Increased expression of SLC25A18 is associated with Alzheimer's disease and is involved in Aß42-induced mitochondrial dysfunction and apoptosis in neuronal cells.

Alzheimer's disease (AD) is currently one of the most serious public health concerns in the world. However, the best approach to treat AD has yet to be discovered, implying that we must continue to work hard to find new AD target genes. In this study, we further analysed Gene Expression Omnibus (GEO) data and discovered that the expression of the Mitochondria glutamate carrier SLC25A18 is associated with AD by screening the differentially expressed genes in different regions of the brains of Alzheimer's disease patients. To verify the expression of SLC25A18 during Alzheimer's disease development, we analysed animal models (5×FAD transgenic AD animal model, chemically induced AD animal model, natural ageing animal model), and the results showed that the expression of SLC25A18 was increased in animal models of AD. Further investigation of the different regions found that SLC25A18 expression was elevated in the EC, TeA, and CA3, and expressed in neurons. Next, We found that Aß42 treatment elevated SLC25A18 expression in Neuro 2A cells. Reducing SLC25A18 expression attenuated mitochondrial dysfunction and neuronal apoptosis caused by Aß42. Overexpression of SLC25A18 increased ATP and intracellular superoxide anions but decreased mitochondrial membrane potential. The results indicate that SLC25A18 affects mitochondrial function and neuronal apoptosis, and is related to AD, which makes it a potential target for treating brain dysfunction.

Malignant Gastrointestinal Neuroectodermal Tumor (GNET) Mimicking Small Bowel Lymphoma: A Case Report.

A malignant gastrointestinal neuroectodermal tumor (GNET) is a rare entity, characterized as a malignant mesenchymal neoplasm occurring exclusively near the gastrointestinal tract, prone to frequent local recurrence and metastasis. Here, we report a case of a 49-year-old male presented with abdominal pain and weight loss. The patient had a remote history of thymic B-cell lymphoma. An abdominal computed tomography (CT) scan revealed a focal wall thickening of the terminal ileum with mesenteric lymphadenopathy, suggestive of lymphoma. A core needle biopsy of the mesenteric node was inconclusive. A right hemicolectomy was subsequently performed. Histologically, abundant multinucleated osteoclast-like giant cells are present. The tumor cells show diffuse strong positivity for S100 and SOX10. EWSR1-ATF1 gene fusion was identified by fluorescence in situ hybridization (FISH), consistent with a diagnosis of GNET. This case emphasizes a diagnostic challenge of a rare malignancy.

Comparative Mitogenome of Phylogenetic Relationships and Divergence Time Analysis within Potamanthidae (Insecta: Ephemeroptera).

Potamanthidae belongs to the superfamily Ephemeroidea but has no complete mt genome released in the NCBI (except for two unchecked and one partial mt genome). Since the sister clade to Potamanthidae has always been controversial, we sequenced seven mt genomes of Potamanthidae (two species from Rhoenanthus and five species from Potamanthus) in order to rebuild the phylogenetic relationships of Potamanthidae in this study. The divergence time of Potamanthidae was also investigated by utilizing five fossil calibration points because of the indeterminate origin time. In addition, because Rhoenanthus coreanus and Potamanthus luteus are always in low-temperature environments, we aimed to explore whether these two species were under positive selection at the mt genome level. Amongst the 13 PCGs, CGA was used as the start codon in COX1, whereas other genes conformed to initiating with an ATN start codon. From this analysis, UUA (L), AUU (I), and UUU (F) had the highest usage. Furthermore, the DHU arm was absent in the secondary structure of S1 in all species. By combining the 13 PCGs and 2 rRNAs, we reconstructed the phylogenetic relationship of Potamanthidae within Ephemeroptera. The monophyly of Potamanthidae and the monophyly of Rhoenanthus and Potamanthus were supported in the results. The phylogenetic relationship of Potamanthidae + (Ephemeridae + Polymitarcyidae) was also recovered with a high prior probability. The divergence times of Potamanthidae were traced to be 90.44 Mya (95% HPD, 62.80-121.74 Mya), and the divergence times of Rhoenanthus and Potamanthus originated at approximately 64.77 Mya (95% HPD, 43.82-88.68 Mya), thus belonging to the late Pliocene Epoch or early Miocene Epoch. In addition, the data indicated that R. coreanus was under negative selection and that ATP8 and ND2 in Potamanthidae had a high evolutionary rate.

Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment: Several Unanswered Questions.

Most patients with hepatocellular carcinoma (HCC) have a poor prognosis. Hepatectomy and local ablation are the main curative treatments for HCC. Nevertheless, the recurrence rate after hepatectomy or ablation is up to 70%, which seriously affects patient prognosis. Several adjuvant therapies have been explored to reduce postoperative recurrence. However, although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival, a standard consensus of national HCC guidelines for adjuvant treatment is lacking. Therefore, there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines. A variety of adjuvant treatment methods, such as antiviral therapy, transarterial chemoembolization or traditional Chinese medicine, are recommended by the Chinese HCC guidelines. However, Western guidelines make few recommendations other than antiviral therapy. Adjuvant immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of Liver Diseases guidelines. This review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.

Prevalence of metabolic syndrome among patients with hepatocellular carcinoma of different etiologies: a retrospective study.

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

Development and external validation of a nomogram for predicting short-term prognosis in patients with acute pulmonary embolism.

BACKGROUND: Accurate assessment and timely intervention play a crucial role in ameliorating poor short-term prognosis of acute pulmonary embolism (APE) patients. The currently employed scoring models exhibit a degree of complexity, and some models may not comprehensively incorporate relevant indicators, thereby imposing limitations on the evaluative efficacy. Our study aimed to construct and externally validate a nomogram that predicts 30-day all-cause mortality risk in APE patients. METHODS: Clinical data from APE patients in Intensive Care-IV database was included as a training cohort. Additionally, we utilized our hospital's APE database as an external validation cohort. The nomogram was developed, and its predictive ability was evaluated using receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis. RESULTS: A collective of 1332 patients and 336 patients were respectively enrolled as the training cohort and the validation cohort in this study. Five variables including age, malignancy, oxygen saturation, blood glucose, and the use of vasopressor, were identified based on the results of the multivariate Cox regression model. The ROC value for the nomogram in the training cohort yielded 0.765, whereas in the validation group, it reached 0.907. Notably, these values surpassed the corresponding ROC values for the Pulmonary Embolism Severity Index, which were 0.713 in the training cohort and 0.754 in the validation cohort. CONCLUSIONS: The nomogram including five indicators had a good performance in predicting short-term prognosis in patients with APE, which was easier to apply and provided better recommendations for clinical decision-making.

Effect of varying auxiliaries on maxillary incisor torque control with clear aligners: A finite element analysis.

INTRODUCTION: This study aimed to evaluate the effects of varying auxiliaries on tooth movement and stress distribution when maxillary central incisors were torqued 1° with a clear aligner through finite element analysis. METHODS: Three-dimensional finite element models, including maxillary alveolar bone, periodontal ligament, dentition, and clear aligner, were constructed. According to the auxiliaries designed on the maxillary central incisor, 5 models were created: (1) without auxiliaries (control model), (2) with the power ridge, (3) with the semi-ellipsoid attachment, (4) with the horizontal rectangular attachment, and (5) with the horizontal cylinder attachment. The tooth movement and periodontal ligament stress distribution after a palatal root torque of 1° were analyzed for each of the 5 models. RESULTS: With 1° torque predicted, the maxillary central incisor without auxiliaries showed a tendency of labial tipping, mesial tipping, and intrusion. The rotation center moved occlusally in the power ridge model. The labiolingual inclination variation increased in the semi-ellipsoid attachment model but decreased in the power ridge model. The maxillary central incisor is twisted in the distal direction in the power ridge model. The maxillary central incisor of the horizontal rectangular attachment and the horizontal cylinder attachment model behaved similarly to the control model. Periodontal stresses were concentrated in the cervical and apical areas. The maximum von Mises stresses were 11.6, 12.4, 3.81, 1.14, and 11.0 kPa in the 5 models. The semi-ellipsoid attachment model exhibited a more uniform stress distribution than the other models. CONCLUSIONS: Semi-ellipsoid attachment performed better efficacy on labiolingual inclination, and power ridge performed better efficacy on root control. However, a distal twist of maxillary incisors could be generated by the power ridge.

