Genome-wide characterization of single-stranded DNA in rice.

Single-stranded DNA (ssDNA) is essential for various DNA-templated processes in both eukaryotes and prokaryotes. However, comprehensive characterizations of ssDNA still lag in plants compared to non-plant systems. Here, we conducted in situ S1-seq (ISS1-seq), with starting gDNA ranging from 5 µg to 250 ng, followed by comprehensive characterizations of ssDNA in rice (Oryza sativa L.). We found that ssDNA loci were substantially associated with a subset of non-B DNA structures and functional genomic loci. Subtypes of ssDNA loci had distinct epigenetic features. Importantly, ssDNA may act alone or partly coordinate with non-B DNA structures, functional genomic loci, or epigenetic marks to actively or repressively modulate gene transcription, which is genomic-region-dependent and associated with the distinct accumulation of RNA Pol II. Moreover, distinct types of ssDNA had differential impacts on the activities and evolution of TEs (especially common or conserved TEs) in the rice genome. Our study showcases an antibody-independent technique for characterizing non-B DNA structures or functional genomic loci in plants. It lays the groundwork and fills a crucial gap for further exploration of ssDNA, non-B DNA structures, or functional genomic loci, thereby advancing our understanding of their biology in plants.

Increased oxygen stimulation promotes chemoresistance and phenotype shifting through PLCB1 in gliomas.

Gliomas, the most common CNS (central nerve system) tumors, face poor survival due to severe chemoresistance exacerbated by hypoxia. However, studies on whether altered hypoxic conditions benefit for chemo-sensitivity and how gliomas react to increased oxygen stimulation are limited. In this study, we demonstrated that increased oxygen stimulation promotes glioma growth and chemoresistance. Mechanically, increased oxygen stimulation upregulates miR-1290 levels. miR-1290, in turn, downregulates PLCB1, while PLCB1 facilitates the proteasomal degradation of ß-catenin and active-ß-catenin by increasing the proportion of ubiquitinated ß-catenin in a destruction complex-independent mechanism. This process inhibits PLCB1 expression, leads to the accumulation of active-ß-catenin, boosting Wnt signaling through an independent mechanism and ultimately promoting chemoresistance in glioma cells. Pharmacological inhibition of Wnt by WNT974 could partially inhibit glioma volume growth and prolong the shortened survival caused by increased oxygen stimulation in a glioma-bearing mouse model. Moreover, PLCB1, a key molecule regulated by increased oxygen stimulation, shows promising predictive power in survival analysis and has great potential to be a biomarker for grading and prognosis in glioma patients. These results provide preliminary insights into clinical scenarios associated with altered hypoxic conditions in gliomas, and introduce a novel perspective on the role of the hypoxic microenvironment in glioma progression. Furthermore, the outcomes reveal the potential risks of utilizing hyperbaric oxygen treatment (HBOT) in glioma patients, particularly when considering HBOT as a standalone option to ameliorate neuro-dysfunctions or when combining HBOT with a single chemotherapy agent without radiotherapy.

Mutasynthesis Generates Antibacterial Benzothiophenic-Containing Nosiheptide Analogues.

Nosiheptide is a bicyclic thiopeptide featuring an indole-containing side ring, which is biologically important in maintaining its potent antibacterial activity. By using mutational biosynthesis, the pharmaceutically significant benzothiophene was introduced into the nosiheptide biosynthetic pathway, resulting in the generation of three bioactive nosiheptide analogues with characteristic benzothiophene-containing side rings. Insights were provided into the transformation relationship of these analogues, which effectively improves the yield of S-NOS-1 with favorable activity against Gram-positive pathogens.

Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells.

