Spinal subdural hematoma as a complication of tenecteplase treatment for acute ischemic stroke: A case report.

Intravenous thrombolysis is an effective treatment for acute ischemic stroke. The ESO recommends that tenecteplase be used for thrombolytic therapy in stroke within 4.5h of onset. However, there are few reports on the complications of intravenous thrombolysis with tenecteplase in stroke, and spinal hematomas are rare. Herein, we report the first case of spinal subdural hematoma secondary to tenecteplase treatment for stroke. A 71-year-old male patient arrived at the stroke center because of left limb weakness that had persisted for 105 min. After intravenous thrombolysis with tenecteplase, the patient experienced unbearable pain in the neck and left shoulder, progressive limb weakness, and sensory disturbance. MRI revealed a spinal subdural hematoma of the cervical vertebrae, and the prognosis was poor after surgical treatment. Once patients develop pain around the spine with intravenous thrombolysis, physicians should be aware of the possibility of a spinal subdural hematoma and promptly perform MRI.

Effect of probiotics at different intervention time on glycemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Background: Type 2 diabetes mellitus(T2DM) is characterized by hyperglycemia. Gut microbiome adjustment plays a positive part in glucose regulation, which has become a hotspot. Probiotics have been studied for their potential to control the gut flora and to treat T2DM. However, the conclusion of its glucose-lowering effect is inconsistent based on different probiotic intervention times. Objectives: To comprehensively evaluate how various probiotic intervention times affect glycemic control in people with T2DM. Methods: We retrieved PubMed, Embase, Web of Science, and Cochrane Library on randomized controlled trials(RCTs)regarding the impact of probiotics on glycemic control in patients with T2DM from the inception to November 16, 2023. Separately, two researchers conducted a literature analysis, data extraction, and bias risk assessment of the involved studies. We followed the PRISMA guidelines, used RevMan 5.4 software for meta-analysis, and assessed the risk of bias by applying the Cochrane Handbook for Systematic Reviews 5.1.0. Results: We included eight RCTs with 507 patients. Meta-analysis revealed that the use of probiotics might considerably reduce levels of glycosylated hemoglobin (HbA1c) {mean deviation (MD) = -0.33, 95% confidence interval (CI) (-0.59, -0.07), p = 0.01}, Insulin {standard mean deviation (SMD) = -0.48, 95% CI (-0.74, -0.22), p = 0.0003} and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR){SMD = -1.36, 95% CI (-2.30, -0.41), p = 0.005} than placebo group. No statistically significant differences were found regarding fasting blood glucose (FBG) and body mass index (BMI) {SMD = -0.39, 95% CI (-0.83, 0.05), p = 0.08}, {SMD = -0.40, 95% CI (-1.07, 0.27), p = 0.25}, respectively. Subgroup analyses, grouped by intervention times, showed that six to eight weeks of intervention improved HbA1c compared to the control group (p < 0.05), both six to eight weeks and 12-24 weeks had a better intervention effect on Insulin, and HOMA-IR (p < 0.05).In contrast, there was no statistically significant variation in the length between FBG and BMI regarding duration. Conclusion: This meta-analysis found probiotics at different intervention times play a positive role in modulating glucose in T2DM, specifically for HbA1c in six to eight weeks, Insulin and HOMA-IR in six to eight weeks, and 12-24 weeks. To confirm our findings, further excellent large-sample research is still required. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023483325.

N-octylpyridine hydrogen sulphate ionic liquid for multifunctional fluorescent response in different solvents.

Ionic liquids (ILs) have attracted considerable interest in the last two decades owing to their unique fluorescent properties. Herein, N-octylpyridine hydrogen sulphate ([OP]HSO4) was synthesised and characterised using 1H NMR and infrared spectroscopies. In addition, the fluorescence spectra of [OP]HSO4 in water, methanol, ethanol and acetonitrile were studied. In a single solvent, as the concentration of the solvent (methanol, ethanol or acetonitrile) increases, the fluorescence intensity of the IL first increases and then decreases. A similar trend was observed in their mixed solvents with water. Moreover, the fluorescence intensity of [OP]HSO4 decreases with increasing temperature. A fluorescence intensity reduction of only 4.46% for [OP]HSO4 after continuous scanning for 40 cycles under the maximum excitation state was analysed. The lack of photobleaching observed in [OP]HSO4 indicates its good photobleaching resistance.

