N6-methyladenosine-driven miR-143/145-KLF4 circuit orchestrates the phenotypic switch of pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is characterized by vascular remodeling predominantly driven by a phenotypic switching in pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanisms for this phenotypic alteration remain incompletely understood. Here, we identified that RNA methyltransferase METTL3 is significantly elevated in the lungs of hypoxic PH (HPH) mice and rats, as well as in the pulmonary arteries (PAs) of HPH rats. Targeted deletion of Mettl3 in smooth muscle cells exacerbated hemodynamic consequences of hypoxia-induced PH and accelerated pulmonary vascular remodeling in vivo. Additionally, the absence of METTL3 markedly induced phenotypic switching in PASMCs in vitro. Mechanistically, METTL3 depletion attenuated m6A modification and hindered the processing of pri-miR-143/145, leading to a downregulation of miR-143-3p and miR-145-5p. Inhibition of hnRNPA2B1, an m6A mediator involved in miRNA maturation, similarly resulted in a significant reduction of miR-143-3p and miR-145-5p. We demonstrated that miR-145-5p targets Krüppel-like factor 4 (KLF4) and miR-143-3p targets fascin actin-bundling protein 1 (FSCN1) in PASMCs. The decrease of miR-145-5p subsequently induced an upregulation of KLF4, which in turn suppressed miR-143/145 transcription, establishing a positive feedback circuit between KLF4 and miR-143/145. This regulatory circuit facilitates the persistent suppression of contractile marker genes, thereby sustaining PASMC phenotypic switch. Collectively, hypoxia-induced upregulation of METTL3, along with m6A mediated regulation of miR-143/145, might serve as a protective mechanism against phenotypic switch of PASMCs. Our results highlight a potential therapeutic strategy targeting m6A modified miR-143/145-KLF4 loop in the treatment of PH.

Histopathological auxiliary system for brain tumour (HAS-Bt) based on weakly supervised learning using a WHO CNS5-style pipeline.

PURPOSE: Classification and grading of central nervous system (CNS) tumours play a critical role in the clinic. When WHO CNS5 simplifies the histopathology diagnosis and places greater emphasis on molecular pathology, artificial intelligence (AI) has been widely used to meet the increased need for an automatic histopathology scheme that could liberate pathologists from laborious work. This study was to explore the diagnosis scope and practicality of AI. METHODS: A one-stop Histopathology Auxiliary System for Brain tumours (HAS-Bt) is introduced based on a pipeline-structured multiple instance learning (pMIL) framework developed with 1,385,163 patches from 1038 hematoxylin and eosin (H&E) slides. The system provides a streamlined service including slide scanning, whole-slide image (WSI) analysis and information management. A logical algorithm is used when molecular profiles are available. RESULTS: The pMIL achieved an accuracy of 0.94 in a 9-type classification task on an independent dataset composed of 268 H&E slides. Three auxiliary functions are developed and a built-in decision tree with multiple molecular markers is used to automatically formed integrated diagnosis. The processing efficiency was 443.0 s per slide. CONCLUSION: HAS-Bt shows outstanding performance and provides a novel aid for the integrated neuropathological diagnostic workflow of brain tumours using CNS 5 pipeline.

Efficacy of pulsed dye laser combined with fractional CO2 laser in the treatment of pediatric burn scars.

