Regulating Second Coordination Shell of Ce Atom Site and Reshaping of Carrier Enable Single-Atom Nanozyme to Efficiently Express Oxidase-like Activity.

Single-atom nanozymes (SANs) are considered to be ideal substitutes for natural enzymes due to their high atom utilization. This work reported a strategy to manipulate the second coordination shell of the Ce atom and reshape the carbon carrier to improve the oxidase-like activity of SANs. Internally, S atoms were symmetrically embedded into the second coordination layer to form a Ce-N4S2-C structure, which reduced the energy barrier for O2 reduction, promoted the electron transfer from the Ce atom to O atoms, and enhanced the interaction between the d orbital of the Ce atom and p orbital of O atoms. Externally, in situ polymerization of mussel-inspired polydopamine on the precursor helps capture metal sources and protects the 3D structure of the carrier during pyrolysis. On the other hand, polyethylene glycol (PEG) modulated the interface of the material to enhance water dispersion and mass transfer efficiency. As a proof of concept, the constructed PEG@P@Ce-N/S-C was applied to the multimodal assay of butyrylcholinesterase activity.

Recent Research on Iridium-Based Electrocatalysts for Acidic Oxygen Evolution Reaction from the Origin of Reaction Mechanism.

As the anode reaction of proton exchange membrane water electrolysis (PEMWE), the acidic oxygen evolution reaction (OER) is one of the main obstacles to the practical application of PEMWE due to its sluggish four-electron transfer process. The development of high-performance acidic OER electrocatalysts has become the key to improving the reaction kinetics. To date, although various excellent acidic OER electrocatalysts have been widely researched, Ir-based nanomaterials are still state-of-the-art electrocatalysts. Hence, a comprehensive and in-depth understanding of the reaction mechanism of Ir-based electrocatalysts is crucial for the precise optimization of catalytic performance. In this review, the origin and nature of the conventional adsorbate evolution mechanism (AEM) and the derived volcanic relationship on Ir-based electrocatalysts for acidic OER processes are summarized and some optimization strategies for Ir-based electrocatalysts based on the AEM are introduced. To further investigate the development strategy of high-performance Ir-based electrocatalysts, several unconventional OER mechanisms including dual-site mechanism and lattice oxygen mediated mechanism, and their applications are introduced in detail. Thereafter, the active species on Ir-based electrocatalysts at acidic OER are summarized and classified into surface Ir species and O species. Finally, the future development direction and prospect of Ir-based electrocatalysts for acidic OER are put forward.

Bergaptol inhibits glioma cell proliferation and induces apoptosis via STAT3/Bcl-2 pathway.

Glioblastoma (GBM) is the most common primary malignant brain tumour and lacks therapeutic options with significant effects. The aberrant activation of STAT3 is a critical factor in glioma progression via activating multiple signalling pathways that promote glioma. Among them, the antiapoptotic gene Bcl-2 could be upregulated by p-STAT3, which is an important reason for the continuous proliferation of glioma. We previously reported that bergaptol, a natural furanocoumarin widely found in citrus products, exerts antineuroinflammatory effects by inhibiting the overactivation of STAT3. Here, we aimed to evaluate whether bergaptol could promote glioma apoptosis by inhibiting the STAT3/Bcl-2 pathway. This study found that bergaptol inhibited the proliferation and migration of GBM cell lines (U87 and A172) and promoted apoptosis in vitro. We also found that bergaptol significantly inhibited the STAT3/Bcl-2 pathway in GBM cells. U87 cells were implanted intracranially into nude mice to establish a glioma model, and glioma-bearing mice were treated with bergaptol (40 mg/kg). Bergaptol treatment significantly inhibited glioma growth and prolonged the glioma-bearing mice's survival time. In addition, bergaptol administration also significantly inhibited the STAT3/Bcl-2 pathway of tumour tissue in vivo. Overall, we found that bergaptol could effectively play an antiglioma role by inhibiting STAT3/Bcl-2 pathway, suggesting the potential efficacy of bergaptol in treating glioma.

MicroRNA-124 conducts neuroprotective effect via inhibiting AK4/ATF3 after subarachnoid hemorrhage.