[Integrated Analysis of Soil Organic Matter Molecular Composition Changes Under Different Land Uses].

The application of biomarkers to study the molecular composition of soil organic matter (SOM) can be used to analyze the source and degradation of SOM and reveal the stability mechanism of soil organic carbon (SOC) at the molecular level. In order to further clarify the effects of different land use patterns (farmland, grassland, and forest) on the molecular composition of SOM, the changes in molecular composition of organic matter (free lipids, cutin, suberin, and lignin) on a global scale were studied using a meta-analysis method. The results showed that there were significant differences in the molecular composition of organic matter under different land use patterns. The contents of free lipids (n-alkanes, n-alkanols, n-alkanoic acids, and cyclic lipids), cutin, and lignin phenols in forest soil were significantly higher than those in grassland and farmland. There was no significant difference in the content of suberin between grassland and forest soil. The ratio of suberin to cutin in grassland was the highest, with an average of 2.96, and the averages of farmland and forest were 1.68 and 2.21, respectively. The ratio of syringic acid to syringaldehyde (Ad/Al)S and the ratio of vanillic acid to vanillin (Ad/Al)V of farmland soil were the largest, which were 1.25 and 1.58, respectively, and were significantly higher than those in grassland (0.46 and 0.69) and forest (0.78 and 0.7). The results of correlation analysis showed that in farmland soil, suberin was significantly correlated with mean annual precipitation (MAP) and clay; cutin was significantly correlated with clay; and lignin was significantly correlated with mean annual temperature (MAT), MAP, sand, and bulk density. In grassland soil, total free lipids were significantly correlated with MAP and bulk density; suberin and cutin were significantly correlated with MAT and MAP; and lignin was significantly correlated with MAP, pH, sand, and bulk density. However, only lignin was significantly correlated with MAP and sand in forest soils. Overall, the contents of SOC and molecular components in forest soil were higher under the three land use practices, and the contribution of plant roots to SOM in grassland soil was greater. In farmland soil, the degradation of lignin was accelerated due to human farming activities. Future research should focus on the regulation of soil physicochemical properties and climatic conditions on the molecular composition of SOM.

The effects of visual art therapy on adults with depressive symptoms: A systematic review and meta-analysis.

Depression constitutes a pervasive global mental health concern and stands as a principal determinant of elevated suicide rates worldwide. Recent empirical investigations have showcased the significant potential of visual art therapy (VAT) in ameliorating symptoms among individuals with depression. Nevertheless, specific studies have yielded findings marked by inconclusiveness, underscoring the imperative need for further research to comprehensively establish its efficacy. This study is a systematic review and meta-analysis of extant research, to ascertain the efficacy and effect size of VAT as an intervention for adults with depressive symptoms. A comprehensive search was conducted across 10 databases. The search encompassed articles published from the inception of these databases up until October 18, 2023. Two researchers screened the literature in accordance with inclusion and exclusion criteria and performed a thorough quality assessment. The original data and the data obtained from the literature were extracted for further analysis. The statistical analysis of the data was performed using Stata 17.0 software. fifteen studies were included, encompassing a total of 932 participants. The outcomes of meta-analysis unveiled a statistically significant effect of VAT in diminishing depressive symptoms among adults (SMD = -0.73; 95% CI, -1.07 to -0.39; p < 0.001; 15 randomised controlled trials (RCTs); low-quality evidence). The subgroup analysis indicated that VAT exhibited heightened effectiveness among adults below 65 years of age, with interventions lasting ≤12 weeks demonstrating superior efficacy. Additionally, sensitivity analysis underscored the robustness and reliability of the findings. VAT appears to alleviate depressive symptoms among adults. Existing research indicates that the effectiveness of VAT is influenced by factors, such as intervention population characteristics and intervention duration. However, to comprehensively probe the efficacy of VAT, future studies should strive for larger sample sizes, multicentre collaborations, and long-term follow-ups.

Atomically Precise Mo2Cu17 Bimetallic Nanocluster: Synergistic Mo2O4-Coupled Copper Alkynyl Cluster for the Improved Hydrogen Evolution Reaction Performance.

