A Case Report of Pregnancy Complicated with Primary Hemophagocytic Lymphohistiocytosis.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by excessive activation of NK cells and cytotoxic T lymphocytes, subsequently leading to macrophage activation and increased cytokine production. Misdiagnosis due to nonspecific clinical presentations and inadequate understanding of the disease can significantly jeopardize the safety of both the mother and the infant. We report a case of pregnancy combined with HLH and conduct a literature review to provide insights into the diagnosis and treatment of pregnancy-related HLH. Case Presentation: We discussed a case of a pregnant woman with persistent postpartum fever, serum ferritin, and elevated liver function, who failed to respond to repeated anti-infective therapy and was diagnosed with HLH after multidisciplinary diagnostic treatment. We gave dexamethasone treatment, and the patient's temperature and blood cells quickly returned to normal. Finally, exome sequencing revealed heterozygous variation in UNC13D gene, so we considered this case as pregnancy combined with primary HLH (pHLH). Conclusion: We report the case of HLH diagnosed during pregnancy and show that early diagnosis and timely intervention can prevent rapid disease progression, reduce maternal mortality rates, and improve survival rates. Additionally, molecular genetic testing can confirm pathogenic gene mutations, providing essential genetic counseling for patients with pHLH who plan to conceive a healthy child.

BRCC3 mediates inflammation and pyroptosis in cerebral ischemia/reperfusion injury by activating the NLRP6 inflammasome.

AIMS: Neuroinflammation and pyroptosis are key mediators of cerebral ischemia/reperfusion (I/R) injury-induced pathogenic cascades. BRCC3, the human homolog of BRCC36, is implicated in neurological disorders and plays a crucial role in neuroinflammation and pyroptosis. However, its effects and potential mechanisms in cerebral I/R injury in mice are unclear. METHODS: Cellular localization of BRCC3 and the interaction between BRCC3 and NLRP6 were assessed. Middle cerebral artery occlusion/reperfusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) models were established in mice and HT22 cells, respectively, to simulate cerebral I/R injury in vivo and in vitro. RESULTS: BRCC3 protein expression peaked 24 h after MCAO and OGD/R. BRCC3 knockdown reduced the inflammation and pyroptosis caused by cerebral I/R injury and ameliorated neurological deficits in mice after MCAO. The effects of BRCC3 on inflammation and pyroptosis may be mediated by NLRP6 inflammasome activation. Moreover, both BRCC3 and its N- and C-terminals interacted with NLRP6, and both BRCC3 and its terminals reduced NLRP6 ubiquitination. Additionally, BRCC3 affected the interaction between NLRP6 and ASC, which may be related to inflammasome activation. CONCLUSION: BRCC3 shows promise as a novel target to enhance neurological recovery and attenuate the inflammatory responses and pyroptosis caused by NLRP6 activation in cerebral I/R injury.

Fine-tuning bromide AIE probes for Hg2+ detection in mitochondria with wash-free staining.

Mercury ions (Hg2+) primarily target mitochondria in the cells. Therefore, the development of novel probes that specifically target mitochondria in the presence of Hg2+ is of immense importance. Most previously reported probes that utilize the softness of S, Te, O, and/or N atoms for Hg2+ binding often face problems such as fluorescence quenching and off-target signals. In this study, bromide-hydrocarbon pyridinium salts were designed to target the mitochondria and chelate Hg2+ via Hg-Br coordination bonds. As a prototype, four aggregation-induced emission (AIE) fluorogens, namely TPP-Br, TPP-Cl, R1, and R2, with a similar D-π-A structure but slight differences in their halogen substituents, were designed. Among them, only TPP-Br achieved the highly selective and sensitive detection of Hg2+ by triggering its AIE properties, resulting in remarkable emission enhancement (80-fold), colorimetry, and the Tyndall effect. TPP-Br exhibited high selectivity and sensitivity to Hg2+ with a detection limit of 0.35 µM, rapid response time (<10 s), and large Stokes shift of 185 nm. Their interaction modes were studied using a combination of 1H nuclear magnetic resonance spectroscopy, scanning electron microscopy, fluorescent lifetime decay, and theoretical calculations. TPP-Br exhibited a low emission background in cells, whereas in the presence of Hg2+, mitochondria were lit up with wash-free staining. This study provides a powerful tool for accurately diagnosing mercury poisoning-related diseases in mitochondria.

Bismacrocycle: Structures and Applications.