Spontaneous subarachnoid hemorrhage (SAH) accounts for approximately 5% of all cases of stroke. SAH is correlated with elevated rates of mortality and disability. Despite significant advancements in comprehending the pathogenesis and surgical management, efficacious clinical interventions remain restricted, and the prognosis is yet to be enhanced. MicroRNAs play a crucial role in various pathological processes in organisms. Revealing these regulatory processes is conducive to the development of new treatment methods. MicroRNA-124 is highly expressed in the nervous system and has significant research value for SAH. This study aims to explore the role of miR-124 in the early post-SAH period on neural function and verify whether it is involved in the pathological and physiological processes of SAH. In this study, we used methods such as comparing the expression levels of miR-124 in cerebrospinal fluid, establishing a rat SAH model, and a mouse embryonic primary neuron hemoglobin stimulation model to verify the downstream proteins of miR-124 in SAH. Through transfection techniques, we adjusted the expression of this small RNA in Vitro and in Vivo models using miR-124 inhibitor and mimic in the primary neuron hemoglobin stimulation model and rat SAH model, and observed the phenotype. Finally, by consulting the literature and verifying in Vivo and in Vitro methods, AK4 and downstream molecule ATF3 were identified as downstream targets of miR-124.

Terahertz fingerprint reveals the effect of alcohols on sodium ions hydration shell.

Ion hydration plays a crucial role in numerous fundamental processes. Various spectroscopic methods are employed to investigate the slowing down of hydration bond dynamics in the proximity of both anions and cations. To date, most of these studies have primarily focused on the properties of binary systems. However, in comparison to ion-water binary systems, ternary systems that involve ions, water, and organic matter are more prevalent in nature and provide more realistic insights into biological processes. This study focuses on ion hydration in water and alcohol mixture using terahertz spectroscopy and x-ray diffraction (XRD). The results reveal a distinct behavior depending on the type of alcohol used. Specifically, the presence of both methanol and ethanol results in the disappearance of absorption peaks associated with NaCl hydrate at low temperatures. In contrast, tert-butanol does not exhibit such an effect, and isopropanol demonstrates a more complex response. By combining these terahertz spectroscopic findings with low-temperature XRD data, we gain insights into the formation, or lack thereof, of NaCl · 2H2O hydrate crystals. Crucially, our observations suggest a dominant correlation between the polarity of the alcohol molecules and its impact on the Na+ hydration. Strongly polar alcohols preferentially solvating the Na+ ion lead to the failure of hydrate formation, while weakly polar alcohols do not have this effect.

The Necessity or Not of Additional Endovascular Therapy to Medical Therapy for Symptomatic Intracranial Artery Stenosis: Insights from 30-Day and 1-Year Results.

BACKGROUND: The optimal treatment between endovascular therapy and medical treatment for symptomatic intracranial artery stenosis is still unclear. This study aimed to compare the safety and efficacy of 2 treatments based on the results from currently published randomized controlled trials (RCTs). METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science were used for searching the RCTs evaluating the addition of endovascular therapy to medical therapy for treating symptomatic intracranial artery stenosis from the inception of these databases to September 30, 2022. P < 0.05 was considered statistically significant. All analyses were performed using STATA version 12.0. RESULTS: A total of 4 RCTs were involved in the current study, including 989 participants. In the 30-day results, the data showed that compared with the medical therapy alone group, the additional endovascular therapy group was associated with a higher risk of death or stroke (relative risk (RR): 2.857; 95% confidence interval (CI): 1.756-4.648; P < 0.001), ipsilateral stroke (RR: 3.525; 95% CI: 1.969-6.310; P < 0.001), death (risk differences (RD): 0.01; 95% CI: 0.004-0.03; P = 0.015), hemorrhagic stroke (RD: 0.03; 95% CI: 0.01-0.06; P < 0.001), and ischemic stroke (RR: 2.221; 95% CI: 1.279-3.858; P = 0.005). In the 1-year results, the additional endovascular therapy group was related to a greater incidence of ipsilateral stroke (RR, 2.247; 95% CI, 1.492-3.383; P < 0.001) and ischemic stroke (RR: 2.092; 95% CI: 1.270-3.445; P = 0.004). CONCLUSIONS: Given that the medical treatment alone was related to a lower risk of stroke and death in the short-term and long-term compared with endovascular therapy combined with medical therapy. Based on this evidence, these findings do not support the addition of endovascular therapy to medical therapy for treating patients with symptomatic intracranial stenosis.

