Rapidly responsive and highly selective NIR fluorescent probe for detecting hydrogen sulfide in food samples and living cells.

Hydrogen sulfide (H2S) is a pungent gas that is one of the key mediators of signal transduction in biological systems, and its presence is related to the freshness of some protein foods. Using phenothiazine derivatives as fluorophores and 2, 4-dinitrobenzene sulfonate (DNBS) fragments as reaction groups, a near-infrared (NIR) probe WX-HS for H2S identification was designed. With the addition of H2S, WX-HS appeared a strong fluorescence signal at 660 nm with short reaction time (90 s) and high sensitivity, and fluorescence state change from non-fluorescent to orange-red. In addition, WX-HS could effectively detect H2S produced during food oxidation. Based on its low cytotoxicity, the WX-HS probe further enabled the detection and imaging of H2S in A549 cells.

Engineering the Band Topology in a Rhombohedral Trilayer Graphene Moiré Superlattice.

Moiré superlattices have become a fertile playground for topological Chern insulators, where the displacement field can tune the quantum geometry and Chern number of the topological band. However, in experiments, displacement field engineering of spontaneous symmetry-breaking Chern bands has not been demonstrated. Here in a rhombohedral trilayer graphene moiré superlattice, we use a thermodynamic probe and transport measurement to monitor the Chern number evolution as a function of the displacement field. At a quarter filling of the moiré band, a novel Chern number of three is unveiled to compete with the well-established number of two upon turning on the electric field and survives when the displacement field is sufficiently strong. The transition can be reconciled by a nematic instability on the Fermi surface due to the pseudomagnetic vector field potentials associated with moiré strain patterns. Our work opens more opportunities to active control of Chern numbers in van der Waals moiré systems.

Chemical Potential Characterization of Symmetry-Breaking Phases in a Rhombohedral Trilayer Graphene.

Rhombohedral trilayer graphene has recently emerged as a natural flat-band platform for studying interaction-driven symmetry-breaking phases. The displacement field (D) can further flatten the band to enhance the density of states, thereby controlling the electronic correlation that tips the energy balance between spin and valley degrees of freedom. To characterize the energy competition, chemical potential measurement─a direct thermodynamic probe of Fermi surfaces─is highly demanding to be conducted under a constant D. In this work, we characterize D-dependent isospin flavor polarization, where electronic states with isospin degeneracies of one and two can be identified. We also developed a method to measure the chemical potential at a fixed D, allowing for the extraction of energy variation during phase transitions. Furthermore, symmetry breaking could also be invoked in Landau levels, manifesting as quantum Hall ferromagnetism. Our work opens more opportunities for the thermodynamic characterization of displacement-field tuned van der Waals heterostructures.

A novel diarylethene-based fluorescence sensor for Zn2+ detection and its application.

A series of fluorometric sensors of Zn2+ have been synthesized due to the significant function of Zn2+ in the human body and environment. However, most of probes reported for detecting Zn2+ have high detection limit or low sensitivity. In this paper, an original Zn2+ sensor, namely 1o, was synthesized by diarylethene and 2-aminobenzamide. When Zn2+ was added, the fluorescence intensity of 1o increased by 11 times within 10 s, along with a fluorescence color change from dark to bright blue, and the detection limit (LOD) was calculated to be 0.329 µM. According to Job's plot curves, the binding mode of 1o and Zn2+ was measured as 1:1, which was further proved by 1H NMR spectra, HRMS and FT-IR spectra. The logic circuit was designed to take advantage of the fact that the fluorescence intensity of 1o can be controlled by Zn2+, EDTA, UV and Vis. In addition, Zn2+ in actual water samples were tested, in which the recovery rate of Zn2+ was between 96.5 % and 109 %. Furthermore, 1o was successfully made into a fluorescent test strip, which could be used to detect Zn2+ in the environment economically and conveniently.

A "Turn-on" Fluorescent Probe Based on Phenothiazine for Selectively Recognizing ClO- and its Practical Applications.

