Adipose Triglyceride Lipase-Mediated Adipocyte Lipolysis Exacerbates Acute Pancreatitis Severity in Mouse Models and Patients.

Dyslipolysis of adipocytes plays a critical role in various diseases. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme in adipocyte autonomous lipolysis. However, the degree of adipocyte lipolysis related to the prognoses in acute pancreatitis (AP) and the role of ATGL-mediated lipolysis in the pathogenesis of AP remain elusive. Herein, the visceral adipose tissue consumption rate in the acute stage was measured in both patients with AP and mouse models. Lipolysis levels and ATGL expression were detected in cerulein-induced AP models. CL316,243, a lipolysis stimulator, and adipose tissue-specific ATGL knockout mice were used to further investigate the role of lipolysis in AP. The ATGL-specific inhibitor, atglistatin, was used in C57Bl/6N and ob/ob AP models. This study indicated that increased visceral adipose tissue consumption rate in the acute phase was independently associated with adverse prognoses in patients with AP, which was validated in mouse AP models. Lipolysis of adipocytes was elevated in AP mice. Stimulation of lipolysis aggravated AP. Genetic blockage of ATGL specifically in adipocytes alleviated the damage to AP. The application of atglistatin effectively protected against AP in both lean and obese mice. These findings demonstrated that ATGL-mediated adipocyte lipolysis exacerbates AP and highlighted the therapeutic potential of ATGL as a drug target for AP.

A Hybrid Model for Fetal Growth Restriction Assessment by Automatic Placental Radiomics on T2-Weighted MRI and Multifeature Fusion.

BACKGROUND: MRI-based placental analyses have been used to improve fetal growth restriction (FGR) assessment by complementing ultrasound-based measurements. However, these are still limited by time-consuming manual annotation in MRI data and the lack of mother-based information. PURPOSE: To develop and validate a hybrid model for accurate FGR assessment by automatic placental radiomics on T2-weighted imaging (T2WI) and multifeature fusion. STUDY TYPE: Retrospective. POPULATION: 274 pregnant women (29.5 ± $$ \pm $$ 4.0 years) from two centers were included and randomly divided into training (N = 119), internal test (N = 40), time-independent validation (N = 43), and external validation (N = 72) sets. FIELD STRENGTH/SEQUENCE: 1.5-T, T2WI half-Fourier acquisition single-shot turbo spin-echo pulse sequence. ASSESSMENT: First, the placentas on T2WI were manually annotated, and a deep learning model was developed to automatically segment the placentas. Then, the radiomic features were extracted from the placentas and selected by three-step feature selection. In addition, fetus-based measurement features and mother-based clinical features were obtained from ultrasound examinations and medical records, respectively. Finally, a hybrid model based on random forest was constructed by fusing these features, and further compared with models based on other machine learning methods and different feature combinations. STATISTICAL TESTS: The performances of placenta segmentation and FGR assessment were evaluated by Dice similarity coefficient (DSC) and the area under the receiver operating characteristic curve (AUROC), respectively. A P-value <0.05 was considered statistically significant. RESULTS: The placentas were automatically segmented with an average DSC of 90.0%. The hybrid model achieved an AUROC of 0.923, 0.931, and 0.880 on the internal test, time-independent validation, and external validation sets, respectively. The mother-based clinical features resulted in significant performance improvements for FGR assessment. DATA CONCLUSION: The proposed hybrid model may be able to assess FGR with high accuracy. Furthermore, information complementation based on placental, fetal, and maternal features could also lead to better FGR assessment performance. TECHNICAL EFFICACY: Stage 2.

Design and application of a novel "turn-on" fluorescent probe for imaging sulfite in living cells and inflammation models.

Sulfite is one of the main existing forms of sulfur dioxide (SO2) in living system, which has been recognized as an endogenous mediator in inflammation. Evidence has accumulated to show that abnormal level of sulfite is associated with many inflammatory diseases, including neurological diseases and cancers. Herein, a novel fluorescent probe named QX-OA was designed and synthesized to detect sulfite. QX-OA was constructed by choosing quinolinium-xanthene as the fluorophore and levulinate as the specific and relatively steady recognition reaction. The probe showed remarkable green turn-on signal at 550 nm, together with high sensitivity (90-fold) and excellent selectivity to sulfite over other possible interfering species. In the meantime, QX-OA was successfully applied to visualize endogenous and exogenous sulfite in Hela cells. In the LPS-induced inflammation model, QX-OA could visualize the dose-dependent increase of sulfite level (0-2 mg/mL). Consequently, QX-OA was determined to be a potential method for detecting sulfite in pre-clinical diagnosis.