OBJECTIVE: The present study aimed to investigate the efficacy and safety of pulsed dye laser (PDL) combined with fractional CO2 laser in the treatment of burn scars in pediatric patients. METHODS: The present retrospective study enrolled 60 pediatric patients with burn scars from July 2017 to June 2021. In the 4-month treatment period, all patients received PDL treatment every 1 month and received fractional CO2 laser treatment every 3 months. The Patient and Observer Scar Assessment Scale (POSAS) was used to evaluate the scar condition before the treatment as well as 6 months after the whole treatment. The satisfaction of the patient's parents was collected and recorded 6 months after the treatment. Complications were recorded during the treatment period and at follow-up visits. RESULTS: Among all patients, 38 (63.33%) cases were scald-induced scars and 22 (36.67%) cases were burn-induced scars. The mean diameter of the scar area was 107.53 ± 2.92 cm2 . For the measurement of the patient part of POSAS, all indices of pain, itching, color, stiffness, thickness, and irregularity, as well as the total scores were remarkably lower after 6 months of the treatment compared with the baseline (p < 0.05). For the observer part of POSAS, the indices of vascularization, pigmentation, thickness, relief, pliability, and surface area, as well as the total scores were markedly decreased after treatment (p < 0.05). The total satisfactory rate was 96.67% (58/60). No severe complications nor scar aggravation was observed. CONCLUSION: The combination of PDL and fractional CO2 laser showed good efficacy in the treatment of pediatric patients with burn scars with no severe complications and can be recommended in clinical application.

SUMOylation of YTHDF2 promotes mRNA degradation and cancer progression by increasing its binding affinity with m6A-modified mRNAs.

N 6-Methyladenosine (m6A) is the most abundant modification within diverse RNAs including mRNAs and lncRNAs and is regulated by a reversible process with important biological functions. Human YTH domain family 2 (YTHDF2) selectively recognized m6A-RNAs to regulate degradation. However, the possible regulation of YTHDF2 by protein post-translational modification remains unknown. Here, we show that YTHDF2 is SUMOylated in vivo and in vitro at the major site of K571, which can be induced by hypoxia while reduced by oxidative stress and SUMOylation inhibitors. SUMOylation of YTHDF2 has little impact on its ubiquitination and localization, but significantly increases its binding affinity of m6A-modified mRNAs and subsequently results in deregulated gene expressions which accounts for cancer progression. Moreover, Disease-free survival analysis of patients with lung adenocarcinoma derived from TCGA dataset reveals that higher expression of YTHDF2 together with higher expression of SUMO1 predicts poor prognosis. Our works uncover a new regulatory mechanism for YTHDF2 recognition of m6A-RNAs and highlight the importance of YTHDF2 SUMOylation in post-transcriptional gene expression regulation and cancer progression.

Exosomal MMP-1 transfers metastasis potential in triple-negative breast cancer through PAR1-mediated EMT.

PURPOSE: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high risk of distant metastasis, in which the intercellular communication between tumor cells also plays a role. Exosomes can be released by tumor cells and promote distant metastasis through intercellular communication or changes in tumor microenvironment, it is an optimized transportation facility for biologically active payloads. This was a hypothesis-generating research on role of exosomal payload in TNBC distant metastasis. METHODS: Exosomes isolated from supernatant of MDA-MB-231 and MDA-MB-231-HM (a highly pulmonary metastatic variant of parental MDA-MB-231 cells) were characterized. MMP-1 level was detected using mass spectrometry and western blot. Transwell assay, wound healing and CCK-8 assay were employed to explore the effect of exosomal MMP-1 on the metastatic capability of TNBC cells in vitro. Human breast cancer lung metastasis model in nude mice was established to observe the effect of exosomal MMP-1 in vivo. Tissue microarray and blood samples of TNBC patients were applied to analyze the relevance between MMP-1 with metastasis. RESULTS: MDA-MB-231-HM cells secrete exosomes enriched MMP-1, which can be taken up and enhance invasion and migration activities of TNBC cells, including MDA-MB-231, MDA-MB-468 and BT549. After ingesting exosomes enriched with MMP-1, cells secret more MMP-1, which may interact with membrane G protein receptor protease activated receptor 1 (PAR1), thereby initiating epithelial-mesenchymal transition (EMT) to enhance capability of migration and invasion. The lung colonization model shows that the expressions of MMP-1 and PAR1 in the metastases of the 231-HM-exo treated mice were both upregulated. Clinically, the enrichment of MMP-1 can be detected in exosomes extracted from serum of patients with metastasis at higher concentration than that in pre-operative patients. Moreover, in patients with multiple distant metastases, the level of MMP-1 in exosomes is also higher than that in patients with single lesion. CONCLUSION: MMP-1 from TNBC cells of high metastasis potential can promote the distant metastasis of transform those with low metastasis potential through PAR1-mediated EMT and is likely to be a potential molecular marker.