In the past half-century, macrocycles with different structures and functions, have played a critical role in supramolecular chemistry. Two macrocyclic moieties can be linked to form bismacrocycle molecules. Compared with monomacrocycle, the unique structures of bismacrocycles led to their specific recognition and assembly properties, also a wide range of applications, including molecular recognition, supramolecular self-assembly, advanced optical material construction, etc. In this review, we focus on the structure of bismacrocycle and their applications. Our goal is to summarize and outline the possible future development directions of bismacrocycle research.

Sensitive and specific detection of saccharide species based on fluorescence: update from 2016.

Increasing evidence supports the critical role of saccharides in various pathophysiological steps of tumor progression, where they regulate tumor proliferation, invasion, hematogenic metastasis, and angiogenesis. The identification and recognition of these saccharides provide a solid foundation for the development of targeted drug preparations, which are however not fully understood due to their complex and similar structures. In order to achieve fluorescence sensing of saccharides, extensive research has been conducted to design molecular probes and nanoparticles made of different materials. This paper aims to provide in-depth discussion of three main topics that cover the current status of the carbohydrate sensing based on the fluorescence sensing mechanism, including a phenylboronic acid-based sensing platform, non-boronic acid entities, as well as an enzyme-based sensing platform. It also highlights efforts made to understand the recognition mechanisms and improve the sensing properties of these systems. Finally, we present the challenge of achieving high selectivity and sensitivity recognition of saccharides, and suggest possible future avenues for exploration.

Dual-key-and-lock AIE probe for thiosulfate and Ag+ detection in mitochondria.

Ag+ ion detection has attracted much attention due to its important role in chemical and biological processes, as well as its potential threat to the environment and human health. Herein, we firstly constructed a dual-key-and-lock sensing strategy for Ag+ detection based on three-component co-assembly. An aggregation-induced emission luminogen (AIEgen), namely triphenylamine-thiophene-pyridinium (abbreviated to TPA-T-Py), showed unique co-assembly capability with Ag+ and S2O32- in PBS buffer (pH 7.4, 0.01 M). Cell imaging further proved that mitochondria can be lit up by TPA-T-Py under the dual key stimulation, which was successfully used for Ag+ and S2O32- detection in vitro. In brief, we provide a promising strategy for the construction of dual-lock imaging agents with organelle-targeting ability.

Dual-ratiometric fluorescence probe for viscosity and hypochlorite based on AIEgen with mitochondria-targeting ability.

Viscous microenvironments are ubiquitous in living organisms. An oxidative stress attack could cause the fluctuation of lymph or blood viscosity, which is closely related to many common diseases. However, the dual-function detection of reactive oxygen species and viscosity is still ineffective due to design defects. Herein, by rational linking a propeller-shaped triphenylamine rotator and a rigid planar anthracene, we report the first dual-ratiometric-response probe for ClO- and viscosity detection. The probe itself shows weak fluorescence background in low-viscous solution or at non-aggregate state, which can largely switch on its blue (414 nm) and yellow fluorescence (600 nm) respectively in response to ClO- and viscosity. Their sensing mechanisms were elucidated through the interruption of FRET and TICT processes for ClO- and viscosity detection, respectively. In addition to its mitochondria targeting ability, TPP-AN was employed for mitochondrial viscosity and ClO- imaging in HeLa cells, providing a potentially useful probe for clinical assays.

G-quadruplex DNAzyme as peroxidase mimetic in a colorimetric biosensor for ultrasensitive and selective detection of trace tetracyclines in foods.

The colorimetric method can determine the initial results even by the naked eyes, but its main challenge for antibiotics detection in food at present is the relatively low sensitivity. Herein, an ultrasensitive colorimetric biosensor based on G-quadruplex DNAzyme was firstly proposed for the rapid detection of trace tetracycline antibiotics like tetracycline, oxytetracycline, chlortetracycline and doxycycline. DNAzyme composed of hemin and G-quadruplex has peroxidase-like activity, and tetracyclines can combine with hemin to form a stable complex and reduce catalytic activity, making the color of solution changes from yellow to green. The limits of detection (LOD) of the proposed colorimetric biosensor for tetracyclines is determined as low as 3.1 nM, which is lower than most of the other colorimetric methods for antibiotics detection. Moreover, the average recovery range of tetracyclines in actual samples is from 89% to 99%, indicating that such strategy may has bright application prospects for tetracyclines detection in foods.

