UPLC-QE-Orbitrap-Based Cell Metabolomics and Network Pharmacology to Reveal the Mechanism of N-Benzylhexadecanamide Isolated from Maca (Lepidium meyenii Walp.) against Testicular Dysfunction.

Testicular dysfunction (TDF) is characterized by testosterone deficiency and is caused by oxidative stress injury in Leydig cells. A natural fatty amide named N-benzylhexadecanamide (NBH), derived from cruciferous maca, has been shown to promote testosterone production. Our study aims to reveal the anti-TDF effect of NBH and explore its potential mechanism in vitro. This study examined the effects of H2O2 on cell viability and testosterone levels in mouse Leydig cells (TM3) under oxidative stress. In addition, cell metabolomics analysis based on UPLC-Q-Exactive-MS/MS showed that NBH was mainly involved in arginine biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, the TCA cycle and other metabolic pathways by affecting 23 differential metabolites, including arginine and phenylalanine. Furthermore, we also performed network pharmacological analysis to observe the key protein targets in NBH treatment. The results showed that its role was to up-regulate ALOX5, down-regulate CYP1A2, and play a role in promoting testicular activity by participating in the steroid hormone biosynthesis pathway. In summary, our study not only provides new insights into the biochemical mechanisms of natural compounds in the treatment of TDF, but also provides a research strategy that integrates cell metabolomics and network pharmacology in order to promote the screening of new drugs for the treatment of TDF.

Screening of the Active Compounds against Neural Oxidative Damage from Ginseng Phloem Using UPLC-Q-Exactive-MS/MS Coupled with the Content-Effect Weighted Method.

The neuroprotective properties of ginsenosides have been found to reverse the neurological damage caused by oxidation in many neurodegenerative diseases. However, the distribution of ginsenosides in different tissues of the main root, which was regarded as the primary medicinal portion in clinical practice was different, the specific parts and specific components against neural oxidative damage were not clear. The present study aims to screen and determine the potential compounds in different parts of the main root in ginseng. Comparison of the protective effects in the main root, phloem and xylem of ginseng on hydrogen peroxide-induced cell death of SH-SY5Y neurons was investigated. UPLC-Q-Exactive-MS/MS was used to quickly and comprehensively characterize the chemical compositions of the active parts. Network pharmacology combined with a molecular docking approach was employed to virtually screen for disease-related targets and potential active compounds. By comparing the changes before and after Content-Effect weighting, the compounds with stronger anti-nerve oxidative damage activity were screened out more accurately. Finally, the activity of the selected monomer components was verified. The results suggested that the phloem of ginseng was the most effective part. There were 19 effective compounds and 14 core targets, and enriched signaling pathway and biological functions were predicted. After Content-Effect weighting, compounds Ginsenosides F1, Ginsenosides Rf, Ginsenosides Rg1 and Ginsenosides Rd were screened out as potential active compounds against neural oxidative damage. The activity verification study indicated that all four predicted ginsenosides were effective in protecting SH-SY5Y cells from oxidative injury. The four compounds can be further investigated as potential lead compounds for neurodegenerative diseases. This also provides a combined virtual and practical method for the simple and rapid screening of active ingredients in natural products.

Expanding the clinicopathological-genetic spectrum of GNE myopathy by a Chinese neuromuscular centre.

GNE myopathy is a heterogeneous group of ultrarare neuromuscular disorders caused by mutations in the GNE gene. An estimated prevalence of 1~21/1,000,000 leads to a deficiency of data and a lack of availability of samples to conduct clinical research on this neuromuscular disorder. Although GNE, which is the mutated gene responsible for the disease, is well known as the key enzyme in the biosynthesis pathway of sialic acid, the clinicopathological-genetic spectrum of GNE mutant patients is still unclear and expanding. This study presents ten unrelated patients with GNE myopathy, discovering five novel missense mutations. Clinical, electrophysiological, imaging, pathological and genetic data are presented in a retrospective manner. Interestingly, several patients in the cohort were found to have peripheral neuropathy and inflammatory cell infiltration in muscle biopsies, which have seldom been reported. This study, conducted by a neuromuscular centre in China, is the first attempt to highlight these abnormal clinicopathological features and associate them with genetic mutations in GNE myopathy.

