Garnet secondary ion mass spectrometry oxygen isotopes reveal crucial roles of pulsed magmatic fluid and its mixing with meteoric water in lode gold genesis.

SignificanceThere is a common consensus that lode gold deposits mostly precipitated from metamorphic fluids via fluid boiling and/or fluid-rock interaction, but whether magmatic hydrothermal fluids and the mixing of such fluids with an external component have played a vital role in the formation of lode gold deposits remains elusive. We use garnet secondary ion mass spectrometry oxygen isotope analysis to demonstrate that the world-class Dongping lode gold deposit has been formed by multiple pulses of magmatic hydrothermal fluids and their mixing with large volumes of meteoric water. This study opens an opportunity to tightly constrain the origin of lode gold deposits worldwide and other hydrothermal systems that may have generated giant ore deposits in the Earth's crust.

Quality Evaluation of Guidelines for the Diagnosis and Treatment of Liver Failure.

OBJECTIVES: This study aimed to systematically assess the methodological quality and key recommendations of the guidelines for the diagnosis and treatment of liver failure (LF), furnishing constructive insights for guideline developers and equipping clinicians with evidence-based information to facilitate informed decision-making. DATA SOURCES: Electronic databases and manual searches from January 2011 to August 2023. STUDY SELECTION: Two reviewers independently screened titles and abstracts, then full texts for eligibility. Fourteen guidelines were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data and checked by two others. Methodological quality of the guidelines was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Of the 14 guidelines, only the guidelines established by the Society of Critical Care Medicine and the American College of Gastroenterology (2023) achieved an aggregate quality score exceeding 60%, thereby meriting clinical recommendations. It emerged that there remains ample room for enhancement in the quality of the guidelines, particularly within the domains of stakeholder engagement, rigor, and applicability. Furthermore, an in-depth scrutiny of common recommendations and supporting evidence drawn from the 10 adult LF guidelines unveiled several key issues: controversy exists in the recommendation, the absence of supporting evidence and confusing use of evidence for recommendations, and a preference in evidence selection. CONCLUSIONS: There are high differences in methodological quality and recommendations among LF guidelines. Improving these existing problems and controversies will benefit existing clinical practice and will be an effective way for developers to upgrade the guidelines.

[68Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study.

PURPOSE: PD-L1 PET imaging, as a non-invasive procedure, can perform a real-time, dynamic and quantitative analysis of PD-L1 expression at tumor sites. In this study, we developed a novel peptide-based PET tracer, [68 Ga]Ga-AUNP-12, for preclinical and first-of-its-kind imaging of PD-L1 expression in patients. METHODS: Radiosynthesis of [68 Ga]Ga-AUNP-12 was conducted. Assays for cellular uptake and binding were conducted on the PANC02, CT26, and B16F10 cell lines. Preclinical models were used to investigate its biodistribution, imaging capacity, and pharmacokinetics. Furthermore, interferon-γ (IFN-γ) was used for development of an animal model with high PD-L1 expression for targeted PET imaging and efficacy evaluation of PD-L1 blocking therapy. In healthy volunteers and cancer patients, the PD-L1 imaging, radiation dosimetry, safety, and biodistribution were further evaluated. RESULTS: In vitro and in vivo animal studies showed that [68 Ga]Ga-AUNP-12 PET imaging displayed a high specificity in evaluating PD-L1 expression. The radiochemical yield of [68 Ga]Ga-AUNP-12 was 71.7 ± 8.2%. Additionally, its molar activity and radiochemical purity were satisfactory. The B16F10 tumor was visualized with the tumor uptake of 6.86 ± 0.71% ID/g and tumor-to-muscle ratio of 6.83 ± 0.36 at 60 min after [68 Ga]Ga-AUNP-12 injection. Furthermore, [68 Ga]Ga-AUNP-12 PET imaging could sensitively detect the PD-L1 dynamic changes in CT26 tumor xenograft models regulated by IFN-γ treatment, and correspondingly can effectively guide immunotherapy. Regarding radiation dosimetry, [68 Ga]Ga-AUNP-12 is safe for human use. The first human study found that [68 Ga]Ga-AUNP-12 can be rapidly cleared from blood and other nonspecific organs through the kidney excretion, leading to form a clear imaging contrast in the clinical framework. The specificity of [68 Ga]Ga-AUNP-12 was validated and tumor uptake strongly correlated with the high PD-L1 expression in patients with lung adenocarcinoma and oesophageal squamous cell carcinoma (OSCC). CONCLUSION: [68 Ga]Ga-AUNP-12 was successfully developed as a PD-L1-specific PET imaging tracer in preclinical and first-in-human studies.

