The influence of sleep disorders on perioperative neurocognitive disorders among the elderly: A narrative review.

This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood-brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD.

ROS-dependent cell death of Heterosigma akashiwo induced by algicidal bacterium Hahella sp. KA22.

Marine algicidal bacteria and their metabolites are considered to be one of the most effective strategies to mitigate the harmful algal blooms (HABs). The bacterium Hahella sp. KA22 has previously been confirmed to have strong algicidal activity against the HABs causing microalgae, Heterosigma akashiwo. In this study, the molecular mechanism of microalgae cell death was detected. The results showed that the cell growth rate and photosynthetic efficiency were inhibited with addition of algicidal strain KA22, while the accumulation of reactive oxygen species (ROS) and oxidative damage in H. akashiwo cells increased. A total of 2056 unigenes were recognized to be differentially expressed in transcriptome sequences. In particular, the transcriptional levels of light-harvesting pigments and structural proteins in the oxygen-evolving-complex were continuously down-regulated, corresponding to the significant reduction of photosynthetic efficiency and the accumulation of ROS. Furthermore, glutamate dehydrogenase was significantly up-regulated in abundance. Meanwhile, calcium-dependent protein kinases were also detected with significant changes. Collectively, algicidal stress caused the suppressed electron transfer in chloroplast and impaired detoxification of intracellular oxidants by glutathione, which may subsequently result in multiple cell regulation and metabolic responses and ultimately lead to the ROS-dependent cell death of H. akashiwo.

Heterogeneous spectrum of CFTR gene mutations in Chinese patients with CAVD and the dilemma of genetic blocking strategy.

In brief: The genetic heterogeneity of CFTR gene mutations in Chinese patients with congenital absence of the vas deferens (CAVD) differs from the hotspot mutation pattern in Caucasians. This paper reviews and suggests a more suitable screening strategy for the Chinese considering the dilemma of CFTR genetic blocking. Abstract: Congenital absence of the vas deferens (CAVD) is a major cause of obstructive azoospermia and male infertility, with CFTR gene mutation as the main pathogenesis. Other genes such as ADGRG2, SLC9A3, and PANK2 have been discovered and proven to be associated with CAVD in recent studies. Multiple CFTR hotspot mutations have been found in Caucasians in several foreign countries, and relevant genetic counseling and preimplantation genetic diagnosis (PGD) have been conducted for decades. However, when we examined research on Chinese CAVD, we discovered that CFTR mutations show heterogeneity in the Chinese Han population, and there is currently no well-established screening strategy. Therefore, we have reviewed the literature, combining domestic and international research as well as our own, aiming to review research progress on the CFTR gene in China and discuss the appropriate scope for CFTR gene detection, the detection efficiency of other CAVD-related genes, and the screening strategy applicable to the Chinese Han population. This study provides more valuable information for genetic counseling and a theoretical basis for PGD and treatment for couples with CAVD when seeking reproductive assistance.

ELOVL2 restrains cell proliferation, migration, and invasion of prostate cancer via regulation of the tumor suppressor INPP4B.

BACKGROUND: Prostate cancer is one of the most common malignancies in men. Members of the elongation of the very-long-chain fatty acid (ELOVL) gene family have been reported to participate in the occurrence and development of various cancers. However, the function of ELOVL gene family members (ELOVLs) in prostate cancer has not been fully elucidated. METHODS: The mRNA expression and prognostic value of ELOVLs in prostate cancer were analyzed using the GEPIA database. The Oncomine database and PrognoScan database were used to further verify the mRNA expression level and prognostic value of ELOVL2 in prostate cancer. RT-qPCR and Western blotting were used to validate the expression levels of ELOVL2 in four prostate cancer cell lines. Immunohistochemistry was performed to detect the ELOVL2 protein expression levels in prostate cancer tissues. Coexpression analysis in the cBioPortal database and enrichment analysis in Kyoto Encyclopedia of Genes and Genomes (KEGG), CCK8, colony formation, and transwell assays were used to identify the functions and mechanisms of ELOVL2. RESULTS: ELOVL2 expression was upregulated in prostate cancer tissues compared with normal tissues. High expression of ELOVL2 indicated a better prognosis in prostate cancer patients. ELOVL2 expression was negatively correlated with Gleason score. Knockdown of ELOVL2 promoted cell proliferation, colony formation, migration, invasion, and the growth of subcutaneous xenografts and activated the PI3K/Akt signaling pathway by downregulating INPP4B, while overexpression of ELOVL2 reversed these effects. In addition, overexpression of INPP4B blocked the promoting effect of sh-ELOVL2 on cell proliferation, colony formation, migration, invasion, and the PI3K/Akt signaling pathway. CONCLUSIONS: Our findings suggest that ELOVL2 might be a prognostic biomarker and therapeutic target for prostate cancer.