Detecting Trivariate Associations in High-Dimensional Datasets.

Detecting correlations in high-dimensional datasets plays an important role in data mining and knowledge discovery. While recent works achieve promising results, detecting multivariable correlations especially trivariate associations still remains a challenge. For example, maximal information coefficient (MIC) introduces generality and equitability to detect bivariate correlations but fails to detect multivariable correlation. To solve the problem mentioned above, we proposed quadratic optimized trivariate information coefficient (QOTIC). Specifically, QOTIC equitably measures dependence among three variables. Our contributions are three-fold: (1) we present a novel quadratic optimization procedure to approach the correlation with high accuracy; (2) QOTIC exceeds existing methods in generality and equitability as QOTIC has general test functions and is applicable in detecting multivariable correlation in datasets of various sample sizes and noise levels; (3) QOTIC achieved both higher accuracy and higher time-efficiency than previous methods. Extensive experiments demonstrate the excellent performance of QOTIC.

Instant Preparation of Ultraclean Gold Nanothorns under Ambient Conditions for SERS Kit-Enabled Mobile Diagnosis.

Availability of surface-enhanced Raman scattering (SERS) substrates with good stability, high sensitivity, and a clean surface is crucial for the practical usefulness of the SERS technology in biochemical sensing, especially for point-of-care testing (POCT). Hereby, we develop a "ready-to-use" SERS kit, which requires only 20 s to fabricate ultraclean gold nanothorn (AuNT)-based SERS chips under ambient conditions with simple solution processing steps. By varying the thickness of the pre-coated platinum (Pt) nanolayer, we can control the size and number density of the grown AuNT. Taking advantage of the ultraclean surface of the instantly obtained fresh AuNT, Raman reporter molecules can also be immediately modified, by means of which specific detection of three analytes including H2O2, NO2-, and ClO- is realized. Furthermore, we propose the concept of an SERS kit and apply it to smartphone-based Raman analysis for POCT applications. This on-site preparation method solves the long-standing challenges hindering the practical use of SERS substrates, such as complicated fabrication processes, interference of residual surfactants, poor surface stability, and easy contamination. Besides performing SERS analysis conveniently and quickly, this SERS kit-enabled POCT technology can integrate remote data terminals and medical resources, which shows great potential for environmental protection or online-healthcare systems.

Hydrophilic Ultralong Organic Nanophosphors.

Ultralong organic phosphorescence (UOP), enabling of persistent luminescence after removal of external excitation light, shows great promise in biological applications such as bioimaging in virtue of antibackground fluorescence interference. Despite of good biocompatibility and outstanding phosphorescent properties, most current organic phosphors are hydrophobic with poor water solubility in the form of bulk crystal with large size, limiting their potential in the biological field. Here, a facile and versatile approach is provided to obtain nanoscale hydrophilic phosphorescent phosphors (HPPs) by physically loading ultralong organic phosphors into hollow mesoporous silica nanoparticles. The as-prepared HPPs can be well suspended in aqueous solution and effectively internalized by HeLa cells with very low cytotoxicity. Such HPPs are successfully applied for afterglow bioimaging in living nude mice with a very high signal-to-noise ratio up to 31. The current study not only provides a universal strategy to realize UOP in aqueous media but also demonstrates their great potential for biomedical purposes as an advanced imaging indicator with long-lived emission lifetime.

MPB, a novel berberine derivative, enhances lysosomal and bactericidal properties via TGF-ß-activated kinase 1-dependent activation of the transcription factor EB.