[18F]SynVesT-1 and [18F]FDG quantitative PET imaging in the presurgical evaluation of MRI-negative children with focal cortical dysplasia type II.

PURPOSE: MRI-negative children with focal cortical dysplasia type II (FCD II) are one of the most challenging cases in surgical epilepsy management. We aimed to utilize quantitative positron emission tomography (QPET) analysis to complement [18F]SynVesT-1 and [18F]FDG PET imaging and facilitate the localization of epileptogenic foci in pediatric MRI-negative FCD II patients. METHODS: We prospectively enrolled 17 MRI-negative children with FCD II who underwent [18F]SynVesT-1 and [18F]FDG PET before surgical resection. The QPET scans were analyzed using statistical parametric mapping (SPM) with respect to healthy controls. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of [18F]SynVesT-1 PET, [18F]FDG PET, [18F]SynVesT-1 QPET, and [18F]FDG QPET in the localization of epileptogenic foci were assessed. Additionally, we developed a multivariate prediction model based on dual trace PET/QPET assessment. RESULTS: The AUC values of [18F]FDG PET and [18F]SynVesT-1 PET were 0.861 (sensitivity = 94.1%, specificity = 78.2%, PPV = 38.1%, NPV = 98.9%) and 0.908 (sensitivity = 82.4%, specificity = 99.2%, PPV = 93.3%, NPV = 97.5%), respectively. [18F]FDG QPET showed lower sensitivity (76.5%) and NPV (96.6%) but higher specificity (95.0%) and PPV (68.4%) than visual assessment, while [18F]SynVesT-1 QPET exhibited higher sensitivity (94.1%) and NPV (99.1%) but lower specificity (97.5%) and PPV (84.2%). The multivariate prediction model had the highest AUC value (AUC = 0.996, sensitivity = 100.0%, specificity = 96.6%, PPV = 81.0%, NPV = 100%). CONCLUSIONS: The multivariate prediction model based on [18F]SynVesT-1 and [18F]FDG PET/QPET assessments holds promise in noninvasively identifying epileptogenic regions in MRI-negative children with FCD II. Furthermore, the combination of visual assessment and QPET may improve the sensitivity and specificity of diagnostic tests in localizing epileptogenic foci and achieving a preferable surgical outcome in MRI-negative FCD II.

Catalyst- and base-free visible light-enabled radical relay trihalomethylation/functional group-migration/carbonylation with CX3SO2Cl.

Herein, we report a visible light-enabled radical trihalomethylation/cyano-migration/carbonylation cascade reaction of 2-hydroxy-2-hex-5-enenitrile with CX3SO2Cl as the CX3-source (X = F, Cl) to obtain 5-oxo-2-(2,2,2-trihaloethyl)pentanenitrile compounds in the absence of a photocatalyst, transition metal and base. This reaction system is also effective to convert (benzo[d]thiazol-2-yl)-pent-4-enol to the corresponding 4-(benzo[d]thiazol-2-yl)-6,6,6-trihalo-hexanone products. These reactions occur under mild conditions, tolerate a wide range of functional groups, and provide alternative approaches for the 1,2-bifunctionalization reaction of unactivated olefins.