Integrative bioinformatics approaches for identifying potential biomarkers and pathways involved in non-obstructive azoospermia.

BACKGROUND: Non-obstructive azoospermia (NOA) is a disease related to spermatogenic disorders. Currently, the specific etiological mechanism of NOA is unclear. This study aimed to use integrated bioinformatics to screen biomarkers and pathways involved in NOA and reveal their potential molecular mechanisms. METHODS: GSE145467 and GSE108886 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NOA tissues and matched obstructive azoospermia (OA) tissues were identified using the GEO2R tool. Common DEGs in the two datasets were screened out by the VennDiagram package. For the functional annotation of common DEGs, DAVID v.6.8 was used to perform Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In accordance with data collected from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, a protein-protein interaction (PPI) network was constructed by Cytoscape. Cytohubba in Cytoscape was used to screen the hub genes. Furthermore, the hub genes were validated based on a separate dataset, GSE9210. Finally, potential micro RNAs (miRNAs) of hub genes were predicted by miRWalk 3.0. RESULTS: A total of 816 common DEGs, including 52 common upregulated and 764 common downregulated genes in two datasets, were screened out. Some of the more important of these pathways, including focal adhesion, PI3K-Akt signaling pathway, cell cycle, oocyte meiosis, AMP-activated protein kinase (AMPK) signaling pathway, FoxO signaling pathway, and Huntington disease, were involved in spermatogenesis. We further identified the top 20 hub genes from the PPI network, including CCNB2, DYNLL2, HMMR, NEK2, KIF15, DLGAP5, NUF2, TTK, PLK4, PTTG1, PBK, CEP55, CDKN3, CDC25C, MCM4, DNAI1, TYMS, PPP2R1B, DNAI2, and DYNLRB2, which were all downregulated genes. In addition, potential miRNAs of hub genes, including hsa-miR-3666, hsa-miR-130b-3p, hsa-miR-15b-5p, hsa-miR-6838-5p, and hsa-miR-195-5p, were screened out. CONCLUSIONS: Taken together, the identification of the above hub genes, miRNAs and pathways will help us better understand the mechanisms associated with NOA, and provide potential biomarkers and therapeutic targets for NOA.

Mutation analysis of the cystic fibrosis transmembrane conductance regulator gene in Chinese congenital absence of vas deferens patients.

To find the variant spectrum of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and evaluate its frequent variants in Chinese congenital absence of vas deferens (CAVD) patients. A total of 276 patients with azoospermia and CAVD (aged from 21 to 44 years old) were investigated from May 2013 to September 2019 in the Third Affiliated Hospital of Sun Yat-sen University. Additionally, 50 healthy, unrelated volunteers were recruited as controls (aged from 21 to 46 years old). The 5'-UTR, exons and their flanking side of the CFTR gene were sequenced by high-throughput sequencing technology. The results were compared with those retrieved from the Ensembl Genome Browser. In addition, all 13 novel variants were further confirmed independently by Sanger sequencing and evaluated in the bioinformatics web servers. A schematic of the variant spectrum of the CFTR gene, including 13 novel variants (12 in CAVD patients, one in the control group), is shown, and the frequent variants in Chinese CAVD patients were 5 T (27.54%), c.-8G > C (7.25%), p.Q1352H (5.98%), and p.I556V (3.08%). 5 T was found to be the most frequent variant. p.Q1352H had a significantly high allelic frequency in CAVD patients (P < 0.05). c.-8G > C and p.I556V had high allelic frequencies but showed no difference between patients and controls (P > 0.05). p.Q1352H is the most common and important missense variant in Chinese patients with CAVD, while the pathological effects of C.-8G > C and p.I556V may be weak after evaluation.

Differences in metabolic potential between particle-associated and free-living bacteria along Pearl River Estuary.

