthotopic mouse model to detect the differentially expressed genes in the brain and blood exosomes of original/recurrent GBM. Results: We found that recurrent GBM had stronger growth capacity and lethality than original GBM in the mouse model. A gene microarray of original tumors and blood exosomes from GBM orthotopic xenografts results showed that DNM3, p65 and CD117 expressions increased, whereas PTEN and p53 expressions decreased in both original tumors and blood exosomes. In the recurrent GBM tumor model, DNM3 and p65 showed increased expressions, whereas ST14 and p53 showed decreased expressions in tumor and blood exosomes of the recurrent GBM mouse model. Conclusion: In summary, we found that DNM3, p65 and p53 had a similar trend in brain and blood exosomes both for original and recurrent GBM, and could serve as potential clinical diagnostic markers for GBM.