The use of 68 Ga-PSMA PET/CT to stratify patients with PI-RADS 3 lesions according to clinically significant prostate cancer risk.

BACKGROUND: Prostate imaging reporting and data system (PI-RADS) category 3 lesions represent a "gray zone," having an equivocal risk of presenting as clinically significant prostate cancer (csPCa). 68 Ga-labelled prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has been identified as a diagnostic tool that can help to predict cases of primary PCa. We aimed to explore diagnostic value of 68 Ga-PSMA PET/CT for csPCa in PI-RADS 3 lesions to aid in decision-making and avoid unnecessary biopsies. METHODS: A total of 78 men with PI-RADS 3 lesions who underwent both 68 Ga-PSMA PET/CT and transrectal ultrasound/magnetic resonance imaging (MRI) fusion-guided biopsy were enrolled. Images were analyzed by respective physicians who were blinded to the pathological results. Receiver operating characteristic (ROC) curve analysis and decision curve analysis were used to evaluate the diagnostic performance of univariate and multivariate analyses. RESULTS: A total of 26/78 men had pathologically confirmed csPCa. A lower ADCT/ADCCLP (0.65 vs. 0.71, p = 0.018), smaller prostate volume (25.27 vs. 42.79 ml, p < 0.001), lower free prostate-specific antigen/total prostate-specific antigen (0.11 vs. 0.16, p < 0.001), higher PSA level (13.45 vs. 7.90 ng/ml, p = 0.001), higher PSA density (0.40 vs. 0.16 ng/ml2 , p < 0.001), higher SUVmax (9.80 vs. 4.40, p < 0.001) and SUVT/BGp (2.41 vs. 1.00, p < 0.001) were associated with csPCa. ROC analysis illustrated the improvement in SUVmax and SUVT/BGp compared with all independent and combined clinical features as well as multiparametric magnetic resonance imaging (mpMRI) features for csPCa detection. The net benefits of SUVmax and SUVT/BGp were superior to those of other features, respectively. With cutoff values of 5.0 for SUVmax and 1.4 for SUVT/BGp, the diagnostic sensitivity and specificity for csPCa were 96.2%, 100% and 80.8%, 84.6%, respectively. CONCLUSION: 68 Ga-PSMA PET/CT is potentially capable of stratifying men with PI-RADS 3 lesions according to the presence of csPCa and has better performance than the model established based on clinical and mpMRI features.

Fluorobenzene and Water-Promoted Rapid Growth of Vertical Graphene Arrays by Electric-Field-Assisted PECVD.

Vertical graphene (VG) arrays show exposed sharp edges, ultra-low electrical resistance, large surface-to-volume ratio, and low light reflectivity, thus having great potential in emerging applications, including field emission, sensing, energy storage devices, and stray light shields. Although plasma enhanced chemical vapor deposition (PECVD) is regarded as an effective approach for the synthesis of VG, it is still challenging to increase the growth rate and height of VG arrays simultaneously. Herein, a fluorobenzene and water-assisted method to rapidly grow VG arrays in an electric field-assisted PECVD system is developed. Fluorobenzene-based carbon sources are used to produce highly electronegative fluorine radicals to accelerate the decomposition of methanol and promote the growth of VG. Water is applied to produce hydroxyl radicals in order to etch amorphous carbon and accelerate the VG growth. The fastest growth rate can be up to 15.9 µm h-1 . Finally, VG arrays with a height of 144 µm are successfully synthesized at an average rate of 14.4 µm h-1 . As a kind of super black material, these VG arrays exhibit an ultra-low reflectance of 0.25%, showing great prospect in stray light shielding.

KOH-promoted cascade C-Cl bond activation and amidation of trichloromethyl aromatic compounds with formamides in water.