Water-soluble fluorescent probes for bisulfite and viscosity imaging in living cells: Pyrene vs. anthracene.

We have designed two mitochondria targetable probes P-Py and P-An by the π-conjugation of polyaromatic hydrocarbons (pyrene vs. anthracene) with 4-dimethylamino pyridinium. They present an amphiphilic property with excellent solubility in the common polar and non-polar solvents. Both of them demonstrated a significant fluorescence response to bisulfite in Tris-HCl buffer solutions (5 mM, pH = 7.4). By a combination of fluorescence, UV-vis, time-resolved emission, 1H NMR, and ESI-MS, their sensing mechanisms have been elaborated to be a Michael addition. Notably, P-Py also exhibits a sensitivity to the viscosity change with a Stokes shift of 140 nm, due to the restriction of C-C bond rotation. By taking advantages of its good water solubility, low toxicity, and high mitochondrial target, the dual responses of P-Py to exogenous SO2 derivatives and viscosity change in mitochondria were explored by confocal fluorescence microscopy.

BRCC3 promotes activation of the NLRP6 inflammasome following cerebral ischemia/reperfusion (I/R) injury in rats.

NOD-like receptor family pyrin domain containing 6 (NLRP6), a novel member of the NLR family, has been confirmed to have an inflammasome-dependent proinflammatory effect in cerebral ischemia/reperfusion injury. NLRP6 assembles a multimeric inflammasome complex comprising the adaptor ASC and the effector pro-caspase-1 to mediate the activation of caspase-1. The molecular mechanism regulating activation of the NLRP6 inflammasome remains unclear. Previous studies have shown that BRCA1-BRCA2-containing complex subunit 3 (BRCC3), a JAMM domain-containing Zn2+ metalloprotease deubiquitinating enzyme, participates in a variety of cellular activities. In this study, we found that BRCC3 expression was increased in the middle cerebral artery occlusion (MCAO) model. BRCC3 siRNA could reduce nerve damage and inflammation. Interestingly, the result of co-immunoprecipitation showed that the interaction between BRCC3 and NLRP6 was enhanced after model, and the result of immunofluorescence showed that the co-localization of BRCC3 and NLRP6 was increased. At the same time, the expression of NLRP6, cleavated-caspase-1 and IL-1ß was decreased after BRCC3 interference. These results illustrate a regulatory mechanism involving the BRCC3-NLRP6 pathway and highlight NLRP6 as a potential therapeutic target for inflammatory diseases.

Facile Colorimetric Nanozyme Sheet for the Rapid Detection of Glyphosate in Agricultural Products Based on Inhibiting Peroxidase-Like Catalytic Activity of Porous Co3O4 Nanoplates.

The rapid and onsite detection of glyphosate herbicides in agricultural products is still a challenge. Herein, a novel colorimetric nanozyme sheet for the rapid detection of glyphosate has been successfully prepared through the physical adsorption of porous Co3O4 nanoplates on a polyester fiber membrane. Glyphosate can specifically inhibit the peroxidase-mimicking catalytic activity of porous Co3O4 nanoplates, thereby the visual detection of glyphosate can be realized by distinguishing the change in the color intensity of the established nanozyme sheet. The prepared nanozyme sheet has good sensitivity and selectivity, with a detection limit of 0.175 mg·kg-1 for glyphosate detection just by the naked eyes. It can effectively detect glyphosate within 10 min, and the color spots can maintain more than 20 min. The nanozyme sheet is not easily affected by the external environment in detection and storage. The merits of the nanozyme sheet facilitate its practical application in the large-scale preliminary screening of glyphosate residues in agricultural products.

A Validated Model to Predict Postoperative Symptom Severity After Mandibular Third Molar Removal.

