Dioxane promoted photochemical O-alkylation of 1,3-dicarbonyl compounds beyond carbene insertion into C-H and C-C bonds.

A photochemical synthesis of enol ethers and furan-3(2H)-ones from 1,3-dicarbonyl compounds and aryl diazoacetates has been developed. Significantly, 1,4-dioxane promoted O-alkylation of various 1,3-dicarbonyl compounds beyond previous carbene insertion into C-H and C-C bonds has been disclosed.

Novel PIP5K1C variant identified in a Chinese pedigree with lethal congenital contractural syndrome 3.

BACKGROUND: Biallelic pathogenic variants in PIP5K1C (MIM #606,102) lead to lethal congenital contractural syndrome 3 (LCCS3, MIM #611,369), a rare autosomal recessive genetic disorder characterized by small gestational age, severe multiple joint contractures and muscle atrophy, early death due to respiratory failure. Currently, 5 individuals with LCCS3 were reported and 5 pathogenic variants in PIP5K1C were identified. Here, we reported the two fetuses in a Chinese pedigree who displayed multiple joint contractures and other congenital anomalies. METHODS: Trio-based whole-exome sequencing (WES) was performed for the parents and the recent fetus to detect the genetic cause for fetus phenotype. RESULTS: A novel variant, NM_012398.3: c.949_952dup, p.S318Ifs*28 and a previously reported variant, c.688_689del, p.G230Qfs*114 (ClinVar database) in PIP5K1C, were detected in the individuals, and these variants were inherited from the mother and father, respectively. We described the features of multiple joint contractures in our fetuses, including bilateral talipes equinovarus, stiffness in the limbs, extended knees, persistently closed hands and overlapping fingers, which have not been delineated detailedly in previously reported LCCS3 individuals. Furthermore, novel phenotype, bilateral dilated lateral ventricles, was revealed in one fetus. CONCLUSIONS: These findings expanded the genetic variant spectrum of PIP5K1C and enriched the clinical features of LCCS3, which will help with the prenatal diagnosis and genetic counseling for this family.

Alcohol drinking, smoking, and cutaneous melanoma risk: Mendelian randomization analysis.

OBJECTIVE: To investigate the causal relationship between poor lifestyle habits, such as smoking and drinking, and cutaneous malignant melanoma. METHOD: In the present study, alcohol consumption and smoking were used as exposure factors, and single nucleotide polymorphisms closely associated with alcohol consumption and smoking were used as instrumental variables, while cutaneous melanoma was set as an outcome variable. Two-sample Mendelian randomization analyses were run between alcohol consumption and melanoma and smoking and melanoma to investigate their causal associations, respectively. RESULTS: We found a positive and statistically significant causal effect of alcohol intake on the risk of cutaneous malignant melanoma (OR: 2.23; 95%CI: 1.11-4.47; p=0.02). The present study showed no significant causal relationship between cigarettes per day and cutaneous melanoma (OR: 0.85; 95%CI: 0.54-1.35; p=0.50) or smoking initiation and cutaneous melanoma (OR: 1.02; 95%CI: 0.74-1.39; p=0.88). CONCLUSIONS: This study provides Mendelian randomization evidence supporting alcohol consumption as a risk factor for cutaneous malignant melanoma. And the causal relationship between smoking and cutaneous malignant melanoma still needs to be further investigated.

Base-free regio- and stereoselective photochemical synthesis of enol ethers from 1,3-dicarbonyl compounds.

A visible light-induced kinetic controlled regioselective O-alkylation of various 1,3-dicarbonyl compounds with diazoacetates and cyclic ethers has been developed. The protocol provides a green and practical approach to highly stereoselective enol ethers under mild and base-free conditions in good to excellent yields.

Novel KCNJ16 variants identified in a Chinese patient with hypokalemic metabolic acidosis.

