Sialyltransferase ST3GAL6 silencing reduces α2,3-sialylated glycans to regulate autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy. / å”¾æ¶²é ¸ç³–åŸºè½¬ç§»é ¶ST3GAL6的沉默可通过减少α2,3-å”¾æ¶²é ¸åŒ–èšç³–é™ä½ŽHSPB8-BAG3è¡¨è¾¾ä»Žè€Œè°ƒæŽ§è‚æ€§è„‘ç— å°é¼ å¤§è„‘ä¸­çš„è‡ªå™¬.

End-stage liver diseases, such as cirrhosis and liver cancer caused by hepatitis B, are often combined with hepatic encephalopathy (HE); ammonia poisoning is posited as one of its main pathogenesis mechanisms. Ammonia is closely related to autophagy, but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear. Sialylation is an essential form of glycosylation. In the nervous system, abnormal sialylation affects various physiological processes, such as neural development and synapse formation. ST3 ß|-galactoside α2,|3-sialyltransferase 6 (ST3GAL6) is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures. We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction, and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3 (LC3) and Beclin-1 were upregulated in ammonia-induced astrocytes. These findings suggest that ST3GAL6 is related to autophagy in HE. Therefore, we aimed to determine the regulatory relationship between ST3GAL6 and autophagy. We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II (MAL-II) and neuraminidase can inhibit autophagy. In addition, silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein ß8 (HSPB8) and Bcl2-associated athanogene 3 (BAG3). Notably, the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression. Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

Sialyltransferase ST3GAL6 silencing reduces α2,3-sialylated glycans to regulate autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy. / å”¾æ¶²é ¸ç³–åŸºè½¬ç§»é ¶ST3GAL6的沉默可通过减少α2,3-å”¾æ¶²é ¸åŒ–èšç³–é™ä½ŽHSPB8-BAG3è¡¨è¾¾ä»Žè€Œè°ƒæŽ§è‚æ€§è„‘ç— å°é¼ å¤§è„‘ä¸­çš„è‡ªå™¬.

End-stage liver diseases, such as cirrhosis and liver cancer caused by hepatitis B, are often combined with hepatic encephalopathy (HE); ammonia poisoning is posited as one of its main pathogenesis mechanisms. Ammonia is closely related to autophagy, but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear. Sialylation is an essential form of glycosylation. In the nervous system, abnormal sialylation affects various physiological processes, such as neural development and synapse formation. ST3 ß|-galactoside α2,|3-sialyltransferase 6 (ST3GAL6) is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures. We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction, and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3 (LC3) and Beclin-1 were upregulated in ammonia-induced astrocytes. These findings suggest that ST3GAL6 is related to autophagy in HE. Therefore, we aimed to determine the regulatory relationship between ST3GAL6 and autophagy. We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II (MAL-II) and neuraminidase can inhibit autophagy. In addition, silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein ß8 (HSPB8) and Bcl2-associated athanogene 3 (BAG3). Notably, the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression. Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

Exploring the mechanism of diabetic cardiomyopathy treated with Qigui Qiangxin mixture based on UPLC-Q/TOF-MS, network pharmacology and experimental validation.

Despite its effectiveness in treating diabetic cardiomyopathy (DCM), Qigui Qiangxin Mixture (QGQXM) remains unclear in terms of its active ingredients and specific mechanism of action. The purpose of this study was to explore the active ingredients and mechanism of action of QGQXM in the treatment of DCM through the comprehensive strategy of serum pharmacology, network pharmacology and combined with experimental validation. The active ingredients of QGQXM were analyzed using Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q/TOF-MS). Network pharmacology was utilized to elucidate the mechanism of action of QGQXM for the treatment of DCM. Finally, in vivo validation was performed by intraperitoneal injection of STZ combined with high-fat feeding-induced DCM rat model. A total of 25 active compounds were identified in the drug-containing serum of rats, corresponding to 121 DCM-associated targets. GAPDH, TNF, AKT1, PPARG, EGFR, CASP3, and HIF1 were considered as the core therapeutic targets. Enrichment analysis showed that QGQXM mainly treats DCM by regulating PI3K-AKT, MAPK, mTOR, Insulin, Insulin resistance, and Apoptosis signaling pathways. Animal experiments showed that QGQXM improved cardiac function, attenuated the degree of cardiomyocyte injury and fibrosis, and inhibited apoptosis in DCM rats. Meanwhile, QGQXM also activated the PI3K/AKT signaling pathway, up-regulated Bcl-2, and down-regulated Caspase9, which may be an intrinsic mechanism for its anti-apoptotic effect. This study preliminarily elucidated the mechanism of QGQXM in the treatment of DCM and provided candidate compounds for the development of new drugs for DCM.