Significant but partial lipoprotein lipase functional loss caused by a novel occurrence of rare LPL biallelic variants.

BACKGROUND: Lipoprotein lipase (LPL) plays a crucial role in triglyceride hydrolysis. Rare biallelic variants in the LPL gene leading to complete or near-complete loss of function cause autosomal recessive familial chylomicronemia syndrome. However, rare biallelic LPL variants resulting in significant but partial loss of function are rarely documented. This study reports a novel occurrence of such rare biallelic LPL variants in a Chinese patient with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) during pregnancy and provides an in-depth functional characterization. METHODS: The complete coding sequences and adjacent intronic regions of the LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes were analyzed by Sanger sequencing. The aim was to identify rare variants, including nonsense, frameshift, missense, small in-frame deletions or insertions, and canonical splice site mutations. The functional impact of identified LPL missense variants on protein expression, secretion, and activity was assessed in HEK293T cells through single and co-transfection experiments, with and without heparin treatment. RESULTS: Two rare LPL missense variants were identified in the patient: the previously reported c.809G > A (p.Arg270His) and a novel c.331G > C (p.Val111Leu). Genetic testing confirmed these variants were inherited biallelically. Functional analysis showed that the p.Arg270His variant resulted in a near-complete loss of LPL function due to effects on protein synthesis/stability, secretion, and enzymatic activity. In contrast, the p.Val111Leu variant retained approximately 32.3% of wild-type activity, without impacting protein synthesis, stability, or secretion. Co-transfection experiments indicated a combined activity level of 20.7%, suggesting no dominant negative interaction between the variants. The patient's post-heparin plasma LPL activity was about 35% of control levels. CONCLUSIONS: This study presents a novel case of partial but significant loss-of-function biallelic LPL variants in a patient with HTG-AP during pregnancy. Our findings enhance the understanding of the nuanced relationship between LPL genotypes and clinical phenotypes, highlighting the importance of residual LPL function in disease manifestation and severity. Additionally, our study underscores the challenges in classifying partial loss-of-function variants in classical Mendelian disease genes according to the American College of Medical Genetics and Genomics (ACMG)'s variant classification guidelines.

Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients: A retrospective cohort study.

BACKGROUND: Early systemic anticoagulation (SAC) is a common practice in acute necrotizing pancreatitis (ANP), and its impact on in-hospital clinical outcomes had been assessed. However, whether it affects long-term outcomes is unknown. This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients. METHODS: During January 2013 and December 2018, ANP patients admitted within 7 days from the onset of abdominal pain were screened. The primary outcome was 90-day readmission after discharge. Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission. RESULTS: A total of 241 ANP patients were enrolled, of whom 143 received early SAC during their hospitalization and 98 did not. Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis (SVT) [risk ratio (RR) = 0.40, 95% CI: 0.26-0.60, P < 0.01] and lower 90-day readmission with an RR of 0.61 (95% CI: 0.41-0.91, P = 0.02) than those who did not. For the quality of life, patients who received early SAC had a significantly higher score in the subscale of vitality (P = 0.03) while the other subscales were all comparable between the two groups. Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57 (95% CI: 0.34-0.96, P = 0.04). Mediation analysis showed that SVT mediated 37.0% of the early SAC-90-day readmission causality. CONCLUSIONS: The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients, and reduced SVT incidence might be the primary contributor.

Improved clinical outcomes in advanced hepatocellular carcinoma treated with transarterial chemoembolization plus atezolizumab and bevacizumab: a bicentric retrospective study.