BACKGROUND: Biallelic pathogenic variants in the KCNJ16 gene result in hypokalemic tubulopathy and deafness (HKTD) (MIM #619406), which is a rare autosomal recessive disease characterized by hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Currently, nine individuals with HKTD have been reported, and seven pathogenic variants in KCNJ16 have been revealed. METHODS: A 5-year-6-month-old Chinese female patient displayed hypokalemic metabolic acidosis, salt wasting, renin-angiotensin-aldosterone system (RAAS) activation, arrhythmia, myocardial damage, cardiogenic shock and secondary diffuse brain oedema. Trio-based whole-exome sequencing (WES) was applied to detect the genetic cause. RESULTS: Novel compound heterozygous variants, c.190A>C (p.Thr64Pro) and c.628C>G (p.His210Asp), in KCNJ16 were detected in the patient, and these variants were inherited from the patient's mother and father, respectively. Then, we systematically reviewed the available clinical manifestations of individuals with HKTD. We found that HKTD patients are at risk of cardiogenic shock and secondary diffuse brain oedema, which urges clinicians to make early diagnoses with prompt treatments. CONCLUSION: These findings expand the variant spectrum of KCNJ16, enrich the clinical characteristics of HKTD, and provide a solid base for the genetic counseling, diagnosis and treatment of this condition.

RNASEH2C c.194G>A is a Chinese-specific founder mutation in three unrelated patients with Aicardi-Goutières syndrome 3.

Biallelic pathogenic variants in RNASEH2C cause Aicardi-Goutières syndrome 3 (AGS3, MIM #610329), a rare early-onset encephalopathy characterized by intermittent unexplained fever, chilblains, irritability, progressive microcephaly, dystonia, spasticity, severe psychomotor retardation and abnormal brain imaging. Currently, approximately 50 individuals with AGS3 and 19 variants in RNASEH2C have been revealed. Here, we reported the novel clinical manifestations and genotypic information of three unrelated Chinese patients with AGS3 caused by pathogenic variants in RNASEH2C. In addition to three novel missense variants (c.101G>A, p.Cys34Tyr; c.401T>A, p.Leu134Gln and c.434G>T, p.Arg145Leu), one missense variant (c.194G>A, p.Gly65Asp) reoccurred in all patients but was completely absent in South Asian and other ethnicities. Our study expanded the variant spectrum of RNASEH2C and identified RNASEH2C c.194G>A as a Chinese-specific founder mutation. The novel phenotypes, including mouth ulcers, hip dysplasia, retarded dentition and hypogonadism, observed in our patients greatly enriched the clinical characteristics of AGS3.

Visible light-induced carbene reactivity of acceptor diazoalkanes: deconstructive difunctionalizations of cyclic ethers with nucleophiles.

A visible light-induced carbene reactivity of acceptor diazoalkanes has been developed for the synthesis of difunctionalized ethers from cyclic ethers and various N/O/S nucleophiles.

Alcohol drinking, smoking, and cutaneous melanoma risk: Mendelian randomization analysis / Consumo de alcohol, tabaquismo y riesgo de melanoma cutáneo: análisis de aleatorización mendeliana

Objective: To investigate the causal relationship between poor lifestyle habits, such as smoking and drinking, and cutaneous malignant melanoma. Method: In the present study, alcohol consumption and smoking were used as exposure factors, and single nucleotide polymorphisms closely associated with alcohol consumption and smoking were used as instrumental variables, while cutaneous melanoma was set as an outcome variable. Two-sample Mendelian randomization analyses were run between alcohol consumption and melanoma and smoking and melanoma to investigate their causal associations, respectively. Results: We found a positive and statistically significant causal effect of alcohol intake on the risk of cutaneous malignant melanoma (OR: 2.23; 95%CI: 1.11-4.47; p = 0.02). The present study showed no significant causal relationship between cigarettes per day and cutaneous melanoma (OR: 0.85; 95%CI: 0.54-1.35; p = 0.50) or smoking initiation and cutaneous melanoma (OR: 1.02; 95%CI: 0.74-1.39; p = 0.88). Conclusions: This study provides Mendelian randomization evidence supporting alcohol consumption as a risk factor for cutaneous malignant melanoma. And the causal relationship between smoking and cutaneous malignant melanoma still needs to be further investigated.(AU)