Electrolytic hydrogen production via water splitting holds significant promise for the future of the energy revolution. The design of efficient and abundant catalysts, coupled with a comprehensive understanding of the hydrogen evolution reaction (HER) mechanism, is of paramount importance. In this study, we propose a strategy to craft an atomically precise cluster catalyst with superior HER performance by cocoupling a Mo2O4 structural unit and a Cu(I) alkynyl cluster into a structured framework. The resulting bimetallic cluster, Mo2Cu17, encapsulates a distinctive structure [Mo2O4Cu17(TC4A)4(PhC≡C)6], comprising a binuclear Mo2O4 subunit and a {Cu17(TC4A)2(PhC≡C)6} cluster, both shielded by thiacalix[4]arene (TC4A) and phenylacetylene (PhC≡CH). Expanding our exploration, we synthesized two homoleptic CuI alkynyl clusters coprotected by the TC4A and PhC≡C- ligands: Cu13 and Cu22. Remarkably, Mo2Cu17 demonstrates superior HER efficiency compared to its counterparts, achieving a current density of 10 mA cm-2 in alkaline solution with an overpotential as low as 120 mV, significantly outperforming Cu13 (178 mV) and Cu22 (214 mV) nanoclusters. DFT calculations illuminate the catalytic mechanism and indicate that the intrinsically higher activity of Mo2Cu17 may be attributed to the synergistic Mo2O4-Cu(I) coupling.

Altered mucosal bacteria and metabolomics in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. AIM: This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. METHODS: The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. RESULTS: High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. CONCLUSION: This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Cross-sectional study of influenza trends and costs in Malaysia between 2016 and 2018.

BACKGROUND AND OBJECTIVES: While influenza circulates year-round in Malaysia, research data on its incidence is scarce. Yet, this information is vital to the improvement of public health through evidence-based policies. In this cross-sectional study, we aimed to determine the trends and financial costs of influenza. METHODS: Data for the years 2016 through 2018 were gathered retrospectively from several sources. These were existing Ministry of Health (MOH) influenza sentinel sites data, two teaching hospitals, and two private medical institutions in the Klang Valley, Malaysia. Expert consensus determined the final estimates of burden for laboratory-confirmed influenza-like illness (ILI) and severe acute respiratory infection (SARI). Economic burden was estimated separately using secondary data supplemented by MOH casemix costing. RESULTS: Altogether, data for 11,652 cases of ILI and 5,764 cases of SARI were extracted. The influenza B subtype was found to be predominant in 2016, while influenza A was more prevalent in 2017 and 2018. The distribution timeline revealed that the highest frequency of cases occurred in March and April of all three years. The costs of influenza amounted to MYR 310.9 million over the full three-year period. CONCLUSIONS: The study provides valuable insights into the dynamic landscape of influenza in Malaysia. The findings reveal a consistent year-round presence of influenza with irregular seasonal peaks, including a notable influenza A epidemic in 2017 and consistent surges in influenza B incidence during March across three years. These findings underscore the significance of continuous monitoring influenza subtypes for informed healthcare strategies as well as advocate for the integration of influenza vaccination into Malaysia's national immunization program, enhancing overall pandemic preparedness.

Polymerizable rotaxane of cucurbituril protecting dopamine based adhesive hydrogels.

The catechol moiety found within mussel proteins plays a pivotal role in enhancing their adhesive properties. Nonetheless, catechol compounds, such as dopamine (DOP) derivatives, are susceptible to oxidation, leading to the formation of quinone. This oxidation process poses a significant challenge in the development of DOP-based hydrogels, hampering their adhesion capabilities and hindering polymerization. To protect DOP moieties from oxidation, DOP and N-(3-aminopropyl)methacrylamide (AMA) moieties were grafted onto the side groups of biocompatible poly(glutamic acid) (PGA). Subsequently, the DOP unit, serving as a second guest, would be captured by a polymerizable rotaxane of cucurbituril (CB[n]), in which the host molecule CB[8] complexed with the first guest, polymerizable methyl viologen (MV), forming a protective function and dynamic cross-linking. Upon exposure to light curing, a composite network emerged through the synergy of covalent cross-linking and supramolecular host-guest complexation of DOP with CB[8]. The generated complexation between DOP and CB[8] could protect the DOP moieties, resulting in photocured hydrogels with exceptional adhesive strength and remarkable tensile capabilities. Moreover, 3D printing technology was used to create various models with these DOP-based hydrogels, demonstrating their promising applications in future.