Lysosome has a crucial role in clearance of endocytosed pathogens from the cell. Small molecules that can boost lysosome function and bactericidal ability to cope with subsequent infection are urgently needed. Here, we report that MPB, a novel berberine derivative, induced lysosome-based degradation and clearance of methicillin-resistant Staphylococcus aureus and enteroinvasive Escherichia coli in macrophages. MPB caused nuclear translocation of transcription factor EB (TFEB), which boosted expression of lysosome genes. TFEB silencing repressed the MPB-mediated enhancements in degradation and bacterial eradication. MPB switched on TFEB nuclear translocation by coupling 2 parallel signaling pathways. MPB-triggered JNK activation led to 14-3-3δ being released from TFEB, which, in turn, caused TFEB nuclear translocation. In addition, MPB induced AMPK activation and subsequent inhibition of mechanistic target of rapamycin activity, which also contributed to TFEB nuclear translocation. Importantly, genetical or pharmaceutical inhibition of TGF-ß-activated kinase 1 (TAK1) reduced MPB action remarkably. MPB acted through TAK1 at lysine 158 to activate JNK and AMPK and, thus, induced TFEB-dependent bactericidal activity in macrophages. Therefore, our study reveals a novel mechanism by which MPB controls JNK and AMPK phosphorylation cascades to activate lysosomal function and bactericidal activity via TAK1 K158-dependent manner, which may offer insight into novel therapeutic strategies to control bacterial infection.-Liu, X., Zhang, N., Liu, Y., Liu, L., Zeng, Q., Yin, M., Wang, Y., Song, D., Deng, H. MPB, a novel berberine derivative, enhances lysosomal and bactericidal properties via TGF-ß-activated kinase 1-dependent activation of the transcription factor EB.

Polyprenylated xanthones from the twigs and leaves of Garcinia nujiangensis and their cytotoxic evaluation.

Inspired by the intriguing structures and bioactivities of polyprenylated xanthones, ten previously undescribed polyprenylated xanthones, nujiangxanthones G-P (1-10), and fifteen known ones (11-25) were isolated from the twigs and leaves of Garcinia nujiangensis. The structures of these compounds were established on the basis of spectroscopic data as well as comparison with the literature. Most of the isolates showed potent cytotoxicity against selected cancer cells. Compound 8 showed the highest effects against MDA-MB-231 and A549 cell lines with IC50 values of 4.12 and 2.67 µM and 16 demonstrated the most potent activity against MCF-7 cell line with an IC50 value of 3.36 µM.

Resibufogenin suppresses transforming growth factor-ß-activated kinase 1-mediated nuclear factor-κB activity through protein kinase C-dependent inhibition of glycogen synthase kinase 3.

Resibufogenin (RB), one of the major active compounds of the traditional Chinese medicine Chansu, has received considerable attention for its potency in cancer therapy. However, the anticancer effects and the underlying mechanisms of RB on pancreatic cancer remain elusive. Here, we found that RB inhibited the viability and induces caspase-dependent apoptosis in human pancreatic cancer cells Panc-1 and Aspc. Resibufogenin-induced apoptosis was through inhibition of constitutive nuclear factor-κB (NF-κB) activity and its target genes' expression, which was caused by downregulation of transforming growth factor-ß-activated kinase 1 (TAK1) levels and suppression of IκB kinase activity in Panc-1 and Aspc cells. This induction of TAK1-mediated NF-κB inactivation by RB was associated with increased glycogen synthase kinase-3 (GSK-3) phosphorylation and subsequent suppression of its activity. Moreover, RB-induced GSK-3 phosphorylation/inactivation acted through activation of protein kinase C but not Akt. Finally, RB suppressed human pancreatic tumor xenograft growth in athymic nude mice. Thus, our findings reveal a novel mechanism by which RB suppresses TAK1-mediated NF-κB activity through protein kinase C-dependent inhibition of GSK-3. Our findings provide a rationale for the potential application of RB in pancreatic cancer therapy.