A KOH-promoted cascade C-Cl bond activation and amidation of trichloromethyl aromatic compounds with formamides using water as a solvent has been developed. This methodology suggested an alternative synthetic approach for the synthesis of aryl amide compounds in the absence of catalysts, additives and organic solvents. In addition, the yields of gram-scale reactions are good and provide a basis for synthetic application.

High neutrophil-lymphocyte ratio indicates a worse response to ursodeoxycholic acid in primary biliary cholangitis: a retrospective cohort study.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by inflammation of the interlobular bile ducts. Ursodeoxycholic acid (UDCA) is the only FDA approved first-line therapy for PBC, but up to 40% of patients with PBC have an incomplete response to UDCA. Neutrophil-to-lymphocyte (NLR) has been used to predict prognosis in various liver diseases. There is limited evidence on the treatment response to UDCA in PBC patients. Our study aimed to evaluate the relationship between NRL and the response to UDCA treatment in PBC patients. METHODS: A total of 257 primary biliary cholangitis (PBC) patients treated with UDCA (13-15 mg/kg/d) were enrolled in this retrospective study. The response to treatment was evaluated based on alkaline phosphatase levels ≤1.67 times the upper limit of the normal value after 12 months of UDCA treatment. Multivariable logistic regression analysis was performed to investigate the association between NLR at baseline and the response to 12 months of UDCA treatment after adjusting for important confounding variables. The stability of the results was evaluated by unadjusted and adjusted models. RESULTS: The results of multiple regression analysis showed that NLR at baseline was positively associated with the nonresponse to UDCA treatment after adjustments for potential confounders (age, sex, BMI, hypertension, arterial plaque, thyroid disease, jaundice, albumin, globulin, total bile acid, ALP, GGT, LDLC, total cholesterol, hemoglobin, and APTT) (OR = 1.370, 95% CI 1.066-1.761). These results reveal that NLR is an independent risk factor for UDCA treatment nonresponse. CONCLUSIONS: Our results suggest that PBC patients with a high NLR had a worse response to UDCA therapy.

Effect of Cathodal Transcranial Direct Current Stimulation for Lower Limb Subacute Stroke Rehabilitation.

Methods: A pilot double-blind and randomized clinical trial. Ninety-one subjects with subacute stroke were treated with cathodal/sham stimulation tDCS based on CGR (physiotherapy 40 min/d and occupational therapy 20 min/d) once daily for 20 consecutive working days. Computer-based stratified randomization (1 : 1) was employed by considering age and sex, with concealed assignments in opaque envelopes to ensure no allocation errors after disclosure at the study's end. Patients were evaluated at T0 before treatment, T1 immediately after the posttreatment assessment, and T2 assessment one month after the end of the treatment. The primary outcome index was assessed: lower limb Fugl-Meyer motor score (FMA-LE); secondary endpoints were other gait assessment and relevant stroke scale assessment. Results: Patients in the trial group performed significantly better than the control group in all primary outcome indicators assessed posttreatment T1 and at follow-up T2: FMA-LE outcome indicators between the two groups in T1 (P = 0.032; effect size 1.00, 95% CI: 0.00 to 2.00) and FMA-LE outcome indicators between the two groups in T2 (P = 0.010; effect size 2.00, 95% CI: 1.00 to 3.00). Conclusion: In the current pilot study, ctDCS plus CGR was an effective treatment modality to improve lower limb motor function with subacute stroke. The effectiveness of cathodal tDCS in poststroke lower limb motor dysfunction is inconclusive. Therefore, a large randomized controlled trial is needed to verify its effectiveness.

Visible-Light-Enabled Ph3P/LiI-Promoted Tandem Radical Trifluoromethylation/Cyclization/Iodination of 1,6-Enynes with Togni's Reagent.

We report the visible-light-induced Ph3P/LiI-promoted intermolecular cascade trifluoromethyl radical addition/5-exo-dig cyclization/iodination of 1,6-enynes with Togni's reagent using LiI as the iodine source without the need of the transition metal, oxidant, and base. This reaction promises to be a useful method for the preparation of trifluoromethyl-substituted and vinyl C-I bond-containing pyrrolidines and benzofuran products with good regioselectivity and functional-group tolerance under ambient conditions.