PURPOSE: The individualized prediction of postoperative symptom severity is essential for selecting interventions after mandibular third molar (M3M) removal. The purpose of the present study was to develop and validate a nomogram for personal prediction of postoperative symptom severity. MATERIALS AND METHODS: A prospective cohort study was performed in the Stomatology Hospital of Tianjin Medical University. The sample was divided into training and testing data sets by time. The demographic, anatomic, radiographic, and operative variables were recorded. The self-reported postoperative symptom severity was recorded and defined as the primary outcome variable. Stepwise forward algorithms were applied to informative predictors based on Akaike's information criterion. Multivariable logistic regression analysis was used to develop the nomogram. An independent testing data set was used to validate the nomogram. Receiver operating characteristic curves and the Hosmer-Lemeshow test were used to assess model performance. P < .05 was considered to indicate statistical significance. RESULTS: The sample included 321 subjects who had undergone M3M removal. An independent validation data set included 103 consecutive patients. The median operation time was 15.0 minutes (interquartile range, 8.3 to 21.6 minutes) in the training data set (n = 218). Patients with serious postoperative symptoms accounted for 48.6 and 47.6% of the training and testing data sets, respectively. Gender, age, smoking status, operation time, Pell-Gregory ramus classification, and preoperative symptoms were identified as predictors and assembled into the nomogram. The area under curve demonstrated adequate discrimination in the validation data set (0.69; 95% confidence interval, 0.59 to 0.80). The nomogram was well calibrated, with a Hosmer-Lemeshow χ2 statistic of 6.33 (P = .78) in the testing data set. The confusion matrix was also summarized, and the accuracy was 63.3 and 65.1% in the training and testing data set, respectively. CONCLUSIONS: The present study has proposed an effective nomogram with potential application in facilitating the individualized prediction of postoperative symptom severity after M3M removal.

Sunlight and UV driven synthesis of Ag nanoparticles for fluorometric and colorimetric dual-mode sensing of ClO.

A photo-responsive compound BINOL-LA (1) having a rigid backbone ending up with two 5-membered cyclic disulfide moieties was designed. BINOL-LA capped Ag nanoparticles (1@Ag NPs) with a network structure were synthesized in a green way by sunlight or UV lamp irradiation. 1@Ag NPs exhibit a selective recognition towards ClO- in aqueous solution with a switch-on fluorescence response and a visual color change, with detection limits of 0.17 µM and 1.54 µM, respectively. The sensing mechanism is based on the ClO--mediated oxidation of AgS bond, resulting in a disaggregation of 1@Ag NPs assembly. With the strategy demonstrated here, ClO- in tap water and lake water can be detected quantitatively in 5 s.

DJ-1 Regulates Microglial Polarization Through P62-Mediated TRAF6/IRF5 Signaling in Cerebral Ischemia-Reperfusion.

The polarization of microglia/macrophage, the resident immune cells in the brain, plays an important role in the injury and repair associated with ischemia-reperfusion (I/R). Previous studies have shown that DJ-1 has a protective effect in cerebral I/R. We found that DJ-1 regulates the polarization of microglial cells/macrophages after cerebral I/R and explored the mechanism by which DJ-1 mediates microglial/macrophage polarization in cerebral I/R. Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen and glucose deprivation/reoxygenation (OGD/R) models were used to simulate cerebral I/R in vivo and in vitro, respectively. DJ-1 siRNA and the DJ-1-based polypeptide ND13 were used to produce an effect on DJ-1, and the P62-specific inhibitor XRK3F2 was used to block the effect of P62. Enhancing the expression of DJ-1 induced anti-inflammatory (M2) polarization of microglia/macrophage, and the expression of the anti-inflammatory factors IL-10 and IL-4 increased. Interference with DJ-1 expression induced pro-inflammatory (M1) polarization of microglia/macrophage, and the expression of the proinflammatory factors TNF-α and IL-1ß increased. DJ-1 inhibited the expression of P62, impeded the interaction between P62 and TRAF6, and blocked nuclear entry of IRF5. In subsequent experiments, XRK3F2 synergistically promoted the effect of DJ-1 on microglial/macrophage polarization, further attenuating the interaction between P62 and TRAF6.

A dansyl-appended N-heterocycle for Cu2+ and S2- recognition via a displacement mode.

A novel l-proline based heterocycle 3 of C2 symmetry has been designed and synthesized for cation and anion recognition in aqueous solution. Ligand 3 shows a strong affinity to Cu2+ ion, and their interaction induces a remarkable fluorescence quenching in DMSO:H2O=9:1 (HEPES buffer, 0.01M, pH7.4) among various metal ions. Both the in-situ generated and isolated 3-Cu2+ complex exhibit specific fluorescence recovery upon addition of S2-, even in the presence of S2O32-, L-histidine, and thiol-containing amino acids. For this dual functional switch, a combination of 1H NMR titration, ESI mass and FT-IR spectra suggest that its sensing behavior is via a displacement mode. Sequential "on-off-on" fluorescence bio-imaging of the heterocycle 3 to Cu2+ and S2- was carried out in HeLa cells.

High-order harmonic generation from 2D periodic potentials in circularly and bichromatic circularly polarized laser fields.