Mechanisms Underlying H2O2-Evoked Carbonyl Modification of Cytoskeletal Protein and Axon Injury in PC-12 Cells.

BACKGROUND/AIMS: To investigate the mechanism that enables oxidative stress and cytoskeleton protein carbonylation to contribute to axonal dysfunction in traumatic brain injury (TBI). METHODS: We created an in vitro model of neuronal oxidative damage by exposing a neuron-like cell line (PC-12) to different concentrations (100 µM, 200 µM, and 300 µM) of H2O2 for 24 h or 48 h. Carbonyl modification of cytoskeletal proteins (ß-actin and ß-tubulin) and its impact on ß-actin/ß-tubulin filament dynamics were determined by enzyme-linked immunosorbent assay, immunostaining, and western blotting. Depolymerization of ß-actin/ß-tubulin filaments was evaluated using the monomer/polymer ratio of each protein via western blotting. Phosphorylation of the neurofilament heavy chain (P-NFH) was used as an axonal injury marker and detected by immunostaining. RESULTS: Our results showed that H2O2 treatment led to increased oxidative stress in PC-12 cells, as indicated by the increased generation of malondialdehyde and 8-hydroxydeoxyguanosine and decreased intracellular glutathione levels. H2O2 treatment also increased carbonyl modification of total proteins and cytoskeleton proteins ß-actin/ß-tubulin, which occurred concurrently with the suppression of proteasome activity. Moreover, H2O2 treatment increased the generation of the axonal injury marker P-NFH, and depolymerization of the ß-actin/ß-tubulin filaments was indicated by increased monomer/polymer ratios of each protein. Lastly, overexpression of the proteasome ß5 subunit in PC-12 cells significantly reduced the H2O2-induced accumulation of carbonylated ß-actin/ ß-tubulin, P-NFH, and ß-actin/ß-tubulin depolymerization. CONCLUSIONS: We concluded that carbonylation of cytoskeleton proteins could lead to depolymerization of their filaments and axonal injury, and proteasome suppression contributes to the accumulation of carbonylated proteins under oxidative conditions.

Reconstruction of Tragus and External Auditory Meatus using Remnant Auricle during Microtia Reconstruction.

This article investigates an effective method with which to reconstruct the tragus and external auditory meatus for microtia reconstruction. The external ear was reconstructed using a delayed postauricular skin flap in patients with congenital microtia. After the first stage of delaying the postauricular skin flap and the second stage of otoplasty with ear framework fabricated from autogenous rib cartilage draping with the delayed skin flap, the third stage involved tragus and external auditory meatus canaloplasty. After designing the remnant auricle flap, the lower part was trimmed and the tragus was reconstructed. The upper part was trimmed into a thin skin flap, which was rotated and used to cover the hollowed wound posterosuperior to the tragus so as to mimic the external auditory meatus. If remnant wounds were present, skin grafting was conducted. In total, 121 patients with congenital microtia were treated from March 2010 to March 2016. The reconstructed tragus and external auditory meatus were well formed, and all wounds healed well. No severe complications such as flap necrosis occurred. Six months postoperatively, the morphology of the reconstructed tragus and external auditory meatus was good. Overall, the patients and their families were satisfied. The use of remnant auricle to reconstruct the tragus and external auditory meatus is an effective auricular reconstruction technique.

Anti-N-methyl-D-aspartate receptor encephalitis associated with intracranial Angiostrongylus cantonensis infection: a case report.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently described paraneoplastic syndrome with prominent neuropsychiatric symptoms. Many of these cases are associated with neoplasma especially teratoma. In addition, a few of cases with anti-NMDAR antibodies triggered by viral infection have been reported, but never by parasitic infection. Here, we report a novel case of NMDA receptor encephalitis in a 51-year-old male related to the development of anti-NMDAR antibodies triggered by Angiostrongylus cantonensis infection.

