Publisher Correction: The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells.

In the version of this article initially published, the institution name for affiliation 3 (Maryland Anderson Cancer Center) was incorrect. The correct institution is MD Anderson Cancer Center. The error has been corrected in the HTML and PDF versions of the article.

Corrigendum: The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells.

This corrects the article DOI: 10.1038/ni.3748.

The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells.

An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells) and the inflammatory TH17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under TH17 cell-inducing conditions and was required for TH17 differentiation and TH17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the TH17-defining transcription factor RORγt. In addition, TAZ attenuated Treg cell development by decreasing acetylation of the Treg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation. In contrast, under Treg cell-skewing conditions, TEAD1 expression and sequestration of TAZ from the transcription factors RORγt and Foxp3 promoted Treg cell differentiation. Furthermore, deficiency in TAZ or overexpression of TEAD1 induced Treg cell differentiation, whereas expression of a transgene encoding TAZ or activation of TAZ directed TH17 cell differentiation. Our results demonstrate a pivotal role for TAZ in regulating the differentiation of Treg cells and TH17 cells.

Nafamostat Mesylate in Combination with the Mouse Amino-Terminal Fragment of Urokinase-Human Serum Albumin Improves the Treatment Outcome of Triple-Negative Breast Cancer Therapy.

Triple-negative breast cancer (TNBC) is highly aggressive and causes a higher proportion of metastatic cases. However, therapies directed to specific molecular targets have rarely achieved clinically meaningful improvements in the outcome of TNBC therapy. A urokinase-type plasminogen activator (uPA), one of the best-validated biomarkers of breast cancer, is an extracellular proteolytic serine protease involved in many pathological and physiological processes, including tumor cell invasion and metastasis. Nafamostat mesylate (NM) is a synthetic compound that inhibits various serine proteases and has been used as a therapeutic agent for the treatment of TNBC. Nevertheless, NM has poor specificity for serine proteases and is easy be hydrolyzed; moreover, the inhibitory mechanism of TNBC therapy is unclear. In this study, we combine NM with a macromolecular drug delivery vehicle, mouse amino-terminal fragment of urokinase-human serum albumin (mATF-HSA), to form a complex (mATF-HSA:NM) using the dilution-incubation-purification method. mATF specifically targets uPAR overexpressed on the surface of TNBC cells; moreover, HSA prevents NM from being hydrolyzed by numerous serine proteases. mATF-HSA:NM showed stronger inhibitory effects on the proliferation and metastasis of TNBC in vitro and in vivo without significant cytotoxicity on normal cells and tissues. In addition, we demonstrated that NM mediates metastasis of TNBC cells through inhibition of uPA using a stable uPA knockdown cell line (MDA-MB231 shuPA). Overall, we have developed a macromolecular complex targeted to treat high uPAR-expressing tumor types, and mATF-HSA can potentially be used to load other types of drugs with tumor-targeting specificity for mouse tumor models and is a promising tool to study tumor biology in mouse tumor models.

Sensory evaluation, chemical structures, and threshold concentrations of bitter-tasting compounds in common foodstuffs derived from plants and maillard reaction: A review.

The bitterness of foodstuffs is often associated with toxicity, which negatively influences product acceptability. However, bitter compounds have many benefits, and a slight bitter taste is sometimes favored. In this review, we summarize the methods used to isolate and evaluate the taste of bitter compounds in different foods. The chemical structures and threshold concentrations of these compounds are also recapped. Although the structures and thresholds of many bitter compounds have been confirmed, further studies are needed to develop detailed bitter-masking strategies and establish the relation between functional groups (hetero-cyclic substituents and bonding types) and taste quality. Furthermore, a comprehensive bitterness database and chemometric data must be provided in order to quickly assess the bitterness of unfamiliar products.

Reusable flexible poly(vinyl alcohol)/chitosan-based polymer carbon dots composite film for acid blue 93 dye adsorption.

The design and synthesis of water-insoluble chitosan-based polymer carbon dots [P(CS-g-CA)CDs] are described. A polyvinyl alcohol/chitosan-based polymer carbon dot [PVA/P(CS-g-CA)CDs] composite film was prepared using a simple casting method to be used in dye adsorption. The composite film was characterized using FT-IR, XPS, transparency, contact angle, and mechanical properties tests, which showed the successful incorporation of P(CS-g-CA)CDs into the film and also revealed that hydrogen bonding improved the mechanical properties of the PVA film. Furthermore, the composite film displayed substantially enhanced hydrophobicity, making it suitable for use in aqueous environments. In addition, the composite film exhibited stable adsorption of acid blue 93 (AB93) at pH 2-9, with an enhanced adsorption capacity of 433.24 mg/g. The adsorption obeyed Langmuir law with an efficiency of more than 89% even after five cycles. Therefore, the PVA/P(CS-g-CA)CDs film is a promising material for the treatment of organic dye-polluted wastewater.