Three Pbx(COO)y Cluster Frameworks Based on a Flexible Triazinetricarboxylic Acid Ligand: Syntheses, Structures, and Fluorescent Sensing Application for Nitrophenols.

Three new metal-organic frameworks (MOFs), namely, [Pb7(TTPCA)4Cl2]·3H2O (1), [Pb7(TTPCA)4(DMA)2(HCOO)2]·H2O (2), and [Pb4(TTPCA)3]·3DMF·2H2O·H3O (3), were synthesized by the H3TTPCA ligand [H3TTPCA = 1,1',1″-(1,3,5-triazine-2,4,6-triyl)-tripiperidine-4-carboxylic acid], with lead(II) nitrate under solvothermal conditions. They were characterized by CHN analysis, IR spectroscopy, UV-vis spectroscopy, and single-crystal and powder X-ray diffraction. In addition, their thermogravimetric analysis and fluorescence properties were studied. Compounds 1-3 were 3D MOF structures with different Pbx(COO)y clusters: ([Pb7(COO)12Cl2]), ([Pb7(COO)12]), and [Pb8(COO)18]. Fluorescence detection of compounds 1-3 shows that they can act as excellent sensors of nitrophenols with a low limit of detection and a high quenching constant.

Antioxidant, Anti-inflammatory and Cytotoxic Activities of Polyphenols Extracted from Chroogomphus rutilus.

Chroogomphus rutilus is a rare fungal species that grows under pine trees and is now widely used as a functional food and pharmaceutical product. However, the chemical constituents and biological activities of Chroogomphus rutilus have been relatively limited. The present study aimed at determining the total polyphenols and flavonoids contents, biological activities and main phenolic compounds of Chroogomphus rutilus from different geographical origins at the stipe and pileus. The results suggested that Chroogomphus rutilus polyphenol extracts revealed a higher antioxidant, anti-inflammatory, and cytotoxic activities, and there were significant differences between samples from different locations and regions. Correlation analysis showed that the contents of total polyphenols and flavonoids were significantly correlated with antioxidant and anti-inflammatory activities. However, only the content of total flavonoids was significantly correlated with cytotoxicity, which means that the cytotoxicity of Chroogomphus rutilus polyphenol extracts may be regulated by flavonoids or other compounds. HPLC-DAD analysis revealed that the main phenolic compound was protocatechuic acid, followed by baicalin, p-hydroxyphenylacetic acid and p-hydroxybenzoic acid, but comparing with the pileus extracts, the stipe extracts can be considered as a higher concentration of phenolic compounds. Therefore, antioxidant, anti-inflammatory and cytotoxic activities of Chroogomphus rutilus polyphenol extracts could be due to the identified compounds. This study investigated a deep knowledge about the constituents and activities of Chroogomphus rutilus and provided the reference for its application in food and pharmaceutical.

A New Dinuclear Cobalt Complex for Copolymerization of CO2 and Propylene Oxide: High Activity and Selectivity.

Based on the ligand H4Salen-8tBu (salen-4), a new dinuclear cobalt complex (salen-4)[Co(III)TFA]2 (salen-4 = 3,5-di-tert-butylsalicylaldehyde-3,3'-diaminobiphenylamine; TFA = trifluoroacetic acid) has been firstly synthesized and characterized. It shows high catalytic activity for the copolymerization of propylene oxide (PO) and carbon dioxide (CO2), yielding regioregular poly(propylene carbonate) (PPC) with little generation of propylene carbonate (PC) by-product. It has been found that (salen-4)[Co(III)TFA]2 shows higher activity at milder conditions, generating a polymer with maximum Mn of 293 kg/mol and a narrow molecular weight distribution PDI of 1.35. The influences of reaction time, CO2 pressure, reaction temperature, nature of the cocatalyst, catalyst dosage and substrate concentration on the molecular weight, yield and selectivity of the polymer were explored in detail. The results showed that the (salen-4)[Co(III)TFA]2/[PPN]TFA catalyst system demonstrated a remarkable TOF as high as 735 h-1. In addition, a hypothetical catalytic reaction mechanism was proposed based on density functional theory (DFT) calculations and the catalytic reaction results of the (salen-4)[Co(III)TFA]2.