Comparison of post-resection survival between hepatocellular carcinoma patients in BCLC stage A or B who experience tumor rupture and patients in BCLC stage C who do not.

Background and aim: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening complication, and patients who experience it are formally assigned to stage T4 in the TNM system, while many clinicians informally assign them to stage C in the more widely used Barcelona Clinic Liver Cancer (BCLC) system. The present study explored whether these re-staging practices are appropriate for HCC patients who suffer tumor rupture. Methods: We retrospectively reviewed the records of 1952 HCC patients who underwent hepatic resection at our hospital between January 2017 and June 2021. We compared recurrence-free and overall survival between 143 patients who had BCLC stage A or B disease at the time of spontaneous rupture and 449 patients who had BCLC stage C disease without rupture. Results: Overall survival rate was significantly higher among the 143 patients (1, 3, 5-year survival rate was 80.3%, 60.4%, 51.4%) with rupture than among the 449 (1, 3, 5-year survival rate was 69.5%, 41.5%, 32.4%) with BCLC stage C disease (hazard ratio 1.65, 95% confidence interval 1.29 to 2.12). The two groups had similar recurrence-free survival (hazard ratio 1.19, 95% confidence interval 0.92 to 1.53), but most patients with rupture were able to receive interventional and potentially curative treatments after recurrence, whereas most patients in BCLC stage C received interventional or supportive care. Similar results were obtained after propensity score matching. Conclusion: HCC patients who experience spontaneous rupture tumor while in BCLC stage A or B have better prognosis than patients in BCLC stage C without rupture. Our results suggest that HCC patients who suffer rupture in BCLC stage A or B should not be assigned to BCLC stage C.

Copper-Catalyzed Enantioconvergent Radical N-Alkylation of Diverse (Hetero)aromatic Amines.

The 3d transition metal-catalyzed enantioconvergent radical cross-coupling provides a powerful tool for chiral molecule synthesis. In the classic mechanism, the bond formation relies on the interaction between nucleophile-sequestered metal complexes and radicals, limiting the nucleophile scope to sterically uncongested ones. The coupling of sterically congested nucleophiles poses a significant challenge due to difficulties in transmetalation, restricting the reaction generality. Here, we describe a probable outer-sphere nucleophilic attack mechanism that circumvents the challenging transmetalation associated with sterically congested nucleophiles. This strategy enables a general copper-catalyzed enantioconvergent radical N-alkylation of aromatic amines with secondary/tertiary alkyl halides and exhibits catalyst-controlled stereoselectivity. It accommodates diverse aromatic amines, especially bulky secondary and primary ones to deliver value-added chiral amines (>110 examples). It is expected to inspire the coupling of more nucleophiles, particularly challenging sterically congested ones, and accelerate reaction generality.

Can humidifier reservoir bacteria colonize the circuit during mechanical ventilation: An in vitro study.