Particulate organic matter (POM) in aquatic ecosystem is critical for biogeochemical cycling and host distinct communities of microbes, compared to its surrounding water. In this study, the structures and functional potentials of microbial communities associated with particles or free-living in water samples from the Pearl River Estuary were investigated using 16S rRNA gene sequencing and GeoChip 5.0 analysis. Significant differences in the community structure and genetic functional potentials between particle-associated bacteria and free-living bacteria were observed across all eight sampling sites. In particle-associated bacteria communities, Rhodobacteraceae and Flavobacteriaceae were more abundant, while SAR11 clade and SAR86 clade were the most abundant in free-living bacteria communities. The richness and abundance of functional genes involved in nutrient cycling and stress response, including carbon degradation, nitrogen fixation, DMSP degradation, and polyphosphate degradation, were much higher in particle-associated bacteria compared with free-living bacteria. Thus, the particle-associated bacteria seem to play a much more important role in the biogeochemical cycles than free-living bacteria. In conclusion, the results from this study highlight the central role played by particle-associated bacteria in structuring microbial assemblages, and their importance for mediating biogeochemical cycling in the estuarine ecosystem.

Olfactory Sensitivity Is Related to Erectile Function in Adult Males.

BACKGROUND: The olfactory system influences human social behavior, in particular the selection of a spouse. However, there is currently a lack of clinical research on the relationship between the olfactory system and erectile dysfunction (ED) in adult males. AIM: We explored the association between olfactory sensitivity and erectile function and its possible mechanisms. RESULTS: A total of 574 patients, adult males aged between 19 and 42 years, diagnosed with ED in the Department of Infertility and Sexual Medicine of the Third Affiliated Hospital of Sun Yat-sen University from 2015 to 2018 were analyzed retrospectively. Among them, 115 patients (20.03%) had rhinologic diseases (RDs). In addition, in 201 adult male patients who underwent nasal surgery in the ENT department from 2012 to 2016, including 29 (14.43%) with ED, nasal congestion, nasal discharge, and hyposmia were the most common complaints based on the numerical rating scale (NRS). Furthermore, a prospective study was performed in a total of 102 sequential outpatients (male adults) with RD only (n = 46), ED only (n = 42) and both RD and ED (n = 14) in 2019, together with 40 healthy (male adults) volunteers as controls. The results showed that ED patients with RD had severe nasal discomfort and decreased erectile function (P < 0.0001). The olfactory sensitivity of patients with ED was lower than that of the controls, and patients with both ED and RD had the worst olfactory sensitivity (P < 0.0001). Spearman correlation analyses showed that sense of smell was positively correlated with the International Index of Erectile Function-5 score (R = 0.507, P ≤ 0.0001) and the Erection Hardness Scale score (R = 0.341, P < 0.0001). Logistic regression analyses showed that having an olfactory disorder (OD), RD, age, and visual analog scale (VAS, over 5) score were risk factors for ED outcome, indicating that OD patients had a 16.479-fold increased risk for an ED outcome (P < 0.05). CONCLUSION: A significant correlation was detected between olfactory sensitivity and erectile function in adult males. In particularly, impairment of olfactory sensitivity is more common in patients with both ED and RD than in patients suffering from a single disease.

The ADRB3 rs4994 polymorphism increases risk of childhood and adolescent overweight/obesity for East Asia's population: an evidence-based meta-analysis.

Whether the Adrenoceptor Beta 3 (ADRB3) gene rs4994 polymorphism could affect the individual risk of childhood and adolescent overweight/obesity remains controversial. This meta-analysis was performed to estimate the prevalence of this polymorphism in overweight/obesity, and test the potential association by summarizing existing evidence. Comprehensive literature search in PubMed, Web of Science, Cochrane Library, Wanfang, and CNKI databases was performed to identify eligible data sets. Finally, 16 studies involving 5,147 overweight/obese cases and 7,350 non-obese controls were included for further synthetic analyses. Odds ratio (OR) and its corresponding 95% confidence intervals (CIs) were statistically calculated. Totally, 69.9% of the included subjects came from East Asia. In the meta-analysis for overall population, statistically significant associations with increased risk of childhood and adolescent overweight/obesity were identified in allele model (OR 1.23, 95% CI 1.10-1.38), heterozygote model (OR 1.39, 95% CI 1.16-1.68), and dominant model (OR 1.31, 95% CI 1.12-1.54). Further stratified analysis according to geographical regions revealed that the statistical significance could only be detected in the East Asia subgroup in allele model, homozygote model, heterozygote model, and dominant model. In summary, our meta-analysis indicated that the ADRB3 rs4994 polymorphism could significantly increase the risk of childhood and adolescent overweight/obesity, especially for the East Asia's population.