Objetivo: Investigar la relación causal entre los malos hábitos de vida, como el tabaquismo y el consumo de alcohol, y el melanoma maligno cutáneo. Método: En el presente estudio, el consumo de alcohol y el tabaquismo se utilizaron como factores de exposición, y los polimorfismos de nucleótido único estrechamente asociados con el consumo de alcohol y el tabaquismo se utilizaron como variables instrumentales, mientras que el melanoma cutáneo se estableció como variable de resultado. Se realizaron análisis de aleatorización mendeliana de dos muestras entre el consumo de alcohol y el melanoma, y entre el tabaquismo y el melanoma, para investigar sus asociaciones causales, respectivamente. Resultados: Se encontró un efecto causal positivo y estadísticamente significativo del consumo de alcohol sobre el riesgo de melanoma maligno cutáneo (OR: 2,23; IC95%: 1,11-4,47; p = 0,02). El presente estudio no mostró una relación causal significativa entre cigarrillos por día y melanoma cutáneo (OR: 0,85; IC95%: 0,54-1,35; p = 0,50) ni entre inicio de fumar y melanoma cutáneo (OR: 1,02; IC95%: 0,74-1,39; p = 0,88). Conclusiones: Este estudio aporta pruebas de aleatorización mendeliana que apoyan el consumo de alcohol como factor de riesgo de melanoma maligno cutáneo. En cuanto a la relación causal entre el tabaquismo y el melanoma maligno cutáneo aún debe investigarse más a fondo.(AU)

Research on the Genetic Mechanism of High-Temperature Groundwater in the Geothermal Anomalous Area of Gold Deposit-Application to the Copper Mine Area of Yinan Gold Mine.

Geothermal energy is new, environmentally friendly, and clean energy, which is of great significance to realize energy saving and emission reduction. The study of the genesis mechanism of geothermal water is the key to its rational development and utilization. In this study, based on 14 sets of water samples from the eastern section of the copper well mining area of Yinan Gold Mine, mineral saturation index, isotope analysis (δ18O, δD), Si-enthalpy mixing equation, and geochemical geothermal temperature scale were used to analyze the thermal storage temperature, recharge characteristics, mixing ratio, circulation depth, and fluid passage to reveal the geothermal water fugitive transmission pattern and genesis mechanism in the study area and to propose a geothermal water genesis model. The study shows that the water supply elevation in the area is between 687.22 and 1164.15 m and a large amount of cold water recharged it. It is inferred that the recharge area is the precipitation in the Northwest Mountain range and surrounding atmosphere. Groundwater flows along the fracture zone in a south-easterly direction. It receives heating from the surrounding rocks, where the water level rises at the fracture zone intersection and is stored in the lower and middle Cambrian thermal reservoirs and continues to receive heating from deeper heat sources. Based on this study and previous regional research data, the fault structure in this area is within the influence range of the energy field of the Yishu fault zone. Yishu fault zone becomes the heating source under the background of cold water. It is inferred that the east-east Yishu fault zone in the study area may also be the recharge area.

Lasers and Intense Pulsed Light for the Treatment of Pathological Scars: A Network Meta-Analysis.

BACKGROUND: Laser and intense pulsed light (IPL) therapies have shown promising effects on pathological scars, but the comparative effectiveness of laser and IPL therapies has not yet been studied. OBJECTIVES: The aim of this study was to compare and rank the efficacy of laser and IPL therapies to determine the most effective treatment method for pathological scars. METHODS: Relevant studies published up to February 2022 were identified by searching PubMed, Web of Science, Cochrane Library, CNKI, and Wanfang databases. We defined Vancouver Scar Scale score as the primary outcome. Both frequentist and Bayesian approaches were used to perform a network meta-analysis. RESULTS: We included 25 trials with a total of 1688 participants. The rankings based on the surface under the cumulative ranking curve for the Vancouver Scar Scale score based on the Bayesian approach suggested IPL + CO2 (96.43%) > pulsed dye laser (PDL) + 1064-nm Nd:YAG (yttrium aluminum garnet) laser (86.21%) > PDL + CO2 (82.15%) > CO2 (58.97%) > 1064-nm Nd:YAG (57.03%) > PDL (52%) > 532-nm Nd:YAG (33.28%) > Er:YAG + IPL (28.38%) > Er:YAG (26.56%) > IPL (15.03%) > control (13.97%). The ranking results based on the frequentist approach were basically consistent with those based on the Bayesian approach. CONCLUSIONS: The results of the network meta-analysis showed that the combination of IPL and CO2 laser has the highest probability of being the most effective intervention. However, our conclusions must be interpreted with caution due to the relatively few evaluation indicators included in our study. Future well-designed randomized controlled trials with large sample sizes are required to confirm our conclusions.

[Analysis of OCRL gene variant in a Chinese pedigree affected with Lowe syndrome].

