Synergistic synthesis of gold nanoflowers as upconversion near-infrared nanoprobe energy acceptor and recognition unit for improved hydrogen sulfide sensing.

A highly sensitive and selective upconversion near-infrared (NIR) fluorescence and colorimetric dual readout hydrogen sulfide (H2S) nanoprobe was constructed based on the excellent NIR fluorescence emission performance of upconversion nanomaterials (UCNPs), the specific recognition effect of synergistically synthesized gold nanoflowers (trypsin-stabled AuNFs (Try-AuNFs)) and the effective NIR fluorescence quenching capability. In this assay, the sensing strategy included three processes. First of all, the synthesized UCNPs can emit 803 nm NIR fluorescence when they were excited by 980 nm excitation light. Secondly, as a result of the principle of fluorescence resonance energy transfer (FRET), Try-AuNFs can effectively quench the NIR fluorescence of UCNPs at 803 nm, which can effectively improve the signal-to-background ratio of nanoprobes, thereby improving the sensitivity of the probes. Thirdly, in the presence of H2S, the Try protective layer on the surface of Try-AuNFs was specifically penetrated, which will subsequently cleave Try-AuNFs via the strong S-Au bond. As such, the NIR fluorescence of UCNPs will be restored, achieving high selectivity and sensitivity detection of H2S. Under optimized conditions, the linear response range of H2S was 0.1-300 µM, and the detection limit was 53 nM. It is worth noting that the Try on the surface of Try-AuNFs via the synergistic effect can increase the steric hindrance of the probe, and this can effectively prevent the interaction between the probe with biothiols (cysteine (Cys), homocysteine (Hcy)) and other natural amino acids (non-thiol-containing) with resultant in the high selectivity regarding the detection of H2S in human serum, which is unlikely to be achieved by AuNFs synthesized by the gold seed method (Se-AuNFs). This work not only provided a new type of UCNPs fluorescence quencher and recognition unit, but also exemplified that the use of the physical properties (steric hindrance) of protein ligands on the surface of nanoflowers can improve the specificity of the probe. This will provide new ideas for the design of other nanoprobes.

Exclusive and Switchable Superoxide Radical Generation by O2-Capture-Based Electron Transfer and Supramolecular Assembly.

Type-I photosensitizers (PSs) can generate free radical anions with a broad diffusion range and powerful damage effect, rendering them highly desirable in various areas. However, it still remains a recognized challenge to develop pure Type-I PSs due to the inefficiency in producing oxygen radical anions through the collision of PSs with nearby substrates. In addition, regulating the generation of oxygen radical anions is also of great importance toward the control of photosensitizer (PS) activities on demand. Herein, a piperazine-based cationic Type-I PS (PPE-DPI) that exhibits efficient intersystem crossing and subsequently captures oxygen molecules through binding O2 to the lone pair of nitrogen in piperazine is reported. The close spatial vicinity between O2 and PPE-DPI strongly promotes the electron transfer reaction, ensuring the exclusive superoxide radical (O2 •-) generation via Type-I process. Particularly, PPE-DPI with cationic pyridine groups is able to associate with cucurbit[7]uril (CB[7]) through host-guest interactions. Thus, supramolecular assembly and disassembly are easily utilized to realize switchable O2 •- generation. This switchable Type-I PS is successfully employed in photodynamic antibacterial control.

Aggregation-induced emission photosensitizer microneedles for enhanced melanoma photodynamic therapy.

The incidence and mortality rates of skin melanoma have been increasing annually. Photodynamic therapy (PDT) enables effective destruction of tumor cells while minimizing harm to normal cells. However, traditional photosensitizers (PSs) suffer from photobleaching, photodegradation and the aggregation-caused quenching (ACQ) effect, and it is challenging for light to reach the deep layers of the skin to maximize the efficacy of PSs. Herein, we developed dissolving microneedles (MNs) loaded with PSs of TPE-EPy@CB[7] through supramolecular assembly. The PSs effectively enhanced the type-I reactive oxygen species (ROS) generation capacity, with a concentration of 2 µM possessing nearly half of the tumor cell-killing ability under 10 min white light irradiation. The MNs were successfully pierced into the targeted site for precise drug delivery. Additionally, the conical structure of the MNs, as well as the lens-like structure after dissolution, facilitated the transmission of light in the subcutaneous tissue, achieving significant inhibition of tumor growth with a tumor suppression rate of 97.8% and no systemic toxicity or side effects in melanoma mice. The results demonstrated the potent melanoma inhibition and biosafety of this treatment approach, exhibiting a new and promising strategy to conquer malignant melanoma.