Transcription factor OsWRKY11 induces rice heading at low concentrations but inhibits rice heading at high concentrations.

The heading date of rice is a crucial agronomic characteristic that influences its adaptability to different regions and its productivity potential. Despite the involvement of WRKY transcription factors in various biological processes related to development, the precise mechanisms through which these transcription factors regulate the heading date in rice have not been well elucidated. The present study identified OsWRKY11 as a WRKY transcription factor which exhibits a pivotal function in the regulation of the heading date in rice through a comprehensive screening of a clustered regularly interspaced palindromic repeats (CRISPR) ‒ CRISPR-associated nuclease 9 mutant library that specifically targets the WRKY genes in rice. The heading date of oswrky11 mutant plants and OsWRKY11-overexpressing plants was delayed compared with that of the wild-type plants under short-day and long-day conditions. Mechanistic investigation revealed that OsWRKY11 exerts dual effects on transcriptional promotion and suppression through direct and indirect DNA binding, respectively. Under normal conditions, OsWRKY11 facilitates flowering by directly inducing the expression of OsMADS14 and OsMADS15. The presence of elevated levels of OsWRKY11 protein promote formation of a ternary protein complex involving OsWRKY11, Heading date 1 (Hd1), and Days to heading date 8 (DTH8), and this complex then suppresses the expression of Ehd1, which leads to a delay in the heading date. Subsequent investigation revealed that a mild drought condition resulted in a modest increase in OsWRKY11 expression, promoting heading. Conversely, under severe drought conditions, a significant upregulation of OsWRKY11 led to the suppression of Ehd1 expression, ultimately causing a delay in heading date. Our findings uncover a previously unacknowledged mechanism through which the transcription factor OsWRKY11 exerts a dual impact on the heading date by directly and indirectly binding to the promoters of target genes.

Toll-like receptor 4-mediated microglial inflammation exacerbates early white matter injury following experimental subarachnoid hemorrhage.

Neuroinflammation has been reported to be associated with white matter injury (WMI) after subarachnoid hemorrhage (SAH). As the main resident immune cells of the brain, microglia can be activated into proinflammatory and anti-inflammatory phenotypes. Toll-like receptor 4 (TLR4), expressed on the surface of the microglia, plays a key role in microglial inflammation. However, the relationship between TLR4, microglial polarization, and WMI following SAH remains unclear. In this study, a total of 121 male adult C57BL/6 wild-type (WT) mice, 20 WT mice at postnatal day 1 (P1), and 41 male adult TLR4 gene knockout (TLR4-/-) mice were used to investigate the potential role of TLR4-induced microglial polarization in early WMI after SAH by radiological, histological, microstructural, transcriptional, and cytological evidence. The results indicated that microglial inflammation was associated with myelin loss and axon damage, shown as a decrease in myelin basic protein (MBP), as well as increase in degraded myelin basic protein (dMBP) and amyloid precursor protein (APP). Gene knockout of TLR4 revised microglial polarization toward the anti-inflammatory phenotype and protected the white matter at an early phase after SAH (24 h), as shown through reduction of toxic metabolites, preservation of myelin, reductions in APP accumulation, reductions in white matter T2 hyperintensity, and increases in FA values. Cocultures of microglia and oligodendrocytes, the cells responsible for myelin production and maintenance, were established to further elucidate the relationship between microglial polarization and WMI. In vitro, TLR4 inhibition decreased the expression of microglial MyD88 and phosphorylated NF-κB, thereby inhibiting M1 polarization and mitigating inflammation. Decrease in TLR4 in the microglia increased preservation of neighboring oligodendrocytes. In conclusion, microglial inflammation has dual effects on early WMI after experimental SAH. Future explorations on more clinically relevant methods for modulating neuroinflammation are warranted to combat stroke with both WMI and gray matter destruction.