Hypochlorous acid (HClO), a highly reactive oxygen species, has important effects on human health. High selectivity and sensitivity remain challenges of fluorescent probes for detection of ClO- with a large Stokes shift. This work designed and synthesized a novel phenothiazine-based fluorescent probe TF which can detect ClO- by colorimetric and fluorescent dual signals. TF displayed turn-on fluorescence effect toward ClO- with high selectivity (≥ 28-folds) and sensitivity (LOD = 0.472 µM), fast response time (< 1 min) and large Stokes shift (150 nm) in PBS (pH = 7.4, 40% DMSO). Meanwhile, TF can visualize ClO- on the mung bean sprouts model and apply as testing strips for portable and rapid detecting ClO- by the naked eyes. A phenothiazine-based fluorescent probe with large Stokes shift was synthesized and its responding rapidly ability to detect ClO- was studied.

Giant ferroelectric polarization in a bilayer graphene heterostructure.

At the interface of van der Waals heterostructures, the crystal symmetry and the electronic structure can be reconstructed, giving rise to physical properties superior to or absent in parent materials. Here by studying a Bernal bilayer graphene moiré superlattice encapsulated by 30°-twisted boron nitride flakes, we report an unprecedented ferroelectric polarization with the areal charge density up to 1013 cm-2, which is far beyond the capacity of a moiré band. The translated polarization ~5 pC m-1 is among the highest interfacial ferroelectrics engineered by artificially stacking van der Waals crystals. The gate-specific ferroelectricity and co-occurring anomalous screening are further visualized via Landau levels, and remain robust for Fermi surfaces outside moiré bands, confirming their independence on correlated electrons. We also find that the gate-specific resistance hysteresis loops could be turned off by the other gate, providing an additional control knob. Furthermore, the ferroelectric switching can be applied to intrinsic properties such as topological valley current. Overall, the gate-specific ferroelectricity with strongly enhanced charge polarization may encourage more explorations to optimize and enrich this novel class of ferroelectricity, and promote device applications for ferroelectric switching of various quantum phenomena.

Clinical features, treatment outcomes and prognostic factors of allopurinol-induced DRESS in 52 patients.

WHAT IS KNOWN AND OBJECTIVE: Allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious and potentially life-threatening drug hypersensitivity syndrome. In this study, we aimed to investigate the clinical features, treatment outcomes, and prognostic factors of allopurinol-induced DRESS. METHODS: Case reports of allopurinol-induced DRESS published by China from January 2000 to August 2021 were retrieved from CNKI, Wan Fang, VIP, and PubMed databases for analysis. RESULTS AND DISCUSSION: This study included 52 patients, consisting of 41 (78.8%) males and 11 (21.2%) females (M:F = 3.7:1). The mean of age was 56.1 ± 17.1 years (range: 18-86 years). The mean of latency periods was 24.6 ± 15.0 days (range:1-63 days). Most patients presented with fever, cutaneous eruption, eosinophilia, lymphadenopathy, and facial edema. 36/52 (69.2%) patients showed two or more internal organs involved. Liver and kidney injuries were the most common visceral manifestation. Pulmonary involvement (34.6%), cardiac involvement (25.0%) and gastrointestinal involvement (21.2%) were relatively less known but severe complications. 2/52 (3.8%) patients showed nervous system involved, presenting as leukoencephalopathy or peripheral neuropathy. 2/52 (3.8%) patients presented with secondary hemophagocytic lymphohistiocytosis.1/52 (1.9%) patient developed pure red cell aplasia and 1/52 (1.9%) patient developed painless thyroiditis. HLA*B 58:01 allele was tested in 18/52 (34.6%) patients. 16/18 (88.9%) cases were positive. 48/52 (92.3%) patients were treated with systemic corticosteroids. 16/52 (30.8%) patients were cured, 23/52 (44.2%) patients received partial recovery, and 13/52 (25.0%) patients were died. Septic shock, gastrointestinal bleeding and multiple organ failure were the leading causes of death. Advanced age, underlying cardiovascular disease, chronic kidney disease and high dose of allopurinol, infection and internal organ involvement (including kidney, heart, lung and gastrointestinal tract) were risk factors for death. WHAT IS NEW AND CONCLUSION: We explored clinical features, treatment outcomes and prognostic factors of 52 allopurinol-induced DRESS cases in China. Ethnicity, especially Han Chinese, and positive HLA-B*58:01 allele are the clearest risk factors so far. Advanced age, underlying cardiovascular disease, chronic kidney disease and high dose of allopurinol, infection and internal organ involvement (including kidney, heart, lung and gastrointestinal tract) were associated with poorer outcomes. Early identification and discontinuation of the causative drug are crucial to the management of DRESS. For patients with severe disease, corticosteroids are recommended as the first-line therapy. However, further studies are needed to address diagnostic criteria of DRESS for early diagnosis, as well as to develop standardized corticosteroid treatment regimens.