Facile Synthesis and Multiple Application of Ultralong-Afterglow Room Temperature Phosphorescence Aggregate Carbon Dots from Simple Raw Materials.

Owing to the ultralong afterglow, room temperature decay phosphorescence nanomaterials have aroused enough attention. In the work, by simple one-pot solid-state thermal decomposition reaction, aggregate carbon dots (CDs) was prepared from trimesic and boric acid. Based on the intermolecular hydrogen bonds and intramolecular π-π stacking weak interaction from precursors, CDs was encapsulated in boron oxide matrix and formed aggregation. The aggregate state of CDs facilitated the triplet excited states (Tn), which could induce the room temperature decay phosphorescence properties. By careful investigation, under different excitation wavelengths at 254 and 365 nm, the aggregate CDs showed > 15 s and > 3 s room temperature phosphorescence emission in the naked eye, which was associated with 1516.12 ms and 718.62 ms lifetime respectively. And the aggregate CDs exhibited widespread application in encoding encryption, optical anti-counterfeiting and fingerprint identification etc. The interesting aggregate CDs revealed unexpected ultralong-afterglow room temperature decay phosphorescence properties and the work opened a window for constructing ultralong-afterglow room temperature decay phosphorescence aggregate CDs nanomaterials.

Therapeutic Potential Targeting Podocyte Mitochondrial Dysfunction in Focal Segmental Glomerulosclerosis.

Background: Podocytes are essential components of the glomerular filtration barrier and essential for the proper filtration function of the glomerulus. Podocyte injury under various stress conditions is the primary pathogenesis and key determinant of focal segmental glomerulosclerosis (FSGS) with prominent clinical manifestations of proteinuria or nephrotic syndrome. Summary: Under physiological conditions, a highly coordinated mitochondrial quality control system, including antioxidant defenses, mitochondrial dynamics (fusion, fission, and mitophagy), and mitochondrial biogenesis, guarantees the sophisticated structure and various functions of podocytes. However, under FSGS pathological conditions, mitochondria encounter oxidative stress, dynamics disturbances, and defective mitochondrial biogenesis. Moreover, mutations in mitochondrial DNA and mitochondria-related genes are also strongly associated with FSGS. Based on these pieces of evidence, bioactive agents that function to relieve mitochondrial oxidative stress and promote mitochondrial biogenesis have been proven effective in preclinical FSGS models. Targeting the mitochondrial network is expected to provide new therapeutic strategies for the treatment of FSGS and delay its progression to end-stage renal disease. Key Messages: Mitochondrial dysfunction plays a key role in podocyte injury and FSGS progression. This review summarized recent advances in the study of mitochondrial homeostatic imbalance and dysfunction in FSGS and discussed the potential of mitochondria-targeted therapeutics in improving FSGS and retarding its progression to end-stage renal disease.

A Uniform Self-Reinforced Organic/Inorganic Hybrid SEI Chelation Strategy on Microscale Silicon Surfaces for Stable-Cycling Anodes in Lithium-Ion Batteries.

A promising anode material for Li-ion batteries, silicon (Si) suffers from volume expansion-induced pulverization and solid electrolyte interface (SEI) instability. Microscale Si with high tap density and high initial Coulombic efficiency (ICE) has become a more anticipated choice, but it will exacerbate the above issues. In this work, the polymer polyhedral oligomeric silsesquioxane-lithium bis (allylmalonato) borate (PSLB) is constructed by in situ chelation on microscale Si surfaces via click chemistry. This polymerized nanolayer has an "organic/inorganic hybrid flexible cross-linking" structure that can accommodate the volume change of Si. Under the stable framework formed by PSLB, a large number of oxide anions on the chain segment preferentially adsorb LiPF6 and further induce the integration of inorganic-rich, dense SEI, which improves the mechanical stability of SEI and provides accelerated kinetics for Li+ transfer. Therefore, the Si4@PSLB anode exhibits significantly enhanced long-cycle performance. After 300 cycles at 1 A g-1 , it can still provide a specific capacity of 1083 mAh g-1 . Cathode-coupled with LiNi0.9 Co0.05 Mn0.05 O2 (NCM90) in the full cell retains 80.8% of its capacity after 150 cycles at 0.5 C.