Triazine Poly(carboxylic acid) Metal-Organic Frameworks and the Fluorescent Response with Lead Oxygen Clusters: [Pb7(COO)12X2] by Halogen Tuning (X = Cl, Br, or I).

A series of novel metal-organic frameworks were synthesized by using semirigid ligand 1,1',1″-(1,3,5-triazine-2,4,6-triyl)tripiperidine-4-carboxylic acid (H3TTPCA) and lead halide (Cl, Br, or I). The three complexes were characterized by elemental analysis, infrared spectroscopy, ultraviolet-visible spectroscopy, powder X-ray diffraction analysis, and thermogravimetric analysis. X-ray single-crystal diffraction analysis demonstrated that all three complexes were three-dimensional inorganic-organic framework structures with Pb-X2 (X = Cl, Br, or I). However, slight differences in the chemical environment were the focus of the coordinated halogen atoms and the different compositions of metal oxygen clusters: [Pb7(COO)12Cl2], [Pb7(COO)12Br2], and [Pb7(COO)12I2]. Because of the fluorescence of the organic ligand, the three complexes showed similar photoluminescence properties at room temperature, but the intensity of emissions decreased gradually with an increase in the atomic radius of coordinated halogen atoms. Interestingly, in the fluorescence response tests, complexes 1 and 2 displayed an optical signal of fluorescence "turn-on" while complex 3 showed an optical signal of fluorescence "turn-off". Here we aim to provide a possible mechanism to explain these unique and contradictory luminescence results.

Accurate prediction of human essential genes using only nucleotide composition and association information.

MOTIVATION: Previously constructed classifiers in predicting eukaryotic essential genes integrated a variety of features including experimental ones. If we can obtain satisfactory prediction using only nucleotide (sequence) information, it would be more promising. Three groups recently identified essential genes in human cancer cell lines using wet experiments and it provided wonderful opportunity to accomplish our idea. Here we improved the Z curve method into the λ-interval form to denote nucleotide composition and association information and used it to construct the SVM classifying model. RESULTS: Our model accurately predicted human gene essentiality with an AUC higher than 0.88 both for 5-fold cross-validation and jackknife tests. These results demonstrated that the essentiality of human genes could be reliably reflected by only sequence information. We re-predicted the negative dataset by our Pheg server and 118 genes were additionally predicted as essential. Among them, 20 were found to be homologues in mouse essential genes, indicating that some of the 118 genes were indeed essential, however previous experiments overlooked them. As the first available server, Pheg could predict essentiality for anonymous gene sequences of human. It is also hoped the λ-interval Z curve method could be effectively extended to classification issues of other DNA elements. AVAILABILITY AND IMPLEMENTATION: http://cefg.uestc.edu.cn/Pheg. CONTACT: fbguo@uestc.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Identification and analysis of genomic islands in Burkholderia cenocepacia AU 1054 with emphasis on pathogenicity islands.

