TREM-1 as a potential prognostic biomarker associated with immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: The tumor immune microenvironment plays a crucial role in the efficacy of various therapeutics. However, their correlation is not yet completely understood in Clear cell renal cell carcinoma (ccRCC). This study aimed to investigate the potential of TREM-1 as a potential novel biomarker for ccRCC. METHODS: We constructed a ccRCC immune prognostic signature. The clinical characteristics, the status of the tumor microenvironment, and immune infiltration were analyzed through the ESTIMATE and CIBERSORT algorithms for the hub gene, while the Gene Set Enrichment Analysis and PPI analysis were performed to predict the function of the hub gene. Immunohistochemical staining was used to detect the expression of TREM-1 in renal clear cell carcinoma tissues. RESULTS: The CIBERSORT and ESTIMATE algorithms revealed that TREM-1 was correlated with the infiltration of 12 types of immune cells. Therefore, it was determined that TREM-1 was involved in numerous classical pathways in the immune response via GSEA analysis. In Immunohistochemical staining, we found that the expression of TREM-1 was significantly upregulated with increasing tumor grade in renal clear cell carcinoma, and elevated TREM-1 expression was associated with poor prognosis. CONCLUSIONS: The results suggest that TREM-1 may act as an implicit novel prognostic biomarker in ccRCC that could be utilized to facilitate immunotherapeutic strategy.

Postoperative subacute static progressive stretch does not increase the risk of distal lower limb venous thromboembolism.

PURPOSE: Static progressive stretch (SPS) can be applied to treat chronic joint stiffness. However, the impacts of subacute application of SPS to the distal lower limbs, where deep vein thrombosis (DVT) is common, on venous thromboembolism remain unclear. This study aims to explore the risk of venous thromboembolism events following subacute application of SPS. METHODS: A retrospective cohort study was conducted on patients diagnosed with DVT following a lower extremity orthopedic surgery before being transferred to the rehabilitation ward from May 2017 to May 2022. Patients with unilateral lower limb comminuted para-articular fractures, transferred to rehabilitation ward for further treatment within 3 weeks after operation, followed up more than 12 weeks since initial manual physiotherapy, and diagnosed DVT by ultrasound before rehabilitation course were included in the study. Patients with polytrauma, without evidence of previous peripheral vascular disease or incompetence, had medication for thrombosis treatment or prophylaxis before the operation, detected with paralysis due to nervous system impairment, infected after operation during the regime, or with acute progression of DVT were excluded. The included patients were randomized to the standard physiotherapy and the SPS integrated groups for observation. Associated DVT and pulmonary embolism data were collected during the physiotherapy course to compare the groups. SSPS 28.0 and GraphPad Prism 9 were used for data processing. A p < 0.05 was set significant difference. RESULTS: In total of 154 patients with DVT participating in this study, 75 of them were treated with additional SPS for postoperative rehabilitation. The participants in the SPS group showed improved range of motion (12.3° ± 6.7°). However, in the SPS group, there was no difference in thrombosis volume between the start and termination (p = 0.106, p = 0.787, respectively), although difference was seen intra-therapy (p < 0.001). Contingency analysis revealed the pulmonary embolism incidence (OR = 0.703) in the SPS group compared to the mean physiotherapy. CONCLUSION: The SPS technique is a safe and reliable option to prevent potential joint stiffness without aggravating the risk of distal DVT for postoperative patients suffering from relevant trauma.

Supramolecular polymer gels: from construction methods to functionality.

Supramolecular polymer gels (SPGs) are precisely designed gels brought together by noncovalent interactions to form three-dimensional network structures of polymers. SPGs combine the merits of supramolecular polymers and gels, such as stimuli-responsiveness, self-healing, and self-adaptation, which endows SPGs with potential application value in the fields of biomaterials, etc. Recently, much effort has been made to design new SPGs and related materials with high performance. Herein, we review the research endeavor and future directions of SPGs depending on the construction methods, topological structures, stimuli-responsiveness, and functionality. We hope that the review will provide reference values for the researchers working in supramolecular chemistry and gels.

Crown Ether-Based Supramolecular Polymers: From Synthesis to Self-Assembly.