Emodin Blocks mPTP Opening and Improves LPS-Induced HMEC-1 Cell Injury by Upregulation of ATP5A1.

BACKGROUND: Emodin has been shown to exert anti-inflammatory and cytoprotective effects. Our study aimed to identify a novel anti-inflammatory mechanism of emodin. METHODS: An LPS-induced model of microvascular endothelial cell (HMEC-1) injury was constructed. Cell proliferation was examined using a CCK-8 assay. The effects of emodin on reactive oxygen species (ROS), cell migration, the mitochondrial membrane potential (MMP), and the opening of the mitochondrial permeability transition pore (mPTP) were evaluated. Actin-Tracker Green was used to examine the relationship between cell microfilament reconstruction and ATP5A1 expression. The effects of emodin on the expression of ATP5A1, NALP3, and TNF-α were determined. After treatment with emodin, ATP5A1 and inflammatory factors (TNF-α, IL-1, IL-6, IL-13 and IL-18) were examined by Western blotting. RESULTS: Emodin significantly increased HMEC-1 cell proliferation and migration, inhibited the production of ROS, increased the mitochondrial membrane potential, and blocked the opening of the mPTP. Moreover, emodin could increase ATP5A1 expression, ameliorate cell microfilament remodeling, and decrease the expression of inflammatory factors. In addition, when ATP5A1 was overexpressed, the regulatory effect of emodin on inflammatory factors was not significant. CONCLUSION: Our findings suggest that emodin can protect HMEC-1 cells against inflammatory injury. This process is modulated by the expression of ATP5A1.

A Ca2+ sensor BraCBL1.2 involves in BraCRa-mediated clubroot resistance in Chinese cabbage.

Clubroot disease caused by Plasmodiophora brassicae (P. brassicae) severely threatens the cultivation of Cruciferous plants, especially Chinese cabbage. Recently, resistance genes in plants have been reported to encode for a Ca2+-permeable channel in the plasma membrane, which can mediate the cytosolic Ca2+ increase in plant cells upon pathogen attack. However, the downstream Ca2+ sensor and decoder are still unknown. In this study, we identified the virulent and avirulent P. brassicae isolates (Pbs) of two near isogenic lines, CR 3-2 and CS 3-2, with CR 3-2 harboring clubroot resistant gene BraCRa. The transcriptomic analysis was then conducted with CR 3-2 after inoculating with virulent isolate PbE and avirulent isolate Pb4. From the differentially expressed genes of transcriptomic data, we identified a Ca2+-sensor encoding gene, BraCBL1.2, that was highly induced in CR 3-2 during infection by Pb4 but not by PbE. Moreover, GUS histochemical staining and subcellular localization analysis revealed that BraCBL1.2 was specifically expressed in the root hair cells of Arabidopsis and encoded a putative Ca2+ sensor localized in the plasma membrane. We also developed an assay to investigate the BraCRa-mediated hypersensitive response (HR) in tobacco leaves. The results suggest that BraCBL1.2 is involved in the BraCRa-mediated plant ETI immune response against P. brassicae. In addition, we verified that overexpression of BraCBL1.2 enhanced clubroot resistance in Arabidopsis. Collectively, our data identified the involvement of a Ca2+ sensor in BraCRa-mediated clubroot resistance in Chinese cabbage, providing a theoretical basis for further research on the resistance of Chinese cabbage to P. brassicae.

Boosted Photocatalytic Performance for Antibiotics Removal with Ag/PW12/TiO2 Composite: Degradation Pathways and Toxicity Assessment.

