Clofazimine broadly inhibits coronaviruses including SARS-CoV-2.

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.

Spatiotemporal formation of the large vacuole regulated by the BIN2-VLG module is required for female gametophyte development in Arabidopsis.

In Arabidopsis thaliana, female gametophyte (FG) development is accompanied by the formation and expansion of the large vacuole in the FG; this is essential for FG expansion, nuclear polar localization, and cell fate determination. Arabidopsis VACUOLELESS GAMETOPHYTES (VLG) facilitates vesicular fusion to form large vacuole in the FG, but the regulation of VLG remains largely unknown. Here, we found that gain-of-function mutation of BRASSINOSTEROID INSENSITIVE2 (BIN2) (bin2-1) increases VLG abundance to induce the vacuole formation at stage FG1, and leads to abortion of FG. Loss-of-function mutation of BIN2 and its homologs (bin2-3 bil1 bil2) reduced VLG abundance and mimicked vlg/VLG phenotypes. Knocking down VLG in bin2-1 decreased the ratio of aberrant vacuole formation at stage FG1, whereas FG1-specific overexpression of VLG mimicked the bin2-1 phenotype. VLG partially rescued the bin2-3 bil1 bil2 phenotype, demonstrating that VLG acts downstream of BIN2. Mutation of VLG residues that are phosphorylated by BIN2 altered VLG stability and a phosphorylation mimic of VLG causes similar defects as did bin2-1. Therefore, BIN2 may function by interacting with and phosphorylating VLG in the FG to enhance its stability and abundance, thus facilitating vacuole formation. Our findings provide mechanistic insight into how the BIN2-VLG module regulates the spatiotemporal formation of the large vacuole in FG development.

Magnetic detection under high pressures using designed silicon vacancy centres in silicon carbide.

Pressure-induced magnetic phase transitions are attracting interest as a means to detect superconducting behaviour at high pressures in diamond anvil cells, but determining the local magnetic properties of samples is a challenge due to the small volumes of sample chambers. Optically detected magnetic resonance of nitrogen vacancy centres in diamond has recently been used for the in situ detection of pressure-induced phase transitions. However, owing to their four orientation axes and temperature-dependent zero-field splitting, interpreting these optically detected magnetic resonance spectra remains challenging. Here we study the optical and spin properties of implanted silicon vacancy defects in 4H-silicon carbide that exhibit single-axis and temperature-independent zero-field splitting. Using this technique, we observe the magnetic phase transition of Nd2Fe14B at about 7 GPa and map the critical temperature-pressure phase diagram of the superconductor YBa2Cu3O6.6. These results highlight the potential of silicon vacancy-based quantum sensors for in situ magnetic detection at high pressures.

Pseudouridine synthase 1 promotes hepatocellular carcinoma through mRNA pseudouridylation to enhance the translation of oncogenic mRNAs.

BACKGROUND AND AIMS: Pseudouridine is a prevalent RNA modification and is highly present in the serum and urine of patients with HCC. However, the role of pseudouridylation and its modifiers in HCC remains unknown. We investigated the function and underlying mechanism of pseudouridine synthase 1 (PUS1) in HCC. APPROACH AND RESULTS: By analyzing the TCGA data set, PUS1 was found to be significantly upregulated in human HCC specimens and positively correlated with tumor grade and poor prognosis of HCC. Knockdown of PUS1 inhibited cell proliferation and the growth of tumors in a subcutaneous xenograft mouse model. Accordingly, increased cell proliferation and tumor growth were observed in PUS1-overexpressing cells. Furthermore, overexpression of PUS1 significantly accelerates tumor formation in a mouse HCC model established by hydrodynamic tail vein injection, while knockout of PUS1 decreases it. Additionally, PUS1 catalytic activity is required for HCC tumorigenesis. Mechanistically, we profiled the mRNA targets of PUS1 by utilizing surveying targets by apolipoprotein B mRNA-editing enzyme 1 (APOBEC1)-mediated profiling and found that PUS1 incorporated pseudouridine into mRNAs of a set of oncogenes, thereby endowing them with greater translation capacity. CONCLUSIONS: Our study highlights the critical role of PUS1 and pseudouridylation in HCC development, and provides new insight that PUS1 enhances the protein levels of a set of oncogenes, including insulin receptor substrate 1 (IRS1) and c-MYC, by means of pseudouridylation-mediated mRNA translation.

Epitope delimitation: A new method for defining epitopes of human IgG-reactive antigenic peptides based on rabbit-recognized epitope motifs.