Supramolecular polymers not only possess many advantages of traditional polymers, but also have many unique characteristics. Supramolecular polymers can be constructed by self-assembly of various noncovalent interactions. Host-guest interaction, as one important type of noncovalent interactions, has been widely applied to construct supramolecular polymers. From the perspective of classification of the recognition system motifs, host-guest recognition motifs mainly include crown ether, cyclodextrin, calixarene, cucurbituril, and pillararene-based host-guest recognition pairs. Crown ethers, as the first-generation macrocyclic hosts, have played a very important part in the development of supramolecular chemistry. Due to the easy modification of crown ethers, various crown ether derivatives have been prepared by attaching some functional groups to the edges of crown ethers, which endowed them with some interesting properties and made them ideal candidates for the fabrication of supramolecular polymers. This review gives a review of the preparation of crown ether-based supramolecular polymers (CSPs) and summarizes crown ether-based recognition pairs, organization methods, topological structures, stimuli-responsiveness, and functional characteristics.

The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas.

BACKGROUND: Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood. METHODS: In this study, we analyzed TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα. Then, we explored the molecular mechanism by which lncRNA HOTAIR regulates PPARα in cell lines in vitro and in a nude mouse glioma model in vivo and explored the effect of the combined application of HOTAIR knockdown and fenofibrate treatment on glioma invasion. RESULTS: For the first time, it was shown that after knockdown of the expression of HOTAIR in gliomas, the expression of PPARα was significantly upregulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both the PPARα agonist fenofibrate and si-HOTAIR, and the results showed that the proliferation and invasion of glioma cells were significantly inhibited. CONCLUSIONS: Our results suggest that HOTAIR can negatively regulate the expression of PPARα and that the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas.

Dopamine receptor D2 on CD4+ T cells is protective against neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease. Recently, neuroinflammation driven by CD4+ T cells has been involved in PD pathophysiology. Human and murine lymphocytes express all the five subtypes of dopamine receptors (DRs), DRD1 to DRD5. However, roles of DRs particularly DRD2 expressed on CD4+ T cells in PD remain elucidated. Global Drd1- or Drd2-knockout (Drd1-/- or Drd2-/-) mice or CD4+ T cell-specific Drd2-knockout (Drd2fl/fl/CD4Cre) mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD with the different mutants. On the 7th day following MPTP injection, mice were assessed for dopaminergic neurodegeneration, locomotor impairments, microglial activation, as well as CD4+ T-cell differentiation and function. Furthermore, in vitro CD4+ T cells were exposed to DRD2 agonist and antagonist and then differentiation and function of the cells were determined. MPTP induced dopaminergic neuronal loss in the nigrostriatal system, motor coordinative and behavioral impairments, microglial activation, and CD4+ T-cell polarization to pro-inflammatory T-helper (Th)1 and Th17 phenotypes. Importantly, either Drd2-/- or Drd2fl/fl/CD4Cre mice manifested more severe dopaminergic neurodegeneration, motor deficits, microglial activation, and CD4+ T-cell bias towards Th1 and Th17 phenotypes in response to MPTP, but Drd1-/- did not further alter MPTP intoxication. DRD2 agonist sumanirole inhibited shift of CD4+ T cells obtained from MPTP-intoxicated mice to Th1 and Th17 phenotypes and DRD2 antagonist L-741,626 reversed sumanirole effects. These findings suggest that DRD2 expressed on CD4+ T cells is protective against neuroinflammation and neurodegeneration in PD. Thus, developing a therapeutic strategy of stimulating DRD2 may be promising for mitigation of PD.

Combination LSD1 and HOTAIR-EZH2 inhibition disrupts cell cycle processes and induces apoptosis in glioblastoma cells.

Glioblastoma (GBM) is the most common primary central nervous system tumor and has a poor prognosis, with a median survival time of only 14 months from diagnosis. Abnormally expressed long noncoding RNAs (lncRNAs) are important epigenetic regulators of chromatin modification and gene expression regulation in tumors, including GBM. We previously showed that the lncRNA HOTAIR is related to the cell cycle progression and can be used as an independent predictor in GBM. Lysine-specific demethylase 1 (LSD1), binding to 3' domain of HOTAIR, specifically removes mono- and di-methyl marks from H3 lysine 4 (H3K4) and plays key roles during carcinogenesis. In this study, we combined a HOTAIR-EZH2 disrupting agent and an LSD1 inhibitor, AC1Q3QWB (AQB) and GSK-LSD1, respectively, to block the two functional domains of HOTAIR and potentially provide therapeutic benefit in the treatment of GBM. Using an Agilent Human ceRNA Microarray, we identified tumor suppressor genes upregulated by AQB and GSK-LSD1, followed by Chromatin immunoprecipitation (ChIP) assays to explore the epigenetic mechanisms of genes activation. Microarray analysis showed that AQB and GSK-LSD1 regulate cell cycle processes and induces apoptosis in GBM cell lines. Furthermore, we found that the combination of AQB and GSK-LSD1 showed a powerful effect of inhibiting cell cycle processes by targeting CDKN1A, whereas apoptosis promoting effects of combination therapy were mediated by BBC3 in vitro. ChIP assays revealed that GSK-LSD1 and AQB regulate P21 and PUMA, respectively via upregulating H3K4me2 and downregulating H3K27me3. Combination therapy with AQB and GSK-LSD1 on tumor malignancy in vitro and GBM patient-derived xenograft (PDX) models shows enhanced anti-tumor efficacy and appears to be a promising new strategy for GBM treatment through its effects on epigenetic regulation.