BACKGROUND: Genomic islands (GIs) are genomic regions that reveal evidence of horizontal DNA transfer. They can code for many functions and may augment a bacterium's adaptation to its host or environment. GIs have been identified in strain J2315 of Burkholderia cenocepacia, whereas in strain AU 1054 there has been no published works on such regions according to our text mining and keyword search in Medline. RESULTS: In this study, we identified 21 GIs in AU 1054 by combining two computational tools. Feature analyses suggested that the predictions are highly reliable and hence illustrated the advantage of joint predictions by two independent methods. Based on putative virulence factors, four GIs were further identified as pathogenicity islands (PAIs). Through experiments of gene deletion mutants in live bacteria, two putative PAIs were confirmed, and the virulence factors involved were identified as lipA and copR. The importance of the genes lipA (from PAI 1) and copR (from PAI 2) for bacterial invasion and replication indicates that they are required for the invasive properties of B. cenocepacia and may function as virulence determinants for bacterial pathogenesis and host infection. CONCLUSIONS: This approach of in silico prediction of GIs and subsequent identification of potential virulence factors in the putative island regions with final validation using wet experiments could be used as an effective strategy to rapidly discover novel virulence factors in other bacterial species and strains.

Association of TNF-α genetic polymorphisms with recurrent pregnancy loss risk: a systematic review and meta-analysis.

BACKGROUND: Several studies on the association of tumor necrosis factor alpha (TNF-α) polymorphisms with recurrent pregnancy loss (RPL) risk have reported conflicting results. The present meta-analysis was conducted to provide a more precise estimation of these relationships and to investigate the real association between TNF-α polymorphisms and RPL. METHODS: An extensive eligible literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library from their inceptions to May 12, 2015. Specific inclusion criteria were used to evaluate articles. The odds ratio (OR) with 95% confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA12.0 software. RESULTS: 10 case-control studies including 1430 RPL patients and 1727 healthy controls were identified. Meta-analysis indicated that TNF-α-308G/A (rs1800629) polymorphism in the TNF-α gene correlated with elevated RPL risk whereas no significant association was observed between TNF-α-238G/A (rs361625) and RPL. CONCLUSIONS: The current meta-analysis demonstrates that TNF-α-308G/A polymorphism in the TNF-α gene is associated with susceptibility to RPL.

An X chromosome-wide association analysis identifies variants in GPR174 as a risk factor for Graves' disease.

BACKGROUND: Graves' disease is a female preponderant autoimmune illness and the contribution of the X chromosome to its risk has long been appreciated. However, no X-linked susceptibility loci have been indentified from recent genome-wide association studies (GWAS). METHODS: We re-examined the X chromosome data from our recent GWAS for Graves' disease by including males that were previously excluded from the X chromosome analyses. The data were analysed using logistic regression analysis including sex as a covariate, and an additive method assuming X chromosome inactivation, implemented in snpMatrix. RESULTS: A cluster of single nucleotide polymorphism (SNPs) at Xq21.1 was found showing association with genome-wide significance, among which rs3827440 was a non-synonymous SNP of GPR174 (P(logistic regression)= 9.52×10(-8); P(snpMatrix)=4.60×10(-9); OR=1.76, 95% CI 1.45 to 2.13). The association was reproduced in an independent sample collection set including 4564 Graves' disease cases and 3968 sex matched controls (combined P(logistic regression)=5.53×10(-21); combined P(snpMatrix)=4.26×10(-22); OR=1.69, 95% CI 1.53 to 1.86). Notably, GPR174 was widely expressed in immune related tissues and rs3827440 genotypes were associated with distinct mRNA levels (p=0.002). GPR174 did not show sex biased gene expression in our expression analysis. Resequencing study suggested the contribution of some rare variants in the GPR174 gene region to disease risk with a collapsing p value of 1.16×10(-3). CONCLUSIONS: The finding of an X-linked risk locus for Graves' disease expands our understanding of the role of the X chromosome in disease susceptibility.

Comparative effectiveness and safety of intravenous methylprednisolone and tacrolimus monotherapy in ocular myasthenia gravis with unsatisfactory prednisone responses: a retrospective study.

BACKGROUND: Oral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy. METHODS: We retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded. RESULTS: Both IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p = 0.002; 69.0% (20/29) vs 40.0% (10/25), p = 0.033; 69.0% (20/29) vs 46.4% (13/28), p = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066-2.975; p = 0.028). All the adverse events were transient and tolerable. CONCLUSION: Our findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.