BACKGROUND: Hhex(human hematopoietically expressed homeobox), also known as PRH, is originally considered as a transcription factor to regulate gene expression due to its homebox domain. Increasing studies show that Hhex plays a significant role in development, including anterior-posterior axis formation, vascular development and HSCs self-renewal etc. Hhex is linked to many diseases such as cancers, leukemia, and type-2 diabetes. Although Hhex is reported to inhibit cell migration and invasion of breast and prostate epithelial cells by upregulating Endoglin expression, the effect and molecular mechanism for lung cancer cell motility regulation remains elusive. METHODS: Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of Hhex regulating lung cancer cell migration by using Western blot, immunoprecipitation, wound-healing scratch assay, laser confocal. RESULTS: Our data indicated that Hhex could inhibit cell migration and cell protrusion formation in lung cancer cells. In addition, Hhex inhibited CFL1 phosphorylation to keep its F-actin-severing activity. RHOGDIA was involved in Hhex-induced CFL1 phosphorylation regulation. Hhex enhanced RHOGDIA interaction with RHOA/CDC42, thus maintaining RHOA/CDC42 at an inactive form. CONCLUSION: Collectively, these data indicate that Hhex inhibited the activation of RHOA/CDC42 by enhancing interaction of RHOGDIA with RHOA/CDC42, and then RHOA/ CDC42-p-CFL1 signaling pathway was blocked. Consequently, the formation of Filopodium and Lamellipodium on the cell surface was suppressed, and thus the ability of lung cancer cells to migrate was decreased accordingly. Our findings show Hhex plays an important role in regulating migration of lung cancer cells and may provide a potential target for lung cancer therapy. Video abstract.

Implication of Increased Serum IL-31 for Primary Biliary Cholangitis.

Interleukin-31 (IL-31) has diverse biological functions. Increased IL-31 has been found in some skin and autoimmune diseases. There has been no study reporting the association between IL-31 and primary biliary cholangitis (PBC). This study was designed to determine serum IL-31 level and to explore its diagnostic value for PBC as well as the association of IL-31 with inflammatory and fibrotic progression. 60 PBC patients, 32 age- and sex-matched patients with chronic hepatitis B (CHB) and 30 age- and sex-matched healthy controls (HC) were recruited. The sera were detected for IL-31, IL-4, interferon gamma (IFN-γ), IL-17 and other laboratory indicators. Serum IL-31 levels were significantly higher in PBC patients (median, IQR, 20.6, 16.7-26.2, pg/ml) than CHB patients (median, IQR, 11.3, 8.0-13.0, pg/ml) and HC (median, IQR, 11.0, 10.0-12.2 pg/ml) (P < .001). Serum IL-31 performed well for identifying PBC, especially for antimitochondrial antibodies (AMA)-negative PBC with AUC of 0.900, optimal cutoff value of 13.6 pg/ml, sensitivity of 87.5% and specificity of 83.9%. Serum IL-31 was positively correlated with platelet count (r = 0.368, P = .004), but negatively with FIB4 (r = -0.307, P = .017) and histological stages (r = -0.364, P = .004) in PBC patients. It was also significantly correlated with IFN-γ (r = 0.404, P = .001) and IL-4 (r = 0.291, P = .026), but not with IL-17 (r = 0.151, P = .259) in PBC patients. Serum IL-31 is increased in and may be a useful marker for PBC, in particular, for AMA-negative PBC. Furthermore, it is inversely associated with fibrotic progression of PBC.

Nosiheptide analogues as potential antibacterial agents via dehydroalanine region modifications: Semi-synthesis, antimicrobial activity and molecular docking study.

The frequent and inappropriate use of antibiotics aggravate the variation and evolution of multidrug-resistant bacteria, posing a serious threat to public health. Nosiheptide (NOS) has excellent lethality against a variety of Gram-positive bacteria, however the physical and chemical drawbacks hamper its routine application in clinical practice. In this study, by using NOS as the starting material, a total of 15 NOS analogues (2a-4e) were semi-synthesized via its dehydroalanine residue reacting with monosubstituted anilines. In vitro antimicrobial susceptibilities of NOS and its analogues against two methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) clinical isolates were determined by broth microdilution assay to determine the minimum inhibitory concentration (MIC). Antimicrobial susceptibility testing data shown that most of the NOS analogues had a better antibacterial effect than the parent compound, with compound 3c exhibiting the highest antibacterial activity against VRE (MIC = 0.0078 mg/L) and MRSA (MIC < 0.0039 mg/L). Molecular docking of synthetic compounds was also performed to verify the binding interactions of NOS analogues with the target. Our data indicated that compound 3c possesses stronger and more complex intermolecular force than other analogues, which is consistent with the results of the biological activity evaluation. Overall, this study identified a number of potential antibacterial NOS analogues that could act as potent therapeutic agents for multidrug-resistant bacterial infections.

Characteristics of serum chemokine profile in primary biliary cholangitis.