Inhibition of microRNA-34a Suppresses Epileptiform Discharges Through Regulating Notch Signaling and Apoptosis in Cultured Hippocampal Neurons.

Epilepsy is characterized by recurrent unprovoked seizures and some seizures can cause neuronal apoptosis, which is possible to make contributions to the epilepsy phenotype, impairments in cognitive function or even epileptogenesis. Moreover, many studies have indicated that microRNA-34a (miRNA-34a) is involved in apoptosis through regulating Notch signaling. However, whether miRNA-34a participates in neuronal apoptosis after seizures remain unclear. Therefore, we aimed to explore the expression of miRNA-34a and its effects on the epileptiform discharge in spontaneous recurrent epileptiform discharges (SREDs) rat hippocampal neuronal pattern. Mg2+-free medium was used to induce SREDs, quantitative reverse-transcription polymerase chain reaction was used to detect the expression of miRNA-34a, western blot was used to determine the expression of Notch pathway and apoptosis-related proteins, and whole cell current clamp recordings was used to observe the alteration of epileptiform discharge. We found obvious apoptosis, increased expression of miRNA-34a and decreased expression of Notch signaling in Mg2+-free-treated neurons. Treatment with miRNA-34a inhibitor decreased the frequency of action potentials, activated Notch signaling and prevented neuronal apoptosis in Mg2+-free-treated neurons. However, treatment with miRNA-34a mimics increased the frequency of action potentials, down-regulated Notch signaling and promoted neuronal apoptosis in Mg2+-free-treated neurons. Furthermore, γ-secretase inhibitor N-[N-(3,5-di-uorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT), an inhibitor of Notch signaling, could weaken anti-apoptosis effect of miRNA-34a inhibitor. These results suggest that inhibition of miRNA-34a could suppress epileptiform discharges through regulating Notch signaling and apoptosis in the rat hippocampal neuronal model of SREDs.

Protein kinase C-ε contributes to a chronic inhibitory effect of IL-1ß on voltage-gated sodium channels in mice with febrile seizure.

This study aimed to understand the role of Interleukin-1ß in mouse febrile seizures. To investigate the chronic effects of raised Interleukin-1ß on seizures, the sodium currents of hippocampal neurons were recorded by whole-cell voltage clamp. Interleukin-1ß inhibited sodium currents in mouse hippocampal neurons and verified that protein kinase C epsilon contributed to the effect of Interleukin-1ß exposure. The inhibitory effect was also identified in neurons from a protein kinase C epsilon null mutant mouse. Action potentials were recorded using a ramp depolarizing current. Peak spike depolarization was significantly reduced by Interleukin-1ß treatment, and was abolished following the administration of a protein kinase C epsilon inhibitor, εV1-2. However, neither Interleukin-1ß nor εV1-2 had any significant effect on spike threshold. Interleukin-1ß reduced the amplitude of action potentials due to its inhibitory effect on sodium channels. This is hypothesised to decrease the release of presynaptic transmitters of neuroexcitability, thus exerting a neuroprotective role in excitotoxicity. To ascertain the role of protein kinase C epsilon on febrile seizures in vivo, a heated water-bath model was used to identify susceptible mice. It was found that protein kinase C epsilon reduced susceptibility to, and frequency of, febrile seizure onset. This may be related to the neuroprotective effect of Interleukin-1ß on hippocampal neurons.

The Therapeutic Effect of ICAM-1-Overexpressing Mesenchymal Stem Cells on Acute Graft-Versus-Host Disease.

BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) do not readily migrate to appropriate sites, and this creates a major obstacle for their use in the treatment of graft-versus-host disease (GVHD). Intercellular adhesion molecule-1 (ICAM-1) can guide the homing of various immune cells to the proper anatomical location within secondary lymphoid organs (SLOs), which are the major niches for generating immune responses or tolerance. MSCs rarely migrate to SLOs after intravenous infusion, and are constitutively low expression of ICAM-1. So in our previous work, ICAM-1 was engineered into a murine MSC line C3H10T1/2 by retrovirus transfection system (ICAM-1MSCs). Here, we hypothesized that ICAM-1highMSCs may significantly improve their immunomodulatory effect. METHODS: We used different co-culture methods combined with real-time PCR and flow cytometry to evaluate ICAM-1highMSCs immunomodulatory effect on dendritic cells (DCs) and T cells in vitro and in vivo. MSCs were labeled with carboxyfluorescein diacetate succinimidylester (CFSE) to detect its distribution in mouse model. RESULTS: Our in vitro analyses revealed ICAM-1 MSCs could suppress DCs maturation according to co-culture methods and suppress the T cell immune response according to the mixed lymphocyte response (MLR) and lymphoblast transformation test (LTT) tests. We found that infusion of ICAM-1highMSCs potently prolonged the survival of GVHD mouse model. The infused ICAM-1highMSCs migrate to SLOs in vivo, and suppressed DCs maturation, suppressed CD4+ T cell differentiation to Th1 cells, and increased the ratios of Treg cells. CONCLUSIONS: Taken together, these data demonstrate that ICAM-1highMSCs had an enhanced immunosuppressive effect on DCs and T cells, which may help explain the protective effect in a GVHD model. This exciting therapeutic strategy may improve the clinical efficacy of MSC-based therapy for GVHD.

A Color-Tunable Fluorescent Supramolecular Hyperbranched Polymer Constructed by Pillar[5]arene-Based Host-Guest Recognition and Metal Ion Coordination Interaction.

Fluorescent supramolecular polymers are an important kind of smart material. In this work, a new fluorescent supramolecular hyperbranched polymer (FSHP) is constructed by orthogonal self-assembly: pillararene-based host-guest interaction and metal ion complexation interaction. The FSHP exhibits concentration-controllable fluorescence emissions. The photoluminescence spectra and light-emitting colors of FSHP can be effectively tuned by changing metal ion types or using mixed metal ions. The fluorescence quenching of FSHP solutions or FSHP-based films would occur when removing the metal ions from the backbone of FSHP. This study supplies a convenient approach toward the construction of structure-tunable fluorescent supramolecular materials with different colors.

Evaluation of the Methods to Predict Total Serum Lipids and to Determine 22 POPs in the Serum of Pregnant Women.

The objectives of this study were to determine the suitability of total serum lipid (TSL) concentrations, which were calculated by three different formulae, for pregnant women and to optimize the improved matrix solid-phase dispersion (MSPD) method. The results showed that the TSL predicted by the three formulae were significantly correlated to our measured values (sums of the total cholesterol, triglycerides and phospholipids contents). In particular, one of formulae was the most statistically suitable for pregnant women. Meanwhile, an improved MSPD method was developed to extract 22 POPs. The developed MSPD method was compared with SPE and EPA (8081 & 8082) to evaluate the performance of each extract method. The method validation showed that the results obtained using the improved MSPD method were closest to the actual concentration (adjusted by lipids), and the dispersion of the data was minimal.

Modulation of immune function by glutamatergic neurons in the cerebellar interposed nucleus via hypothalamic and sympathetic pathways.

Our recent work has shown that the cerebellar interposed nucleus (IN) contains glutamatergic neurons that send axons directly to the hypothalamus. In the present study, we aimed to demonstrate modulation of cellular and humoral immunity by glutamatergic neurons in the cerebellar IN by means of gene interventions of glutaminase (GLS), an enzyme for glutamate synthesis, and to reveal pathways transmitting the immunomodulation. Injection of GLS-shRNA lentiviral vector into bilateral cerebellar IN downregulated GLS expression in the IN. The silencing of GLS gene in the cerebellar IN decreased interleukin (IL)-2 and interferon (IFN)-γ production, B-cell number, and IgM antibody level in response to antigen bovine serum albumin (BSA). On the contrary, injection of GLS lentiviral vector into bilateral cerebellar IN upregulated GLS expression in the IN. The GLS gene overexpression in the IN caused opposite immune effects to the GLS gene knockdown. Simultaneously, the GLS gene silencing in the cerebellar IN reduced and the GLS overexpression elevated glutamate content in the hypothalamus, but they both did not affect glycine and GABA contents in the hypothalamus. In addition, the immune changes caused by the GLS gene interventions in the IN were accompanied by alteration in norepinephrine content in the spleen and mesenteric lymph nodes but not by changes in adrenocortical and thyroid hormone levels in serum. These findings indicate that glutamatergic neurons in the cerebellar IN regulate cellular and humoral immune responses and suggest that such immunoregulation may be conveyed by cerebellar IN-hypothalamic glutamatergic projections and sympathetic nerves that innervate lymphoid tissues.