Long non-coding RNA MIR17HG impedes FOSL2-mediated transcription activation of HIC1 to maintain a pro-inflammatory phenotype of microglia during intracerebral haemorrhage.

Activation and polarization of microglia play decisive roles in the progression of intracerebral haemorrhage (ICH), and lactate exposure correlates with microglia polarization. This study explores molecules influencing lactate production and microglia phenotype alteration following ICH. A murine model of ICH was induced by intracerebral injection of collagenase. The mice experienced autonomous neurological function recovery, haematoma resolution and rapid lactate production, along with a gradual increase in angiogenesis activity, neuronal recovery and an M1-to-M2 phenotype change of microglia. Galloflavin, a lactate dehydrogenase antagonist, suppressed this phenotype change and the functional recovery in mice. FOS like 2 (FOSL2) was significantly upregulated in the brain tissues from day 7 post-ICH. Overexpression of FOSL2 induced an M1-to-M2 phenotype shift in microglia and accelerated lactate production in vivo and in haemoglobin-treated microglia in vitro. Long non-coding RNA MIR17HG impeded FOSL2-mediated transcription activation of hypermethylated in cancer 1 (HIC1). MIR17HG overexpression induced pro-inflammatory activation of microglia in mice, which was blocked by further HIC1 overexpression. Overall, this study demonstrates that MIR17HG maintains a pro-inflammatory phenotype of microglia during ICH progression by negating FOSL2-mediated transcription activation of HIC1. Specific inhibition of MIR17HG or upregulation of FOSL2 or HIC1 may favour inflammation inhibition and haematoma resolution in ICH.

Biocompatible Fluorescent Biosensor Reveals the Level and Distribution of Indole-3-Acetic Acid Signals in Plants.

To fully understand the function of the phytohormone indole-3-acetic acid (IAA) in regulating plant growth and development, we need to monitor their levels and distribution with high spatial and temporal resolution. In this work, an anthracene-based fluorescent biosensor for IAA was prepared using bovine serum albumin (BSA) as a bio-template. The single linear oxygen (1O2) specifically produced by IAA catalyzed with horseradish peroxidase (HRP) turns on the fluorescence of the probe, enabling specific trace sensing of IAA in the presence of multiple structural analogues. The presence of the bio-template BSA extends the biocompatibility of the probe, enabling visual monitoring of the level and distribution signal of endogenous IAA of plants in the field of bioimaging. In addition, the strategy has shown potential for application in portable paper-based sensors and in vivo fluorescent flower culture. This work provides a technical and theoretical basis for exploring the growth regulatory mechanisms of IAA in plants at the molecular level.

Quantitative Cerebral Blood Volume Image Synthesis from Standard MRI Using Image-to-Image Translation for Brain Tumors.

Background Cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast-enhanced (DSC) MRI are useful but not commonly available in clinical scenarios. Purpose To test image-to-image translation techniques for generating CBV maps from standard MRI sequences of brain tumors using the bookend technique DSC MRI as ground-truth references. Materials and Methods A total of 756 MRI examinations, including quantitative CBV maps produced from bookend DSC MRI, were included in this retrospective study. Two algorithms, the feature-consistency generative adversarial network (GAN) and three-dimensional encoder-decoder network with only mean absolute error loss, were trained to synthesize CBV maps. The performance of the two algorithms was evaluated quantitatively using the structural similarity index (SSIM) and qualitatively by two neuroradiologists using a four-point Likert scale. The clinical value of combining synthetic CBV maps and standard MRI scans of brain tumors was assessed in several clinical scenarios (tumor grading, prognosis prediction, differential diagnosis) using multicenter data sets (four external and one internal). Differences in diagnostic and predictive accuracy were tested using the z test. Results The three-dimensional encoder-decoder network with T1-weighted images, contrast-enhanced T1-weighted images, and apparent diffusion coefficient maps as the input achieved the highest synthetic performance (SSIM, 86.29% ± 4.30). The mean qualitative score of the synthesized CBV maps by neuroradiologists was 2.63. Combining synthetic CBV with standard MRI improved the accuracy of grading gliomas (standard MRI scans area under the receiver operating characteristic curve [AUC], 0.707; standard MRI scans with CBV maps AUC, 0.857; z = 15.17; P < .001), prediction of prognosis in gliomas (standard MRI scans AUC, 0.654; standard MRI scans with CBV maps AUC, 0.793; z = 9.62; P < .001), and differential diagnosis between tumor recurrence and treatment response in gliomas (standard MRI scans AUC, 0.778; standard MRI scans with CBV maps AUC, 0.853; z = 4.86; P < .001) and brain metastases (standard MRI scans AUC, 0.749; standard MRI scans with CBV maps AUC, 0.857; z = 6.13; P < .001). Conclusion GAN image-to-image translation techniques produced accurate synthetic CBV maps from standard MRI scans, which could be used for improving the clinical evaluation of brain tumors. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Branstetter in this issue.