Clinical Features and Blood Indicators for Severity and Prognosis in COVID-19 Patients.

BACKGROUND: This study aimed to analyze the clinical manifestations and blood indicators to deepen the understanding of Coronavirus disease 2019 (COVID-19). METHODS: COVID-19 patients admitted to C10 West Ward, Tongji Hospital in Wuhan City ("West Ward") between January 31 and March 28, 2020, were retrospectively analyzed. RESULTS: A total of 61 COVID-19 patients were hospitalized, wherein the non-critical Group had 30 cases, while the critical group had 31 (including 14 survivors and 17 deaths). Age, the proportion of fever cases, white blood cell (WBC), basophils, red blood cell (RBC), hemoglobin, lactate dehydrogenase (LDH), C-reactive protein (CRP), high-sensitivity troponin, pro-BNP (brain natriuretic peptide), prothrombin time (PT), and D-dimer were higher in the critical group while lymphocytes, eosinophils, albumin were lower compared with those of the non-critical group (all p < 0.05). WBC (p = 0.008), basophils (p = 0.034), and LDH (p = 0.005) of the death subgroup climbed remarkably in comparison with those of the survival subgroup. CONCLUSIONS: Advanced age, high fever, increases in indicators such as WBC, basophils, CRP, LDH, high-sensitivity troponin, pro-BNP, and D-dimer, and decreases in indicators, including lymphocytes, eosinophils, and albumin, might forebode a critical condition.

The prevalence and genetic disorders spectrum of thalassemia among breast cancer patients in Jiangxi province, China.

Background: Thalassemia is a common inherited hematological disease with genetic disorders characterized by imbalanced synthesis of the globin chains. Due to the improvement of treatment methods, patients with thalassemia can survive for a long time. Therefore, it is not uncommon for patients with thalassemia suffering from malignant tumors. However, there are quite few reports on thalassemia patients complicated with breast cancer. Herein, we try to investigate the prevalence and genetic disorders spectrum of thalassemia in patients with breast cancer. Methods: Blood routing tests and serum ferritin analysis were conducted in 1887 breast cancer patients treated in the department of radiation oncology during 1 April 2020 and 30 March 2022. The suspected thalassemia carriers with small mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MCH) or mean corpuscular hemoglobin concentration (MCHC) but the concentration of serum ferritin within normal limits were further investigated by polymerase chain reaction (PCR) and flow through hybridization gene chip to detect common mutations of α-globin and ß-globin genes using Thalassemia Geno Array Diagnostic Kit. The prevalence and genetic mutation spectrum of thalassemia among breast cancer patients were analyzed. Results: Four hundred and eighty-nine suspected thalassemia carriers were detected by complete blood cell counts and serum ferritin analysis among 1887 breast cancer patients. One hundred and seven cases (5.7%) were identified as carriers of thalassemia, of which 55 cases (51.4%) were α-thalassemia, 50 cases (46.7%) were ß-thalassemia, and 2 cases (1.9%) were co-inheritance of α-thalassemia and ß-thalassemia simultaneously. In α-thalassemia, the most prevalent genotype is -SEA/αα; as for ß-thalassemia, ßIVS-II-654/ß is the most common genotype. The degree of anemia is more severe in ß-thalassemia than in α-thalassemia. Conclusion: This is the first comprehensive molecular epidemiological investigation on thalassemia among breast cancer patients. Our data indicated that thalassemia was not uncommon in breast cancer patients. The physicians should have the knowledge to avoid misdiagnosis as iron deficiency anemia.

Diagnosis of hepatocellular carcinoma based on salivary protein glycopatterns and machine learning algorithms.