Deciphering ER stress-unfolded protein response relationship by visualizing unfolded proteins in the ER.

Despite the consensus that accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen, i.e. ER stress, activates the unfolded protein response (UPR), studies under physiological and pathophysiological conditions suggest that ER stress may not always trigger the UPR, and the UPR can be activated in an ER stress-independent way. To better understand how the UPR is regulated and its relationship with ER stress requires direct detection of unfolded proteins in the ER, a method that is still lacking. Here, we report a strategy of visualizing unfolded protein accumulation in the ER lumen in living cells by employing an engineered ER stress sensor, PERK, which forms fluorescence puncta upon unfolded protein binding, in a fast and reversible way. Our reporter enables us to clarify the involvement of unfolded proteins in UPR activation under several physiological conditions and suggests that persistent unfolded protein accumulation in the ER despite UPR attenuation predicts cell death.

Bronchial arterial chemoembolization with Drug-Eluting beads plus sequential chemotherapy for the treatment of stage III and IV lung squamous cell carcinoma.

PURPOSE: This retrospective study aimed to investigate the effectiveness and safety of bronchial arterial chemoembolization with drug-eluting beads (DEB-BACE) plus chemotherapy versus chemotherapy alone in patients with stage III and IV lung squamous cell carcinoma (LSCC) who are not appropriate candidates for radiochemotherapy. MATERIALS AND METHODS: In this retrospective analysis, we screened all adult patients undergoing either DEB-BACE plus chemotherapy or chemotherapy alone for stage III or IV LCSS at authors' center from January 2018 to August 2021. Each 21-day chemotherapy cycle consisted of intravenous injection of gemcitabine (1.0 g/m2) on days 1 and 8 and cisplatin 75 (mg/m2) on day 1. The planned cycles were 4. DEB-BACE consisted of microcatheter infusion of CalliSpheres beads carrying cisplatin (75 mg/m2) and gemcitabine (1.0 g/m2), at 3 weeks prior to chemotherapy. The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS), pulmonary response, and adverse events (AEs). RESULTS: The final analysis included 95 patients in the chemotherapy group and 41 patients in the combination treatment group. The median OS was 14 months (95 % CI 11.0-17.0) in the chemotherapy group and 19 months (95 % CI 18.0-24.0) in the combination group (P = 0.015). In multivariate Cox regression analysis, DEB-BACE plus chemotherapy was associated with lower risk of death versus chemotherapy only (HR 0.16, 95 % CI 0.05-0.52; log rank test P = 0.003). The median PFS was 6 months (95 % CI 4.0-7.0) in the chemotherapy group and 8 months (95 % CI 6.0-8.0) in the combination group (P = 0.015). The pulmonary objective response rate (ORR) and disease control rate (DCR) were 48.4 % and 62.1 % in chemotherapy group versus 82.9 % and 90.2 % in combination group (P < 0.001 and = 0.001, respectively). AEs occurred in 133 patients (97.8 %). The rate of bone marrow suppression was 48.4 % (46/95) in the chemotherapy group versus 7.3 % (3/41) in the combination group (P < 0.001). CONCLUSION: Compared with chemotherapy alone, DEB-BACE plus chemotherapy was associated with longer survival outcomes and lower rate of bone marrow suppression.

Cerebellar fastigial nuclear GABAergic projections to the hypothalamus modulate immune function.