Effects of moisture content on the enolization products formation in glucose-proline Maillard reaction models.

BACKGROUND: 2,3-Dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) and 5-hydroxymethylfurfural (HMF) are two main enolization products in the Maillard reaction and found in some foodstuffs. For many years, whether they are functional or noxious to human health has been a matter of debate. Thus, insight into their formation pathways is important to manage Maillard reaction products. In this study, DDMP and HMF were quantified and compared with regard to their formation and degradation in the d-glucose and l-proline Maillard reaction models using different moisture contents (0, 0.1, 0.5, 1.0, and 4.0 mL) at 150 °C for various heating times. RESULTS: DDMP was predominantly generated in dry or low water-content heating models along with n increased 1-deoxyglucosone (1-DG) generation via 2,3-enolization. However, increasing moisture content resulted in a decay of reaction intensity, 1-DG, and DDMP due to a change in the reaction mechanism from 2,3-enolization to 1,2-enolization, which facilitated 3-deoxyglucosone (3-DG) and HMF formation. CONCLUSION: Increased moisture content in glucose-proline models reduced reaction intensity and also inhibited DDMP and facilitated HMF formation by promoting the pathway change from 2,3-enolization to 1,2-enolization to generate more 3-DG. A water content of 1.0 mL was identified as a critical value, from which the 1,2-enolization became a primary pathway occurring in the Maillard reaction. © 2022 Society of Chemical Industry.

Carbon dots crosslinked chitosan/cellulose sponge capture of methyl blue by an adsorption process.

For environmental protection, organic dyes and solvents of industrial wastewater must be eliminated. Here, a citric acid-based carbon dots (CA-CDs) crosslinked chitosan/microcrystalline cellulose (CS/MCC/CA-CDs) sponge was synthesized to study its adsorption performance for methyl blue (MB) dye. The morphology of the sponge was a tangled fibre with a bundle formed by hydrogen bonds between CA-CDs and the CS/MCC composite matrix. The abundant amount of tangled fibre bundle units can offer plentiful active adsorption sites to collect the dye molecules. The adsorption capacity of the CS/MCC/CA-CDs sponge toward MB was 306.8 mg/g at pH 10 and a temperature of 298 K. In addition, the pseudo-second-order kinetic model was matched with the adsorption kinetic experimental data, and the adsorption isotherm data can be described by the Langmuir models. This study proposed that the CS/MCC/CA-CDs sponge adsorbent creates tremendous potential application value in wastewater treatment due to its fast kinetics, high adsorption capacity, simple preparation, and eco-friendly properties.

Potent inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 by photosensitizers compounds.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) posed a major challenge to the public health. Currently, no proven antiviral treatment for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is available. Here we report compounds pentalysine ß-carbonylphthalocyanine zinc (ZnPc5K) and chlorin e6 (ce6) potently inhibited the viral infection and replication in vitro with EC50 values at nanomolar level. These compounds were first identified by screening a panel of photosensitizers for photodynamic viral inactivation. Such viral inactivation strategy is implementable, and has unique advantages, including resistance to virus mutations, affordability compared to the monoclonal antibodies, and lack of long-term toxicity.

SICD: Novel Single-Access-Point Indoor Localization Based on CSI-MIMO with Dimensionality Reduction.

With the rise of location-based services and the rapidly growing requirements related to their applications, indoor localization based on channel state information-multiple-input multiple-output (CSI-MIMO) has become an important research topic. However, indoor localization based on CSI-MIMO has some disadvantages, including noise and high data dimensions. To overcome the above drawbacks, we proposed a novel method of indoor localization based on CSI-MIMO, named SICD. For SICD, a novel localization fingerprint was first designed which can reflect the time-frequency and space-frequency characteristics of CSI-MIMO under a single access point (AP). To reduce the redundancy in the data of CSI-MIMO amplitude, we developed a data dimensionality reduction algorithm. Moreover, by leveraging a log-normal distribution, we calculated the conditional probability of the naive Bayes classifier, which was used to predict the moving object's location. Compared with other state-of-the-art methods, the results of the experiment confirm that the SICD effectively improves localization accuracy.

Thiophene enantiomers from the aerial parts of Eclipta prostrata.

Ten thiophene derivatives (1-10), including two previously undescribed ones (1 and 2), have been obtained and structurally characterized from the aerial parts of a traditional Chinese herb Eclipta prostrata. Six of them with one chiral center were identified to be scalemic mixtures, and the pure enantiomers of two isolates (1 and 3) were successfully separated via chemical derivatization and chiral HPLC, with the absolute configurations being established by analysis of optical rotations. All the thiophenes were subjected to a series of assays and compounds 9 and 10 exhibited mild antibacterial activity against Staphylococcus aureus.[Formula: see text].