Consecutive nightly measurements are needed for accurate evaluation of nocturnal erectile capacity when the first-night laboratory recording is abnormal.

Multiple measurements of nocturnal penile tumescence and rigidity (NPTR) are widely accepted as a method to differentiate psychogenic erectile dysfunction (ED) from organic ED. However, direct evidence remains limited regarding the first-night effect on NPTR measurement using the RigiScan. Here, we evaluated the first-night effect on the results of NPTR measurement to validate the necessity of NPTR measurement for two consecutive nights, particularly when abnormal first-night measurements are recorded in a laboratory setting. We retrospectively reviewed 105 patients with a complaint of ED, who underwent NPTR measurement using the RigiScan in the Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China), for two consecutive nights, during the period from November 2015 to May 2016. NPTR parameters were collected and analyzed. We found that more effective nocturnal erections were detected during the second night than during the first night (P <0.001). Twenty percent of all patients had no effective erection during the first night, but exhibited at least one effective erection during the second night. The negative predictive value of NPTR measurement during the first night was 43.2%; this was significantly lower than that on the second night (84.2%; P = 0.003). Most NPTR parameters were better on the second night than on the first night. The first-night effect might be greater among patients younger than 40 years of age. In conclusion, two consecutive nightly measurements of NPTR can avoid a false-abnormal result caused by the first-night effect; moreover, these measurements more accurately reflect erectile capacity, especially when the first-night record is abnormal in a laboratory setting.

Tamlana fucoidanivorans sp. nov., isolated from algae collected in China.

A Gram-stain-negative, aerobic, non-motile and rod-shaped marine bacterium, CW2-9T, was isolated from algae collected from Fujian Province in PR China. 16S rRNA gene sequence analysis showed that this strain was affiliated with the genus Tamlana in the family Flavobacteriaceae of the class Flavobacteriia and was very similar to the type strain Tamlana sedimentorum MCCC 1A10799T (96.3 % sequence similarity). The whole genome of strain CW2-9T comprised 3 997 513 bp with a G+C content of 34.3 mol%. The average nucleotide identity value between strain CW2-9T and T. sedimentorum MCCC 1A10799T was 73.8 %. Growth was observed from 15 to 40 °C (optimum, 30 °C), at pH from pH 5.0 to 10.0 (pH 8.0) and in the presence of 0-4 % (w/v) NaCl (0-1 %). The major fatty acids (>10 % of the total) were iso-C15 : 0, iso G-C15 : 1, iso-C17 : 0 3-OH and anteiso-C15 : 0. The predominant menaquinone was MK-6. The combined phylogenetic, physiological and chemotaxonomic data indicate that strain CW2-9T represents a novel species in the genus Tamlana, for which the name Tamlana fucoidanivorans sp. nov. is proposed. The type strain is CW2-9T (=CICC 24749T=KCTC 72389T).

Tropicibacter alexandrii sp. nov., a novel marine bacterium isolated from the phycosphere of a dinoflagellate, Alexandrium minutum.

An aerobic, Gram-negative, rod-shaped, non-motile bacterium was isolated from a liquid culture of the dinoflagellate Alexandrium minutum and designated as strain LMIT003T. Analyses of 16S rRNA gene sequences revealed that this strain is affiliated with the genus Tropicibacter in the family Rhodobacteraceae of the class Alphaproteobacteria and shows high similarity (97.3%) with the type species Tropicibacter naphthalenivorans C02T. Phylogenetic analysis based on core genes showed that the isolate groups with members of the genus Tropicibacter. The G + C content of strain LMIT003T was determined to be 61.9 mol%. The major fatty acids identified included summed feature 8 (C18:1 ω7c/C18:1 ω6c), C18:0, C12:1 3-OH and C16:0. The sole respiratory lipoquinone was found to be ubiquinone-10. The major polar lipids were found to be phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids and four unidentified phospholipids. The draft genome size of strain LMIT003T was determined to be 4.8 Mbp. The average nucleotide identity values between strain LMIT003T and reference Tropicibacter species were determined to be 78.7% (T. naphthalenivorans) and 74.2% (Tropicibacter phthalicicus). Based on physiological, chemotaxonomic and phylogenetic analysis, strain LMIT003T is concluded to represent a novel species in the genus Tropicibacter, for which the name Tropicibacter alexandrii sp. nov., is proposed. The type strain is LMIT003T (= CICC 24660T = KCTC 62895T).

