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The treatment of brain abscess induced by carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a clinical challenge around the world. Apart from novel β-lactam/β-lactamase inhibitors and polymyxins, there are few sufficiently powerful antibiotics that are effective against CRPA-induced infections. Considering the blood-brain barrier factor, there are even fewer drugs that can be used to treat intracranial CRPA-induced infections. In this article, we reported a case of CRPA-induced brain abscess that was successfully treated with intravenous ceftazidime/avibactam and intrathecal colistimethate sodium in a child after intracranial tumor resection.

Chromosomal abnormality is one of the important causes of dysplasia in children. However, due to regional and ethnic differences, the reported rates of chromosomal abnormalities in patients with dysplasia vary greatly. Moreover, the clinical manifestations in children with rare chromosomal diseases were heterogeneous. So, we retrospectively analyzed the karyotype results of 436 children with dysplasia and conducted a detailed analysis of rare chromosomal diseases. The results showed that chromosomal abnormalities were present in 181 of 436 cases. Intellectual disability, dysmorphology, congenital malformations, the disorder of sexual development, and short stature were the main five clinical symptoms in children with chromosomal abnormalities. Moreover, 136 cases of Trisomy 21 (Tri21) were detected, of which 130 were standard Tri21, 5 were robertsonian Tri21, and 1 was chimera type. In addition, 16 cases of rare abnormal karyotype, including complex Tri21, complex Turner syndrome, 4p-syndrome, 18q-syndrome, and 5p-syndrome, were also detected. In summary, chromosome abnormality is one of the important causes of dysplasia in children. Furthermore, prenatal screening and diagnosis could play a great significance in preventing dysplasia in children. In addition, the retrospective analysis of rare cases is valuable for clinical diagnosis and risk assessment of recurrence.

C21H25EuN2O10, monoclinic, P21/n (no. 14), a = 14.1635(8) Å, b = 12.1381(6) Å, c = 14.4528(7) Å, β = 104.361(2)°, V = 2407.1(2) Å3, Z = 4, Rgt(F) = 0.0304, wRref(F2) = 0.0893, T = 296 K.

C16H11BF2N2, monoclinic, P21/c (no. 14), a = 9.0978(14) Å, b = 18.580(3) Å, c = 15.476(2) Å, β = 99.516(5)°, V = 2580.0(7) Å3, Z = 8, Rgt(F) = 0.0406, wRref(F2) = 0.1307, T = 193 K.

C32H50Eu2N16O24, monoclinic, P21/c (no. 14), a = 7.685(5) Å, b = 13.482(5) Å, c = 23.240(5) Å, β = 93.578(5)°, V = 2403.2(19) Å3, Z = 2, Rgt(F) = 0.0235, wRref(F2) = 0.0577, T = 293 K.

C18H15BN2O2, monolinic, P21/n (no. 14), a = 13.61(2) Å, b = 7.389(11) Å, c = 16.34(2) Å, β = 113.91(2)°, V = 1502(4) Å3, Z = 4, R gt(F) = 0.0544, wR ref(F 2) = 0.1651, T = 273 K.

C17H13BN2O2, orthorhombic, Pbca (no. 61), a = 10.0820(14) Å, b = 13.1135(19) Å, c = 20.644(3) Å, V = 2729.4 Å3, Z = 8, Rgt(F) = 0.0373, wRref(F2) = 0.1005, T = 193 K.

C18H15BN2O2, monoclinic, P21/c (no. 14), a = 6.8522(9) Å, b = 8.4333(11) Å, c = 13.1908(18) Å, β = 95.880(5)°, V = 758.24(17) Å3, Z = 2, Rgt(F) = 0.0381, wRref(F2) = 0.1068, T = 193 K.

C18H17BN2O2, monoclinic, P21/c (no. 14), a = 12.5782(14) Å, b = 13.6724(14) Å, c = 8.7113(9) Å, β = 97.819(6)°, V = 1484.2(3) Å3, Z = 4, Rgt(F) = 0.0482, wRref(F2) = 0.1357, T = 193 K.