Photocatalyst is the core of photocatalysis and directly determines photocatalytic performance. However, low quantum efficiency and low utilization of solar energy are important technical problems in the application of photocatalysis. In this work, a series of polyoxometalates (POMs) [H3PW12O40] (PW12)-doped titanium dioxide (TiO2) nanofibers modified with various amount of silver (Ag) nanoparticles (NPs) were prepared by utilizing electrospinning/photoreduction strategy, and were labelled as x wt% Ag/PW12/TiO2 (abbr. x% Ag/PT, x = 5, 10, and 15, respectively). The as-prepared materials were characterized with a series of techniques and exhibited remarkable catalytic activities for visible-light degradation tetracycline (TC), enrofloxacin (ENR), and methyl orange (MO). Particularly, the 10% Ag/PT catalyst with a specific surface area of 155.09 m2/g and an average aperture of 4.61 nm possessed the optimal photodegradation performance, with efficiencies reaching 78.19% for TC, 93.65% for ENR, and 99.29% for MO, which were significantly higher than those of PW12-free Ag/TiO2 and PT nanofibers. Additionally, various parameters (the pH of the solution, catalyst usage, and TC concentration) influencing the degradation process were investigated in detail. The optimal conditions are as follows: catalyst usage: 20 mg; TC: 20 mL of 20 ppm; pH = 7. Furthermore, the photodegradation intermediates and pathways were demonstrated by HPLC-MS measurement. We also investigated the toxicity of products generated during TC removal by employing quantitative structure-activity relationship (QSAR) prediction through a toxicity estimation software tool (T.E.S.T. Version 5.1.2.). The mechanism study showed that the doping of PW12 and the modification of Ag NPs on TiO2 broadened the visible-light absorption, accelerating the effective separation of photogenerated carriers, therefore resulting in an enhanced photocatalytic performance. The research provided some new thoughts for exploiting efficient and durable photocatalysts for environmental remediation.

Insight into the invasion process and immune-protective evaluation of Tp0971, a membrane lipoprotein from Treponema pallidum.

IMPORTANCE: The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum (T. pallidum) subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation "the stealth pathogen." There are many hurdles to studying syphilis pathogenesis, most notably the difficulty of culturing and genetically manipulating T. pallidum, as well as the absence of an effective vaccine for T. pallidum prevention. T. pallidum infection in humans is a complex and lengthy process. In this study, we investigated the invasion process and the function of the infection-dependent antigen Tp0971 as an immunogen to inhibit the dissemination of T. pallidum in an animal infection model. This enables a better understanding of the specific pathogenic mechanism of this pathogen, syphilis pathogenesis, and vaccine research.

Identification of Key Genes and Pathways in the Hippocampus after Traumatic Brain Injury: Bioinformatics Analysis and Experimental Validation.

BACKGROUND: Traumatic brain injury (TBI) is a common brain injury with a high morbidity and mortality. The complex injury cascade triggered by TBI can result in permanent neurological dysfunction such as cognitive impairment. In order to provide new insights for elucidating the underlying molecular mechanisms of TBI, this study systematically analyzed the transcriptome data of the rat hippocampus in the subacute phase of TBI. METHODS: Two datasets (GSE111452 and GSE173975) were downloaded from the Gene Expression Omnibus (GEO) database. Systematic bioinformatics analyses were performed, including differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) network construction, and hub gene identification. In addition, hematoxylin and eosin (HE), Nissl, and immunohistochemical staining were performed to assess the injured hippocampus in a TBI rat model. The hub genes identified by bioinformatics analyses were verified at the mRNA expression level. RESULTS: A total of 56 DEGs were shared in the two datasets. GSEA results suggested significant enrichment in the MAPK and PI3K/Akt pathways, focal adhesion, and cellular senescence. GO and KEGG analyses showed that the common DEGs were predominantly related to immune and inflammatory processes, including antigen processing and presentation, leukocyte-mediated immunity, adaptive immune response, lymphocyte-mediated immunity, phagosome, lysosome, and complement and coagulation cascades. A PPI network of the common DEGs was constructed, and 15 hub genes were identified. In the shared DEGs, we identified two transcription co-factors and 15 immune-related genes. The results of GO analysis indicated that these immune-related DEGs were mainly enriched in biological processes associated with the activation of multiple cells such as microglia, astrocytes, and macrophages. HE and Nissl staining results demonstrated overt hippocampal neuronal damage. Immunohistochemical staining revealed a marked increase in the number of Iba1-positive cells in the injured hippocampus. The mRNA expression levels of the hub genes were consistent with the transcriptome data. CONCLUSIONS: This study highlighted the potential pathological processes in TBI-related hippocampal impairment. The crucial genes identified in this study may serve as novel biomarkers and therapeutic targets, accelerating the pace of developing effective treatments for TBI-related hippocampal impairment.