Analyte-triggered cascade signal amplification strategy for highly sensitive detection of iodate in table salt with dual-readout signals.

A novel and highly sensitive upconversion fluorescence and colorimetric dual readout iodate (IO3-) nanosensor system was constructed by using both the outstanding optical performance of NaYF4:Yb, Tm upconversion nanoparticles (UCNPs) and the analyte-triggered cascade signal amplification (CSA) technique. The construction of the sensing system consisted of three processes. First, IO3- oxidized o-phenylenediamine (OPD) to diaminophenazine (OPDox), while IO3- was reduced to I2. Second, the generated I2 can further oxidize OPD to OPDox. This mechanism has been verified by 1H NMR spectra titration analysis and HRMS measurement, which effectively improves the selectivity and sensitivity of the measurement of IO3-. Third, the generated OPDox can effectively quench the fluorescence of UCNPs via the inner filter effect (IFE), realize analyte-triggered CSA, and allow quantitative determination of IO3-. Under the optimized conditions, the fluorescence quenching efficiency showed a good linear relationship to IO3- concentration in the range of 0.06-100 µM, and the detection limit reached 0.026 µM (3RSD/slope). Moreover, this method was applied to detect IO3- in table salt samples, yielding satisfactory determination results with excellent recoveries (95.5-105%) and high precision (RSD <5.5%). These results suggest that the dual-readout sensing strategy with well-defined response mechanisms has promising application prospects in physiological and pathological studies.

Fabrication of Supramolecular System Derived from Poly ß-cyclodextrin Coupling Quinoline Dderivative and Its Fluorescence Sensing of Zinc Ion in Pure Water Environment.

Cyclodextrin (CD) is an important guest material owing to the water solubility and biocompatibility. In the paper, an organic small molecule was synthesized. According to supramolecular self-assembly, the organic molecule was bounded to the cavity of Poly ß-cyclodextrin, which was characterized by IR, SEM and TEM et al. After self-assembly interaction, the morphology has changed obviously comparing with precursors. Simultaneously, the supramolecular self-assembly complex exhibited good water solubility. Moreover, By Gaussian calculation, the high binding activity between organic molecule and cyclodextrin was confirmed. By fluorescence investigation, the supramolecular system showed high fluorescence sensing activity for Zn2+ in pure water environment, which could track the dynamic change of Zn2+ in organisms. In addition, the supramolecular system exhibited low cytotoxicity. The work provided an interesting pathway for constructing water-soluble and low cytotoxic fluorescence sensor for Zn2+.

Label-free fluorescence detection of alkaline phosphatase activity using a G-triplex based dumbbell-shaped probe.

Based on the fluorescence enhancement property of the G-triplex (G3)-Thioflavin T (ThT) complex, a fluorescent biosensor was successfully constructed for detection of ALP using a G3-based dumbbell-shaped probe (DP). In this work, calf intestinal ALP (CIP) can act on the 5'-terminal phosphate of DP, thereby regulating the subsequent DNA ligation reaction and enzyme cleavage of the DP nick. When the DP is digested by exonuclease, the released G3 can bind to ThT, resulting in enhanced fluorescence signal. The linear range of the sensor for CIP detection is 0.00002-0.002 U/µL, and the detection limit is 1.8 × 10-5 U/µL. The proposed method has the advantages of simplicity, no fluorophore labeling, and low cost, which was successfully applied to the screening of enzyme inhibitors and ALP determination in human serum samples. To the best of our knowledge, this is the first report of a biosensor using G3-ThT as the signal indicator for ALP detection, which should promote the further exploitation of applying G3-ThT complex in the field of various targets recognition and analysis.