C16H12BBrN2, monoclinic, P21 (no. 4), a = 4.7061(3) Å, b = 10.4639(6) Å, c = 13.5675(8) Å, β = 97.512(2)°, V = 662.39(7) Å3, Z = 2, Rgt(F) = 0.0384, wRref(F2) = 0.0995, T = 189.98 K.

Context: Mitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown.Objective: To investigate how SAT mitochondria change following diet-induced and bariatric surgery-induced weight-loss interventions in 4 independent weight-loss studies.Methods: The DiOGenes study is a European multicenter dietary intervention with an 8-week low caloric diet (LCD; 800 kcal/d; n = 261) and 6-month weight-maintenance (n = 121) period. The Kuopio Obesity Surgery study (KOBS) is a Roux-en-Y gastric bypass (RYGB) surgery study (n = 172) with a 1-year follow-up. We associated weight-loss percentage with global and 2210 mitochondria-related RNA transcripts in linear regression analysis adjusted for age and sex. We repeated these analyses in 2 studies. The Finnish CRYO study has a 6-week LCD (800-1000 kcal/d; n = 19) and a 10.5-month follow-up. The Swedish DEOSH study is a RYGB surgery study with a 2-year (n = 49) and 5-year (n = 37) follow-up.Results: Diet-induced weight loss led to a significant transcriptional downregulation of oxidative phosphorylation (DiOGenes; ingenuity pathway analysis [IPA] z-scores: -8.7 following LCD, -4.4 following weight maintenance; CRYO: IPA z-score: -5.6, all P < 0.001), while upregulation followed surgery-induced weight loss (KOBS: IPA z-score: 1.8, P < 0.001; in DEOSH: IPA z-scores: 4.0 following 2 years, 0.0 following 5 years). We confirmed an upregulated oxidative phosphorylation at the proteomics level following surgery (IPA z-score: 3.2, P < 0.001).Conclusions: Differentially regulated SAT mitochondria-related gene expressions suggest qualitative alterations between weight-loss interventions, providing insights into the potential molecular mechanistic targets for weight-loss success. [ABSTRACT FROM AUTHOR]

Reverse causality has made it difficult to establish the causal directions between obesity and prediabetes and obesity and insulin resistance. To disentangle whether obesity causally drives prediabetes and insulin resistance already in non-diabetic individuals, we utilized the UK Biobank and METSIM cohort to perform a Mendelian randomization (MR) analyses in the non-diabetic individuals. Our results suggest that both prediabetes and systemic insulin resistance are caused by obesity (p = 1.2×10−3 and p = 3.1×10−24). As obesity reflects the amount of body fat, we next studied how adipose tissue affects insulin resistance. We performed both bulk RNA-sequencing and single nucleus RNA sequencing on frozen human subcutaneous adipose biopsies to assess adipose cell-type heterogeneity and mitochondrial (MT) gene expression in insulin resistance. We discovered that the adipose MT gene expression and body fat percent are both independently associated with insulin resistance (p≤0.05 for each) when adjusting for the decomposed adipose cell-type proportions. Next, we showed that these 3 factors, adipose MT gene expression, body fat percent, and adipose cell types, explain a substantial amount (44.39%) of variance in insulin resistance and can be used to predict it (p≤2.64×10−5 in 3 independent human cohorts). In summary, we demonstrated that obesity is a strong determinant of both prediabetes and insulin resistance, and discovered that individuals' adipose cell-type composition, adipose MT gene expression, and body fat percent predict their insulin resistance, emphasizing the critical role of adipose tissue in systemic insulin resistance. Author summary: Obesity is a global health epidemic predisposing to type 2 diabetes (T2D) and other cardiometabolic disorders. Previous studies have shown that obesity has a causal effect on T2D; however, it remains unknown whether obesity causes prediabetes and insulin resistance already in non-diabetic individuals. By utilizing almost half a million individuals from the UK Biobank and the Finnish METSIM cohort, we identified a significant causal effect of obesity on prediabetes and insulin resistance among the non-diabetic individuals. Next, we investigated the role of subcutaneous adipose tissue in these obesogenic effects. We discovered that the adipose mitochondrial gene expression and body fat percent are independently associated with insulin resistance after adjusting for the tissue heterogeneity. For the latter, we estimated the adipose cell type proportions by utilizing single-nucleus RNA sequencing of frozen adipose tissue biopsies. Moreover, we established a prediction model to estimate insulin resistance using body fat percent and adipose RNA-sequencing data, which enlightens the importance of adipose tissue in insulin resistance and provides a helpful tool to impute the insulin resistance for existing adipose RNA-sequencing cohorts. Overall, we discover the potential causal effect of obesity on prediabetes and insulin resistance and the key role of adipose tissue in insulin resistance. [ABSTRACT FROM AUTHOR]