The use of precise epitope peptides as antigens is essential for accurate serological diagnosis of viral-infected individuals, but now it remains an unsolvable problem for mapping precise B cell epitopes (BCEs) recognized by human serum. To address this challenge, we propose a novel epitope delimitation (ED) method to uncover BCEs in the delineated human IgG-reactive (HR) antigenic peptides (APs). Specifically, the method based on the rationale of similarities in humoral immune responses between mammalian species consists of a pair of elements: experimentally delineated HR-AP and rabbit-recognized (RR) BCE motif and corresponding pair of sequence alignment analysis. As a result of using the ED approach, after decoding four RR-epitomes of human papillomavirus types 16/18-E6 and E7 proteins utilizing rabbit serum against each recombinant protein and sequence alignment analysis of HR-APs and RR-BCEs, 19 fine BCEs in 17 of 22 known HR-APs were defined based on each corresponding RR-BCE motifs, including the type-specificity of each delimited BCE in homologous proteins. The test with 22 known 16/20mer HR-APs demonstrated that the ED method is effective and efficient, indicating that it can be used as an alternative method to the conventional identification of fine BCEs using overlapping 8mer peptides.

Auricular Vagal Nerve Stimulation Inhibited Central Nerve Growth Factor/Tropomyosin Receptor Kinase A/Phospholipase C-Gamma Signaling Pathway in Functional Dyspepsia Model Rats With Gastric Hypersensitivity.

OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.

[Research progress on active ingredients of Coicis Semen].

As a common medicinal and edible resource in China, Coicis Semen has a long history of cultivation and medicinal use. Traditional Chinese medicine(TCM) clinically believes that Coicis Semen has the effect of strengthening the spleen and tonifying the lungs, clearing heat and dampness, removing pus and paralysis, and stopping diarrhea. Therefore, it is used to treat edema, foot odor, spleen deficiency, diarrhea, and other symptoms. The above effects are closely related to the active ingredients of Coicis Semen, such as esters, fatty acids, polysaccharides, proteins, as well as phenolic acids, sterols, flavonoids, lactams, triterpenes, alkaloids, and adenosine. Modern research has found that Coicis Semen also has anti-cancer, anti-inflammatory, antioxidant, hypoglycemic, and hypotensive effects and other pharmacological activities, and it can improve immunity and regulate lipid metabolism. Coicis Semen is widely distributed in China, mainly produced in Guizhou, Yunnan, Fujian, Sichuan, and other places, and the quality of Coicis Semen from different origins varies. From ancient times to the present, Coicis Semen processing methods have experienced the process from simple to complex, and the types of auxiliary materials are more extensive, such as soil, bran, and river sand. These processing methods have been inherited from generation to generation. Nowadays, the commonly used methods are bran-fried, stir-fried, sand-fried, etc. In this paper, by reviewing the relevant literature in China and abroad in recent years, the main active ingredients and related pharmacological effects of Coicis Semen are sorted out, and the effects of different origins and processing methods on the chemical composition of Coicis Semen are summarized, with a view to providing references for the comprehensive development and utilization of Coicis Semen and the further study of its mechanism of action.

Development and validation of a prognostic nomogram model incorporating routine laboratory biomarkers for preoperative patients with endometrial cancer.

BACKGROUND: Some biomarkers collected from routine laboratory tests have shown important value in cancer prognosis. The study aimed to evaluate the prognostic significance of routine laboratory biomarkers in patients with endometrial cancer (EC) and to develop credible prognostic nomogram models for clinical application. METHODS: A total of 727 patients were randomly divided into a training set and a validation set. Cox proportional hazards models were used to evaluate each biomarker's prognostic value, and independent prognostic factors were used to generate overall survival (OS) and progression-free survival (PFS) nomgrams. The efficacy of the nomograms were evaluated by Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration curves, X-tile analysis and Kaplan‒Meier curves. RESULTS: Ten significant biomarkers in multivariate Cox analysis were integrated to develop OS and PFS nomograms. The C-indices of the OS- nomogram in the training and validation sets were 0.885 (95% confidence interval (CI), 0.810-0.960) and 0.850 (95% CI, 0.761-0.939), respectively; those of the PFS- nomogram in the training and validation sets were 0.903 (95% CI, 0.866-0.940) and 0.825 (95% CI, 0.711-0.939), respectively. ROC, DCA and calibration curves showed better clinical application value for the nomograms incorporating routine laboratory biomarkers. X-tile analysis and Kaplan‒Meier curves showed that the nomograms were stable and credible in evaluating patients at different risks. CONCLUSIONS: Nomogram models incorporating routine laboratory biomarkers, including NLR, MLR, fibrinogen, albumin and AB blood type, were demonstrated to be simple, reliable and favourable in predicting the outcomes of patients with EC.