Low-Resolution ADCs for Two-Hop Massive MIMO Relay System under Rician Channels.

This paper works on building an effective massive multi-input multi-output (MIMO) relay system by increasing the achievable sum rate and energy efficiency. First, we design a two-hop massive MIMO relay system instead of a one-hop system to shorten the distance and create a Line-of-Sight (LOS) path between relays. Second, we apply Rician channels between relays in this system. Third, we apply low-resolution Analog-to-Digital Converters (ADCs) at both relays to quantize signals, and apply Amplify-and-Forward (AF) and Maximum Ratio Combining (MRC) to the processed signal at relay R1 and relay R2 correspondingly. Fourth, we use higher-order statistics to derive the closed-form expression of the achievable sum rate. Fifth, we derive the power scaling law and achieve the asymptotic expressions under different power scales. Last, we validate the correctness of theoretical analysis with numerical simulation results and show the superiority of the two-hop relay system over the one-hop relay system. From both closed-form expressions and simulation results, we discover that the two-hop system has a higher achievable sum rate than the one-hop system. Besides, the energy efficiency in the two-hop system is higher than the one-hop system. Moreover, in the two-hop system, when quantization bits q = 4, the achievable sum rate converges. Therefore, deploying low-resolution ADCs can improve the energy efficiency and achieve a fairly considerable achievable sum rate.

An Indoor Localization System Using Residual Learning with Channel State Information.

With the increasing demand of location-based services, neural network (NN)-based intelligent indoor localization has attracted great interest due to its high localization accuracy. However, deep NNs are usually affected by degradation and gradient vanishing. To fill this gap, we propose a novel indoor localization system, including denoising NN and residual network (ResNet), to predict the location of moving object by the channel state information (CSI). In the ResNet, to prevent overfitting, we replace all the residual blocks by the stochastic residual blocks. Specially, we explore the long-range stochastic shortcut connection (LRSSC) to solve the degradation problem and gradient vanishing. To obtain a large receptive field without losing information, we leverage the dilated convolution at the rear of the ResNet. Experimental results are presented to confirm that our system outperforms state-of-the-art methods in a representative indoor environment.

Structural characterization and biological evaluation of chemical constituents from Ilex cornuta.

One new ursane-type triterpenoid (1), one new ursane-type triterpenoid glycoside (2), and one new oleanane-type triterpenoid glycoside (3), along with 20 known compounds, were isolated from the leaves of Ilex cornuta. The structures of these natural products were elucidated on the basis of detailed spectroscopic analyses and chemical derivation. Our biological evaluation established that selective compounds showed moderate to significant antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) methods.

Addition of lipophilic grape seed proanthocyanidin effectively reduces acrylamide formation.

BACKGROUND: In this article the relationship between lipophilic grape seed proanthocyanidin (LGSP) and acrylamide formation in potato-based products was investigated. The acrylamide, reducing sugar, asparagine, and 3-aminopropionamide contents were determined by high-performance liquid chromatography mass spectrometry (HPLC-MS). Sensory evaluation was used to evaluate the quality of the products. RESULTS: The results showed that LGSP presented greater inhibition effect on the acrylamide formation than the commonly used commercial antioxidants. Furthermore, 81.5% and 84.7% of acrylamide was reduced in potato crisps and French fries after adding 0.1% and 0.05% LGSP (w/w) in palm oil, respectively. When the concentrations of LGSP were less than 0.1%, there was no significant difference between LGSP-treated samples and control sample for sensory evaluation. CONCLUSION: Thus, LGSP is effective in reducing the level of acrylamide and maintaining the reasonable sensory attributes of potato fried foods. The results indicate that LGSP may be used as a potential additive for reducing acrylamide formation in fried foods. © 2019 Society of Chemical Industry.

New e:b-Friedo-Hopane Type Triterpenoids from Euphorbia peplus with Simiarendiol Possessing Significant Cytostatic Activity against HeLa Cells by Induction of Apoptosis and S/G2 Cell Cycle Arrest.

Seven rare e:b-friedo-hopane-type triterpenoids including four new (1-4) and three known (5-7) ones with 5 being first reported as a natural product, together with five other known triterpenoids (8-12), were isolated from the nonpolar fractions of the ethanolic extract of Euphorbia peplus. Structural assignments for these compounds were based on spectroscopic analyses and quantum chemical computation method. The structural variations for the C-21 isopropyl group, including dehydrogenation (1 and 3) and hydroxylation at C-22 (simiarendiol, 2), were the first cases among e:b-friedo-hopane-type triterpenoids. Simiarendiol (2) bearing a 22-OH showed significant cytostatic activity against HeLa and A549 human tumor cell lines with IC50 values of 3.93 ± 0.10 and 7.90 ± 0.31 µM, respectively. The DAPI staining and flow cytometric analysis revealed that simiarendiol (2) effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in a dose-dependent manner in HeLa cells.