OBJECTIVES: Hepatocellular carcinoma (HCC) is difficult to diagnose early and progresses rapidly, making it one of the most deadly malignancies worldwide. This study aimed to evaluate whether salivary glycopattern changes combined with machine learning algorithms could help in the accurate diagnosis of HCC. METHODS: Firstly, we detected the alteration of salivary glycopatterns by lectin microarrays in 118 saliva samples. Subsequently, we constructed diagnostic models for hepatic cirrhosis (HC) and HCC using three machine learning algorithms: Least Absolute Shrinkage and Selector Operation, Support Vector Machine (SVM), and Random Forest (RF). Finally, the performance of the diagnostic models was assessed in an independent validation cohort of 85 saliva samples by a series of evaluation metrics, including area under the receiver operator curve (AUC), accuracy, specificity, and sensitivity. RESULTS: We identified alterations in the expression levels of salivary glycopatterns in patients with HC and HCC. The results revealed that the glycopatterns recognized by 22 lectins showed significant differences in the saliva of HC and HCC patients and healthy volunteers. In addition, after Boruta feature selection, the best predictive performance was obtained with the RF algorithm for the construction of models for HC and HCC. The AUCs of the RF-HC model and RF-HCC model in the validation cohort were 0.857 (95% confidence interval [CI]: 0.780-0.935) and 0.886 (95% CI: 0.814-0.957), respectively. CONCLUSIONS: Detecting alterations in salivary protein glycopatterns with lectin microarrays combined with machine learning algorithms could be an effective strategy for diagnosing HCC in the future.

Recent Advances in Chitosan and its Derivatives in Cancer Treatment.

Cancer has become a main public health issue globally. The conventional treatment measures for cancer include surgery, radiotherapy and chemotherapy. Among the various available treatment measures, chemotherapy is still one of the most important treatments for most cancer patients. However, chemotherapy for most cancers still faces many problems associated with a lot of adverse effects, which limit its therapeutic potency, low survival quality and discount cancer prognosis. In order to decrease these side effects and improve treatment effectiveness and patient's compliance, more targeted treatments are needed. Sustainable and controlled deliveries of drugs with controllable toxicities are expected to address these hurdles. Chitosan is the second most abundant natural polysaccharide, which has excellent biocompatibility and notable antitumor activity. Its biodegradability, biocompatibility, biodistribution, nontoxicity and immunogenicity free have made chitosan become a widely used polymer in the pharmacology, especially in oncotherapy. Here, we make a brief review of the main achievements in chitosan and its derivatives in pharmacology with a special focus on their agents delivery applications, immunomodulation, signal pathway modulation and antitumor activity to highlight their role in cancer treatment. Despite a large number of successful studies, the commercialization of chitosan copolymers is still a big challenge. The further development of polymerization technology may satisfy the unmet medical needs.

Machine learning reveals salivary glycopatterns as potential biomarkers for the diagnosis and prognosis of papillary thyroid cancer.

The diagnosis of thyroid cancer, especially papillary thyroid cancer (PTC), is increasing rapidly worldwide. In this study, we aimed to study the glycosylation of salivary proteins associated with PTC and assess the likelihood that salivary glycopatterns may be a potential biomarker of PTC diagnosis. Firstly, 22 benign thyroid nodule (BTN) samples, 27 PTC samples, and 30 healthy volunteers (HV) samples were collected to probe the difference of salivary glycopatterns associated with PTC using lectin microarrays. Then, five machine learning models including K-Nearest Neighbor (KNN), Multilayer Perceptron (MLP), Logistic Regression (LR), Random Forest (RF), and Support Vector Machine (SVM) were established to distinguish HV, BTN and PTC based on the changes of salivary glycopatterns. As a result, SVM had the best diagnostic effect with an accuracy rate of 92 % in testing set. Besides, lectin microarrays were used to explore the differences in salivary glycopatterns of 26 paired salivary samples of PTC patients before and after operation in order to probe into salivary glycopatterns as potential biomarkers for prognosis of PTC patients. The results showed that the levels of salivary glycopatterns recognized by 6 different lectins in patients after the operation almost convergenced with HVs. This study could help to screen and assess patients with PTC and their prognosis based on precise changes of salivary glycopatterns.

Fulvestrant May Falsely Increase 17ß-Estradiol Levels in Immunoassays: A Case Report of a 57-Year-Old Postmenopausal Patient With Recurrent Estrogen Receptor-Positive Breast Cancer.