Although chemokines have been believed to exert a pivotal role in pathogenesis of primary biliary cholangitis (PBC), comprehensive analysis of circulating chemokine profile in PBC has been little performed. The aim of this study is to determine serum chemokine profile and to explore its association with the development and progression of PBC. Sixty PBC patients and 30 healthy controls (HC) were enrolled. The sera were detected for 14 chemokines using multiplex immunoassay. The expression of CD3 and CD68 in the portal area of liver tissues was determined by immunohistochemistry in 6 PBC patients. The characteristics of chemokine profile in PBC were analyzed. Serum concentrations of most chemokines were higher, but TARC/CCL17, MDC/CCL22 and ENA-78/CXCL5 were lower in PBC patients than those in HC (all P < 0.05). Most of increased chemokines remained significant in both early and advanced PBC patients. PBC stage was correlated inversely with MCP-4/CCL13(r = -0.373), TARC/CCL17(r = -0.365), ENA-78/CXCL5 (r = -0.418) and I-TAC/CXCL11(r = -0.262), but positively with fractalkine/CX3CL1(r = 0.325). There were significant correlations between serum levels of IP-10/CXCL10 (r = 0.971, P = 0.001) and I-TAC/CXCL11 (r = 0.883, P = 0.020) and CD3 expression within the portal area, and between MIP-3α/CCL20 and CD68 expression within the portal area (r = 0.886, P = 0.019). In PBC patients, there were significant correlations among each other of MCP-4/CCL13, TARC/CCL17, MDC/CCL22, CTACK/CCL27, ENA-78/CXCL5, IP-10/CXCL10, I-TAC/CXCL11, excepting correlations of CTACK/CCL27 with IP-10/CXCL10 and I-TAC/CXCL11. Also, there were strong correlations among each other of CCL3/MIP-1α, CCL4/MIP-1ß and IL-8/CXCL8. The only negative correlation was found in the serum between fractalkine/CX3CL1 and TARC/CCL17 (r = -0.311, P = 0.016). Serum levels of most chemokines are increasing throughout the development and progression of PBC, with the exception of chemokines, mainly attractive for neutrophil and eosinophil (e.g. ENA-78/CXCL5, MCP-4/CCL13), decreasing in advanced PBC, and of chemokines, dominantly responsible for Th2 chemotaxis (e.g. TARC/CCL17), decreasing in early PBC and associating negatively with PBC progression.

The deubiquitinase USP22 regulates PD-L1 degradation in human cancer cells.

BACKGROUND: Many cancers evade immune surveillance by overexpressing PD-L1. PD-L1 interacted with its receptor PD-1, resulting in reduction of T cell proliferation and activation and thereafter cancer cell death mediated by T-lymphocyte. Understanding the mechanisms that regulate PD-L1 was of vital importance for immune checkpoint blockade therapy (ICBT). METHODS: Human non-small cell lung cancer cells and 293FT cells were used to investigate the function of USP22 upon PD-L1 and CSN5 by WB, Immunoprecipitation, Immunofluorescence and Flow cytometry analysis. B16-F10 cells were used to explore the role of USP22 on tumorigenesis and T cell cytotoxicity. The relationship between USP22 and PD-L1 expression was investigated by Immunohistochemistry analysis in human non-small cell lung cancer samples. RESULTS: Our data showed that USP22 interacted with PD-L1 and promoted its stability. USP22 deubiquitinated PD-L1 and inhibited its proteasome degradation. Moreover, USP22 also interacted with CSN5 and stabilized CSN5 through deubiquitination. Either USP22 or CSN5 could facilitate the interaction of PD-L1 with the other one. Furthermore, USP22 removed K6, K11, K27, K29, K33 and K63-linked ubiquitin chain of both CSN5 and PD-L1. In addition, USP22 depletion inhibited tumorigenesis and promoted T cell cytotoxicity. Besides, USP22 expression positively correlated with PD-L1 expression in human non-small cell lung cancer samples. CONCLUSIONS: Here, we suggested that USP22 is a new regulator for PD-L1. On the one hand, USP22 could directly regulate PD-L1 stability through deubiquitination. On the other hand, USP22 regulated PD-L1 protein level through USP22-CSN5-PD-L1 axis. In addition, USP22 depletion inhibited tumorigenesis and promoted T cell cytotoxicity. Besides, USP22 expression positively correlated with PD-L1 expression in human non-small cell lung cancer samples. Together, we identified a new regulator of PD-L1 and characterized the important role of USP22 in PD-L1 mediated immune evasion. Targeting USP22 might be a new solution to ICBT. Video abstract.