PURPOSE: The aim of the present study was to assess the efficacy and safety of transarterial chemoembolization (TACE) combined with atezolizumab and bevacizumab (hereafter, TACE-Atez/Bev) in the treatment of advanced hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: Clinical information was collected from consecutive patients with advanced HCC who received treatment with TACE-Atez/Bev or Atez/Bev from April 2021 and October 2022. Treatment response, overall survival (OS), and progression-free survival (PFS) were the primary outcomes of this study. Adverse events (AEs) were the secondary outcomes. Propensity score matching (PSM) analysis was applied to reduce bias between two groups. RESULTS: This study included 62 patients in the TACE-Atez/Bev group and 77 patients in the Atez/Bev group. The objective response rate (ORR) of the TACE-Atez/Bev group and the Atez/Bev group were 38.7% and 16.9% (P=0.004). However, there was no statistical difference in disease control rate between the two groups (69.4% vs 63.6%, P=0.479). Before PSM, the median OS was 14 months in the TACE-Atez/Bev group and 10 months in the Atez/Bev group (P=0.014). The median PFS in the TACE-Atez/Bev and Atez/Bev groups was 10 months and 6 months, respectively (P=0.001). After PSM, the median OS in the two groups was 14 months and 9 months, respectively (P=0.01). The median PFS was 7 months and 6 months, respectively (P=0.036). Multivariable analysis showed that treatment method was independent prognostic factors affecting OS. CONCLUSIONS: Compared with Atez/Bev treatment, TACE-Atez/Bev showed better OS, PFS, and ORR for Chinese patients with advanced HCC, with an acceptable safety profile.

SO2F2-Mediated Fluorination of P(O)-H and P(O)-OH Compounds under Mild Conditions.

With the increasing relevance of organophosphorus fluorine compounds in the pharmaceutical industry, their synthesis has attracted great attention. Herein, we report an efficient fluorination strategy for P(O)-H and P(O)-OH compounds using sulfuryl fluoride as the fluorination reagent. Avoiding the use of expensive or complex prepreparation reagents for fluoridation, this strategy could conveniently construct a variety of fluorophosphonates and phosphonofluoridates under mild conditions and without additional oxidants.

Nickel-Catalyzed Selective C-H Cyanation via Aromatic Thianthrenium Salts.

Here, we report the first case of nickel-catalyzed C-H cyanation via arylthianthrenium salts. The reaction features the use of air-stable and inexpensive NiCl2·6H2O as a catalyst for the highly selective construction of cyanation products by aromatic pre-thianthrenation. The mechanism study shows that the formation of aryl radicals is involved. Also, this protocol can be applied to the late-stage functionalization of bioactive molecules and is readily scalable, further showcasing the synthetic utility.

Expression of concern: A cascade process for directly converting nitriles (RCN) to cyanamides (RNHCN) via SO2F2-activated Tiemann rearrangement.

Expression of concern for 'A cascade process for directly converting nitriles (RCN) to cyanamides (RNHCN) via SO2F2-activated Tiemann rearrangement' by Guofu Zhang et al., Org. Biomol. Chem., 2019, 17, 7684-7688, https://doi.org/10.1039/C9OB01547G.

Frameshift coding sequence variants in the LPL gene: identification of two novel events and exploration of the genotype-phenotype relationship for variants reported to date.

BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme for triglyceride hydrolysis. Homozygous or compound heterozygous LPL variants cause autosomal recessive familial chylomicronemia syndrome (FCS), whereas simple heterozygous LPL variants are associated with hypertriglyceridemia (HTG) and HTG-related disorders. LPL frameshift coding sequence variants usually cause complete functional loss of the affected allele, thereby allowing exploration of the impact of different levels of LPL function in human disease. METHODS: All exons and flanking intronic regions of LPL were Sanger sequenced in patients with HTG-related acute pancreatitis (HTG-AP) or HTG-AP in pregnancy. Previously reported LPL frameshift coding sequence variants were collated from the Human Gene Mutation Database and through PubMed keyword searching. Original reports were manually evaluated for the following information: zygosity status of the variant, plasma LPL activity of the variant carrier, disease referred for genetic analysis, patient's age at genetic analysis, and patient's disease history. SpliceAI was employed to predict the potential impact of collated variants on splicing. RESULTS: Two novel rare variants were identified, and 53 known LPL frameshift coding sequence variants were collated. Of the 51 variants informative for zygosity, 30 were simple heterozygotes, 12 were homozygotes, and 9 were compound heterozygotes. Careful evaluation of the 55 variants with respect to their clinical and genetic data generated several interesting findings. First, we conclude that 6-7% residual LPL function could significantly delay the age of onset of FCS and reduce the prevalence of FCS-associated syndromes. Second, whereas a large majority of LPL frameshift coding sequence variants completely disrupt gene function through their "frameshift" nature, a small fraction of these variants may act wholly or partly as "in-frame" variants, leading to the generation of protein products with some residual LPL function. Third, we identified two candidate LPL frameshift coding sequence variants that may retain residual function based on genotype-phenotype correlation or SpliceAI-predicted data. CONCLUSIONS: This study reported two novel LPL variants and yielded new insights into the genotype-phenotype relationship as it pertains to LPL frameshift coding sequence variants.