Hydrochemical analysis and identification of open-pit mine water sources: a case study from the Dagushan iron mine in Northeast China.

The identification of open-pit mine water sources is of great significance in preventing water disasters. Combined with hydrochemistry and multivariate statistical analysis, this paper systematically analyzed the hydraulic connections between aquifers and the complex seepage water sources in the pit and roadway of Dagushan iron mine through qualitative analysis and quantitative calculation. According to the hydrochemical characteristics of the study area, the causes of seepage water at different positions in the mining area were reasonably explained. The results show that there is a possible hydraulic connection or similar source of water body between the bedrock fissure aquifer and the eluvium pore aquifer. The water seepage of 2# roadway mainly comes from bedrock fissure aquifer in the north of mining area. The reason for serious water seepage in the 3# roadway and the western side of the pit is that the fault connects the shallow alluvial pore aquifer and bedrock fissure aquifer. The source of water on the southern side pit comes from the river and groundwater on the southern side of the mine. The results presented here provide significant guidance for the management of mine water seepage problems.

Activation of FGD5-AS1 Promotes Progression of Cervical Cancer through Regulating BST2 to Inhibit Macrophage M1 Polarization.

Accumulating evidence has elucidated the biological function of lncRNAs in various tumors. FGD5 antisense RNA 1 (FGD5-AS1) is identified as a significant tumor regulator in malignancies. Up to now, the detailed function of FGD5-AS1 in cervical cancer and its underlying molecular mechanisms remain uninvestigated. Bone marrow stromal cell antigen 2 (BST2) can play critical roles in immune response, and the roles of BST2 in cervical cancer was explored currently. The level of FGD5-AS1 and BST2 was detected by qRT-PCR in cervical cancer cells. FGD5-AS1 and BST2 expression was significantly upregulated in cervical cancer cells. Then, the decrease of FGD5-AS1 greatly repressed cervical cancer cell growth in vitro. In addition, FGD5-AS1 silencing repressed BST2 expression and suppressed M2 macrophage polarization. Mechanistically, we confirmed that FGD5-AS1 sponged miR-129-5p to reduce its inhibition on BST2. Furthermore, lack of BST2 depressed cervical cancer cell growth, while inducing apoptosis. Loss of BST2 induced M1 macrophage polarization while blocking M2 macrophage polarization. For another, we demonstrated that FGD5-AS1-triggered M2 macrophage polarization was remarkably reversed by miR-129-5p via suppressing BST2. In conclusion, FGD5-AS1 induced M2 macrophage polarization via sponging miR-129-5p and modulating BST2, thus contributing to cervical cancer development. Our findings revealed FGD5-AS1/miR-129-5p/BST2 as a new potential target for cervical cancer.

Analysis of different hematoma expansion shapes caused by different risk factors in patients with hypertensive intracerebral hemorrhage.

OBJECTIVE: To elucidate the relationship between the risk factors and hematoma expansion(HE)shapes. PATIENTS AND METHODS: From February 2013 to November 2018, 60 patients diagnosed as basal ganglia ICH were divided into the filled type hematoma expansion group (FTE group) and the expanded type hematoma expansion group (ETE group). we performed follow-up CT and three-dimensional reconstruction for the patients and compared the hematoma before and after the expansion of size and extent. RESULTS: The regression analysis showed that the irregular sign (odds ratio, 3.64; 95 % CI, 1.46-9.12), black hole sign (odds ratio, 3.85; 95 % CI, 1.40-10.60), blend sign (odds ratio, 2.86; 95 % CI, 1.03-7.95), and early use of dehydration (odds ratio, 4.59; 95 % CI, 1.59-13.19) were possible risk factors for the ETE group, while the high systolic blood pressure (odds ratio, 1.51; 95 % CI, 1.04-2.30), early use of dehydration (odds ratio, 3.27; 95 % CI, 1.10-9.69) and low density low-density band (odds ratio, 4.52; 95 % CI, 1.54-13.28) were possible risk factors for the FTE group. CONCLUSIONS: The irregular sign, black hole sign, blend sign and early use of dehydration may be the main risk factors for ETE, whereas early use of dehydration, high systolic blood pressure, and low density low-density band may be the main risk factors for FTE.