[Review of clinical effects of disk-up sinus reamer(DSR)-based internal sinus floor elevation with implantation in 10 years].

PURPOSE: To analyze the bone remodeling around the implant 10 years after disk-up sinus reamer(DSR)-based internal sinus floor elevation with implantation and to investigate the influence of different factors on implant retention. METHODS: The clinical and imaging data of patients undergoing DSR-based sinus floor elevation with simultaneous implantation were collected from the Department of Dental Implantology, Affiliated Hospital of Qingdao University from January 2008 to December 2011. Panoramic film and CBCT were used to measure the changes of bone mass around implant in different periods. Kaplan-Meier and Log-rank tests were used to analyze the effects of different factors on implant retention with SPSS 26.0 software package. RESULTS: The study included 98 patients with a total of 128 implants. During the follow-up of 0-168 months, 7 implants failed, and the remaining formed good osseointegration and functioned, with a 10-year cumulative retention rate of 94.53%. The height of bone formation was (0.29±0.15) mm at the top and (2.74±0.66) mm in the sinus of 75 implant sites with complete imaging data obtained ten years after surgery. Kaplan-Meier and Log-rank tests showed that 8 factors including initial bone height, elevated bone height, mucosal perforation, implant length, implant torsion, diabetes, smoking and periodontitis had significant effects on implant retention. CONCLUSIONS: The DSR-based internal sinus floor elevation with implantation is a reliable and stable bone augmentation operation for vertical bone defect in maxillary posterior region, with a 10-year cumulative retention rate of no less than 94%. Initial bone height, elevated bone height, mucosal perforation, implant length, implant torsion, diabetes, smoking and periodontitis are the important factors affecting the long-term retention rate of implants.

Effects of Cu2O nanoparticles on the kinetic characteristics of rapid chlorophyll fluorescence induction and related genes in wheat seedlings.

Metal nanoparticles could be accumulated in soils, which threatens the ecological stability of crops. Investigating the effects of cuprous oxide nanoparticles (Cu2O-NPs) on photosystem Ⅱ (PSⅡ) of wheat seedling leaves holds considerable importance in comprehending the implications of Cu2O-NPs on crop photosynthesis. Following the hydroponic method, we investigated the effects of 0, 10, 50, 100, and 200 mg·L-1 Cu2O-NPs on chlorophyll fluorescence induction kinetics and photosynthetic-related genes in wheat seedlings of "Zhoumai 18". The results showed that, with the increases of Cu2O-NPs concentrations, chlorophyll contents in wheat leaves decreased, and the standardization of the OJIP curve showed a clearly K-phase (ΔK＞0). Cu2O-NPs stress increased the parameters of active PSⅡ reaction centers, including the absorption flux per active RC (ABS/RC), the trapping flux per active RC (TRo/RC), the electron transport flux per active RC (ETo/RC), and the dissipation flux per active RC (DIo/RC). Cu2O-NPs stress decreased the parameters of PSⅡ energy distribution ratio including the maximum quantum yield of PSⅡ (φPo), the quantum yield of electron transport from QA (φEo), and the probability that a trapped exciton moved an electron further than QA (Ψo), while increased the quantum ratio for heat dissipation (φDo). Moreover, there was a decrease in photosynthetic quantum yield Y(Ⅱ), photochemical quenching coefficient (qP), net photosynthetic rate (Pn), stomatal conductance (gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) of leaves with the increases of Cu2O-NPs concentration. Under Cu2O-NPs stress, the expression levels of genes which included PSⅡ genes (PsbD, PsbP, Lhcb1), Rubisco large subunit genes (RbcL), cytochrome b6/f complex genes (PetD, Rieske), and ATP synthase genes (AtpA, AtpB, AtpE, AtpI) were downregulated. These results indicated that Cu2O-NPs stress altered the activity and structure of PSⅡ in wheat seedlings, affected the activity of PSⅡ reaction centers, performance parameters of PSⅡ donor and acceptor sides. PSⅡ related genes were downregulated and exhibited significant concentration effects.