The East Asian-specific LPL p.Ala288Thr (c.862G > A) missense variant exerts a mild effect on protein function.

BACKGROUND: Lipoprotein lipase (LPL) is the key enzyme responsible for the hydrolysis of triglycerides. Loss-of-function variants in the LPL gene are associated with hypertriglyceridemia (HTG) and HTG-related diseases. Unlike nonsense, frameshift and canonical GT-AG splice site variants, a pathogenic role for clinically identified LPL missense variants should generally be confirmed by functional analysis. Herein, we describe the clinical and functional analysis of a rare LPL missense variant. METHODS: Chinese patients with HTG-associated acute pancreatitis (HTG-AP) were screened for rare nonsense, frameshift, missense or canonical GT-AG splice site variants in LPL and four other lipid metabolism-related genes (APOC2, APOA5, GPIHBP1 and LMF1) by Sanger sequencing. The functional consequences of the LPL missense variant of interest were characterized by in vitro expression in HEK-293T and COS-7 cells followed by Western blot and LPL activity assays. RESULTS: Five unrelated HTG-AP patients were found to be heterozygous for a rare East Asian-specific LPL missense variant, c.862G > A (p.Ala288Thr). All five patients were adult males, and all were overweight and had a long history of alcohol consumption. Transfection of LPL wild-type and c.862G > A expression vectors into two cell lines followed by Western blot analysis served to exclude the possibility that the p.Ala288Thr missense variant either impaired protein synthesis or increased protein degradation. Contrary to a previous functional study that claimed that p.Ala288Thr had a severe impact on LPL function (reportedly having 36% normal activity), our experiments consistently demonstrated that the variant had a comparatively mild effect on LPL functional activity, which was mediated through its impact upon LPL protein secretion (~ 20% reduced secretion compared to wild-type). CONCLUSIONS: In this study, we identified the East Asian-specific LPL c.862G > A (p.Ala288Thr) missense variant in five unrelated HTG-AP patients. We demonstrated that this variant exerted only a relatively mild effect on LPL function in two cell lines. Heterozygosity for this LPL variant may have combined with alcohol consumption to trigger HTG-AP in these patients.

Ambient particulate matter exposure plus chronic ethanol ingestion exacerbates hepatic fibrosis by triggering the mitochondrial ROS-ferroptosis signaling pathway in mice.

BACKGROUND: Chronic ethanol ingestion causes persistent oxidative stresses in the liver, leading to hepatic injury and fibrosis, but the underlying mechanisms remain unclear. Recently, ambient particulate matter (PM) has been confirmed to aggravate high-fat diet-induced liver fibrosis by enhancing oxidative stress. Thus, we hypothesized that oxidative stress induced by ambient PM exposure increases the severity of liver fibrosis caused by ethanol ingestion. METHODS AND RESULTS: C57BL/6 mice were subjected to ambient PM inhalation, ethanol ingestion or ambient PM-plus-ethanol ingestion for 12 weeks. Oxidative stress, mitochondrial reactive oxygen species (MtROS), liver fibrosis and ferroptosis indicators in the liver were evaluated. In vitro, oxidative stress, MtROS, ferroptosis indicators, profibrotic molecules and fibrosis markers in hepatic stellate (LX-2) cells were also determined. We found that ethanol ingestion markedly elevated hepatic oxidative stress and MtROS levels, triggered hepatic ferroptosis, and induced liver fibrosis, along with upregulation of the profibrotic molecule TGF-ß1 and fibrosis marker collagen-I, in mice. Moreover, the combination of ambient PM and ethanol accelerated these adverse effects. Importantly, the combination of PM exposure and ethanol ingestion had a synergistic effect on these changes. In vitro, LX-2 cells activated with PM2.5 alone or combined with ethanol showed upregulation of TGF-ß1 and collagen-I. In addition, the levels of MtROS, the oxidative stress marker 4-hydroxynonenal (4-HNE) and ferroptosis-related proteins and the GSH/GSSG ratio were significantly increased in PM2.5 plus ethanol-treated LX-2 cells. After pretreatment with a MtROS scavenger (Mito-TEMPO), we found that Mito-TEMPO treatment inhibited ferroptosis and oxidative stress in PM2.5 plus ethanol-treated LX-2 cells. Furthermore, a specific ferroptosis inhibitor (Fer-1) decreased the levels of ferroptosis-related proteins and profibrotic molecules in activated LX-2 cells co-exposed to PM2.5 and ethanol. CONCLUSION: In this study, we revealed that ambient PM exposure induced profibrotic effects and that combined exposure to ambient PM and chronic ethanol ingestion exacerbated hepatic fibrosis, which may trigger ferroptosis by increasing MtROS, thereby activating hepatic stellate cells.