We studied the high-order harmonic generation (HHG) from 2D solid materials in circularly and bichromatic circularly polarized laser fields numerically by simulating the dynamics of single-active-electron processes in 2D periodic potentials. Contrary to the absence of HHG in the atomic case, circular HHGs below the bandgap with different helicities are produced from intraband transitions in solids with C 4 symmetry driven by circularly polarized lasers. Harmonics above the bandgap are elliptically polarized due to the interband transitions. High-order elliptically polarized harmonics can be generated efficiently by both co-rotating and counter-rotating bicircular mid-infrared lasers. The cutoff energy, ellipticity, phase, and intensity of the harmonics can be tuned by the control of the relative phase difference between the 1ω and 2ω fields in bicircularly polarized lasers, which can be utilized as an ultrafast optical tool to image the structure of solids.

Rational design of an "on-off-on" fluorescent switch for Cu2+ and histidine based on chiral macrocyclic dioxopolyamine.

A novel chemosensor 1 having a chiral macrocyclic dioxopolyamine of C2 symmetry as a receptor and anthracene as a signal unit has been designed and synthesized for cations and α-amino acids recognition in DMSO-HEPES buffer (1:9, v/v, pH 7.2). The ligand exhibited selective response to Cu2+ even in the presence of other metal ions with a fluorescence "switch-off" behavior. Additionally, the in situ generated 1-Cu2+ ensemble displayed specific recognition to histidine by a "switch-on" fluorescence response. For this dual functional switch, its sensing behavior via a displacement mode was confirmed by 1H NMR titration and ESI mass spectroscopy. Sequential "on-off-on" fluorescence responses of 1 to Cu2+ and histidine are successfully applied in HeLa cells.

Hypoxia exposure upregulates MALAT-1 and regulates the transcriptional activity of PTB-associated splicing factor in A549 lung adenocarcinoma cells.

Hypoxia has been reported to be a critical microenvironmental factor that induces cancer metastasis and proliferation in gastric, liver and hepatic cancers; however, the underlying mechanisms of this are largely unknown. Long noncoding RNAs (lncRNAs) have emerged as crucial factors of several aspects of tumor malignancy, including tumorigenesis, metastasis and chemoresistance. However, the potential association of lncRNAs with hypoxia-induced cancer malignancy remains to be determined. In the present study, the differential expression of lncRNAs following the induction of hypoxia in A549 lung adenocarcinoma cells was analyzed reverse transcription-quantitative polymerase chain reaction. It was identified that the lncRNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) was upregulated significantly by hypoxia in A549 cells. By considering its promotive effects on malignant tumor behaviors, in the present study, it was identified that upregulated MALAT-1 released the binding of PTB-associated splicing factor (PSF) to its target gene, GAGE6, and thus promoted proliferation, migration and invasion of A549 cells following hypoxia exposure. These results advance the overall understanding of the mechanism of hypoxia-induced lung cancer metastasis and may assist in the development of novel therapeutics.

Nonadiabatic redshifts in high-order harmonic generation from solids.

We studied the multi-plateau high-order harmonic generation (HHG) from solids numerically. It is found that the HHG spectra in the second and higher plateaus are redshifted in short laser pulses due to the nonadiabatic effect. The corresponding FWHMs also increase as a function of the harmonic order, suggesting the step-by-step excitation of higher conduction bands in the HHG process. Although the system is symmetric in the coordinate space, even-order harmonics are present. It is due to the fact that the symmetry of electron motions and the population in the higher conduction bands is broken in the k space and time domain based on the indirect step-by-step excitation model. Our numerical results are in good agreement with recent experimental measurements of Ndabashimiye et al. [Nature 534, 520 (2016)].

Silk fibroin-coated PLGA dimpled microspheres for retarded release of simvastatin.

The surface physical features and chemical components of polymeric particles play an important role in drug delivery systems. In this study, PLGA blank microspheres and simvastatin-loaded PLGA microspheres with dimpled surface structure were prepared by single emulsion-solvent evaporation method in the absence of any additives. Subsequently, glutaraldehyde cross-linking was optimized for silk fibroin coating on simvastatin-loaded PLGA dimpled microspheres due to good solubility of simvastatin in alcohol. Furthermore, simvastatin release kinetics was investigated for silk-coated or plain PLGA dimpled microspheres. These drug carriers may have potential applications for alveolar ridge preservation with local delivery of simvastatin.