Effects of acupuncture on microglial polarization and the TLR4/TRIF/MyD88 pathway in a rat model of traumatic brain injury.

OBJECTIVE: Neuroinflammation caused by traumatic brain injury (TBI) can lead to neurological deficits. Acupuncture can inhibit neuroinflammation and promote nerve repair; however, the specific mechanism is still unclear. The purpose of this study was to explore whether acupuncture could modulate the M1 and M2 phenotypic polarization of microglia in a rat model of TBI via the toll-like receptor 4 (TLR4)/intracellular toll-interleukin-1 receptor (TIR) domain-containing adaptor inducing interferon-ß (TRIF)/myeloid differentiation factor 88 (MyD88) pathway. METHODS: A total of 90 adult male Sprague-Dawley (SD) rats, SPF grade, were randomly divided into a normal group, model group and acupuncture group. Each group was further divided into three subgroups (first, third, and fifth day groups) according to the treatment time (n = 10 rats/subgroup). We used the modified neurological severity score (mNSS) method to quantify neurological deficits before and after modeling. We used Nissl staining to observe the pathological changes in brain tissue, flow cytometry to detect the proportion of M1 and M2 polarized microglia in the injured area on the first, third and fifth day, and co-immunoprecipitation (Co-IP) to examine TLR4/TRIF/MyD88 expression in microglia on the first, third and fifth day, as well as expression of the amount of binding of TLR4 with TRIF and MyD88. RESULTS: Compared to the model group, mNSS in the acupuncture group gradually decreased and pathological morphology improved. The proportion of CD11b/CD86 positive cells was decreased, while that of CD11b/CD206 was increased in the acupuncture group. Expression of IP TLR4, IP TRIF and IP MyD88 also decreased in the acupuncture group. CONCLUSION: The results of this study demonstrate that one of the mechanisms through which acupuncture mitigates neuroinflammation and promotes nerve repair in TBI rats may be inhibition of M1 phenotypic polarization and promotion of M2 phenotypic polarization through inhibition of the TLR4/TRIF/MyD88 signaling pathway.

Acupuncture promotes nerve repair through the benign regulation of mTOR-mediated neuronal autophagy in traumatic brain injury rats.

AIMS: Recent investigations have already proved the neuroprotective efficacy of acupuncture in clinical practice in the treatment of neurological diseases, such as traumatic brain injury (TBI). Since growing evidence has suggested that neuronal autophagy was involved in multiple stages of TBI, this study aims to clarify the autophagy mediating mechanism underlying the neuroprotective effect of acupuncture in TBI rats. METHODS: Three experiments were carried out to detect changes in neuronal autophagy and identify the potential molecular mechanism underlying the neuroprotective effect of acupuncture for TBI treatment. Feeney's free-falling epidural impingement method was used to establish the moderate TBI rat model; modified neurological severity scoring (mNSS) was used for neurological recovery evaluation. Nissl and HE staining were used to examine the histopathological changes. Immunofluorescence was used to detect the LC3-positive cell rate. The transmission electron microscope (TEM) was used to investigate the morphology and quantity of autophagosomes. Western blotting was used to determine the protein expressions of LC3, p62, beclin1, mTOR, ULK1, p-mTOR, and p-ULK1. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for gene expressions analysis of LC3 mRNA and p62 mRNA. Co-immunoprecipitation (CO-IP) method was used to identify the protein interaction of mTOR and ULK1. RESULTS: On Day 3 after TBI, acupuncture accelerated the removal of damaged cellular structures by promoting neuronal autophagy; on Day 7 and Day 14 after TBI, acupuncture inhibited neuronal autophagy, preventing excessive autophagy and thus alleviated nerve damage. In addition, the simultaneous treatment with 3-MA or rapamycin at different stages after TBI attenuated the effect of acupuncture. CONCLUSION: Acupuncture has a benign regulatory effect on neuronal autophagy in different stages of TBI, possibly through the mTOR/ULK1 pathway.

