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Background Although the diagnostic value of plasma heat-shock protein 90α (HSP90α) in hepatocellular carcinoma (HCC) has been previously reported, the causal effect of the plasma HSP90α levels on HCC prognosis remains largely unclear. To this extent, we sought to assess whether the plasma HSP90α acts as a prognostic factor for HCC patients. Methods A total of 2150 HCC patients were included in this retrospective study between August 2016 and July 2021. Plasma HSP90α levels were tested within a week before treatment and their association with prognosis was assessed. Results An optimal cutoff value of 143.5 for the HSP90α based on the overall survival (OS) was determined using the X-tile software. HCC patients with HSP90α p p Conclusions Our study confirmed that the plasma HSP90α level can be used as a prognostic biomarker for HCC.

The differentiation of embryonic stem cells (ESCs) into germ cells

RNA modification is a dynamic and reversible process regulated by a series of writers, erasers and readers (WERs). Abnormal changes of WERs will disrupt the RNA modification homeostasis of their target genes, leading to the dysregulation of RNA metabolisms such as RNA stability and translation, and consequently to diseases such as cancer. A public repository hosting the regulatory relationships between WERs and their target genes will help in understanding the roles of RNA modifications in various physiological and pathological conditions. Previously, we developed a database named ‘m6A2Target’ to host targets of WERs in m6A, one of the most prevalent RNA modifications in eukaryotic cells. To host all RNA modification (RM)-related WER–target associations, we hereby present an updated database, named ‘RM2Target’ (http://rm2target.canceromics.org/). In this update, RM2Target encompasses 1 619 653 WER–target associations for nine RNA modifications in human and mouse, including m6A, m6Am, m5C, m5U, m1A, m7G, pseudouridine, 2′-O-Me and A-to-I. Extensive annotations of target genes are available in RM2Target, including but not limited to basic gene information, RNA modifications, RNA–RNA/RNA–protein interactions and related diseases. Altogether, we expect that RM2Target will facilitate further downstream functional and mechanistic studies in the field of RNA modification research.

Background Toxoplasma gondii (T. gondii) is a neuroinvasive parasite causing neuroinflammation, which is associated with a higher risk for several psycho-behavioral disorders. There is an urgent need to identify drugs capable of improving cognitive deficits induced by T. gondii infection. (1, 3)/(1, 6)-β-glucan, an active ingredient in mushrooms, could significantly enhance immunity. However, the effects of β-glucan against neuroinflammation and cognitive decline induced by T. gondiiinfection remain unknown. The present study aimed to investigate the neuroprotective effect of β-glucan on goal-directed behavior of mice chronically infected by T. gondii Wh6 strain. Methods A mice model of chronic T. gondii Wh6 infection was established by gavage of 10 cysts. Intraperitoneal injection of β-glucan was manipulated two weeks before T. gondiiinfection. Y-maze test and temporal order memory (TOM) test were performed to assess the goal-directed behavior. Golgi-Cox staining, transmission electron microscopy, immunofluorescence, Real-Time PCR and western blot assays were used to detect prefrontal cortex-associated pathological change and neuroinflammation. Results We reported that administration of β-glucan significantly prevented T. gondii Wh6-induced goal-directed behavioral impairment assessed behaviorally by Y-maze test and TOM test. In the prefrontal cortex, β-glucan could counter T. gondii Wh6 -induced degeneration of neurites, impairment of synaptic ultrastructure, and decrease of pre- and postsynaptic protein levels. Also, β-glucan significantly prevented the hyperactivation of pro-inflammatory microglia and astrocytes, as well as the upregulation of proinflammatory cytokines caused by chronic T. gondii Wh6 infection. Conclusion This study revealed that β-glucan prevents goal-directed behavioral impairment induced by chronic T. gondii infection in mice. These findings suggested that β-glucan may be an effective drug candidate to prevent T. gondii-associated psycho-behavioral disorders including goal-directed behavioral injury.

Toxoplasma gondii (T. gondii) is a neuroinvasive parasite closely associated with a higher risk for several psycho-behavioral disorders. β-glucan is an immunomodulating ingredient extracted from mushrooms. In this study, we evaluated the effect of β-glucan on cognitive decline induced by T. gondii infection in mice chronically infected with T. gondii Wh6 strain. We demonstrated that intraperitoneal administration of β-glucan significantly prevented T. gondii Wh6-induced goal-directed behavioral impairment assessed behaviorally by Y-maze test and TOM test. In the prefrontal cortex, β-glucan countered T. gondii Wh6-induced degeneration of neurites, impairment of synaptic ultrastructure and decrease of pre- and postsynaptic protein levels. Meanwhile, β-glucan significantly prevented microglial and astrocytes hyperactivation and proinflammatory cytokines upregulation caused by chronic T. gondii Wh6 infection. This study revealed that β-glucan prevents goal-directed behavioral impairment induced by chronic T. gondiiinfection in mice, provides an effective drug candidate for the prevention of T. gondii-related psycho-behavioral disorders.