Combined central and peripheral demyelination: a case report resembling encephalomyeloradiculoneuropathy.

Combined central and peripheral demyelination (CCPD) is an extremely rare disease characterized by inflammatory demyelination in both the central and peripheral nervous systems. Herein, we reported case of a 14-year-old teenager who initially presented with the symptoms of acute myelitis (AM). Subsequently, the patient developed symptoms consistent with Guillain-Barré syndrome (GBS), which was supported by nerve conduction studies (NCV) and cerebrospinal fluid (CSF) analysis. Throughout the course of the disease, the patient experienced abdominal pain and abnormal liver function. After a comprehensive evaluation, we determined that the abnormal liver function was a result of hepatitis E virus (HEV) infection, which may have acted as a trigger for GBS. The patient was treated with corticosteroids, intravenous immunoglobulin and Rituximab, resulting in symptom relief and clinical improvement after therapy and follow-up. This case highlights the potential responsiveness and reversibility of CCPD. Given the heterogeneous nature of CCPD, there is currently no standardized diagnostic criteria or clear consensus on its treatment. Therefore, we recommend a thorough assessment of all possibilities and the development of consolidated management guidelines based on available data for this disorder.

Case report: MOG-IgG-associated encephalitis with Epstein-Barr virus infection and Alzheimer's pathologic change in cerebrospinal fluid.

Immunoglobulin G antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) associated disease is a rare, demyelinated disease in the central nerve system (CNS) predominately involving optic nerve, spinal cord, and brain leading to optic neuritis (ON), transverse myelitis (TM), encephalitis. The phenotype of MOG-IgG-associated encephalitis is similar to acute disseminated encephalomyelitis (ADEM) presenting with seizures, abnormal behavioral and psychological symptoms, and cognitive impairment. A few brain biopsies show multiple sclerosis (MS) pattern histopathology with T cells, macrophages, and complement activation. To date, how MOG-IgG is produced is unknown. Herein, we report a case of a 32-year-old male with MOG-IgG-associated encephalitis presenting MOG-IgG in cerebrospinal fluid (CSF) but seronegative, as well as Epstein-Barr virus (EBV) infection and Alzheimer's pathologic change in CSF (Aß42 = 317 pg/ml, T-Tau = 538 pg/ml, p-Tau =10.09 pg/ml). With a combination treatment of administering intravenous immunoglobulin (0.4 mg/kg/d, 5 days) with a low dose of methylprednisolone (80 mg/d, 5 days) and rituximab (100 mg/week, 3 weeks), the patient recovered significantly after 3 months follow-up. This case provides us with new thoughts into the production of MOG-IgG and the possible pathologic mechanism of MOG-IgG-associated disease (MOG-AD) and simultaneously further confirms the interaction between EBV and changes of CSF biomarkers of Alzheimer's disease (AD).

Stereoisomeric engineering of aggregation-induced emission photosensitizers towards fungal killing.

Fungal infection poses and increased risk to human health. Photodynamic therapy (PDT) as an alternative antifungal approach garners much interest due to its minimal side effects and negligible antifungal drug resistance. Herein, we develop stereoisomeric photosensitizers ((Z)- and (E)-TPE-EPy) by harnessing different spatial configurations of one molecule. They possess aggregation-induced emission characteristics and ROS, viz. 1O2 and O2-• generation capabilities that enable image-guided PDT. Also, the cationization of the photosensitizers realizes the targeting of fungal mitochondria for antifungal PDT killing. Particularly, stereoisomeric engineering assisted by supramolecular assembly leads to enhanced fluorescence intensity and ROS generation efficiency of the stereoisomers due to the excited state energy flow from nonradiative decay to the fluorescence pathway and intersystem (ISC) process. As a result, the supramolecular assemblies based on (Z)- and (E)-TPE-EPy show dramatically lowered dark toxicity without sacrificing their significant phototoxicity in the photodynamic antifungal experiments. This study is a demonstration of stereoisomeric engineering of aggregation-induced emission photosensitizers based on (Z)- and (E)-configurations.

Preparation, characterization and cell labelling of strong pH-controlled bicolor fluorescence carbonized polymer dots.