Inhibition of SIRT1/2 upregulates HSPA5 acetylation and induces pro-survival autophagy via ATF4-DDIT4-mTORC1 axis in human lung cancer cells.

Sirtuins have emerged as a promising novel class of anti-cancer drug targets. Inhibition of SIRT1 and SIRT2 induces apoptosis in cancer cells and they play multifaceted roles in regulating autophagy. In the present study, we found that salermide, a SIRT1/2-specific inhibitor or small interfering RNAs (siRNAs) to block SIRT1/2 expression could induce autophagy in human NSCLC cells. Moreover, SIRT1/2 inhibition increased the expression levels of ATF4 and DDIT4 and downregulated p-RPS6KB1 and p-EIF4EBP1, two downstream molecules of mTORC1. Moreover, ATF4 or DDIT4 knockdown attenuated salermide-induced autophagy, suggesting that SIRT1/2 inhibition induced autophagy through the ATF4-DDIT4-mTORC1 axis. Mechanistically, SIRT1/2 inhibition led to HSPA5 acetylation and dissociation from EIF2AK3, leading to ER stress response and followed by upregulation of ATF4 and DDIT4, triggering autophagy. Silencing of the autophagic gene ATG5 in lung cancer cells resulted in increased apoptotic cell death induced by SIRT1/2 inhibition. Our data show that inhibition of SIRT1/2 induces pro-survival autophagy via acetylation of HSPA5 and subsequent activation of ATF4 and DDIT4 to inhibit the mTOR signaling pathway in NSCLC cells. These findings suggest that combinatorial treatment with SIRT1/2 inhibitors and pharmacological autophagy inhibitors is an effective therapeutic strategy for cancer therapy.

A Novel Surface Acoustic Wave Sensor Array Based on Wireless Communication Network.

A novel surface acoustic wave (SAW) sensor array based on wireless communication network is prepared. The array is composed of four SAW sensors, a wireless communication network module, and a global positioning system (GPS) module. The four SAW sensors of the array are coated with triethanolamine, polyepichlorohydrin, fluoroalcoholpolysiloxane, and L-glutamic acid hydrochloride to detect hydrogen sulfide (H2S), 2-chloroethyl ethyl sulfide (CEES), dimethylmethylphosphonate (DMMP), and ammonia (NH3) at film thicknesses of 50⁻100 nm. The wireless communication network module consists of an acquisition unit, a wireless control unit, and a microcontroller unit. By means of Zigbee and Lora technologies, the module receives and transmits the collected data to a PC work station in real-time; moreover, the module can control the sensor array's working mode and monitor the working status. Simultaneously, the testing location is determined by the GPS module integrated into the SAW sensor array. H2S, CEES, DMMP, and NH3 are detected in 300 m at different concentrations. Given the practical future application in environment in the future, the low, safe concentrations of 1.08, 0.59, 0.10, and 5.02 ppm for H2S, CEES, DMMP, and NH3, respectively, are detected at the lowest concentration, and the sensitivities of different sensors of the sensor array are 32.4, 14.9, 78.1 and 22.6 Hz/ppm, respectively. With the obtained fingerprints and pattern recognition technology, the detected gases can be recognized.

Selective Surface Acoustic Wave-Based Organophosphorus Sensor Employing a Host-Guest Self-Assembly Monolayer of ß-Cyclodextrin Derivative.

Self-assembly and molecular imprinting technologies are very attractive technologies for the development of artificial recognition systems and provide chemical recognition based on need and not happenstance. In this paper, we employed a b-cyclodextrin derivative surface acoustic wave (SAW) chemical sensor for detecting the chemical warfare agents (CWAs) sarin (O-Isoprophyl methylphosphonofluoridate, GB). Using sarin acid (isoprophyl hydrogen methylphosphonate) as an imprinting template, mono[6-deoxy-6-[(mercaptodecamethylene)thio]]-ß-cyclodextrin was prepared by self-assembled method on one of the SAW oscillators. After templates' removal, a sensitive and selective molecular imprinting (MIP) monolayer for GB was prepared. Electrochemical impedance spectroscopy and atomic force microscope (AFM) were used to characterize this film. Comparing the detection results to GB by MIP film and non-MIP film, the molecularly imprinting effect was also proved. The resulting SAW sensor could detect sarin as low as 0.10 mg/m3 at room temperature and the frequency shift was about 300 Hz. The response frequency increased linearly with increasing sarin concentration in the range of 0.7 mg/m3~3.0 mg/m3. When sarin was detected under different temperatures, the SAW sensor exhibited outstanding sensitivity and reliability.