Kinetic-Modulated Crystal Phase of Ru for Hydrogen Oxidation.

Crystal-phase-engineering provides a powerful strategy for regulating the catalytic performance yet remains great challenge. Herein, the kinetic-modulated crystal-phase-control of Ru nanosheet assemblies (Ru NAs) is demonstrated by simply altering the concentration of citric acid (CA). Detailed experimental results reveal that high concentration of CA retards the growth kinetics and thus leads to the formation of metastable face-centered cubic (fcc) Ru NAs, while low concentration of CA results in the fast growth kinetics and the preferential formation of Ru NAs with stable hexagonal close packed (hcp) phase. Moreover, Ru NAs with different phases are used as catalyst for hydrogen oxidation reaction (HOR) to evaluate the effects of crystal phase on catalytic performance. Impressively, Ru NAs with fcc phase display a mass activity of 2.75 A mgRu -1 at 50 mV, which is much higher than those of Ru NAs with fcc/hcp (1.02 A mgRu -1 ) and hcp (0.74 A mgRu -1 ) phases. Theoretical calculations show that fcc Ru NAs display weaker adsorption toward * H and lower energy barrier toward the rate-determining step (RDS) during HOR. This work provides a facile strategy for regulating the crystal phase of Ru nanocrystals, which may attract rapid interests of researchers in materials, chemistry, and catalysis.

Ratiometric luminescent sensor based on BSA-coated gold/silver nanoclusters for the selective determination and spatiotemporal imaging of gallic acid in plants.

A new fluorescence sensing strategy has been developed. Four bimetallic nanoclusters, gold/silver, gold/copper, gold/molybdenum and gold/cobalt, were prepared using bovine serum albumin (BSA) as a reducing and stabilizing agent. The fluorescence properties of four nanoclusters were explored by solid-state UV and XPS. The gold/silver nanoclusters (BSA-Au/Ag NCs) with the best ratiometric fluorescence properties for gallic acid (GA) in plants were selected to realize the sensitive detection of GA. GA affected the conformation of BSA, thereby disrupting the luminescent environment of the nanoclusters, resulting in a pronounced fluorescence quenching at 566 nm. The ratiometric fluorescence signal (I566/I453) was used for trace detection of GA in plants. It has a wide response range of 1.25-40.0 µM and a low detection limit of 45.27 nM. GA was detected at 19.49 µM in the plant extract, and the spiked recoveries ranged from 96.09 to 104.6%. In addition, due to the non-toxic and biocompatible properties of BSA, BSA-Au/Ag NCs have also been validated for fluorescence imaging of plant tissues. It realized the comparison of GA content in different parts of plants and the difference of GA content in plants after abiotic stress. Therefore, the developed strategy offers potential application for the analytical study of active substances in plants.

Biocompatible Abscisic Acid-Sensing Supramolecular Hybridization Probe for Spatiotemporal Fluorescence Imaging in Plant Tissues.