As a class of important carbon nanomaterial, carbonized polymer dots (CPDs), also called carbon dots (CDs), have aroused wide interest owing to their unique water solubility, fluorescence properties, and rich surface functional groups. However, the directional tuning of the fluorescence properties of CPDs remains incomplete because of the influence of many factors like diameter, solvent and surface groups. Particularly, most carbonized polymer dots are synthesized in a neutral pH environment. Herein, by modulating the pH (strongly acidic or alkaline) of dextrin water solution, bicolor fluorescence emission (blue and yellow) CPDs were prepared by a hydrothermal reaction. Through systematic characterization, it was found that the different fluorescence properties are regulated by the diameters and surface groups of the carbon cores. Simultaneously, the pH value affected the nucleation process. Based on the excellent fluorescence properties, cell fluorescence imaging and cytotoxicity were tested. The bicolor fluorescence CPDs obtained by tuning the pH provide an important theoretical basis for the design of broadband CPDs.

Use of RNAi With OsMYB76R as a Reporter for Candidate Genes Can Efficiently Create and Verify Gametophytic Male Sterility in Rice.

Gametophytic male sterility (GMS) plays an important role in the study of pollen development and seed propagation of recessive nuclear male sterile lines insensitive to the environmental conditions in hybrid rice breeding. Since the inherent phenotypic and genetic characteristics of GMS, it is very difficult to find and identify the GMS mutants. However, due to the abundance of gene transcription data, a large number of pollen-specific genes have been found, and most of them may be associated with GMS. To promote the study of these genes in pollen development and heterosis utilization, in this study, an easy and efficient method of creating and identifying GMS was established using RNAi and OsMYB76R as a reporter. First, the OsC1/OsMYB76 gene involved in anthocyanin synthesis was modified, and we have validated that the modified OsMYB76R is workable as the same as the pre-modified OsMYB76 gene. Then, the ascorbic acid oxidase gene OsPTD1 was downregulated using RNAi, driven by its own promoter that resulted in abnormal pollen tube growth. Finally, the RNAi elements were linked with OsMYB76R and transformed into an osmyb76 mutant, and the distortion of purple color segregation was found in T1 and F1 generations. This indicates that the OsPTD1 GMS was prepared successfully. Compared to current methods, there are several advantages to this method. First, time is saved in material preparation, as one generation less needs to be compared than in the conventional method, and mutation screening can be avoided. In addition, for identification, the cost is lower; PCR, electrophoresis, and other processes are not needed; and no expensive chemicals or instruments are required. Finally, the results are more accurate, with much lower background effects, and no damage to the plant. The result is an easy, efficient, low-cost, and accurate method of preparing and identifying GMS genes.

[Effects of melatonin on oxidative stress and apoptosis-related gene signaling pathways following testicular torsion in rats].

OBJECTIVE: To investigate the effects of melatonin on the oxidative stress and signaling pathways of apoptosis-related genes following testicular torsion/detorsion in male rats. METHODS: Twenty-four healthy male Sprague-Dawley rats were randomly divided into a control, a torsion and a melatonin group of equal number. The torsion model was made in the animals of the latter two groups by 720° torsion of the left testis for 2 hours. The rats of the torsion and melatonin groups received intraperitoneal injection of isotonic saline and melatonin (17 mg/kg) respectively at 15 minutes prior to detorsion. At 24 hours after modeling, testis tissues were collected from the rats for detection of the apoptosis of the germ cells by flow cytometry (FCM), analysis of the expressions of Fas, Fas ligand (FasL) and Bax mRNA by quantitative real-time PCR (qRT-PCR), measurement of the cytochrome C content released from the mitochondrion by Western blot, and determination of the total antioxidant capacity (T-AOC) and the levels of myeloperoxidase (MPO) and malodialdehyde (MDA) by spectrophotometry. RESULTS: Compared with the torsion group, the rats treated with melatonin showed significantly increased normal testicular cells (ï¼»77.81 ± 6.52ï¼½% vs ï¼»88.61 ± 7.93ï¼½%, P < 0.05), decreased early apoptotic germ cells (ï¼»16.74 ± 3.16ï¼½% vs ï¼»6.97 ± 1.65ï¼½%, P < 0.05), down-regulated expressions of Fas (ï¼»4.52 ± 0.29ï¼½ vs ï¼»2.66 ± 0.37ï¼½, P < 0.01), FasL (ï¼»2.82 ± 0.30ï¼½ vs ï¼»1.73 ± 0.18ï¼½, P < 0.01) and Bax mRNA (ï¼»2.39 ± 0.18ï¼½ vs ï¼»1.50 ± 0.14ï¼½, P < 0.01), reduced levels of cytochrome C (ï¼»1.40 ± 0.38ï¼½ vs ï¼»0.67 ± 0.30ï¼½, P < 0.01), MPO (ï¼»0.52 ± 0.15ï¼½ vs ï¼»0.19 ± 0.10ï¼½ U/g prot, P < 0.01) and MDA ï¼»6.37 ± 1.73ï¼½ vs ï¼»3.98 ± 0.90ï¼½ nmol/mg prot, P < 0.01) and elevated T-AOC (ï¼»0.76 ± 0.25ï¼½ vs ï¼»1.55 ± 0.32ï¼½ U/mg prot, P < 0.01). CONCLUSIONS: Melatonin has a significant protective effect on spermatogenesis after testicular torsion by regulating the expressions of apoptosis-related genes and increasing T-AOC in the testis tissue.