Our previous work has shown that the cerebellar fastigial nucleus (FN) is involved in modulation of lymphocyte function. Herein, we investigated effect of FN γ-aminobutyric acid (GABA)-ergic projections to the hypothalamus on lymphocytes to understand pathways and mechanisms underlying cerebellar immunomodulation. By injection of Texas red dextran amine (TRDA), an anterograde tracer, into FN, we found that the TRDA-labeled fibers from the FN traveled through the superior cerebellar peduncle (SCP), crossed in decussation of SCP (XSCP), entered the hypothalamus, and primarily terminated in the lateral hypothalamic area (LHA). Further, by injecting Fluoro-Ruby (FR), a retrograde tracer, in LHA, we observed that the FR-stained fibers retrogradely passed through XSCP and reached FN. Among these FR-positive neurons in the FN, there were GABA-immunoreactive cells. We then microinjected vigabatrin, which is an inhibitor of GABA-transaminase (GABA-T) that degrades GABA, bilaterally into FN. The vigabatrin treatment increased both number of GABA-immunoreactive neurons in FN-LHA projections and GABA content in the hypothalamus. Simultaneously, vigabatrin significantly reduced concanavalin A (Con A)-induced lymphocyte proliferation, anti-sheep red blood cell (SRBC) IgM antibody level, and natural killer (NK) cell number and cytotoxicity. In support of these findings, we inhibited GABA synthesis by using 3-mercaptopropionic acid (3-MP), which antagonizes glutamic acid decarboxylase (GAD). We found that the inhibition of GABA synthesis caused changes that were opposite to those when GABA was increased with vigabatrin. These findings show that the cerebellar FN has a direct GABAergic projection to the hypothalamus and that this projection actively participates in modulation of lymphocytes.

Advances in the study of IL-17 in neurological diseases and mental disorders.

Interleukin-17 (IL-17), a cytokine characteristically secreted by T helper 17 (Th17) cells, has attracted increasing attention in recent years because of its importance in the pathogenesis of many autoimmune or chronic inflammatory diseases. Recent studies have shown that neurological diseases and mental disorders are closely related to immune function, and varying degrees of immune dysregulation may disrupt normal expression of immune molecules at critical stages of neural development. Starting from relevant mechanisms affecting immune regulation, this article reviews the research progress of IL-17 in a selected group of neurological diseases and mental disorders (autism spectrum disorder, Alzheimer's disease, epilepsy, and depression) from the perspective of neuroinflammation and the microbiota-gut-brain axis, summarizes the commonalities, and provides a prospective outlook of target application in disease treatment.

Multistep sequence-controlled supramolecular polymerization by the combination of multiple self-assembly motifs.

The precise sequence control of polymer chain is an important research topic of polymer chemistry. Although some methods such as iterative synthesis and supramolecular polymerization have been developed to fabricate sequence-controllable polymer, it is still a great challenge to consecutively prepare multiple supramolecular polymers with different sequence structures. In this work, through the reasonable utilization of assembly motifs, we integrated multiple host-guest recognitions and metal coordination interactions to prepare different sequence-controlled supramolecular polymers by a multistep assembly strategy. This research provides inspiration for the design and preparation of supramolecular polymers with different sequence structures.

Expression of Concern: Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic agent for noninvasive cancer molecular imaging and drug delivery.

Expression of Concern for 'Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic agent for noninvasive cancer molecular imaging and drug delivery' by Jianxin Liu et al., Biomater. Sci., 2018, 6, 2838-2849, https://doi.org/10.1039/C8BM00726H.

HMGB1 in nervous system diseases: A common biomarker and potential therapeutic target.

High-mobility group box-1 (HMGB1) is a nuclear protein associated with early inflammatory changes upon extracellular secretion expressed in various cells, including neurons and microglia. With the progress of research, neuroinflammation is believed to be involved in the pathogenesis of neurological diseases such as Parkinson's, epilepsy, and autism. As a key promoter of neuroinflammation, HMGB1 is thought to be involved in the pathogenesis of Parkinson's disease, stroke, traumatic brain injury, epilepsy, autism, depression, multiple sclerosis, and amyotrophic lateral sclerosis. However, in the clinic, HMGB1 has not been described as a biomarker for the above-mentioned diseases. However, the current preclinical research results show that HMGB1 antagonists have positive significance in the treatment of Parkinson's disease, stroke, traumatic brain injury, epilepsy, and other diseases. This review discusses the possible mechanisms by which HMGB1 mediates Parkinson's disease, stroke, traumatic brain injury, epilepsy, autism, depression, multiple sclerosis, amyotrophic lateral sclerosis, and the potential of HMGB1 as a biomarker for these diseases. Future research needs to further explore the underlying molecular mechanisms and clinical translation.