Application and the Effect of the Triple Prerehabilitation Nursing Model in the Perioperative Period of Knee Arthroplasty in Diabetic Patients.

Objective: The aim of the study was to explore the application and the effect of the triple prerehabilitation nursing model in the perioperative period of knee arthroplasty in diabetic patients. Methods: The prospectively included 60 patients with diabetes who underwent total knee replacement were admitted from August 2021 to April 2022 and were divided into 2 groups according to the (1 : 1) ratio. The control group was mainly given routine nursing care. On the basis of the control group, the observation group received triple prerehabilitation nursing. The postoperative knee flexion, hospital for the special surgery knee score (HSS), the daily living ability (Barthel) score, the modified fall efficacy scale (MFES) score, the recovery of the lower-limb muscle strength, and the incidence of complications were compared between the two groups. Results: The knee flexion degree and lower-limb muscle recovery of the observation group were better than those of the control group at 3 d, 7 d, and 14 d after operation (P < 0.05). The HSS score, Barthel score, and MFES score of the observation group were higher than those of the control group (P < 0.05). There was no significant difference in postoperative complications between the two groups (P > 0.05). Conclusion: The triple prerehabilitation nursing care for diabetic patients undergoing total knee replacement can promote the recovery of limb function.

The Influence of Acupuncture Parameters on Efficacy and the Possible Use of Acupuncture in Combination with or as a Substitute for Drug Therapy in Patients with Ulcerative Colitis.

Background: Ulcerative colitis (UC) is an inflammatory disease of the colonic mucosa, which is accompanied by chronic, idiopathic characteristics. Acupuncture may be an effective therapy for UC. Here we focused on manual acupuncture and electroacupuncture (MA/EA), two widely used and studied acupuncture interventions, to probe the effects of acupuncture parameters on clinical efficacy in patients with UC and the use of MA/EA alone or with other drugs to support their wider adoption in clinical practice. Methods: The PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure Database, and Wanfang databases were searched from inception to April 27, 2021. Randomized clinical trials (RCTs) published in Chinese or English were included, and subgroup analyses were performed according to acupuncture parameter, acupuncture type, and control medicine type. The risk of bias was assessed using the Cochrane Risk of Bias tool and modified Jadad scale, and Review Manager 5.4 and Stata 14.0 were used to perform a meta-analysis. Sources of heterogeneity were explored; sensitivity analysis was performed; and the GRADE methodology was used to assess the evidence level. Results: Sixteen studies (1454 individuals) were included. Retention of the needle [10-30 minutes (RR 1.18, 95% CI [1.11, 1.26], P < 0.01; heterogeneity: χ 2 = 6.25, df = 6 (P=0.40), I2 = 4%)], the frequency of MA [once every other day (RR 1.21, 95% CI [1.08, 1.35], P < 0.01; heterogeneity: χ 2 = 0.80, df = 1 (P=0.37), I2 = 0%)], and the length of treatment [8 weeks (RR 1.35, 95% CI [1.01, 1.81], P=0.04)] improved clinical efficacy at the end of treatment compared with medications alone. MA (RR 1.18, 95% CI [1.11, 1.25], P < 0.01; heterogeneity: χ 2 = 6.19, df = 7 (P=0.52), I2 = 0%) increased clinical efficacy compared with medications. Furthermore, MA plus medications (RR 1.26, 95% CI [1.13, 1.40], P < 0.01; heterogeneity: χ 2 = 0.95, df = 2 (P=0.62), I2 = 0%) and EA plus medications (RR 1.36, 95% CI [1.13, 1.63], P < 0.01; heterogeneity: χ 2 = 0.13, df = 1 (P=0.72), I2 = 0%) both dramatically improved clinical efficacy. The clinical efficacy of MA plus mesalazine or MA plus metronidazole and sulfasalazine was greater than with mesalazine or metronidazole and sulfasalazine alone. Similarly, EA plus sulfasalazine was more effective than sulfasalazine alone. MA/EA resulted in fewer adverse reactions than medical therapies. The use of MA plus medications significantly reduced Baron scores. GRADE evaluations indicated that the evidence strength was moderate to low but mostly low. Conclusions: Our study provides the latest evidence to allow us to speculate about the possible optimal MA parameters to treat patients with UC. The low number of adverse reactions and high efficacy make MA/EA a possible supplement to or replacement for traditional UC drugs. The variable parameter settings preferred by patients and acupuncturists may be an important factor limiting the wider clinical deployment of acupuncture as a potential UC therapy.