Selectively light-up hydrogen peroxide in hypoxic cancer cells with a novel fluorescent probe.

A novel fluorescent turn-on probe (HCyHP) was developed in a simple two-step synthesis for monitoring of exogenous and endogenous H2O2 levels in biological samples and hypoxic cancer diagnosis.

A fast responsive, highly selective and light-up fluorescent probe for the two-photon imaging of carboxylesterase in living cells.

A fast responsive and two photon fluorescent probe (HCyNAc) for carboxylesterase (CaE) has been designed based on the D-π-A structure of hemicyanine and naphthalene derivatives. After enzymatic reaction, HCyNAc enabled light-up fluorescence assay of CaE over other biologically-relevant species and enzymes, including ROS. Two-photon imaging of endogenous CaE was confirmed in HeLa cells using HCyNAc under 800 nm NIR excitation.

A new tetraphenylethylene based AIE sensor with light-up and tunable measuring range for adenosine triphosphate in aqueous solution and in living cells.

An AIE based tetraphenylethylene derivative (TPPTPE) was synthesized for light-up sensing of ATP in aqueous solution. The measuring range for ATP can be tuned by varying the concentration of the TPPTPE. A one-step straightforward quantitative analysis of the ATP level in cell lysates can be realized using the TPPTPE. Moreover, the TPPTPE can be used for monitoring apyrase activity in aqueous solution and detecting ATP both in living cancer cell lines and in living normal cell lines.

A selective and light-up fluorescent probe for ß-galactosidase activity detection and imaging in living cells based on an AIE tetraphenylethylene derivative.

An aggregation induced emission (AIE) based bioimaging probe, TPE-Gal, was designed for light-up imaging of ß-galactosidase in living cells. The applicability of TPE-Gal in imaging endogenous ß-galactosidase activity was confirmed in OVCAR-3 cells.

Hairpin-shaped DNA Templated Copper Nanoparticles for Fluorescence Detection of Adenosine Triphosphate Based on Ligation-mediated Exonuclease Cleavage.

DNA-templated copper nanoparticles (CuNPs) have recently received considerable interest as functional fluorescent probes for biochemical analysis. In this work, a novel ATP-dependent ligation reactions (ATP-DLR) based ATP assay strategy was proposed by using hairpin-shaped (HS) DNA templated CuNPs as a fluorescent probe. Nick sealing by T4 DNA ligase leads to the formation of intact HS DNA, which can resist the exonuclease cleavage and be taken as the template for CuNPs formation, resulting in strong fluorescence. The proposed ATP detection is label free, sensitive and highly selective, and it has good linearity from 0.02 to 4 µM and a detection limit of 7 nM. This strategy is expected to promote the exploitation and application of DNA-templated CuNPs in biochemical and biomedical studies, and holds great promise in fluorescence detection for other ligation-related biomolecules.