Switchable, Reagent-Controlled C(sp3)-H Selective Iodination and Acetoxylation of 8-Methylquinolines.

An efficient Pd-catalyzed C(sp3)-H selective iodination of 8-methylquinolines is reported herein for the first time. Because of the versatility of organic iodides, the method offers a facile access to various C8-substituted quinolines. By slightly switching the reaction conditions, an efficient C(sp3)-H acetoxylation of 8-methylquinolines has also been enabled. Both approaches feature mild reaction conditions, good tolerance of functional groups, and a broad substrate scope.

Thioamide directed iridium(I)-catalyzed C-H arylation of ferrocenes with aryl boronic acids.

The first Ir(I)-catalyzed thioamide-assisted C-H arylation of ferrocenes with aryl boronic acids under base-free mild reaction conditions in the presence of Ag2CO3 as an oxidant with eco-friendly 2-MeTHF as a solvent was developed. This reaction has a wide range of substrates (37 examples) and functional group tolerance (18-94% yields), and provides promising access to aryl thioamide-ferrocene compounds with good yields and regioselectivity.

Effects of molecular weight of polyaspartic acid on nitrogen use efficiency and crop yield.

BACKGROUND: In the past decades, ever-increasing fertilizer use has led to a continuous increase in agricultural output. However, serious waste of resources occurs because of the low utilization of fertilizers. Polyaspartic acid (PASP) is a biodegradable polymer that can be used as a fertilizer synergist in agricultural production to improve the nutrient utilization capacity of plants. For polymers, the molecular weight (MW) often affects their effectiveness. However, little information is available on the effects of PASP MW in agriculture, especially on nitrogen leaching and plant element uptake. RESULTS: This work was conducted to identify the effect of PASPs with three different MWs - PASP-1 (MW: 5517), PASP-2 (MW: 6934), and PASP-3 (MW: 7568) - on nitrogen leaching, lettuce growth, and wheat cultivation. The results revealed that PASP favored plant growth and nitrogen accumulation in the soil, independent of crop species. PASP with a higher MW improved yields and the agronomic characteristics of lettuce and wheat. Furthermore, apparent amelioration of nitrogen use efficiency for lettuce (7.6%, 12.8%, and 15.0%) and wheat (4.6%, 8.1%, and 9.2%) was observed in the treatments with PASP addition. The effects and merits of PASPs on preventing ammonium nitrogen leaching and improving lettuce and wheat productivity were as follows: PASP-3 > PASP-2 > PASP-1. CONCLUSION: The MW of PASP is an essential factor affecting inorganic nitrogen leaching and crop productivity, and PASP with a higher MW (7568) is recommended for application in agriculture. © 2022 Society of Chemical Industry.

A Hybrid Method Using HAVOK Analysis and Machine Learning for Predicting Chaotic Time Series.

The prediction of chaotic time series systems has remained a challenging problem in recent decades. A hybrid method using Hankel Alternative View Of Koopman (HAVOK) analysis and machine learning (HAVOK-ML) is developed to predict chaotic time series. HAVOK-ML simulates the time series by reconstructing a closed linear model so as to achieve the purpose of prediction. It decomposes chaotic dynamics into intermittently forced linear systems by HAVOK analysis and estimates the external intermittently forcing term using machine learning. The prediction performance evaluations confirm that the proposed method has superior forecasting skills compared with existing prediction methods.

The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.

Na-Ln Heterometallic Coordination Polymers: Structure Modulation by Na+ Concentration and Efficient Detection to Tetracycline Antibiotics and 4-(Phenylazo)aniline.