Design, Synthesis and Antiproliferative Evaluation of Novel Disulfides Containing 1,3,4-Thiadiazole Moiety.

A series of novel disulfides containing 1,3,4-thiadiazole moiety were designed, synthesized, and the structures of all products were identified by spectral data (IR, NMR, and high resolution (HR)-MS). Their in vitro antiproliferative activities were evaluated using 2-(2-methoxy-4-nitro-phenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfopheyl)-2H-tetrazolium monosodium salt (CCK-8) assay against human cancer cell lines, A549 (human lung cancer cell), HeLa (human cervical cancer cell), SMMC-7721 (human liver cancer cell) and normal cell lines L929. The bioassay results indicated that most of the tested compounds 6a-k, 7a-k and 8a-k exhibited antiproliferation with different degrees, and some compounds showed better effects than positive control 5-fluorouracil (5-FU) against various cancer cell lines. Among these compounds, compound 6e exhibited the most potent inhibitory activity against A549 cells with IC50 value of 3.62 µM. Compounds 6i, 7a, 7g, 8a and 8b showed significantly antiproliferative activities against HeLa cells with IC50 values of 3.88, 3.76, 3.59, 3.38 and 3.12 µM, respectively. Compounds 6a, 7a and 8a owned high antiproliferative activities against SMMC-7721 cells with IC50 values of 2.54, 2.69 and 2.31 µM, respectively. Furthermore, all of the tested compounds showed weak cytotoxic effect against the normal cell lines L929. Based on the preliminary results, the substituent groups are vital for improving the potency and selectivity of this class of compounds.

Low expression of B-cell-associated protein 31 in human primary hepatocellular carcinoma correlates with poor prognosis.

AIMS: The aim of the present study was to investigate the prognostic value of B-cell associated protein 31 (BAP31) in human primary hepatocellular carcinoma (HCC). METHODS AND RESULTS: BAP31 levels were evaluated by immunohistochemistry on tissue microarrays. The integral optical density, representing the expression level of BAP31 in each tissue sample, was calculated with image-pro plus. Immunohistochemical analysis of BAP31 levels in 74 paired HCC tissues and peritumoral non-cancerous tissues showed that BAP31 expression was significantly higher in HCC tumour tissues (P = 0.025). The prognostic value of BAP31 in HCC was evaluated in 234 cases in a training cohort and in 63 cases in a validation cohort. The expression level of BAP31 was significantly correlated with overall survival (OS) in both the training cohort and the validation cohort. The lower the level of BAP31 expression in HCC tissue, the poorer the prognosis. Univariate and multivariate analyses showed that the expression level of BAP31 in HCC was an independent prognostic factor for OS in both the training cohort and the validation cohort. CONCLUSIONS: BAP31 expression is an independent prognostic factor for OS of patients with postoperative HCC, and low expression levels of BAP31 in HCC may indicate poor outcomes of HCC patient after surgical resection.

Hepatitis B virus X protein induces the histone H3 lysine 9 trimethylation on the promoter of p16 gene in hepatocarcinogenesis.