The MMP-8 rs11225395 Promoter Polymorphism Increases Cancer Risk of Non-Asian Populations: Evidence from a Meta-Analysis.

This meta-analysis aimed to systematically review the evidence on cancer risk of the MMP-8 rs11225395 promoter polymorphism. Relevant studies published by 12 June 2019 were identified by systematically searching PubMed, Web of Science, Cochrane Library, CNKI and Wanfang databases. R programs and STATA software were used to calculate odds ratio (OR) and 95% confidence interval (CI). In total, 7375 cancer samples and 8117 controls were included by integrating 15 case-control data sets. Pooled estimates from the statistical analysis revealed no statistical significance for the association between this polymorphism and cancer risk. All pooled estimates resulting from subgroup analyses by cancer type and sample size were not materially altered and did not draw significantly different conclusions. The stratified analyses according to geographic region showed the statistical significance for increased cancer risk of the MMP-8 rs11225395 polymorphism in non-Asian populations under the allele model (OR = 1.11, 95% CI: 1.04-1.19), homozygote model (OR = 1.22, 95% CI: 1.05-1.41), heterozygote model (OR = 1.21, 95% CI: 1.07-1.36), and dominant model (OR = 1.21, 95% CI: 1.08-1.35). However, no statistical significance was detected in Asian populations. In conclusion, these findings suggested that the MMP-8 rs11225395 polymorphism is associated with elevated susceptibility to cancer in non-Asian populations.

A novel mutation (-195C>A) in the promoter region of CFTR gene is associated with Chinese Congenital Bilateral Absence of Vas Deferens (CBAVD).

Congenital bilateral absence of vas deferens (CBAVD), a frequent cause of obstructive azoospermia and male infertility in Chinese, is mainly due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aim to explore the promoter region of CFTR gene in CBAVD patients and study the mutations by functional analysis, and to discuss the significance of mutation testing in this area. We performed screening analysis on 65 CBAVD patients and 50 controls to detect mutations in the CFTR gene, and studied the functions of promoter mutations using reporter gene constructs, transient transfection techniques and subsequent assessment of transcriptional activity and expression levels. Mutations c.-195C>A and c.-34C>T in the promoter region of the CFTR gene were detected in 4 of our Chinese CBAVD patients, one of which was novel (c.-195C>A) and located in the conservative area, as well as the binding site of SP1 transcription factor through the prediction of bioinformatics analysis. By reverse transcription qPCR assay and luciferase assay, we validated it as a functional disease-causing variant that down-regulates the CFTR gene expression, and this effect was related to the amount of transcription factors. This study was the first to explore the promoter region of the CFTR gene in Chinese, and we believe that mutations in this region are associated with Chinese CBAVD patients. We also suggest a systematic strategy for genotyping Chinese CBAVD couples, which should help in developing reproductive counseling.

Aureibaculum marinum gen. nov., sp. nov., a Novel Bacterium of the Family Flavobacteriaceae Isolated from the Bohai Gulf.

A novel Gram-stain-negative bacterium, designated strain BH-SD17T, was isolated from a marine sediment sample in the Bohai Gulf, Yellow Sea, China. Cells of strain BH-SD17T are aerobic, yellow-colored, non-flagellated rods. Growth occurs between 15 and 40 °C (optimum, 30 °C), at pH 6.0-8.5 (optimum, 7.5) and with 1.0-8.0% (w/v) NaCl (optimum, 3.0%). Strain BH-SD17T contains phosphatidylethanolamine and two unidentified lipids as the major polar lipids. The predominant fatty acids are iso-C15:0 (28.5%), iso-C15:1 G (24.4%), and iso-C17:0 3-OH (12.3%). The major respiratory quinone is MK-6. Strain BH-SD17T shows moderate 16S rRNA gene sequence similarity to existing identified strains, is most closely related to the genera Lutimonas (92.1-92.4%), Lutibacter (91.6-92.3%), and Taeania (91.9%). Phylogenetic trees based on 16S rRNA gene sequences show that strain BH-SD17T forms a distinct lineage within the family Flavobacteriaceae. Based on the results of phenotypic, chemotaxonomic and phylogenetic analysis, strain BH-SD17T is considered to represent a novel genus and species in the family Flavobacteriaceae, for which the name Aureibaculum marinum is proposed. The type strain is BH-SD17T (=CCTCC AB 2017072T=KCTC 62204T).