2-BFI Provides Neuroprotection Against Fluorosis by Stabilizing Endoplasmic Reticulum-Mitochondria Contact Sites and Inhibiting Activation of the NLRP3 Inflammasome.

2-(2-benzofu-ranyl)-2-imidazoline (2-BFI) is a drug that has attracted much attention in recent years. It has a therapeutic effect on brain diseases in animal models such as Alzheimer's disease and cerebral infarction. However, whether 2-BFI affords neuroprotection against the toxicity of fluoride, which can cross the blood-brain barrier and cause neurological dysfunction is not known. We investigated the cell viability and apoptosis of SH-SY5Y cells and primary cultures of cortical neurons exposed to fluoride, and 2-BFI was used to protect both two kinds of cells against the effects of fluoride. We found that 2-BFI can provide neuroprotection on SH-SY5Y cells and primary cultures of cortical neurons upon fluorosis by maintaining the stability of endoplasmic reticulum-mitochondria contact sites and inhibiting activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. This study may provide a new method for protecting against the neurotoxicity induced by fluoride exposure.

Nitidine chloride induces cardiac hypertrophy in mice by targeting autophagy-related 4B cysteine peptidase.

Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.

Statins and risk of venous thromboembolic diseases: A two-sample mendelian randomization study.

BACKGROUND AND AIMS: In observational studies, statins have been suggested to have protective effects on venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). To this aim, we performed a two-sample mendelian randomization (MR) analysis to determine whether these associations were causal. METHODS AND RESULTS: Data on the single nucleotide polymorphisms (SNPs) related to statin medication were obtained from the FinnGen study, and data for VTE, PE and DVT of lower extremities (LEDVT) were from the UK Biobank study, respectively. Inverse variance weighted (IVW) method was used as the principal analysis of MR, and sensitivity analysis was performed to detect horizontal pleiotropy and heterogeneity. MR estimates showed an inverse causal association between statin medication and the risk of VTE (odds ratio [OR]: 0.999, 95% CI: 0.998-1.000, P = 0.004), PE (OR: 0.999, 95% CI: 0.999-1.000, P = 0.011) and LEDVT (OR: 0.999, 95% CI: 0.999-1.000, P = 0.008). CONCLUSION: Our findings provide direct evidence that statins might decrease the risk of VTE, PE and LEDVT in agreement with observational studies. The specific mechanism of statin therapy for venous thromboembolism needs to be further studied.

Chemical and metabolic profiling of Codonopsis Radix extract with an integrated strategy using ultra-high-performance liquid chromatography coupled with mass spectrometry.

Codonopsis radix was commonly used as food materials or herbal medicines in many countries. However, the comprehensive analysis of chemical constituents, and in vivo xenobiotics of Codonopsis radix remain unclear. In the present study, an integrated strategy with feature-based molecular networking using ultra-high-performance liquid chromatography coupled with mass spectrometry was established to systematically screen the chemical constituents and the in vivo xenobiotics of Codonopsis radix. A step-by-step manner based on a composition database, visual structure classification, discriminant ions, and metabolite software prediction was proposed to overcome the complexities due to the similar structure of chemical constituents and metabolites of Codonopsis radix. As a result, 103 compounds were tentatively characterized, 20 of which were identified by reference standards. Besides, a total of 50 xenobiotics were detected in vivo, including 26 prototypes and 24 metabolites, while the metabolic features of the pyrrolidine alkaloids were elucidated for the first time. The metabolism reactions of pyrrolidine alkaloids and sesquiterpene lactones included oxidation, methylation, hydration, hydrogenation, demethylation, glucuronidation, and sulfation. This study provided a generally applicable approach to the comprehensive investigation of the chemical and metabolic profile of traditional Chinese medicine and offered reasonable guidelines for further screening of quality control indicators and pharmacodynamics mechanism of Codonopsis radix.

Counterintuitive effects of isotopic doping on the phase diagram of H2-HD-D2 molecular alloy.