Supramolecular interactions in cocrystals of benzoic acid derivatives with selective COX-2 inhibitor etoricoxib.

The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5-chloro-2-(6-methylpyridin-3-yl)-3-[4-(methylsulfonyl)phenyl]pyridine, C18H15ClN2O2S} have been synthesized and characterized by single-crystal X-ray diffraction; these are etoricoxib-benzoic acid (1/1), C18H15ClN2O2S·C7H6O2 (ETR-Bz), etoricoxib-4-fluorobenzoic acid (1/1), C18H15ClN2O2S·C7H5FO2 (ETR-PFB), and etoricoxib-4-nitrobenzoic acid (1/1), C18H15ClN2O2S·C7H5NO4 (ETR-PNB). Powder X-ray diffraction and thermal differential scanning calorimetry-thermogravimetry (DSC-TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals.

Single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 gene is associated with gallstone disease in Han Chinese.

BACKGROUND AND AIMS: Gallstone disease (GD) is a common disease of multigenetic origin; however, the major susceptibility loci for GD in human populations remain unidentified. This study aimed to identify the genetic factors contributing to gallstone development in Chinese. METHODS: A genome-wide scan was conducted in 12 Han Chinese GD families to identify linkage loci. The linkage region showing the highest logarithm of odds score encompasses the sterol 12α-hydroxylase gene (CYP8B1). Replication analysis with an independent sample of 192 GD patients and 192 unrelated, matched controls was carried out to verify the associations between CYP8B1 polymorphisms and GD. RESULTS: Three loci (D3S1266, D4S406, and D9S1682) showed suggestive or nominal evidence of linkage in all 12 GD families. The logarithm of odds score of D3S1266 reached 2.71 in the families with late-onset patients. The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 showed significant association to GD (P = 0.022), and carriers of the A allele had lower risk of GD (odds ratio = 1.46, 95% confidence interval: 1.055-2.034) compared with carriers of the G allele. CONCLUSIONS: The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of the CYP8B1 gene is associated with risk of GD in Chinese Han and appears to be responsible for the observed linkage with D3S1266.

Comparison of Dexmedetomidine Versus Propofol in Mechanically Ventilated Patients With Sepsis: A Meta-Analysis of Randomized Controlled Trials.

Purpose: The aim of the present study was to evaluate the effects of dexmedetomidine compared with propofol in mechanically ventilated patients with sepsis. Methods: We searched PubMed, EMBASE, and Cochrane Library for randomized controlled trials comparing the effects of dexmedetomidine versus propofol in septic patients requiring mechanical ventilation from inception to December 2021. The primary outcome was 28/30-day mortality and secondary outcomes were ventilator-free days and the length of ICU stay. Pooled relative risk (RR), mean deviation (MD), along with 95% confidence intervals (CI) were used to express outcomes by the software of Review Manager 5.3. Results: Seven studies with a total of 1,212 patients were eligible for meta-analysis. The results primarily showed that dexmedetomidine had no significant effects on the 28/30-day mortality (RR = 1.04 [0.85-1.26], p = 0.70, I2 = 3%). As for secondary outcomes, the administration of dexmedetomidine was not associated with longer-ventilator-free days (MD = 0.50 [-2.15, 3.15], p = 0.71, I2 = 24%) compared with propofol. However, our results revealed dexmedetomidine could shorten the length of ICU stay (MD = -0.76 [-1.34, -0.18], p = 0.01, I2 = 33%). Conclusion: Administration of dexmedetomidine for sedation in septic patients who required mechanical ventilation had no effect on 28/30-day mortality and ventilator-free days, but it could shorten the length of ICU stay.

Consistent Clustering Pattern of Prokaryotic Genes Based on Base Frequency at the Second Codon Position and its Association with Functional Category Preference.