Our previous study showed hepatitis B virus X protein (HBx) suppresses the p16 expression in hepatocarcinogenesis. In this study we explored the relationship between HBx and trimethylation of H3K9 (H3K9me3), and elucidated the underlying mechanisms in HBx inducing the tumor suppressor p16 gene silence. SMMC-7721 and HepG2 hepatoma cell lines were transfected with HBx-expressing plasmid. Immunohistochemistry, Western blotting and real-time polymerase chain reaction, were performed to detect the expressions of HBx, H3K9me3, and jumonji domain-containing protein 2B (JMJd2B). H3K9me3 enrichment on the p16 promoter was measured by immunoprecipitation-PCR (ChIP-PCR) analyses, and 39 cases of hepatitis B virus (HBV) associated-hepatocellular carcinoma (HCC) and corresponding noncancerous liver tissues were also examined. We demonstrated that HBx was able to upregulate H3K9me3 and suppress JMJd2B mRNA and protein levels in SMMC-7721 and HepG2 hepatoma cell lines. JMJd2B, as a specific target of H3K9me3 for demethylation, was inversely correlated with the levels of H3K9me3 in SMMC-7721 (r=-0.666, P<0.05) and HepG2 cells (r=-0.625, P<0.05). The ChIP-PCR data indicated that HBx remarkably increased H3K9me3 on the p16 promoter region. Immunohistochemistry analysis showed that H3K9me3 expression in HBx positive HCC samples were significantly higher than that in HBx negative HCC tissues and were associated with decreased levels of JMJd2B expression. JMJd2B immunoreactivity was also remarkably inversed to that of HBx in HCC tissues (r=-0.630, P<0.05). Our results provide evidence that HBx is able to induce H3K9me3 on the p16 promoter via the decrease of demethylase JMJd2B expression and thus promote the repression of p16 gene expression to enhance hepatocarcinogenesis.

Facile synthesis of boron- and nitride-doped MoS2 nanosheets as fluorescent probes for the ultrafast, sensitive, and label-free detection of Hg(2+).

Bulk MoS2, a prototypical transition metal chalcogenide material, is an indirect band gap semiconductor with negligible photoluminescence. In this study, we have developed, for the first time, a simple and low-cost synthetic strategy to prepare boron- and nitrogen-doped MoS2 (B,N-MoS2) nanosheets. Through boron and nitrogen doping, the band gap of MoS2 increases from 1.20 eV to 1.61 eV, and the obtained B,N-MoS2 nanosheets exhibit an enhanced fluorescence. The B,N-MoS2 nanosheets can be used as a green and facile sensing platform for label-free detection of Hg(2+) because of their high sensitivity and selectivity toward Hg(2+). In addition, detection can be easily accomplished through one-step rapid (within 2 min) operation, with a limit as low as 1 nM. This study demonstrates that the introduction of boron and nitrogen elements into ultrathin MoS2 nanosheets for enhanced fluorescence properties is feasible through a facile and general preparation strategy and may also offer a unique idea as a potential way to design more efficient MoS2-based sensors and fluorescent materials.

Characteristics of dyslexia and dysgraphia in a Chinese patient with semantic dementia.

We describe a 44-year-old Chinese-speaking patient with semantic dementia (SD), who demonstrates dyslexia and dysgraphia. The man was administered a series of neuropsychological inspections, including general language tests and reading and writing examinations. The patient demonstrated surface dyslexia when reading single Chinese characters aloud. While most writing errors demonstrated by the patient were orthographically similar errors and noncharacter responses, such as pictograph, logographeme, and stroke errors, rather than phonologically plausible errors that were homophonous or different only in tone from the targets. We suggest that the type of acquired dysgraphia demonstrated by Chinese-speaking SD patients is determined by the unique features of the Chinese writing system.

Coumarin Glycosides Reverse Enterococci-Facilitated Enteric Infections.

Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens, thereby exacerbating infections. However, there are few effective therapeutic strategies to prevent and intervene in enterococci-mediated polymicrobial infections. Here, we find that enterococci at high density drive the expansion and pathogenicity of enteric Salmonella enterica serotype Typhimurium (S. Tm). Subsequently, we show that the driving role of enterococci in such infections is counteracted by dietary coumarin glycosides in vivo. Enterococci, which are tolerant of iron-deficient environments, produce ß-glucosidases to hydrolyze coumarin glycosides into bioactive aglycones, inhibiting S. Tm growth and ameliorating the severity of S. Tm-induced symptoms by inducing iron limitation. Overall, we demonstrate that coumarin glycosides as a common diet effectively reverse enterococci-facilitated enteric infections, providing an alternative intervention to combat polymicrobial infections.