BACKGROUND: Although the circuit condensate, an ideal bacterial reservoir during mechanical ventilation, may flow into the humidifier reservoir, no studies have investigated if humidifier reservoir colonized bacteria colonize other circuit locations with airflow. AIMS: We aimed to prove whether the humidifier reservoir colonized bacteria colonize other circuit locations with airflow and provide some advice on the disposal of condensate in the clinical setting. STUDY DESIGN: An in vitro experiment was conducted. Mechanical ventilation simulators (n = 90) were divided into sterile water group (n = 30) and broth group (n = 60). In the sterile water group, sterile water was used for humidification, either Acinetobacter baumannii or Pseudomonas aeruginosa were inoculated to humidifier water in the humidifier reservoir, each accounted for 50% of the simulators. The broth group was performed the same as the sterile water group except for the addition of broth into the humidified water. After 24, 72, and 168 h of continuous ventilation, the humidifier water and different locations of the circuits were sampled for bacterial culture. RESULTS: All bacterial culture results of the sterile water group were negative. Bacteria in the humidifier water continued to proliferate in the broth group. With prolonged ventilation, the bacteria at the humidifier reservoir outlet increased. The bacteria at the humidifier reservoir outlet were much more in the Pseudomonas aeruginosa subgroup than in the Acinetobacter baumannii subgroup and the difference was statistically significant (p < .05). During continuous ventilation, no bacterial growth occurred at 10 cm from the humidifier reservoir outlet and the Y-piece of the ventilator circuits. CONCLUSIONS: Sterile water in the humidifier reservoir was not conducive to bacterial growth. Even if bacteria grew in the humidifier reservoir and could reach the humidifier reservoir outlet, colonization of further circuit locations with the airflow was unlikely. During a certain mechanical ventilation time, the amount of bacteria reaching the outlet of the humidifier reservoir varied due to different mobility of bacteria. RELEVANCE TO CLINICAL PRACTICE: In a clinical setting, nurses should not worry about a small amount of condensate backflow into the humidifier reservoir. Draining condensate into the humidifier reservoir can be used as a low risk and convenient method in clinical practice.

Drug target prediction through deep learning functional representation of gene signatures.

Many machine learning applications in bioinformatics currently rely on matching gene identities when analyzing input gene signatures and fail to take advantage of preexisting knowledge about gene functions. To further enable comparative analysis of OMICS datasets, including target deconvolution and mechanism of action studies, we develop an approach that represents gene signatures projected onto their biological functions, instead of their identities, similar to how the word2vec technique works in natural language processing. We develop the Functional Representation of Gene Signatures (FRoGS) approach by training a deep learning model and demonstrate that its application to the Broad Institute's L1000 datasets results in more effective compound-target predictions than models based on gene identities alone. By integrating additional pharmacological activity data sources, FRoGS significantly increases the number of high-quality compound-target predictions relative to existing approaches, many of which are supported by in silico and/or experimental evidence. These results underscore the general utility of FRoGS in machine learning-based bioinformatics applications. Prediction networks pre-equipped with the knowledge of gene functions may help uncover new relationships among gene signatures acquired by large-scale OMICs studies on compounds, cell types, disease models, and patient cohorts.

Diversity of Gibberellin 2-oxidase genes in the barley genome offers opportunities for genetic improvement.

INTRODUCTION: Gibberellin (GA) is a vital phytohormone in regulating plant growth and development. During the "Green Revolution", modification of GA-related genes created semi-dwarfing phenotype in cereal crops but adversely affected grain weight. Gibberellin 2-oxidases (GA2oxs) in barley act as key catabolic enzymes in deactivating GA, but their functions are still less known. OBJECTIVES: This study investigates the physiological function of two HvGA2ox genes in barley and identifies novel semi-dwarf alleles with minimum impacts on other agronomic traits. METHODS: Virus-induced gene silencing and CRISPR/Cas9 technology were used to manipulate gene expression of HvGA2ox9 and HvGA2ox8a in barley and RNA-seq was conducted to compare the transcriptome between wild type and mutants. Also, field trials in multiple environments were performed to detect the functional haplotypes. RESULTS: There were ten GA2oxs that distinctly expressed in shoot, tiller, inflorescence, grain, embryo and root. Knockdown of HvGA2ox9 did not affect plant height, while ga2ox8a mutants generated by CRISPR/Cas9 increased plant height and significantly altered seed width and weight due to the increased bioactive GA4 level. RNA-seq analysis revealed that genes involved in starch and sucrose metabolism were significantly decreased in the inflorescence of ga2ox8a mutants. Furthermore, haplotype analysis revealed one naturally occurring HvGA2ox8a haplotype was associated with decreased plant height, early flowering and wider and heavier seed. CONCLUSION: Our results demonstrate the potential of manipulating GA2ox genes to fine tune GA signalling and biofunctions in desired plant tissues and open a promising avenue for minimising the trade-off effects of Green Revolution semi-dwarfing genes on grain size and weight. The knowledge will promote the development of next generation barley cultivars with better adaptation to a changing climate.