Inhibition of NF-κB Reduces Renal Inflammation and Expression of PEPCK in Type 2 Diabetic Mice.

Renal gluconeogenesis is markedly promoted in patients with type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains largely unknown. Renal gluconeogenesis is found to be negatively regulated by insulin. T2DM is characterized by chronic and subacute inflammation; however, inflammation has been well recognized to induce insulin resistance. Therefore, this study aimed to investigate whether the enhanced renal gluconeogenesis in T2DM was partially due to the renal inflammation-mediated insulin resistance. If so, whether inflammation inhibitor could partially reverse such change. Diabetic db/db mice and db/m mice were used in our study. Typically, diabetic db/db mice were intraperitoneally treated with 1 mg/kg NF-κB inhibitor parthenolide (PTN) or saline as control every other day. Twelve weeks after treatment, animal samples were collected for measurements. Our results suggested that the expression levels of the inflammatory factors and the gluconeogenic rate-limiting enzyme phosphoenolpyruvate carboxykinase (PEPCK) were up-regulated in renal cortex of both db/db mice and T2DM patients. Moreover, reduced insulin signaling, as well as up-regulated expression of downstream genes FOXO1 and PGC-1ɑ, could be detected in renal cortex of db/db mice compared with that of db/m mice. Consistent with our hypothesis, PTN treatment could alleviate renal inflammation and insulin resistance in db/db mice. Moreover, it could also down-regulate the renal expression of PEPCK, indicating that inflammation could be one of the triggers of insulin resistance and the enhanced renal gluconeogenesis in db/db mice. This study can shed light on the role of inflammation in the enhanced renal gluconeogenesis in T2DM, which may yield a novel target for hyperglycemia.

Epigenetic inactivation of the candidate tumor suppressor gene ASC/TMS1 in human renal cell carcinoma and its role as a potential therapeutic target.

This study investigated the epigenetic alteration and biological function of the pro-apoptotic gene ASC/TMS1 in renal cell carcinoma. ASC/TMS1 was downregulated in five out of six RCC cell lines. A significant downregulation was also detected in sixty-seven paired renal tumors compared with adjacent non-cancerous tissues. The downregulation of ASC/TMS1 was correlated with promoter hypermethylation and could be restored with demethylation treatment. Re-expression of ASC/TMS1 in silenced RCC cell lines inhibited cell viability, colony formation, arrested cell cycle, induced apoptosis, suppressed cell invasion and repressed tumorigenicity in SCID mice. The antitumorigenic function of ASC/TMS1 in renal cancer was partially regulated by activation of p53 and p21 signaling. In addition, restoration of ASC/TMS1 sensitizes RCC cells to DNA damaging agents. Knockdown of ASC/TMS1 reduced DNA damaging agents-induced p53 activation and cell apoptosis. Moreover, ASC/TMS1 hypermethylation was further detected in 41.1% (83/202) of RCC tumors, but only 12% in adjacent non-cancerous tissues. ASC/TMS1 methylation was significantly correlated with higher tumor nuclear grade. In conclusion, ASC/TMS1 is a novel functional tumor suppressor in renal carcinogenesis. ASC/TMS1 tumor specific methylation may be a useful biomarker for designing improved diagnostic and therapeutic strategies for RCC.

Frequent epigenetic suppression of tumor suppressor gene glutathione peroxidase 3 by promoter hypermethylation and its clinical implication in clear cell renal cell carcinoma.