The prognosis for female patients with locoregionally recurrent breast cancer has improved with the concurrent local and systemic treatment under multiple disciplinary teams. Radiotherapy is a valuable local treatment measure for unresectable locoregional recurrent breast cancer; however, reirradiation in previously irradiated areas is still a matter of debate. Antihormonal therapy achieves an overall survival benefit for most of these patients with estrogen receptor-positive (ER+) breast cancer in both adjuvant and metastatic settings. Fulvestrant is an ER antagonist and selective ER downregulator widely used in antihormonal therapy, especially in recurrent postmenopausal ER+ breast cancers. However, fulvestrant closely resembles 17ß-estradiol in its molecular structure which may result in false increases in serum 17ß-estradiol levels in commercially available immunoassays leading to incorrect medical decisions. Herein, we report a case of a 57-year-old postmenopausal patient with recurrent ER+ breast cancer treated with concurrent fulvestrant and reirradiation. There was a good clinical response, and the combination treatment was well tolerable. During the quarterly follow-up, we monitored a gradual increase of the serum 17ß-estradiol level in immunoassays, unexpectedly, because the patient underwent natural menopause 8 years ago. To rule out the suspected fulvestrant cross-reactivity with 17ß-estradiol in immunoassay, the patient's serum 17ß-estradiol levels were subsequently tested with the more sensitive and specific liquid chromatography-mass spectrometry (LC-MS) method, which confirmed 17ß-estradiol levels at the postmenopausal level. Concomitant fulvestrant with reirradiation seems to be a safe and effective therapy for locoregionally recurrent ER+ breast cancer. However, a falsely increased 17ß-estradiol may result from cross-reactivity between 17ß-estradiol and its molecular analog compounds, for example, fulvestrant. Therefore, it is important for the clinicians with the knowledge of this interaction to prevent unnecessary erroneous interpretation of results and avoid wrong medical decisions.

Impact of the COVID-19 Pandemic on ST-Elevation Myocardial Infarction Management in Hunan Province, China: A Multi-Center Observational Study.

Background: This study aimed to investigate the impact of the COVID-19 pandemic on ST-segment elevation myocardial infarction (STEMI) care in China. Methods: We conducted a multicenter, retrospective cohort study in Hunan province (adjacent to the epidemic center), China. Consecutive patients presenting with STEMI within 12 h of symptom onset and receiving primary percutaneous coronary intervention, pharmaco-invasive strategy and only thrombolytic treatment, were enrolled from January 23, 2020 to April 8, 2020 (COVID-19 era group). The same data were also collected for the equivalent period of 2019 (pre-COVID-19 era group). Results: A total of 610 patients with STEMI (COVID-19 era group n = 286, pre-COVID-19 era group n = 324) were included. There was a decline in the number of STEMI admissions by 10.5% and STEMI-related PCI procedures by 12.7% in 2020 compared with the equivalent period of 2019. The key time intervals including time from symptom onset to first medical contact, symptom onset to door, door-to-balloon, symptom onset to balloon and symptom onset to thrombolysis showed no significant difference between these two groups. There were no significant differences for in-hospital death and major adverse cardiovascular events between these two groups. Conclusion: During the COVID-19 pandemic outbreak in China, we observed a decline in the number of STEMI admissions and STEMI-related PCI procedures. However, the key quality indicators of STEMI care were not significantly affected. Restructuring health services during the COVID-19 pandemic has not significantly adversely influenced the in-hospital outcomes.

Electrochemical α-thiolation and azidation of 1,3-dicarbonyls.

A highly efficient electrochemical α-thiolation and azidation of 1,3-dicarbonyl compounds is developed. This electrochemical process is conducted under mild conditions without the use of a chemical oxidant, and exhibits a wide scope with good functional group tolerance. The applicability of this methodology was successfully demonstrated by modifying an anti-inflammatory drug on a gram scale.

Role of ammonia for brain abnormal protein glycosylation during the development of hepatitis B virus-related liver diseases.

BACKGROUND: Ammonia is the most typical neurotoxin in hepatic encephalopathy (HE), but the underlying pathophysiology between ammonia and aberrant glycosylation in HE remains unknown. RESULTS: Here, we used HBV transgenic mice and astrocytes to present a systems-based study of glycosylation changes and corresponding enzymes associated with the key factors of ammonia in HE. We surveyed protein glycosylation changes associated with the brain of HBV transgenic mice by lectin microarrays. Upregulation of Galß1-3GalNAc mediated by core 1 ß1,3-galactosyltransferase (C1GALT1) was identified as a result of ammonia stimulation. Using in vitro assays, we validated that upregulation of C1GALT1 is a driver of deregulates calcium (Ca2+) homeostasis by overexpression of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in astrocytes. CONCLUSIONS: We demonstrated that silencing C1GALT1 could depress the IP3R1 expression, an effective strategy to inhibit the ammonia-induced upregulation of Ca2+ activity, thereby C1GALT1 and IP3R1 may serve as therapeutic targets in hyperammonemia of HE.