Feather mites of the genus Passeroptes Fain (Acariformes: Dermationidae) from passerines (Aves: Passeriformes) of China.

Five new species of the feather mite genus Passeroptes (Acariformes: Dermationidae) are recorded from birds of the order Passeriformes in China: P. lioparis sp. nov. from Chrysotus chrysotis (Blyth) (Paradoxornithidae); P. motacillae sp. nov. from Motacilla cinerea Tunstall (Motacillidae); P. cyanodermae sp. nov. from Cyanoderma ruficeps Blyth (Timaliidae); P. periparus sp. nov. from Periparus ater (Linnaeus) (Paridae); P. aegithalos sp. nov. from Aegithalos iouschistos bonvaloti (Oustalet) (Aegithalidae).

A SAW-based chemical sensor for detecting sulfur-containing organophosphorus compounds using a two-step self-assembly and molecular imprinting technology.

This paper presents a new effective approach for the sensitive film deposition of surface acoustic wave (SAW) chemical sensors for detecting organophosphorus compounds such as O-ethyl-S-2-diisopropylaminoethyl methylphosphonothiolate (VX) containing sulfur at extremely low concentrations. To improve the adsorptive efficiency, a two-step technology is proposed for the sensitive film preparation on the SAW delay line utilizing gold electrodes. First, mono[6-deoxy-6-[(mercaptodecamethylene)thio]]-ß-cyclodextrin is chosen as the sensitive material for VX detection, and a ~2 nm-thick monolayer is formed on the SAW delay line by the binding of Au-S. This material is then analyzed by atomic force microscopy (AFM). Second, the VX molecule is used as the template for molecular imprinting. The template is then removed by washing the delay line with ethanol and distilled water, thereby producing the sensitive and selective material for VX detection. The performance of the developed SAW sensor is evaluated, and results show high sensitivity, low detection limit, and good linearity within the VX concentration of 0.15-5.8 mg/m3. The possible interactions between the film and VX are further discussed.

[A Case of EML4-ALK Fusion V1 Subtype Lung Adenocarcinoma 
Detected by RNA-based NGS].

Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide. For lung adenocarcinoma, identifying specific gene mutations, fusions, and giving corresponding targeted drugs can greatly improve the survival time of the patients. Among them, anaplastic lymphoma kinase (ALK) fusion occurs in 3%-7% of non-small cell lung cancer (NSCLC). In clinical practice, a variety of detection methods can be used to determine the ALK fusion status, but false negative test results are possible. This paper retrospectively analyzed the diagnosis and treatment of a patient with lung adenocarcinoma, judged the ALK fusion status by various detection methods. Among them, immunohistochemistry (IHC)(Ventana D5F3), RNA based next-generation sequencing (RNA-based NGS) confirmed positive echinoderm microtubule associated protein like 4 (EML4)-ALK fusion, while DNA-based NGS was negative. This paper analyzed the detection methods of ALK fusion, in order to clarify which detection method is the most accurate and simple to choose in different clinical cases and guide the subsequent treatment.
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High-sensitivity THz-ATR imaging of cerebral ischemia in a rat model.