Achieving detection of the phytohormone abscisic acid (ABA) is of critical importance for understanding plant growth and development. We report a hybrid supramolecular fluorescent probe that uses bovine serum albumin (BSA) as a host. Aggregation-induced emission of fluorescent chromophores (AIEgens) enables luminescence in the presence of BSA. ABA and its aptamer act as a switch to trigger this fluorescent system, the strategy that exhibits high sensitivity to abscisic acid with a detection limit of 0.098 nM. The probe test strip also enables visualization of ABA content from plants by colorimetric observation with the naked eye. In particular, the high biocompatibility and small molecular size of the prepared fluorescent probe allow for effective monitoring of ABA in plant tissues by fluorescence imaging. This strategy provides a new perspective to achieve the detection of endogenous and exogenous ABA in plants and has important implications for plant biology research.

Reduced PTCH2 expression is associated with glioma development through its regulation of the PTEN/AKT signaling pathway.

Mutations in the human protein patched homolog (PTCH) gene have been demonstrated to be associated with cancer development in several types of malignancy. However, the underlying mechanism of PTCH-associated cancer development remains poorly understood, to the best of our knowledge. In the present study, the expression of PTCH2 in glioma tumor tissues from The Cancer Genome Atlas (TCGA) database and clinical patients with glioma were measured. Reduced expression levels of PTCH2 were observed in patients with glioma with poor prognose. In vitro, overexpression of PTCH2 significantly suppressed the proliferation and invasion of the glioma cell lines, LN229 and U87-MG. Mechanistically, PTCH2 upregulated the expression of tumor suppressor PTEN, thereby leading to the suppression of pro-survival AKT signals in glioma. Reduced expression of PTEN and enhanced expression of AKT promoted glioma development in vitro and in vivo. Blockade of PTCH2/AKT signals efficiently strengthened the anticancer effects of chemotherapy and prolonged the survival time in tumor-bearing mice, which provided a novel insight into potential treatment strategies for glioma in the clinic.

PDIA4 promotes glioblastoma progression via the PI3K/AKT/m-TOR pathway.

Protein disulfide isomerase A4 (PDIA4) is highly expressed in clear cell ovarian carcinoma and lung cancer. Through analysis of TCGA database and CGGA database, we noted that PDIA4 is a key promotor of glioblastoma (GBM). However, the detailed role and molecular mechanism of PDIA4 in GBM remain unclear. In this study, the expression pattern and biological role of PDIA4 in GBM was investigated. PDIA4 was overexpressed in GBM tumor samples and cell lines and positively correlated with pathological grades in glioma patients. In addition, downregulation of PDIA4 promoted apoptosis and inhibited proliferation of GBM. Meanwhile, there was a concurrent decrease in aerobic glycolysis metabolites. Mechanistically, PDIA4 downregulation promoted the apoptosis of GBM cells by increased the expression of apoptosis pathway proteins (caspase 3, caspase 9 and Bax). Downregulation of PDIA4 decreased energy demand and inhibited GBM growth in vitro and in vivo. Besides, such effect also inhibited the PI3K/AKT/m-TOR pathway by inhibiting protein phosphorylation levels of PI3K, AKT and m-TOR. After addition of PI3K/AKT/mTOR pathway activator 740Y-P, the effect of PDIA4 knockdown on GBM was reversed. Therefore, we believe that PDIA4 regulates the proliferation via activating the PI3K/AKT/m-TOR pathway and suppression of apoptosis in glioblastoma. It could be used as a potential target for the treatment of GBM.

Arabidopsis SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2 inhibit WRKY75 function in abscisic acid-mediated leaf senescence and seed germination.

The plant-specific VQ gene family participates in diverse physiological processes but little information is available on their role in leaf senescence. Here, we show that the VQ motif-containing proteins, Arabidopsis SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2 are negative regulators of abscisic acid (ABA)-mediated leaf senescence. Loss of SIB1 and SIB2 function resulted in increased sensitivity of ABA-induced leaf senescence. In contrast, overexpression of SIB1 significantly delayed this process. Moreover, biochemical studies revealed that SIBs interact with WRKY75 transcription factor. Loss of WRKY75 function decreased sensitivity to ABA-induced leaf senescence, while overexpression of WRKY75 significantly accelerated this process. Chromatin immunoprecipitation assays revealed that WRKY75 directly binds to the promoters of GOLDEN 2-LIKE1(GLK1) and GLK2, to repress their expression. SIBs repress the transcriptional function of WRKY75 and negatively regulate ABA-induced leaf senescence in a WRKY75-dependent manner. In contrast, WRKY75 positively modulates ABA-mediated leaf senescence in a GLK-dependent manner. In addition, SIBs inhibit WRKY75 function in ABA-mediated seed germination. These results demonstrate that SIBs can form a complex with WRKY75 to regulate ABA-mediated leaf senescence and seed germination.