The goal of this study is to identify novel tumor suppressor genes silenced by promoter methylation in clear cell renal cell carcinoma (ccRCC) and discover new epigenetic biomarkers for early cancer detection. Reactive oxygen species (ROS) is a major cause of DNA damage that correlates with cancer initiation and progression. Glutathione peroxidase 3 (GPX3), the only known extracellular glycosylated enzyme of GPXs, is a major scavenger of ROS. GPX3 has been identified as a tumor suppressor in many cancers. However, the role of GPX3 in ccRCC remains unclear. This study aimed to investigate its epigenetic alteration in ccRCC and possible clinicopathological association. In our study, GPX3 methylation and down-regulation were detected in 5 out of 6 ccRCC cell lines and the GPX3 mRNA and protein expression level in ccRCC tumors was significantly lower than in adjacent non-malignant renal tissues (p<0.0001). Treatment with 5-Aza-2'-deoxycytidine restored GPX3 expression in ccRCC cells. Aberrant methylation was further detected in 77.1% (162/210) of RCC primary tumors, but only 14.6% (7/48) in adjacent non-malignant renal tissues. GPX3 methylation status was significantly associated with higher tumor nuclear grade (p=0.014). Thus, our results showing frequent GPX3 inactivation by promoter hypermethylation in ccRCC may reveal the failure in the cellular antioxidant system in ccRCC and may be associated with renal tumorigenesis. GPX3 tumor specific methylation may serve as a biomarker for early detection and prognosis prediction of ccRCC.

DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer.

UNLABELLED: Deleted in lung and esophageal cancer 1 (DLEC1), located at 3p22-p21.3, is involved in the carcinogenesis of multiple cancers, but its role in prostate cancer (PrCa) remains unclear. Here, we studied the epigenetic alteration of DLEC1 and its functions in prostate cancer. We found that DLEC1 was highly expressed in normal prostate tissues, normal prostatic epithelium cell line (RWPE-1), and benign prostatic hyperplasia cell line (BPH-1), but frequently downregulated by promoter methylation in PrCa cell lines. Pharmacologic demethylation could restore DLEC1 expression. DLEC1 was downregulated in prostate tumor tissues compared with their adjacent non-malignant tissues. DLEC1 was methylated in 76/110 primary tumors, but rarely in benign prostatic hyperplasia tissues. DLEC1 methylation was associated with higher PSA levels (p = 0.016), higher Gleason scores (p = 0.015), and more advanced tumor stages (p = 0.003). Furthermore, DLEC1 methylation was detected in 11/30 urine sediment samples from PrCa patients, but seldom in ones from BPH patients. Ectopic expression of DLEC1 inhibited the colony formation of PrCa cells, through inducing cell apoptosis. DLEC1 also suppressed PrCa cell migration. Moreover, DLEC1 inhibited NF-κB transcription activity in PrCa and HEK293 cells. Taken together, our data demonstrate that DLEC1 functions as a tumor suppressor but is frequently methylated in prostate cancer. DLEC1 methylation is associated with prostate cancer progression, which could be a non-invasive epigenetic biomarker for PrCa diagnosis. KEY MESSAGES: • Promoter methylation of DLEC1 is a potential prognostic biomarker for PrCa. • DLEC1, a functional tumor suppressor, is frequently methylated in PrCa. • DLEC1 suppresses prostate cancer growth and metastatic behavior. • DLEC1 mediates tumor-suppressive activities through NF-κB signaling.

Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis.

Interferon regulatory factor 8 (IRF8), as a central element of IFN-γ-signaling, plays a critical role in tumor suppression. However, its expression and underlying molecular mechanism remain elusive in renal cell carcinoma (RCC). Here, we examined IRF8 expression and methylation in RCC cell lines and primary tumors, and further assessed its tumor suppressive functions. We found that IRF8 was widely expressed in human normal tissues including kidney, but frequently downregulated by promoter methylation in RCC cell lines. IRF8 methylation was detected in 25% of primary tumors, but not in adjacent non-malignant renal tissues, and associated with higher tumor nuclear grade of RCC. Ectopic expression of IRF8 inhibited colony formation and migration abilities of RCC cells, through inducing cell cycle G2/M arrest and apoptosis. IFN-γ could induce IRF8 expression in RCC cells, together with increased cleaved-PARP. We further found that IRF8 inhibited expression of oncogenes YAP1 and Survivin, as well as upregulated expression of tumor suppressor genes CASP1, p21 and PTEN. Collectively, our data demonstrate that IRF8 as a functional tumor suppressor is frequently methylated in RCC, and IRF8-mediated interferon signaling is involved in RCC pathogenesis.