C16H11BF2N2, monoclinic, P21/c (no. 14), a = 9.0978(14) Å, b = 18.580(3) Å, c = 15.476(2) Å, β = 99.516(5)°, V = 2580.0(7) Å3, Z = 8, Rgt(F) = 0.0406, wRref(F2) = 0.1307, T = 193 K. [ABSTRACT FROM AUTHOR]

C21H25EuN2O10, monoclinic, P21/n (no. 14), a = 14.1635(8) Å, b = 12.1381(6) Å, c = 14.4528(7) Å, β = 104.361(2)°, V = 2407.1(2) Å3, Z = 4, Rgt(F) = 0.0304, wRref(F2) = 0.0893, T = 296 K. [ABSTRACT FROM AUTHOR]

C16H11BF2N2, monoclinic, P21/c (no. 14), a = 9.0978(14) Å, b = 18.580(3) Å, c = 15.476(2) Å, β = 99.516(5)°, V = 2580.0(7) Å3, Z = 8, Rgt(F) = 0.0406, wRref(F2) = 0.1307, T = 193 K. [ABSTRACT FROM AUTHOR]

The 24-h rhythm of behavioral and physiological processes is a typical biological phenomenon regulated by a group of circadian rhythm genes. Dysfunction of the circadian rhythm can cause a wide range of problems, such as cancer and metabolic diseases. In recent decades, increased understanding of the roles of circadian rhythm genes in the bone remodeling process have been documented, including osteoblastic bone formation, osteoclastic bone resorption, and osteoblast/osteoclast communication. A timely review of the current findings may help to facilitate the new field of circadian rhythmic bone remodeling research. Targeted pharmacological modulation of circadian rhythm genes is a possible therapeutic approach through which to overcome bone remodeling problems in the future. [ABSTRACT FROM AUTHOR]

Osteoporosis is a metabolic bone disease characterized by a decrease in bone mass and degradation of the bone microstructure, which increases bone fragility and fracture risk. However, the molecular mechanisms of osteoporosis remain unclear. Long non-coding RNAs (lncRNAs) have become important epigenetic regulators controlling the expression of genes and affecting multiple biological processes. Accumulating evidence of the involvement of lncRNAs in bone remolding has increased understanding of the molecular mechanisms underlying osteoporosis. This review aims to summarize recent progress in the elucidation of the role of lncRNAs in bone remodeling, and how it contributes to osteoblast and osteoclast function. This knowledge will facilitate the understanding of lncRNA roles in bone biology and shed new light on the modulation and potential treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

C32H50Eu2N16O24, monoclinic, P21/c (no. 14), a = 7.685(5) Å, b = 13.482(5) Å, c = 23.240(5) Å, β = 93.578(5)°, V = 2403.2(19) Å3, Z = 2, Rgt(F) = 0.0235, wRref(F2) = 0.0577, T = 293 K. [ABSTRACT FROM AUTHOR]