Monitoring MgCl2 hydrate formation from aqueous solutions using terahertz time-domain spectroscopy.

The interaction of MgCl2 with H2O is heavily involved in biological and chemical processes. In this work, freezing-induced hydrate formation from MgCl2 aqueous solution was monitored using terahertz time-domain spectroscopy. At low temperatures, two phase transitions from brine to hydrate formation could be clearly observed, and the formation of hydrate was accompanied by the emergence of new THz fingerprint peaks at 1.02, 1.56, and 1.84 THz, respectively. Integrating XRD and quantum chemical calculations, we attributed the absorption peaks to the vibrational modes of the formed MgCl2·12H2O. This demonstrates the potential of THz spectroscopy for application in the detection of biological processes in low-temperature environments, such as cell freezing.

Folate-grafted glycyl-glycine-melphalan conjugate self-assembled amphilphilc nanomicelles augmented drug delivery, cytotoxicity and cellular uptake in human ovarian cancer cells.

OBJECTIVES: Folic acid was coupled to melphalan using glycyl-glycine (FA-Gly-Gly-Melphalan) to synthesise self-assembled nanomicelles for targeting ovarian cancer cells, SKOV3. METHODS AND RESULTS: FA-Gly-Gly-Melphalan self-assembled nanomicelles were prepared with critical micellar concentration (CMC) of 12-µg/ml. The mean particle size of FA-Gly-Gly-Melphalan self-assembled nanomicelles was measured to be 95.9 ± 3.4-nm significantly (p < 0.05) higher than 73.8 ± 6.3-nm of Gly-Gly-Melphalan self-assembled nanomicelles. Subsequently, zeta-potential of FA-Gly-Gly-Melphalan self-assembled nanomicelles was estimated to be -28.0 ± 1.5-mV significantly (p < 0.05) lower than -36.6 ± 2.7-mV of Gly-Gly-Melphalan self-assembled nanomicelles. The IC50 of FA-Gly-Gly-Melphalan self-assembled nanomicelles was estimated to be 4.1-µg/ml significantly (p < 0.001) lower than 14.2-µg/ml of Gly-Gly-Melphalan self-assembled nanomicelles and >18-µg/ml of melphalan. FA-Gly-Gly-Melphalan self-assembled nanomicelles preferentially accumulated in cytoplasm of SKOV3 cells nearby nucleus via receptor mediated endocytosis pathway after 24-h of incubation period, whilst Gly-Gly-Melphalan self-assembled nanomicelles were not incorporated sufficiently. CONCLUSION: FA-Gly-Gly-Melphalan self-assembled nanomicelles warrant in depth in vivo study for their safety, efficacy, and potency in clinical settings.

Application of terahertz spectroscopy on monitoring crystallization and isomerization of azobenzene.

Terahertz spectroscopy provides a powerful and informative link between infrared spectroscopy and microwave spectroscopy, and is now beginning to make its transition from initial development to broader use by chemists, materials scientists and biologists. In this study, utilizing terahertz spectroscopy we monitored the crystallization and isomerization of azobenzene. In flash-frozen trans-azobenzene solutions, the processes of crystallization and phase transition were observed. A new phase has been experimentally confirmed to exist stably at low temperatures. The results on gradual-frozen experiment indicate that the formation of the observed new phase is determined by the cooling rate. Besides, based on the distinctive spectral features of the isomers, the thermal- and photo-induced isomerization processes of azobenzene were investigated. This work presents that the terahertz spectroscopy has a great potential to study the phase transitions and crystallization of liquid samples under different freezing conditions.