Molecular hydrogen forms the archetypical quantum solid. Its quantum nature is revealed by behavior which is classically impossible and by very strong isotope effects. Isotope effects between [Formula: see text], [Formula: see text], and HD molecules come from mass difference and the different quantum exchange effects: fermionic [Formula: see text] molecules have antisymmetric wavefunctions, while bosonic [Formula: see text] molecules have symmetric wavefunctions, and HD molecules have no exchange symmetry. To investigate how the phase diagram depends on quantum-nuclear effects, we use high-pressure and low-temperature in situ Raman spectroscopy to map out the phase diagrams of [Formula: see text]-HD-[Formula: see text] with various isotope concentrations over a wide pressure-temperature (P-T) range. We find that mixtures of [Formula: see text], HD, and [Formula: see text] behave as an isotopic molecular alloy (ideal solution) and exhibit symmetry-breaking phase transitions between phases I and II and phase III. Surprisingly, all transitions occur at higher pressures for the alloys than either pure [Formula: see text] or [Formula: see text] This runs counter to any quantum effects based on isotope mass but can be explained by quantum trapping of high-kinetic energy states by the exchange interaction.

The automatic detection of diabetic kidney disease from retinal vascular parameters combined with clinical variables using artificial intelligence in type-2 diabetes patients.

BACKGROUND: Diabetic kidney disease (DKD) has become the largest cause of end-stage kidney disease. Early and accurate detection of DKD is beneficial for patients. The present detection depends on the measurement of albuminuria or the estimated glomerular filtration rate, which is invasive and not optimal; therefore, new detection tools are urgently needed. Meanwhile, a close relationship between diabetic retinopathy and DKD has been reported; thus, we aimed to develop a novel detection algorithm for DKD using artificial intelligence technology based on retinal vascular parameters combined with several easily available clinical parameters in patients with type-2 diabetes. METHODS: A total of 515 consecutive patients with type-2 diabetes mellitus from Xiangyang Central Hospital were included. Patients were stratified by DKD diagnosis and split randomly into either the training set (70%, N = 360) or the testing set (30%, N = 155) (random seed = 1). Data from the training set were used to develop the machine learning algorithm (MLA), while those from the testing set were used to validate the MLA. Model performances were evaluated. RESULTS: The MLA using the random forest classifier presented optimal performance compared with other classifiers. When validated, the accuracy, sensitivity, specificity, F1 score, and AUC for the optimal model were 84.5%(95% CI 83.3-85.7), 84.5%(82.3-86.7), 84.5%(82.7-86.3), 0.845(0.831-0.859), and 0.914(0.903-0.925), respectively. CONCLUSIONS: A new machine learning algorithm for DKD diagnosis based on fundus images and 8 easily available clinical parameters was developed, which indicated that retinal vascular changes can assist in DKD screening and detection.

Vasoprotective Effects of Hyperoside against Cerebral Ischemia/Reperfusion Injury in Rats: Activation of Large-Conductance Ca2+-Activated K+ Channels.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and ß1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and ß1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels ß1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.

Coherent Control and Magnetic Detection of Divacancy Spins in Silicon Carbide at High Pressures.

Spin defects in silicon carbide appear to be a promising tool for various quantum technologies, especially for quantum sensing. However, this technique has been used only at ambient pressure until now. Here, by combining this technique with diamond anvil cell, we systematically study the optical and spin properties of divacancy defects created at the surface of SiC at pressures up to 40 GPa. The zero-field-splitting of the divacancy spins increases linearly with pressure with a slope of 25.1 MHz/GPa, which is almost two-times larger than that of nitrogen-vacancy centers in diamond. The corresponding pressure sensing sensitivity is about 0.28 MPa/Hz-1/2. The coherent control of divacancy demonstrates that coherence time decreases as pressure increases. Based on these, the pressure-induced magnetic phase transition of Nd2Fe14B sample at high pressures was detected. These experiments pave the way to use divacancy in quantum technologies such as pressure sensing and magnetic detection at high pressures.

Analysis of Spatial-Temporal Variation in Floral Volatiles Emitted from Lagerstroemia caudata by Headspace Solid-Phase Microextraction and GC-MS.

Lagerstroemia caudata is a rare aromatic species native to southeastern China, but its floral scent properties and release dynamics remain unclear. This study is the first systematic analysis of spatial-temporal variation in volatile organic compounds (VOCs) emitted from L. caudata by headspace solid-phase microextraction (HS-SPME) with gas chromatography-mass spectrometry (GC-MS). Thirty-two VOCs were identified, 20 of which were detected for the first time. Aldehydes, alcohols, and monoterpenoids were the main VOC categories, each with different releasing rhythms. Total emission of VOCs was much higher in the full-blooming stage (140.90 ng g-1min-1) than in the pre-blooming (36.54 ng g-1min-1) or over-blooming (24.92 ng g-1min-1). Monoterpenoids, especially nerol, geraniol, and linalool, were the characteristic VOCs for full-blooming flowers. Daily emissions of nine compounds (nerol, geraniol, linalool, citronellol, ß-citral, (E)-citral, phenylethyl alcohol, 2-heptanol, 2-nonanol) correlated closely with the opening of L. caudata, presenting an apparent diurnal pattern of scent emission. Tissue-specific emission was found in most isolated floral parts. Stamen was the most significant source of floral VOCs, considering its high emission levels of total VOC (627.96 ng g-1min-1). Our results extend the information on floral VOCs of Lagerstroemia and provide a theoretical basis for breeding new cultivars with desirable floral scents.