Catalytic Enantioselective Construction of Chiroptical Boron-Stereogenic Compounds.

The construction of main group heteroatom-stereogenic compounds is of great importance due to their intriguing chemical, physical, biological, and stereoelectronic properties. Despite that organoboron compounds are widely used in organic chemistry, the creation of a tetrahedral boron-stereogenic center in one enantiomeric form remains highly challenging. Given the labile nature of ligands attached to the tetracoordinate boron atom, only a handful of enantioenriched boron-stereogenic compounds have been reported via resolution or a chiral substrate-induced diastereoselective approach. To date catalytic asymmetric synthesis of boron-stereogenic compounds has remained unknown. Here, we demonstrate the first catalytic enantioselective construction of boron-stereogenic compounds via an asymmetric copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. This enantioselective CuAAC reaction not only gives access to a wide range of novel highly functionalized boron-stereogenic heterocycles in high yields with good to excellent enantioselectivities but also produces optically active terminal alkyne and triazole moieties with various potential application prospects. Further transformation of the chiral tetracoordinate boron compounds delivers several complex heterocyclic entities bearing boron-stereogenic centers without the loss of enantiopurity. Moreover, the X-ray structure, the barrier to racemization, and the HOMO/LUMO gap of selected tetracoordinate boron compounds are investigated. Notably, these novel N,N π-conjugated boron-stereogenic compounds exhibit bright fluorescence. The optical properties, including circular dichroism, quantum yield, and circular polarized luminescence spectroscopies, are examined. These features expand the chemical space of the chiroptical boron-based dye platform, which could have great potential applications in chiral optoelectronic materials.

Predictive value of brachial artery flow-mediated dilation on coronary artery abnormality in acute stage of Kawasaki disease.

Coronary artery abnormalities (CAAs) are a severe complication of Kawasaki disease (KD) that may lead to cardiovascular events. Given the evidence that brachial artery flow-mediated dilation (FMD) decreases in children after the onset of KD, we hypothesized that it could be an early marker of CAA development in the acute stage and investigated its relationship with variation in the coronary artery diameter. A total of 326 sex- and age-matched children were enrolled, including 120 with KD, 109 febrile children and 97 healthy controls. In this study, FMD was significantly decreased in the KD group compared with the febrile and healthy groups. FMD was lower in the CAA group than in the no coronary artery abnormality group. The comparison of FMD showed an obvious difference among the CAA subgroups. The FMD in the coronary aneurysm (CA) group showed a strong negative correlation with the pretreatment maximum coronary artery Z-score (preZmax). While preZmax was 2.5, the receiver operating characteristic curve indicated an optimal cutoff point of 3.44% for FMD. FMD ≤ 3.44% could be considered as a signal of coronary lesions in acute stage of KD.

Increased levels of ferritin on admission predicts intensive care unit mortality in patients with COVID-19.