OBJECTIVE: To explore the genotype-phenotype correlation of a Chinese pedigree affected with Lowe syndrome. METHODS: Whole exome sequencing (WES) and Sanger sequencing were carried out for the proband and members of his pedigree. RESULTS: The proband, a 3-year-and-5-month-old male, presented with multiple anomalies including congenital cataract, glaucoma, brain dysplasia, renal dysfunction and cognitive impairment. WES revealed that he has harbored a novel hemizygous missense variant of the OCRL gene, namely NM_000276.3: c.1255T>C (p.Trp419Arg) (GRCh37/hg19), which was derived from his unaffected mother. The same variant was not found in his elder brother who was healthy. The variant was predicted to be pathogenic according to ACMG/AMP guideline. Compared with previously reported cases of Lowe syndrome, our patient has displayed rare features including corpus callosum dysplasia, reduction of white matter, cerebral hypoplasia, laryngomalacia, sebaceous cyst, recurrent eczema, cryptorchidism, hypoglycemia and irritability. CONCLUSION: Above finding has expanded the mutational spectrum of the OCRL gene, enriched clinical features of Lowe syndrome, and enabled genetic counseling for this pedigree.

[Clinical and genetic analysis of a novel CHD4 gene variant in a Chinese patient with Sifrim-Hitz-Weiss syndrome].

OBJECTIVE: To explore the genotype-phenotype correlation of a case with Sifrim-Hitz-Weiss syndrome (SIHIWES) caused by a novel CHD4 gene variant. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and her parents. Whole-exome sequencing (WES) was carried out for the patient.Suspected variant was verified by Sanger sequencing. RESULTS: The proband, a 2-year-old Chinese girl, presented with global developmental delay, intellectual disability, distinctive facial features and multiple congenital anomalies. Her prenatal manifestations included increased nuchal thickness, cranial and facial anomalies, and decreased fetal movement. WES has identified a novel variant in the CHD4 gene, namely NM_001273:c.2989C>G (p.Leu997Val) (GRCh37/hg19).Comparison of her phenotype with previously reported SIHIWES cases suggested that our patient's prenatal presentations were unreported before, with novel features including funduscopic anomaly, facial dysmorphisms such as asymmetrical ears, drooping eyelid, long philtrum and downturned mouth. CONCLUSION: Above findings have expanded the mutational spectrum of the CHD4 gene and revealed novel phenotypes in Chinese patients with SIHIWES.

Optimization of Total Polar Compounds Quantification in Frying Oils by Low-field Nuclear Magnetic Resonance.

To improve the accuracy of total polar compounds (TPC) quantification in frying oils by low-field nuclear magnetic resonance (LF-NMR), an optimized statistical method was proposed. The method uses a specially designed sequence to detect the NMR signal in frying oils, and establishes the TPC prediction model by partial least squares (PLS) regression on relaxation properties extracted from the NMR signal. Compared with inversion recovery (IR) and Carr-Purcell-Meiboom-Gill (CPMG) sequences, the designed sequence provides more relaxation information. The experimental result shows that the proposed method is more accurate than reported methods that are based on longitudinal and transverse relaxation times in the TPC quantification of frying oils.

[Prognosis of 212 children with asthma: a 5-year follow-up study].

OBJECTIVE: To study the prognosis of childhood asthma and the factors influencing asthmatic attacks and prognosis. METHODS: The medical data of 212 children with asthma who were followed up for more than 5 years were retrospectively studied. RESULTS: During the 5-year follow up, asthmatic attacks termination was found in 121 cases (57.1%) and asthma persistence was observed in 91 cases. Respiratory tract infections were found as the major factors inducing asthmatic attacks (71.7%), followed by inhaled allergens (17.0%).The children with asthma induced by respiratory tract infections had a higher remission rate of asthmatic attacks (61.2%) than those induced by allergens (41.7%) or exercises (26.3%). Three risk factors for asthma persistence were identified: concurrent allergic rhinitis and eczema, parental asthma and allergy-induced wheezing. CONCLUSIONS: The 5-year follow-up study demonstrated that asthmatic attacks stopped in the majority of children with asthma. Respiratory tract infections may be the major factors inducing acute asthma attacks. The children with asthma induced by respiratory infections may experience a better outcome. Atopic children or children with the genetic background of atopy are at high risks for the development of persistent asthma.