Defining the regulatory role of programmed cell death 4 in laryngeal squamous cell carcinoma.

Programmed cell death 4 (PDCD4) is decreased in many different kinds of malignant tumors. EMT endows tumor cells invasive and metastatic properties. However, few studies have determined the role of PDCD4 in the regulation of EMT in the context of laryngeal carcinoma. We examined the relationship between PDCD4 and EMT-associated proteins E-cadherin and N-cadherin using laryngeal carcinoma tissues. Gene manipulation was used to define the regulatory capacity of PDCD4. We report that PDCD4 and E-cadherin/N-cadherin expression were significantly changed in the carcinoma tissues, and their expression was associated with pathological grade, metastatic state, and clinical stage. The suppression of PDCD4 (and consequently, E-cadherin) was concomitant with increased proliferation and G2-phase arrest, decreased apoptosis, and increased cell invasion. PDCD4 upregulation reversed the above-mentioned results. In nude mice, PDCD4 knockdown increased tumor growth and pathological features, confirming the tumorigenic role of PDCD4. Finally, PDCD4 silencing was associated with dysregulation of the carcinogenic Wnt-ß-catenin and the STAT3-miR-21 signaling pathways. This study revealed a dynamic regulatory relationship between PDCD4 and critical factors for EMT, establishing a broad, functional role for PDCD4 in laryngeal carcinoma, which may be propagated by the STAT3-miR-21 pathway. These findings provide new information on an EMT-associated target that may lead to a novel therapy.

Acid-Promoted D-A-D Type Far-Red Fluorescent Probe with High Photostability for Lysosomal Nitric Oxide Imaging.

To accurately monitor the variations of lysosomal nitric oxide (NO) under physiological condition remains a great challenge for understanding the biological function of NO. Herein, we developed a new chemotype probe, namely, MBTD, for acid-promoted and far-red fluorescence imaging of lysosomal NO in vitro and ex vivo. MBTD was rationally designed by incorporating o-phenylenediamino (OPD) moiety into the donor-acceptor-donor (D-A-D) type fluorophore based on a dual intramolecular charge transfer (ICT) mechanism. Compared to previously reported OPD-based NO probes, MBTD displays several distinct advantages including large stroke shift, huge on-off ratio with minimal autofluorescence, and high NO specificity. Particularly, MBTD exhibits an acid-promoted response to NO with high acid tolerance, which greatly improves the spatial resolution to lysosomal NO by excluding the background noise from other nonacidic organelles. Furthermore, MBTD displayed much longer-lived and more stable fluorescence emission in comparison with the commercialized NO probe. MBTD was employed for ratiometric examination of the exogenous or endogenous NO of macrophages. More importantly, MBTD was able to detect the variation of lysosomal NO level in an acute liver injury mouse model ex vivo, implying the potential of MBTD for real-time monitoring the therapeutic efficacy of drug candidates for the treatment of acute liver injury. MBTD as a novel type of NO probe might open a new avenue for precisely sensing lysosomal NO-related pathological and therapeutic process.

Routes of odd-even harmonic emission from oriented polar molecules.

We study odd-even high-harmonic generation (HHG) from oriented asymmetric molecules with different symmetries in strong laser fields. A model based on strong-field approximations is used which allows us to resolve the contributions of different emission routes to odd-even HHG. The comparison between the HHG yields of all routes versus one certain route demonstrates that the routes in which the electron ionizes from the gerade component of the asymmetric orbital contribute mainly to odd-even HHG. We show that the potential mechanism is associated with effects of intramolecular interference in tunneling ionization as the bound electron passes through the barrier formed by the laser field and the asymmetric Coulomb potential. The influences of different emission routes on asymmetric orbital imagining with odd-even HHG are also addressed.

Total synthesis of (±)-tanshinol B, tanshinone I, and (±)-tanshindiol B and C.

A concise and efficient approach was established for the divergent total synthesis of (±)-tanshindiol B and C and tanshinone I from a ubiquitous ene intermediate in 1-2 steps. This critical intermediate was derived from (±)-tanshinol B, which was synthesized in 50% overall yield over 3 steps using an ultrasound-promoted cycloaddition as a key step. Compared to a previously reported strategy, our approach is more step-economic, thus greatly improving the synthetic efficiency. The bioactivity evaluation indicates that the diol stereochemistry of the tanshidiols has an impact on the EZH2 inhibitory activity.