A novel dehydrogenase 17ß-HSDx from Rhodococcus sp. P14 with potential application in bioremediation of steroids contaminated environment.

Steroids are endocrine disrupting compounds in human and are distributed in various environments. Our previous study showed that a marine bacterium Rhodococcus sp. P14 was able to efficiently degrade one typical steroid estradiol. In this study, we showed that P14 could also use other steroids, including estriol and testosterone, as sole carbon source for growth. Two dehydrogenation products, 16-hydroxestrone and androst-4-ene-3, 17-dione, were detected during estriol and testosterone degradation, respectively. By screening the genome, a short chain dehydrogenase gene was identified and named as 17ß-HSDx. Expression of 17ß-HSDx was induced in P14 when estriol, estradiol or testosterone was used as single carbon source. In addition, 17ß-HSDx was shown to have dehydrogenation ability of transforming estriol to 16-hydroxestrone, estradiol to estrone and testosterone to androst-4-ene-3, 17-dione. This is the first short chain dehydrogenase identified in bacteria with dehydrogenation ability on various steroids substrates. Overall, this study reveals that 17ß-HSDx has potential application in the bioremediation of steroids contaminated environment.

Modeling of PH Domains and Phosphoinositides Interactions and Beyond.

Pleckstrin homology (PH) domains form a large family of protein modules within membrane-targeting domains. PH domains can function as lipid-binding modules, and in particular bind with different specificities and affinities to phosphoinositides (PIs). Understanding the association of PH domains to PIs is critical for many aspects of cellular biology. Bioinformatics and computational modeling approaches have become standard tools to study the structure and dynamics of PH domains and PIs. In this review, recent advances in the binding specificity of PH domains and their interactions with PIs, using bioinformatics tools for the prediction of PIs binding sites, performing molecular dynamics simulations to study PH domains-PIs interactions, as well as the computational inhibitor design for PH domains guided signaling pathways have been discussed.

Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18.

BACKGROUND: Bone mineral density quantitative trait locus 18 (BMND18, OMIM #300910) is a type of early-onset osteogenesis imperfecta (OI) caused by loss-of-function mutations in the PLS3 gene, which encodes plastin-3, a key protein in the formation of actin bundles throughout the cytoskeleton. Here, we report a patient with PLS3 mutation caused BMND18 and evaluated all the reported disease-causing mutations by bioinformatic analysis. METHODS: Targeted gene sequencing was performed to find the disease-causing mutation in our patient. Bioinformatic analyses mainly including homology modelling and molecular dynamics stimulation were conducted to explore the impact of the previously reported mutations on plastin-3. RESULTS: Gene sequencing showed a novel nonsense mutation (c.745G > T, p.E249X), which locates at a highly conserved region containing residues p.240-266 (LOOP-1) in the PLS3 gene. Further bioinformatic analyses of the previously reported mutations revealed that LOOP-1 is predicted to physically connect the calponin-homology 1 (CH1) and CH2 domains of the ABD1 fragment and spatially locates within the interface of ABD1 and ABD2. It is crucial to the conformation transition and actin-binding function of plastin-3. CONCLUSIONS: This report identified a novel mutation that truncates the PLS3 gene. Moreover, bioinformatic analyses of the previous reported mutations in PLS3 gene lead us to find a critical LOOP-1 region of plastin-3 mutations at which may be detrimental to the integral conformation of plastin-3 and thus affect its binding to actin filament.

Influence of the ABCB1 polymorphisms on the response to Taxane-containing chemotherapy: a systematic review and meta-analysis.

PURPOSE: Multidrug resistance mediated by ABCB1 has been perceived to be one of the obstacles for cancer chemotherapy. This meta-analysis was performed to verify the effect of the ABCB1 rs1045642 and rs1128503 polymorphisms on the response to Taxane-containing chemotherapy. METHODS: Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were employed to evaluate the impact of these two ABCB1 polymorphisms. R scripts were developed to perform the meta-analysis. RESULTS: A total of nine articles (including nine studies for rs1045642 and five for rs1128503) were collected in our systematic review. However, our meta-analysis showed no significant effect of these two ABCB1 polymorphisms on the response to Taxane-containing regimens. CONCLUSIONS: This study highlights the unsuitability of relying on the ABCB1 rs1045642 and rs1128503 polymorphisms as therapeutic response biomarkers of Taxane-containing chemotherapy. Further polycentric studies in larger and multiracial populations are needed to validate the conclusions.