Potential mechanisms mediating PM2.5-induced alterations of H3N2 influenza virus infection and cytokine production in human bronchial epithelial cells.

Exposure to particulate matter (PM) has been associated with increased hospital admissions for influenza. Airway epithelial cells are a primary target for inhaled environmental insults including fine PM (PM2.5) and influenza viruses. The potentiation of PM2.5 exposure on the effects of influenza virus on airway epithelial cells has not been adequately elucidated. In this study, the effects of PM2.5 exposure on influenza virus (H3N2) infection and downstream modulation of inflammation and antiviral immune response were investigated using a human bronchial epithelial cell line, BEAS-2B. The results showed that PM2.5 exposure alone increased the production of pro-inflammatory cytokines including interleukin-6 (IL-6) and IL-8 but decreased the production of the antiviral cytokine interferon-ß (IFN-ß) in BEAS-2B cells while H3N2 exposure alone increased the production of IL-6, IL-8, and IFN-ß. Importantly, prior exposure to PM2.5 enhanced subsequent H3N2 infectivity, expression of viral hemagglutinin protein, as well as upregulation of IL-6 and IL-8, but reduced H3N2-induced IFN-ß production. Pre-treatment with a pharmacological inhibitor of nuclear factor-κB (NF-κB) suppressed pro-inflammatory cytokine production induced by PM2.5, H3N2, as well as PM2.5-primed H3N2 infection. Moreover, antibody-mediated neutralization of Toll-like receptor 4 (TLR4) blocked cytokine production triggered by PM2.5 or PM2.5-primed H3N2 infection, but not H3N2 alone. Taken together, exposure to PM2.5 alters H3N2-induced cytokine production and markers of replication in BEAS-2B cells, which in turn are regulated by NF-κB and TLR4.

Volumetric apparent diffusion coefficient (ADC) histogram metrics as imaging biomarkers for pretreatment predicting response to fertility-sparing treatment in patients with endometrial cancer.

OBJECTIVES: To investigate the feasibility of volumetric apparent diffusion coefficient (ADC) histogram analysis for prediction of fertility-sparing treatment (FST) response in patients with endometrial cancer (EC). METHODS: Pretreatment data of 54 EC patients with FST were retrospectively analyzed. Treatment response at each follow-up was pathologically evaluated. The associations of ADC histogram metrics (volume, minADC, maxADC, meanADC; 10th, 25th, 50th, 75th and 90th ADC percentiles; skewness; kurtosis) and baseline clinical characteristics with complete response (CR) at the second and third follow-ups, two-consecutive CR, and recurrence at the final follow-up were evaluated by uni- and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used for diagnostic performance evaluation. RESULTS: Compared with non-CR patients, CR patients had significantly higher minADC and 10th and 25th ADC percentiles at the second follow-up (P = 0.008, 0.039, and 0.034, respectively) and higher minADC, older age, lower HE4 level, and higher overweight rate at the third follow-up (P = 0.001, 0.040, 0.021, and 0.004, respectively). Patients with two-consecutive CR had a significantly higher minADC than those without (P = 0.018). There was no association between ADC metrics or clinical characteristics and recurrence (all P > 0.05). MinADC yielded the largest AUC in predicting CR (0.688 and 0.735 at the second and third follow-up, respectively) and the presence of two-consecutive CR (0.753). When combined with patient age and HE4 level, the prediction of CR could be further improved at the third follow-up, with an AUC of 0.786. CONCLUSION: Pretreatment minADC could be a potential imaging biomarker for predicting FST response. Clinical characteristics may have incremental value to minADC in predicting CR.

Volumetric ADC histogram analysis for preoperative evaluation of LVSI status in stage I endometrioid adenocarcinoma.