Possible effects of Treponema pallidum infection on human vascular endothelial cells.

Pathogens can affect host cells in various ways, and the same effect can be found in the Treponema pallidum acting on the endothelium of host vessels, and the mechanism is often complex and multiple. Based on the existing T. pallidum of a cognitive framework, the first concerns involving T. pallidum or the bacteria protein directly acted on vascular endothelial cells of the host, the second concerns mainly involved in the process of T. pallidum infection in vivo blood lipid change, secretion of cytokines and the interactions between immune cells indirectly. Through both direct and indirect influence, this study explores the role of host by T. pallidum infect in the process of the vascular endothelium.

Energy Saving and Energy Generation Smart Window with Active Control and Antifreezing Functions.

Windows are the least energy efficient part of the buildings, as building accounts for 40% of global energy consumption. Traditional smart windows can only regulate solar transmission, while all the solar energy on the window is wasted. Here, for the first time, the authors demonstrate an energy saving and energy generation integrated smart window (ESEG smart window) in a simple way by combining louver structure solar cell, thermotropic hydrogel, and indium tin oxides (ITO) glass. The ESEG smart window can achieve excellent optical properties with ≈90% luminous transmission and ≈54% solar modulation, which endows excellent energy saving performance. The outstanding photoelectric conversion efficiency (18.24%) of silicon solar cells with louver structure gives the smart window excellent energy generation ability, which is more than 100% higher than previously reported energy generation smart window. In addition, the solar cell can provide electricity to for ITO glass to turn the transmittance of hydrogel actively, as well as the effect of antifreezing. This work offers an insight into the design and preparation together with a disruptive strategy of easy fabrication, good uniformity, and scalability, which opens a new avenue to realize energy storage, energy saving, active control, and antifreezing integration in one device.

A Biomimetic Approach for Spatially Controlled Cell Membrane Engineering Using Fusogenic Spherical Nucleic Acid.

Engineering of the cell plasma membrane using functional DNA is important for studying and controlling cellular behaviors. However, most efforts to apply artificial DNA interactions on cells are limited to external membrane surface due to the lack of suitable synthetic tools to engineer the intracellular side, which impedes many applications in cell biology. Inspired by the natural extracellular vesicle-cell fusion process, we have developed a fusogenic spherical nucleic acid construct to realize robust DNA functionalization on both external and internal cell surfaces via liposome fusion-based transport (LiFT) strategy, which enables applications including the construction of heterotypic cell assembly for programmed signaling pathway and detection of intracellular metabolites. This approach can engineer cell membranes in a highly efficient and spatially controlled manner, allowing one to build anisotropic membrane structures with two orthogonal DNA functionalities.

A Stable Polyoxometalate-Based Metal-Organic Framework with Active CoMoO4 Layers for Electroreduction and Visible-Light-Driven Water Oxidation.

Polyoxometalate-based MOFs afford a great opportunity in terms of water oxidation. Herein, a new PMOF (SYNU-1) has been constructed with active CoMoO4 layers and TPPE ligands. In SYNU-1, each TPPE ligand bridges eight Co(II) and Mo(VI) cations to give a 3D (3,4,5)-connected (62·83·10)(63)(65·85) framework. SYNU-1 CPE exhibits electroreduction toward nitrite and bromate. Furthermore, SYNU-1 catalyst demonstrates electrocatalytic OER activity with a low overpotential of 364 mV. Strikingly, the heterogeneous catalyst SYNU-1 shows a high O2 yield (79.05%) for visible light water oxidation with good stability and reusability.