Motivation: Mapping bias causes preferential alignment to the reference allele, forming a major obstacle in allele-specific expression (ASE) analysis. The existing methods, such as simulation and SNP-aware alignment, are either inaccurate or relatively slow. To fast and accurately count allelic reads for ASE analysis, we developed a novel approach, ASElux, which utilizes the personal SNP information and counts allelic reads directly from unmapped RNA-sequence (RNA-seq) data. ASElux significantly reduces runtime by disregarding reads outside single nucleotide polymorphisms (SNPs) during the alignment. Results: When compared to other tools on simulated and experimental data, ASElux achieves a higher accuracy on ASE estimation than non-SNP-aware aligners and requires a much shorter time than the benchmark SNP-aware aligner, GSNAP with just a slight loss in performance. ASElux can process 40 million read-pairs from an RNA-sequence (RNA-seq) sample and count allelic reads within 10 min, which is comparable to directly counting the allelic reads from alignments based on other tools. Furthermore, processing an RNA-seq sample using ASElux in conjunction with a general aligner, such as STAR, is more accurate and still ~4x faster than STAR + WASP, and ~33x faster than the lead SNP-aware aligner, GSNAP, making ASElux ideal for ASE analysis of largescale transcriptomic studies. We applied ASElux to 273 lung RNA-seq samples from GTEx and identified a splice-QTL rs11078928 in lung which explains the mechanism underlying an asthma GWAS SNP rs11078927. Thus, our analysis demonstrated ASE as a highly powerful complementary tool to cis-expression quantitative trait locus (eQTL) analysis. [ABSTRACT FROM AUTHOR]

C18H15BN2O2, monolinic, P21/n (no. 14), a = 13.61(2) Å, b = 7.389(11) Å, c = 16.34(2) Å, β = 113.91(2)°, V = 1502(4) Å3, Z = 4, Rgt(F) = 0.0544, wRref(F2) = 0.1651, T = 273 K. [ABSTRACT FROM AUTHOR]

C18H15BN2O2, monolinic, P21/n (no. 14), a = 13.61(2) Å, b = 7.389(11) Å, c = 16.34(2) Å, β = 113.91(2)°, V = 1502(4) Å3, Z = 4, Rgt(F) = 0.0544, wRref(F2) = 0.1651, T = 273 K. [ABSTRACT FROM AUTHOR]

C18H17BN2O2, monoclinic, P21/c (no. 14), a = 12.5782(14) Å, b = 13.6724(14) Å, c = 8.7113(9) Å, β = 97.819(6)°, V = 1484.2(3) Å3, Z = 4, Rgt(F) = 0.0482, wRref(F2) = 0.1357, T = 193 K. [ABSTRACT FROM AUTHOR]

C18H15BN2O2, monoclinic, P21/c (no. 14), a = 6.8522(9) Å, b = 8.4333(11) Å, c = 13.1908(18) Å, β = 95.880(5)°, V = 758.24(17) Å3, Z = 2, Rgt(F) = 0.0381, wRref(F2) = 0.1068, T = 193 K. CCDC no.: 2045109 [ABSTRACT FROM AUTHOR]

C17H13BN2O2, orthorhombic, Pbca (no. 61), a = 10.0820(14) Å, b = 13.1135(19) Å, c = 20.644(3) Å, V = 2729.4 Å3, Z = 8, Rgt(F) = 0.0373, wRref(F2) = 0.1005, T = 193 K. [ABSTRACT FROM AUTHOR]

C18H17BN2O2, monoclinic, P21/c (no. 14), a = 12.5782(14) Å, b = 13.6724(14) Å, c = 8.7113(9) Å, β = 97.819(6)°, V = 1484.2(3) Å3, Z = 4, Rgt(F) = 0.0482, wRref(F2) = 0.1357, T = 193 K. [ABSTRACT FROM AUTHOR]

C18H15BN2O2, monoclinic, P21/c (no. 14), a = 6.8522(9) Å, b = 8.4333(11) Å, c = 13.1908(18) Å, β = 95.880(5)°, V = 758.24(17) Å3, Z = 2, Rgt(F) = 0.0381, wRref(F2) = 0.1068, T = 193 K. CCDC no.: 2045109 [ABSTRACT FROM AUTHOR]

C17H13BN2O2, orthorhombic, Pbca (no. 61), a = 10.0820(14) Å, b = 13.1135(19) Å, c = 20.644(3) Å, V = 2729.4 Å3, Z = 8, Rgt(F) = 0.0373, wRref(F2) = 0.1005, T = 193 K. [ABSTRACT FROM AUTHOR]