OBJECTIVES: To investigate the value of volumetric ADC histogram metrics for evaluating lymphovascular space invasion (LVSI) status in stage I endometrioid adenocarcinoma (EAC). METHODS: Preoperative MRI of 227 patients with stage I EAC were retrospectively analyzed. ADC histogram data were derived from the whole tumor with ROIs drawn on all slices of DWI scans (b = 0, 1000 s/mm2). The Student t-test was performed to compare ADC histogram metrics (minADC, maxADC, and meanADC; 10th, 25th, 50th, 75th, and 90th percentiles of ADC; skewness; and kurtosis) between the LVSI-positive and LVSI-negative groups, as well as between stage Ia and Ib EACs. ROC curve analysis was carried out to evaluate the diagnostic performance of ADC histogram metrics in predicting LVSI status in EAC. RESULTS: The minADC and meanADC and 10th, 25th, 50th, 75th, and 90th percentiles of ADC were significantly lower in LVSI-positive EACs compared with those in the LVSI-negative groups for stage I, Ia, and Ib EACs (all p < 0.05). MeanADC ≤ 0.857 × 10-3 mm2/s, meanADC ≤ 0.854 × 10-3 mm2/s, and the 90th percentile of ADC ≤ 1.06 × 10-3 mm2/s yielded the largest AUC of 0.844, 0.844, and 0.849 for evaluating LVSI positivity in stage I, Ia, and Ib tumors, respectively, with sensitivity of 75.4%, 75.0%, and 76.2%; specificity of 80.0%, 83.1%, and 82.1%; and accuracy of 79.3%, 81.5%, and 79.6%, respectively. CONCLUSION: Volumetric ADC histogram metrics might be helpful for the preoperative evaluation of LVSI status and personalized clinical management in patients with stage I EAC. KEY POINTS: • Volumetric ADC histogram analysis helps evaluate LVSI status preoperatively. • LVSI-positive EAC is associated with a reduction in multiple volumetric ADC histogram metrics. • MeanADC and the 90th percentile of ADC were shown to be best in evaluating LVSI- positivity in stage Ia and Ib EACs, respectively.

Palladium-Catalyzed Direct Decarbonylative Cyanation of Aryl Carboxylic Acids.

The direct transformation of aryl carboxylic acids to aryl nitrile compounds is an interesting topic because carboxylic acids are not only abundant in nature but are also inexpensive and stable. Here, the synthesis of a series of aryl nitriles by palladium-catalyzed decarbonylative cyanation of carboxylic acids without base has been achieved. The successful decarbonylative cyanation of drug molecules and Gram-scale reaction to verify the practicality and operability of this method are analyzed.

A late-stage functionalization tool: sulfonyl fluoride mediated deoxymethylation of phenols.

The late-stage functionalization of drugs and natural products has been identified as a promising approach to accelerate the discovery of new bioactive compounds. Due to the presence of the "Magic Methyl Effect", the direct deoxymethylation of phenolic hydroxyl groups, which are widespread in natural molecules, is a challenging task. A mild and rapid strategy for direct phenol deoxymethylation under metal catalysis using SO2F2 is described in this paper, while good functional group tolerance and high chemoselectivity allow this strategy to be one of the powerful tools for LSF. The power of this new platform is showcased through gram-scale and orthogonal experiments.

Plasma Manganese Levels and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study.

Manganese (Mn) intake has been found to be linked with risk of type 2 diabetes. However, the role of Mn in the development of gestational diabetes mellitus (GDM) remains to be investigated. This prospective study included pregnant women from the Tongji Maternal and Child Health Cohort. A total of 2327 participants with plasma specimens before 20 weeks were included. Among the pregnant women, 9.7% (225/2327) were diagnosed with GDM. After adjustment, pregnant women with the third and highest quartile of plasma Mn levels had 1.31-fold (RR, 2.31 [1.48, 3.61]) and 2.35-fold (RR, 3.35 [2.17, 5.17]) increased risk of GDM compared with those with the lowest quartile. A 1 standard deviation increment of ln-transformed plasma Mn levels (0.53 µg/L) was related to elevated risks of GDM with RRs of 1.28 [1.17, 1.40]. The positive associations between Mn and GDM remained consistent in all the subgroups. The weighted quantile sum index was significantly related to GDM (RR, 1.60 [1.37, 1.86]). The contribution of Mn (58.69%) to the metal mixture index was the highest related to GDM. Higher plasma Mn levels were found to be linked with elevated fasting and 2 h post-load blood glucose. This study revealed relationships of higher plasma Mn levels in early pregnancy and increased risk of GDM, suggesting that though essential, excess Mn in the body might be a potential important risk factor for GDM.