The fast label-free detection of the extent and degree of cerebral ischemia has been the difficulty and hotspot for precise and accurate neurosurgery. We experimentally demonstrated that the fresh cerebral tissues at different ischemic stages within 24 hours can be well distinguished from the normal tissues using terahertz (THz) attenuated total reflection (ATR) imaging system. It was indicated that the total reflectivity of THz wave for ischemic cerebral tissues was lower than that for normal tissues. Especially, compared to the images stained with 2,3,5-triphenyl tetrazolium chloride (TTC), the ischemic tissues can be detected using THz wave with high sensitivity as early as the ischemic time of 2.5 hours, where THz images showed the ischemic areas became larger and diffused as the ischemic time increasing. Furthermore, the THz spectroscopy of cerebral ischemic tissues at different ischemic times was obtained in the range of 0.5-2.0 THz. The absorption coefficient of ischemic tissue increased with the increase of ischemic time, whereas the refractive index decreased with prolonging the ischemic time. Additionally, it was found from hematoxylin and eosin (H&E) staining microscopic images that, with the ischemic time increasing, the cell size and cell density of the ischemic tissues decreased, whereas the intercellular substance of the ischemic tissues increased. The result showed that THz recognition mechanism of the ischemia is mainly based on the increase of intercellular substance, especially water content, which has a stronger impact on absorption of THz wave than that of cell density. Thus, THz imaging has great potential for recognition of cerebral ischemia and it may become a new method for intraoperative real-time guidance, recognition in situ, and precise excision.

Tumor microenvironment targeting for glioblastoma multiforme treatment via hybrid cell membrane coating supramolecular micelles.

Glioblastoma multiforme (GBM) is one of the most common primary intracranial tumors in the central nervous system with poor prognosis, high invasiveness, risk of recurrence and low survival rate. Thus, it is urgent and vital to develop drug effective delivery systems that efficiently to traverse the blood-brain barrier and targeted transport therapeutic agents into the GBM tumor site for the treatment of brain tumors. Recently, amphiphilic cucurbit[7]uril-polyethylene glycol-hydrophobic Chlorin e6 (CB[7]-PEG-Ce6) polymer was designed, prepared, and self-assembled into micells (CPC) in an aqueous solution, and chemo drug methyl-triazeno-imidazole-carboxamide (MTIC), loaded into the cavity of CB[7] was subsequently coated with hybrid membrane mUMH (HMC3 membrane: macrophage membrane: U87MG membrane = 1:1:2) to afford mUMH@CPC@MTIC. The surface hybrid membrane mUMH potentially enhance the targeted delivery of CPC@MTIC to GBM tissue. Bioactive MTIC was released from the cavity of CB[7] in response to the high spermine level in GBM tumor microenvironments for effective tumor chemotherapy. The biomimetic mUMH@CPC@MTIC exhibited superior antitumor efficacy against GBM in mice. These findings provide new strategies for the design of biomimetic nanoparticle-based drug delivery systems and promising therapy of GBM.

Study of the relationship among biomarkers, cell and tissue of glioma through Raman spectroscopy.

Glioma is the most common brain tumors with high mortality and recurrence rates. Currently, the diagnosis methods for glioma are mainly based on tissue level, cellular level and biomarker level. In this paper, the characteristics of biomarkers (γ-aminobutyric acid and matrix mtalloproteinses-2), U87MG glioma cell and tissue were studied based on Raman spectroscopy, respectively. The results showed that the γ-aminobutyric acid concentration exhibited a linear relation with the intensity of characteristic peaks in 800-1600 cm-1 region, whereas the spectral baseline increased with the increasing of sample concentration in 200-700 cm-1 region. The Raman characteristics of matrix mtalloproteinses-2 in 20-1800 cm-1 region was investigated. Especially, it is demonstrated that the matrix mtalloproteinses-2 showed sixteen low-wavenumber Raman peaks in the range of 20-300 cm-1. Moreover, the U87MG glioma cell showed seven different Raman characteristic peaks in 600-1800 cm-1 region. Compared with the normal tissue, the Raman intensity of tumor tissue showed apparent intensity differences in 300-1800 cm-1, where the intensity changes of these Raman peaks were related to the reducing of the lipid metabolic pathways, and increase of the RNA in tumor tissue region. Furthermore, it is found that the Raman spectra of U87MG glioma cell and tumor tissue had corresponding peaks in the Raman spectra of the liquid γ-aminobutyric acid and matrix mtalloproteinses-2. It is suggested that the γ-aminobutyric acid and matrix mtalloproteinses-2 contributed to the formation and growth of glioma cell and tissue. Thus, Raman spectroscopy not only can diagnose glioma at the biomarkers, cellular and tissue level, but also analyze the relationship among the three. Furthermore, the results provided a physical marker for the detection of glioma in clinically.

TMEM216 promotes primary ciliogenesis and Hedgehog signaling through the SUFU-GLI2/GLI3 axis.