Due to the growth of interest in single-cell genomics, computational methods for distinguishing true variants from artifacts are highly desirable. While special attention has been paid to false positives in variant or mutation calling from single-cell sequencing data, an equally important but often neglected issue is that of false negatives derived from allele dropout during the amplification of single cell genomes. In this paper, we propose a simple strategy to reduce the false negatives in single-cell sequencing data analysis. Simulation results show that this method is highly reliable, with an error rate of 4.94×10-5, which is orders of magnitude lower than the expected false negative rate (~34%) estimated from a single-cell exome dataset, though the method is limited by the low SNP density in the human genome. We applied this method to analyze the exome data of a few dozen single tumor cells generated in previous studies, and extracted cell specific mutation information for a small set of sites. Interestingly, we found that there are difficulties in using the classical clonal model of tumor cell growth to explain the mutation patterns observed in some tumor cells. [ABSTRACT FROM AUTHOR]

C16H12BBrN2, monoclinic, P21 (no. 4), a = 4.7061(3) Å, b = 10.4639(6) Å, c = 13.5675(8) Å, β = 97.512(2)°, V = 662.39(7) Å3, Z = 2, Rgt(F) = 0.0384, wRref(F2) = 0.0995, T = 189.98 K. [ABSTRACT FROM AUTHOR]

C16H12BBrN2, monoclinic, P21 (no. 4), a = 4.7061(3) Å, b = 10.4639(6) Å, c = 13.5675(8) Å, β = 97.512(2)°, V = 662.39(7) Å3, Z = 2, Rgt(F) = 0.0384, wRref(F2) = 0.0995, T = 189.98 K. [ABSTRACT FROM AUTHOR]

Genetic factors underlying coronary artery disease (CAD) have been widely studied using genome-wide association studies (GWASs). However, the functional understanding of the CAD loci has been limited by the fact that a majority of GWAS variants are located within non-coding regions with no functional role. High cholesterol and dysregulation of the liver metabolism such as non-alcoholic fatty liver disease confer an increased risk of CAD. Here, we studied the function of non-coding single-nucleotide polymorphisms in CAD GWAS loci located within liver-specific enhancer elements by identifying their potential target genes using liver cis -eQTL analysis and promoter Capture Hi-C in HepG2 cells. Altogether, 734 target genes were identified of which 121 exhibited correlations to liver-related traits. To identify potentially causal regulatory SNPs, the allele-specific enhancer activity was analyzed by (1) sequence-based computational predictions, (2) quantification of allele-specific transcription factor binding, and (3) STARR-seq massively parallel reporter assay. Altogether, our analysis identified 1,277 unique SNPs that display allele-specific regulatory activity. Among these, susceptibility enhancers near important cholesterol homeostasis genes (APOB, APOC1, APOE , and LIPA) were identified, suggesting that altered gene regulatory activity could represent another way by which genetic variation regulates serum lipoprotein levels. Using CRISPR-based perturbation, we demonstrate how the deletion/activation of a single enhancer leads to changes in the expression of many target genes located in a shared chromatin interaction domain. Our integrative genomics approach represents a comprehensive effort in identifying putative causal regulatory regions and target genes that could predispose to clinical manifestation of CAD by affecting liver function. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are global health challenges characterized by the progressive degeneration of nerve cells, leading to cognitive and motor impairments. The brain-gut-bone axis, a complex network that modulates multiple physiological systems, has gained increasing attention owing to its profound effects on the occurrence and development of neurodegenerative diseases. No comprehensive review has been conducted to clarify the triangular relationship involving the brain-gut-bone axis and its potential for innovative therapies for neurodegenerative disorders. In light of this, a new perspective is aimed to propose on the interplay between the brain, gut, and bone systems, highlighting the potential of their dynamic communication in neurodegenerative diseases, as they modulate multiple physiological systems, including the nervous, immune, endocrine, and metabolic systems. Therapeutic strategies for maintaining the balance of the axis, including brain health regulation, intestinal microbiota regulation, and improving skeletal health, are also explored. The intricate physiological interactions within the brain-gut-bone axis pose a challenge in the development of effective treatments that can comprehensively target this system. Furthermore, the safety of these treatments requires further evaluation. This review offers a novel insights and strategies for the prevention and treatment of neurodegenerative diseases, which have important implications for clinical practice and patient well-being., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)