Th1, Th2, and Th17 cells are dysregulated, but only Th17 cells relate to C-reactive protein, D-dimer, and mortality risk in Stanford type A aortic dissection patients.

BACKGROUND: T helper (Th) cells are closely involved in vascular inflammation, endothelial dysfunction, and atherogenesis, which are the hallmarks of aortic dissection (AD). This study aimed to evaluate the clinical value of Th1, Th2, and Th17 cell measurements in Stanford type A AD patients. METHODS: Stanford type A AD patients (N=80) and non-AD patients with chest pain (N = 40) were recruited. Then, Th1, Th2, and Th17 cells in peripheral blood CD4+ T cells from all participants were detected by flow cytometry. The 30-day mortality of Stanford type A AD patients was recorded. RESULTS: Th1 and Th17 cells were higher, while Th2 cells were lower in Stanford type A AD patients compared with non-AD patients (all p < 0.001). Meanwhile, Th1 cells (area under curve (AUC): 0.734, 95% confidence interval (CI): 0.640-0.828), Th2 cells (AUC: 0.841, 95% CI: 0.756-0.925), and Th17 cells (AUC: 0.898, 95% CI: 0.839-0.957) could distinguish Stanford type A patients from non-AD patients. Moreover, Th1 cells (p = 0.037) and Th17 cells (p = 0.001) were positively related to CRP, and Th17 cells (p = 0.039) were also positively associated with D-dimer in Stanford type A AD patients. Furthermore, Th17 cells were elevated in deaths compared with survivors (p = 0.001), also, it could estimate 30-day mortality risk in Stanford type A AD patients with an AUC of 0.741 (95% CI: 0.614-0.867), which was similar to the value of CRP (AUC: 0.771, 95% CI: 0.660-0.882), but lower than the value of D-dimer (AUC: 0.818, 95% CI: 0.722-0.913). CONCLUSION: Th1, Th2, and Th17 cells are dysregulated, but only the Th17 cells relate to CRP, D-dimer, and 30-day mortality risk in Stanford type A AD patients.

Whole-tumor histogram analysis of apparent diffusion coefficient for differentiating adenosquamous carcinoma and adenocarcinoma from squamous cell carcinoma in patients with cervical cancer.

BACKGROUND: Differentiating adenosquamous carcinoma (ASC) and adenocarcinoma (AC) from squamous cell carcinoma (SCC) precisely is crucial for treatment strategy and prognosis prediction in patients with cervical cancer (CC). PURPOSE: To differentiate ASC and AC from SCC in patients with CC using the apparent diffusion coefficient (ADC) histogram analysis. MATERIAL AND METHODS: A total of 118 patients with histologically diagnosed ASC, AC, and SCC were included. The ADC histogram parameters were extracted from ADC maps. Receiver operating characteristic analysis was performed to evaluate the diagnostic performance of each ADC histogram parameter in differentiating the subtypes of CC. The predictors for histologic subtypes were further selected using univariate and multivariate logistic regression analyses. RESULTS: The ADCmean, ADCmax, ADCP10, ADCP25, ADCP75, ADCP90, ADCmedian, and ADCmode of the ASC were significantly lower than those of the AC; and ADCkurtosis and ADCskewness of the ASC were lower than those of the SCC. The ADCmean, ADCmax, ADCP10, ADCP25, ADCP75, ADCP90, ADCmedian, and ADCmode of AC were significantly higher than those of the SCC. The ADCP10 and ADCP10 + diameter yielded the AUCs of 0.753 and 0.778 in differentiating ASC from AC. The ADCmedian and ADCmedian + diameter yielded the AUCs of 0.807 and 0.838 in differentiating AC from SCC. The ADCskewness yielded the AUC of 0.713 in differentiating ASC from SCC. CONCLUSION: The ADCP10 and ADCP10 + diameter, ADCmedian, and ADCmedian + diameter performed well in differentiating ASC from AC and AC from SCC, respectively. However, ADCskewness exhibited a limited ability in differentiating ASC from SCC.