On the basis of the lanthanide metalloligand [Ln(ODA)3]3- (H2ODA = oxydiacetic acid), three new Na-Ln heterometallic coordination polymers, [Ln(ODA)3Na2]n [Ln = Eu (1) and Gd (2)] and [Tb(ODA)3Na3(H2O)2]n (3), had been assembled by adjusting the concentration of Na+ ions in the reaction system. The investigations of fluorescence sensing showed that 1 could be a ratiometric probe to detect tetracycline (TC) and oxytetracycline (OTC) with high sensitivity and low detection limits, 71.92 ppb for the former and 45.54 ppb for the latter, and 3 could selectively sense 4-(phenylazo)aniline through the turn-off pathway with 14.59 ppb of detection limits. Moreover, the competing and circulating experiments indicated that both 1 and 3 had satisfactory antiinterference and recyclability for the corresponding analytes. All of these results implied that 1 and 3 should be potential fluorescent sensors for the detection of TC/OTC and 4-(phenylazo)aniline, and the possible sensing mechanism had also been discussed in depth.

Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling.

Celastrol, derived from the roots of the Tripterygium Wilfordi, shows a striking effect on obesity. In the present study, the role of celastrol in cholestasis was investigated using metabolomics and transcriptomics. Celastrol treatment significantly alleviated cholestatic liver injury in mice induced by α-naphthyl isothiocyanate (ANIT) and thioacetamide (TAA). Celastrol was found to activate sirtuin 1 (SIRT1), increase farnesoid X receptor (FXR) signaling and inhibit nuclear factor-kappa B and P53 signaling. The protective role of celastrol in cholestatic liver injury was diminished in mice on co-administration of SIRT1 inhibitors. Further, the effects of celastrol on cholestatic liver injury were dramatically decreased in Fxr-null mice, suggesting that the SIRT1-FXR signaling pathway mediates the protective effects of celastrol. These observations demonstrated a novel role for celastrol in protecting against cholestatic liver injury through modulation of the SIRT1 and FXR.

LncRNA SNHG3 promotes bladder cancer proliferation and metastasis through miR-515-5p/GINS2 axis.

Growing evidence suggests that long non-coding RNAs (lncRNAs) are associated with carcinogenesis. LncRNA small nucleolar RNA host gene 3 (SNHG3) is up-regulated in various cancers and positively associated with poor prognosis of these cancers. However, the precise role of lncRNA SNHG3 in bladder cancer (Bca) remains unclear. In our research, we first reported that lncRNA SNHG3 was up-regulated in bladder cancer tissues and positively related to poor clinical prognosis. Moreover, knockdown of lncRNA SNHG3 significantly suppressed the proliferation, migration, invasion and EMT process of Bca cells in vitro and vivo. Mechanistically, we revealed that suppression of SNHG3 evidently enhanced miR-515-5p expression and decreased GINS2 expression at posttranscriptional levels. Moreover, SNHG3 positively regulated GINS2 expression by sponging miR-515-5p under a competing endogenous RNA (ceRNA) mechanism. To sum up, our study suggested lncRNA SNHG3 acted as a microRNA sponge and an oncogenic role in the progression of bladder cancer.

Lanthanide Metal-Organic Frameworks Assembled from Unexplored Imidazolylcarboxylic Acid: Structure and Field-Induced Two-Step Magnetic Relaxation.

A series of 3D homologous metal-organic frameworks, [M(H0.5L)2] [M = Dy (1), Ho (2), Yb (3), Sm (4), Gd (5), and Y (6); H2L = 5-(1H-imidazol-1-yl)isophthalic acid], were isolated. In these complexes, the metal centers behave as hexacoordinated environments with distorted octahedral geometries, which is unusual in the lanthanide series, linking to each other and producing a fascinating 3D architecture. Magnetically, 1 features a field-driven dual-magnetic relaxation, which is rarely observed in high-dimensional coordination polymers. Analysis on the dilution sample (1@Y) and ab initio calculation unveil that the thermally assisted slow relaxation is mostly caused by the single-ion magnetism of DyIII itself.