Primary cilia are enriched in signaling receptors, and defects in their formation or function can induce conditions such as polycystic kidney disease, postaxial hexadactyly, and microphthalmia. Mammalian Hedgehog (Hh) signaling is important in the development of primary cilia, and TMEM216, a transmembrane protein that localizes to the base of cilia, is also implicated in ciliogenesis in zebrafish. Here, we found that Tmem216-deficient mice had impaired Hh signaling and displayed typical ciliopathic phenotypes. These phenomena were also observed in cells deficient in TMEM216. Furthermore, TMEM216 interacted with core Hh signaling proteins, including SUFU, a negative regulator of Hh, and GLI2/GLI3, transcription factors downstream of Hh. The competition between TMEM216 and SUFU for binding to GLI2/GLI3 inhibited the cleavage of GLI2/GLI3 into their repressor forms, which resulted in the nuclear accumulation of full-length GLI2 and the decreased nuclear localization of cleaved GLI3, ultimately leading to the activation of Hh signaling. Together, these data suggest that the TMEM216-SUFU-GLI2/GLI3 axis plays a role in TMEM216 deficiency-induced ciliopathies and Hh signaling abnormalities.

Correlation Between Air Quality Index and Tear Film Lipid Layer Thickness: Comparison Between Patients with Sjogren's Syndrome and with Meibomian Gland Dysfunction.

PURPOSE: To evaluate the effect of air pollution on the tear film stability by analyzing the correlation between Air Quality Index (AQI) and Lipid Layer thickness (LLT) in Xuzhou. METHODS: As a prospective descriptive observational study, 284 patients with meibomian gland dysfunction (MGD), 157 patients with Sjögren's syndrome (SS), and 264 healthy volunteers were included. The tear film lipid layer thickness of the three groups of subjects was measured weekly and compared with the air quality index to analyze the correlation between the two indicators. Logistic regression analysis and linear regression analysis were used to analyze the effect of AQI on the thickness of the tear film lipid layer. The change of LLT with air pollution at different AQI levels was also analyzed. RESULTS: There are obvious seasonal differences in the changes of air pollution index in Xuzhou. Significant differences could be observed in the thickness of the lipid layer of the tear film among the three groups. LLT in the MGD group and SS group decreased with the aggravation of air pollution, while remained unchanged in the control group. There was strong evidence of correlation between LLT of the MGD group (F = 353.494, p < 0.01, adjusted R2 = 0.695) and the SS group (F = 502.404, p < 0.01, adjusted R2 = 0.764) with AQI, while there was minor correlation between LLT with AQI in control group (F = 8.525, p < 0.01, adjusted R2 = 0.046). CONCLUSIONS: Air pollution can cause a decrease in the thickness of the tear film lipid layer, thereby affecting tear film stability, leading to the occurrence of dry eye.

Crotonylated BEX2 interacts with NDP52 and enhances mitophagy to modulate chemotherapeutic agent-induced apoptosis in non-small-cell lung cancer cells.

Brain expressed X-linked gene 2 (BEX2) encoded protein was originally identified to promote transcription by interacting with several transcription factors in the DNA-binding complexes. Recently, BEX2 was found to be localized in cytosol and/or mitochondria and regulate apoptosis in cancer cells and tumor growth. However, the molecular mechanism underlying its roles in cancer cells remains unclear. Here, we report that crotonylated BEX2 plays an important role in inhibiting chemotherapeutic agent-induced apoptosis via enhancing mitophagy in human lung cancer cells. BEX2 promotes mitophagy by facilitating interaction between NDP52 and LC3B. Moreover, BEX2 crotonylation at K59 is critical in the BEX2-mediated mitophagy in lung cancer cells. The K59R mutation of BEX2 inhibits mitophagy by affecting the interaction of NDP52 and LC3B. BEX2 expression is elevated after anticancer drug treatment, and its overexpression inhibits chemotherapy-induced apoptosis. In addition, inhibition of BEX2-regulated mitophagy sensitizes tumor cells to apoptosis. Furthermore, BEX2 promotes tumor growth and inhibits apoptosis by regulating mitophagy in vivo. We also confirm that BEX2 is overexpressed in lung adenocarcinoma and is associated with poor prognosis in lymph node metastasis-free cancer. Therefore, combination treatment with pharmaceutical approaches targeting BEX2-induced mitophagy and anticancer drugs may represent a potential strategy for NSCLC therapy.