In 2002, our research group observed a gene clustering pattern based on the base frequency of A versus T at the second codon position in the genome of Vibrio cholera and found that the functional category distribution of genes in the two clusters was different. With the availability of a large number of sequenced genomes, we performed a systematic investigation of A2-T2 distribution and found that 2694 out of 2764 prokaryotic genomes have an optimal clustering number of two, indicating a consistent pattern. Analysis of the functional categories of the coding genes in each cluster in 1483 prokaryotic genomes indicated, that 99.33% of the genomes exhibited a significant difference (p < 0.01) in function distribution between the two clusters. Specifically, functional category P was overrepresented in the small cluster of 98.65% of genomes, whereas categories J, K, and L were overrepresented in the larger cluster of over 98.52% of genomes. Lineage analysis uncovered that these preferences appear consistently across all phyla. Overall, our work revealed an almost universal clustering pattern based on the relative frequency of A2 versus T2 and its role in functional category preference. These findings will promote the understanding of the rationality of theoretical prediction of functional classes of genes from their nucleotide sequences and how protein function is determined by DNA sequence.

CASQ1-related myopathy: The first report from China and the literature review.

Calsequestrin 1 (CASQ1) is the most crucial Ca2+ binding protein localized in the sarcoplasmic reticulum (SR) of skeletal muscle. With high capacity and low affinity for Ca2+, CASQ1 plays a significant role in maintaining a large amount of Ca2+ necessary for muscle contraction. However, only five mutations in CASQ1 have been identified to date. Here, we report a 42-year-old Chinese female patient who presented with a 12 years history of slowly progressive upper limb weakness, predominantly affecting distal muscles, which was uncommon comparing to other CASQ1-related patients. Next-generation sequencing (NGS) analysis revealed a novel heterozygous mutation (c.766G > A, p.Val256Met) in CASQ1. Functional studies confirmed the likely pathogenicity of this variant. Muscle histopathology revealed rare optically empty vacuoles in myofibers and atypical eosinophilic granules in the cytoplasm, which has not been observed before. We also performed a literature review on all the pathogenic mutations in CASQ1 and summarized their genetic and clinical characteristics. This is the first report on CASQ1-related myopathy from China, further expanding the mutation spectrum of CASQ1 gene and provides new insights into the function of CASQ1.

Feasibility of Predicting Pelvic Lymph Node Metastasis Based on IVIM-DWI and Texture Parameters of the Primary Lesion and Lymph Nodes in Patients with Cervical Cancer.

RATIONALE AND OBJECTIVES: To investigate the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and texture parameters of primary lesions and lymph nodes for predicting pelvic lymph node metastasis in patients with cervical cancer. MATERIALS AND METHODS: A total of 143 patients with cervical cancer confirmed by surgical pathology were analyzed retrospectively and 125 patients were enrolled in primary lesions study, 83 patients and 134 lymph nodes were enrolled in lymph nodes study. Patients and lymph nodes were randomly divided into training group and test group at a ratio of 2: 1. The IVIM-DWI parameters and 3D texture features of primary lesions and lymph nodes of all patients were measured. The least absolute shrinkage and selection operator algorithm, spearman's correlation analysis, independent two-sample t-test and Mann-Whitney U-test were used to select texture parameters. Multivariate Logistic regression analysis and receiver operating characteristic curves were used to model and evaluate diagnostic performances. RESULTS: In primary lesions study, model 1 was constructed by combining f value, original_shape_Sphericity and original_firstorder_Mean of primary lesions. In lymph nodes study, model 2 was constructed by combining short diameter, circular enhancement and rough margin of lymph nodes. Model 3 was constructed by combining ADC, f value and original_glszm_Small Area Emphasis of lymph nodes. The areas under curve of model 1, 2 and 3 in training group and test group were 0.882, 0.798, 0.907 and 0.862, 0.771, 0.937 respectively. CONCLUSION: Models based on IVIM-DWI and texture parameters of primary lesions and lymph nodes both performed well in diagnosing pelvic lymph node metastasis of cervical cancer and were superior to morphological features of lymph nodes. Especially, parameters of lymph nodes showed higher diagnostic efficiency and clinical significance.