BACKGROUND: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19). METHODS: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n = 17), severe (n = 40) and critical groups (n = 43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve. RESULTS: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 µg/L vs. 501.90 µg/L, p < 0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p = 0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP. CONCLUSION: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la hiperferritinemia podría ser un factor predictivo de la mortalidad en pacientes hospitalizados con enfermedad por coronavirus de 2019 (COVID-19). MÉTODOS: Se incluyó un total de 100 pacientes hospitalizados con COVID-19 en la unidad de cuidados intensivos (UCI), clasificándose como grupos moderado (n = 17), grave (n = 40) y crítico (n = 43). Se recopiló la información clínica y de laboratorio, comparándose los niveles de ferritina entre los diferentes grupos. Se evaluó la asociación entre ferritina y mortalidad mediante un análisis de regresión logística. Además, se evaluó la eficacia del valor predictivo utilizando la curva ROC (receiver operating characteristic). RESULTADOS: La cantidad de ferritina fue significativamente superior en el grupo de pacientes críticos en comparación con el grupo de pacientes graves. La media de concentración de ferritina fue cerca de 3 veces superior en el grupo de muerte que en el grupo de supervivientes (1.722,25 µg/L vs. 501,90 µg/L, p < 0,01). La concentración de ferritina guardó una correlación positiva con otras citoquinas inflamatorias tales como interleucina (IL)-8, IL-10, proteína C reactiva (PRC) y factor de necrosis tumoral (TNF)-α. El análisis de regresión logística demostró que la ferritina era un factor predictivo independiente de la mortalidad intrahospitalaria. En especial, el grupo de ferritina alta estuvo asociado a una mayor incidencia de la mortalidad, con un valor de odds ratio ajustado de 104,97 [intervalo de confianza (IC) del 95% 2,63-4.185,89; p = 0,013]. Además, el valor de ferritina tuvo una ventaja de capacidad discriminativa en el área bajo la curva ROC (AUC) de 0,822 (IC 95% 0,737-0,907] superior al de procalcitonina y PRC. CONCLUSIÓN: El valor de ferritina medido durante el ingreso puede servir de factor independiente para prevenir la mortalidad intrahospitalaria en los pacientes de COVID-19 en la UCI.

Catalytic Asymmetric Synthesis of Silicon-Stereogenic Dihydrodibenzosilines: Silicon Central-to-Axial Chirality Relay.

A Rh-catalyzed asymmetric synthesis of silicon-stereogenic dihydrodibenzosilines featuring axially chiral 6-membered bridged biaryls is demonstrated. In the presence of a RhI catalyst with a chiral diphosphine ligand, a wide range of dihydrodibenzosilines containing both silicon-central and axial chiralities are conveniently constructed in excellent enantioselectivities via dehydrogenative C(sp3 )-H silylation. Absolute configuration analysis by single-crystal X-ray structures revealed a novel silicon central-to-axial chirality relay phenomenon, which we believe will inspire further research in the field of asymmetric catalysis and chiroptical materials.

The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study.

BACKGROUND: The inflammatory reaction is the main cause of acute respiratory distress syndrome and multiple organ failure in patients with Coronavirus disease 2019, especially those with severe and critical illness. Several studies suggested that high-dose vitamin C reduced inflammatory reaction associated with sepsis and acute respiratory distress syndrome. This study aimed to determine the efficacy and safety of high-dose vitamin C in Coronavirus disease 2019. METHODS: We included 76 patients with Coronavirus disease 2019, classified into the high-dose vitamin C group (loading dose of 6g intravenous infusion per 12 hr on the first day, and 6g once for the following 4 days, n=46) and the standard therapy group (standard therapy alone, n=30). RESULTS: The risk of 28-day mortality was reduced for the high-dose vitamin C versus the standard therapy group (HR=0.14, 95% CI, 0.03-0.72). Oxygen support status was improved more with high-dose vitamin C than standard therapy (63.9% vs 36.1%). No safety events were associated with high-dose vitamin C therapy. CONCLUSION: High-dose vitamin C may reduce the mortality and improve oxygen support status in patients with Coronavirus disease 2019 without adverse events.

[Increased levels of ferritin on admission predicts intensive care unit mortality in patients with COVID-19]. / El incremento de ferritina sérica durante el ingreso predice la mortalidad de los pacientes de COVID-19 en Cuidados Intensivos.

BACKGROUND: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19). METHODS: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n=17), severe (n=40) and critical groups (n=43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve. RESULTS: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25µg/L vs. 501.90µg/L, p<0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p=0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP. CONCLUSION: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.

Hexafluoroisopropanol-Enabled Copper-Catalyzed Asymmetric Halogenation of Cyclic Diaryliodoniums for the Synthesis of Axially Chiral 2,2'-Dihalobiaryls.

An efficient asymmetric halogenation of cyclic diaryliodonium salts is demonstrated, which gives access to a wide range of axially chiral 2,2'-dihalobiaryls in good to excellent yields and with excellent enantioselectivities. The use of CuX with chiral bisoxazoline ligand and tetrabutylammonium halides in the unique solvent of hexafluoroisopropanol (HFIP) led to the best results in the process. The axially chiral 2,2'-dihalobiaryls can be transformed into a number of enantiopure chiral ligands that could be potentially useful in asymmetric catalysis.