Characterization of a pathogenic variant in GBA for Parkinson's disease with mild cognitive impairment patients.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and mild cognitive impairment (MCI) is a well-established risk factor for the development of dementia in PD. A growing body of evidence suggests that low expression of glucocerebrosidase (GBA) promotes the transmission of α-synuclein (α-Syn) interpolymers and the progression of PD. However, how GBA mutations affect the pathogenesis of PD via abnormal aggregation of α-Syn is unclear, and no clinically valid PD-MCI genetic markers have been identified. Here, we first located a GBA eQTL, rs12411216, by analysing DHS, eQTL SNP, and transcription factor binding site data using the UCSC database. Subsequently, we found that rs12411216 was significantly associated with PD-MCI (P < 0.05) in 306 PD patients by genotyping. In exploring the relationship between rs12411216 and GBA expression, the SNP was found to be associated with GBA expression in 50 PD patients through qPCR verification. In a further CRISPR/Cas9-mediated genome editing module, the SNP was identified to cause a decrease in GBA expression, weaken enzymatic activity and enhance the abnormal aggregation of α-Syn in SH-SY5Y cells. Additionally, using an electrophoretic mobility shift assay, we confirmed that the binding efficiency of transcription factor E2F4 was affected by the rs12411216 SNP. In conclusion, our results showed that rs12411216 regulated GBA expression, supporting its potential role as a PD-MCI genetic biomarker and highlighting novel mechanisms underlying Parkinson's disease.

Engineering Functional DNA-Protein Conjugates for Biosensing, Biomedical, and Nanoassembly Applications.

DNA and protein are the most important two classes of biomacromolecules forming the basis of life. The conjugation of the two using crosslinking chemistries enables a combination of molecular recognition, enzymatic catalysis, and Watson-Crick hybridization properties. The DNA-protein conjugate with combined properties enables a broad range of applications, such as sensitive and selective bioassays, therapeutic agents, and building blocks for programmable nanoassemblies. In this review, we survey the conjugates from the aspects of conjugation chemistries as well as applications in biomedical and nanotechnology fields. We highlight the functions of both biological moieties of a conjugate for target binding and signal transduction in bioassays. We also review the use of DNA-protein conjugates for the construction of a variety of functional and dynamic nanostructures, from isolated hybrid cages to three-dimensional (3D) protein crystalline lattices. Moreover, these conjugates have been used as carriers to deliver enzymes or functional nucleic acids for disease treatments and gene editing.

One-dimensional co-crystallized coordination polymers showing reversible mechanochromic luminescence: cation-anion interaction directed rapid self-recovery.

Three one-dimensional (1D) chain polymers (1D-9HAC, 1D-Cd-9AC, and 1D-Cd-9AC-HBIM) that exhibit different intermolecular interactions and stacking patterns have been designed and synthesized. Only 1D-Cd-9AC-HBIM with rigid (anion) and flexible (cation) units alternately arranged exhibits mechanochromic luminescence, which can be recovered through rapid solvent treatment or a self-recovery process.

Three resorcin[4]arene-based lanthanide-coordination polymers with multifunctional photoluminescence sensing properties.

By utilizing a novel octacarboxylate-functionalized resorcin[4]arene as organic linkers, three lanthanide-coordination polymers, namely, [(CH3)2NH2][Ln2(HL)(H2O)7]·2H2O (Ln = Tb (1), Eu (2) and Gd (3), H8L = 2,8,14,20-tetra-pentyl-4,6,10,12,16,18,22,24-octa-carboxymethoxy-resorcin[4]arene) have been solvothermally synthesized and structurally characterized. Isostructural 1-3 display unique two dimensional sandwich-based layers built with Ln3+ cations and bowl-shaped HL7- anions. Remarkably, 1 and 2 produce intensive green and red emissions respectively and long lifetimes thanks to the antenna effect of HL7- anions. The energy level testing of 3 indicates that the newly designed ligand H8L has a very efficient intersystem crossing process. More importantly, luminescent investigations reveal that 1 and 2 can selectively detect N,N'-dimethylformamide and Fe3+ ions with turn-on-type and turn-off-type responses, respectively.