Deep learning has made unprecedented progress in image restoration (IR), where residual block (RB) is popularly used and has a significant effect on promising performance. However, the massive stacked RBs bring about burdensome memory and computation cost. To tackle this issue, we aim to design an economical structure for adaptively connecting pair-wise RBs, thereby enhancing the model representation. Inspired by the topological structure of lattice filter in signal processing theory, we elaborately propose the lattice block (LB), where couple butterfly-style topological structures are utilized to bridge pair-wise RBs. Specifically, each candidate structure of LB relies on the combination coefficients learned through adaptive channel reweighting. As a basic mapping block, LB can be plugged into various IR models, such as image super-resolution, image denoising, image deraining, etc. It can avail the construction of lightweight IR models accompanying half parameter amount reduced, while keeping the considerable reconstruction accuracy compared with RBs. Moreover, a novel contrastive loss is exploited as a regularization constraint, which can further enhance the model representation without increasing the inference expenses. Experiments on several IR tasks illustrate that our method can achieve more favorable performance than other state-of-the-art models with lower storage and computation.

The visualization of biological sequences with various functional elements is fundamental for the publication of scientific achievements in the field of molecular and cellular biology. However, due to the limitations of the currently used applications, there are still considerable challenges in the preparation of biological schematic diagrams. Here, we present a professional tool called IBS 2.0 for illustrating the organization of both protein and nucleotide sequences. With the abundant graphical elements provided in IBS 2.0, biological sequences can be easily represented in a concise and clear way. Moreover, we implemented a database visualization module in IBS 2.0, enabling batch visualization of biological sequences from the UniProt and the NCBI RefSeq databases. Furthermore, to increase the design efficiency, a resource platform that allows uploading, retrieval, and browsing of existing biological sequence diagrams has been integrated into IBS 2.0. In addition, a lightweight JS library was developed in IBS 2.0 to assist the visualization of biological sequences in customized web services. To obtain the latest version of IBS 2.0, please visit https://ibs.renlab.org.

Infection of Zika virus (ZIKV) may cause microcephaly and other neurological disorders, while no vaccines and drugs are available. Our study revealed that rottlerin confers a broad antiviral activity against several enveloped viruses, including ZIKV, vesicular stomatitis virus, and herpes simplex virus, but not against two naked viruses (enterovirus 71 and encephalomyocarditis virus). Rottlerin does not have a direct virucidal effect on the virions, and its antiviral effect is independent of its regulation on PKCδ or ATP. Both pretreatment and post-treatment of rottlerin effectively reduce the viral replication of ZIKV. The pretreatment of rottlerin disturbs the endocytosis of enveloped viruses, while the post-treatment of rottlerin acts at a late stage through disturbing the maturation of ZIKV. Importantly, administration of rottlerin in neonatal mice significantly decreased the ZIKV replication in vivo, and alleviated the neurological symptoms caused by ZIKV. Our work suggests that rottlerin exerts an antiviral activity at two distinct steps of viral infection, and can be potentially developed as a prophylactic and therapeutic agent.

Background The optimal locoregional treatment for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is unclear. This study aimed to investigate the efficacy of Gamma knife radiosurgery (GKR) versus transcatheter arterial chemoembolization (TACE) in HCC patients with PVTT. Methods This retrospective study included 544 HCC patients with PVTT (GKR, 202; TACE, 342). Propensity score matching (PSM) analysis identified 171 matched pairs of patients. The primary endpoint was overall survival (OS). Results Before PSM, the GKR group exhibited longer median OS (mOS) than the TACE group (17.2 vs. 8.0 months, p p p = 0.001; 14.5 vs. 6.5 months, p = 0.001, respectively) and comparable OS for patients with PVTT I. After PSM, the GKR group had also a longer mOS than the TACE group (15.8 vs. 10.4 months, p p Conclusions GKR was associated better OS than TACE in HCC patients with PVTT, especially for patients with PVTT II-IV. Clinical Trials Registration The study was registered in the Chinese Clinical Trials Registry under the registration number ChiCTR2100051057.