Serum Neurofilament Light Chain in Wilson's Disease: A Promising Indicator but Unparallel to Real-Time Treatment Response.

BACKGROUND: Wilson's disease (WD) currently lacks a promising indicator that could reflect neurological impairment and monitor treatment outcome. We aimed to investigate whether serum neurofilament light chain (sNfL) functions as a candidate for disease assessment and treatment monitoring of WD. METHODS: We assessed preclinical and manifested WD patients' sNfL levels compared to controls and analyzed the differences between patients with various clinical symptoms. We then explored the correlation between clinical scales and sNfL levels. And repeated measurements were performed in 34 patients before and after treatment. RESULTS: WD patients with neurological involvement had significantly higher sNfL levels than both hepatic patients and controls. Positive correlations were found between Unified Wilson's Disease Rating Scale scores and sNfL and between semiquantitative magnetic resonance imaging scales and sNfL levels in WD patients. However, in the treatment follow-up analysis, the trend of sNfL before and after treatment disaccorded with clinical response. CONCLUSION: These findings suggest that sNfL levels can be an ideal indicator for the severity of neurological involvement but fail to evaluate change in disease condition after treatment. © 2022 International Parkinson and Movement Disorder Society.

Synthesis and crystal structures of unsymmetrical wave-shaped heptathienoacenes.

Three unsymmetrical wave-shaped heptathienoacenes (UHT-1, UHT-2 and UHT-3) with sulfur atoms at different isomeric locations in the two terminal thiophene rings were designed and synthesized. The synthetic strategy contains two crucial steps, including the cross-coupling of two different dithienothiophene isomers (DTT) from dithieno[2,3-b:3',2'-d]thiophene (bb-DTT), dithieno[2,3-b:2',3'-d]thiophene (bt-DTT) and dithieno[2,3-b:3',4'-d]thiophene (bs-DTT) as building blocks through the Negishi coupling and intramolecular cyclization reactions with (SnBu3)2S. X-ray crystal structures of UHT-1, UHT-2 and UHT-3 show that the molecules adopt a wave-shaped geometry with multiple intermolecular interactions, such as S-S, S-C and S-H, which result in different crystal packing patterns. The isomeric location of the sulfur atoms of the two terminal thiophene rings of UHT-1, UHT-2 and UHT-3 plays an important role in tuning π-electronic conjugation and spectroscopic behaviors.

2-(Naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via ROS-mediated MAPK, AKT, and STAT3 signaling pathways in HepG2 human hepatocellular carcinoma cells.

1,4-naphthoquinone and its derivatives have attracted widespread attention due to their multiple biological activities, such as induction of cancer cell apoptosis; however, most of these compounds have high cytotoxicity. In this study, in order to reduce their toxicity and increase their potential anti-tumor effects, we synthesized a novel 1,4-naphthoquinone derivative named 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ), and investigated its apoptotic effects and underlying mechanism. Our results showed that NTDMNQ inhibited the viability of HepG2, Hep3B, and Huh7 human hepatocellular carcinoma (HCC) cells. It also increased the accumulation of cells in the G0/G1 phase of the cell cycle by increasing the expression levels of p-p53, p21 and p27, while decreasing the levels of Cyclin D1, Cyclin E, Cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. Inhibition of reactive oxygen species (ROS) by the ROS scavenger N-acetyl-L-cysteine (NAC) decreased apoptosis in NTDMNQ-treated cells. Western blot analysis showed that NTDMNQ increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and signal transducer and activator of transcription-3 (STAT3); these effects were blocked by NAC. Both the JNK inhibitor (SP600125) and p38 inhibitor (SB203580) reversed the phosphorylation of STAT3, and the ERK inhibitor (FR180204) and AKT inhibitor (LY294002) reduced the expression of STAT3. Taken together, these findings suggest that NTDMNQ induces apoptosis via ROS-mediated MAPK, AKT and STAT3 signaling pathways in HepG2 cells, and may be a potent anticancer agent.