Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation.

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.

Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

Potassium deficiency diagnosis method of apple leaves based on MLR-LDA-SVM.

Introduction: At present, machine learning and image processing technology are widely used in plant disease diagnosis. In order to address the challenges of subjectivity, cost, and timeliness associated with traditional methods of diagnosing potassium deficiency in apple tree leaves. Methods: The study proposes a model that utilizes image processing technology and machine learning techniques to enhance the accuracy of detection during each growth period. Leaf images were collected at different growth stages and processed through denoising and segmentation. Color and shape features of the leaves were extracted and a multiple regression analysis model was used to screen for key features. Linear discriminant analysis was then employed to optimize the data and obtain the optimal shape and color feature factors of apple tree leaves during each growth period. Various machine-learning methods, including SVM, DT, and KNN, were used for the diagnosis of potassium deficiency. Results: The MLR-LDA-SVM model was found to be the optimal model based on comprehensive evaluation indicators. Field experiments were conducted to verify the accuracy of the diagnostic model, achieving high diagnostic accuracy during different growth periods. Discussion: The model can accurately diagnose whether potassium deficiency exists in apple tree leaves during each growth period. This provides theoretical guidance for intelligent and precise water and fertilizer management in orchards.

Heat shock protein family A member 8 serving as a co-activator of transcriptional factor ETV4 up-regulates PHLDA2 to promote the growth of liver cancer.

Heat shock protein family A member 8 (HSPA8) participates in the folding or degradation of misfolded proteins under stress and plays critical roles in cancer. In this study, we investigated the function of HSPA8 in the development of liver cancer. By analyzing the TCGA transcriptome dataset, we found that HSPA8 was upregulated in 134 clinical liver cancer tissue samples, and positively correlated with poor prognosis. IHC staining showed the nuclear and cytoplasmic localization of HSPA8 in liver cancer cells. Knockdown of HSPA8 resulted in a decrease in the proliferation of HepG2 and Huh-7 cells. ChIP-seq and RNA-seq analysis revealed that HSPA8 bound to the promoter of pleckstrin homology-like domain family A member 2 (PHLDA2) and regulated its expression. The transcription factor ETV4 in HepG2 cells activated PHLDA2 transcription. HSPA8 and ETV4 could interact with each other in the cells and colocalize in the nucleus. From a functional perspective, we demonstrated that HSPA8 upregulated PHDLA2 through the coactivating transcription factor ETV4 to enhance the growth of liver cancer in vitro and in vivo. From a therapeutic perspective, we identified both HSPA8 and PHDLA2 as novel targets in the treatment of HCC. In conclusion, this study demonstrates that HSPA8 serves as a coactivator of ETV4 and upregulates PHLDA2, leading to the growth of HCC, and is a potential therapeutic target in HCC treatment.

Establishment and validation of a diagnostic nomogram for significant histopathologic changes of hepatic injury in HBV-infected patients.

Background: Significant histopathologic changes of hepatic injury (SHCHI) play a decisive role in evaluating the condition and initiating antiviral in hepatitis B virus (HBV)-infected patients, especially those with normal or mildly elevated alanine transaminase levels. Considering that non-invasive methods were established through experience with chronic hepatitis C, the aim of this study was to establish and verify a nomogram based on hepatitis B for diagnosing SHCHI. Methods: Three hundred eighty-four patients who fulfilled requirements for participation were randomly assigned to training cohort (n=270) and validation cohort (n=114) according to 7:3. The selection criteria for clinical factors were based on the previous research papers. SHCHI was subgrouped as followed: grade ≥ G2 inflammation and/or stage ≥ S2 fibrosis. The predictive accuracy and discriminative ability of nomogram were determined by a concordance index (C-index), calibration curve and the area under the receiver-operating characteristic curve (AUROC). We also compared diagnostic value of nomogram with model for AST-to-PLT ratio index (APRI) score and model for Fibrosis-4 (FIB-4) score. Results: Two hundred and two patients (74.44%) and 87 patients (76.32%) were diagnosed as SHCHI, in the training and validation cohort. Logistic regression analysis illustrated that hepatitis B e antigen (HBeAg), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and prothrombin time (PT) all independently served as risk factors for SHCHI (P<0.05) and were thus utilized to create the nomogram. The nomogram had well-fitted calibration curves and attained excellent concordance indices of 0.80 and 0.75. The sensitivity of nomogram in the diagnosis of SHCHI was 79.7%, the specificity was 68.1%. The area under the curve {AUC; 0.80 [95% confidence interval (CI): 0.74-0.86]} for diagnosing SHCHI by the nomogram was greater in comparison to that of APRI [0.78 (95% CI: 0.71-0.84)], and FIB-4 [0.76 (95% CI: 0.69-0.82)]. Patients with nomogram scores less than 119 were considered to have a lower risk of SHCHI. Conclusions: The constructed nomogram is suitable to serve as a SHCHI screening tool in chronic HBV-infected patients. But the dependability of the nomogram will necessitate further confirmation in a prospective study and further external validation is needed.

Quantitative analysis of the risk of type 2 diabetes and fatty liver in non-obese individuals by computed tomography.

PURPOSE: To explore the risk of fatty liver and type 2 diabetes with quantitative parameters of abdominal computed tomography (CT) in a non-obese population. METHODS: A retrospective analysis of abdominal CT and hospitalization records of inpatients admitted from May 2019 to May 2021 were divided into a non-obese control group (n = 143 cases) and a non-obese diabetes group (n = 105 cases). The measured abdominal CT parameters included body width, liver and spleen CT values, and the ratio of the liver CT value to the spleen CT value (L/S ratio). Logistic regression was used to analyze the risk factors for diabetes in non-obese individuals. RESULTS: Three variables including body width (P < 0.001), liver CT value (P = 0.013), and L/S ratio (P = 0.002) were significantly correlated with the presence of diabetes in non-obese individuals. CONCLUSION: Body width, liver CT value, and L/S ratio can be used to indicate the risk of type 2 diabetes in non-obese individuals.

LINC00839 knockdown restrains the metastatic behavior of nasopharyngeal carcinoma by sponging miR-454-3p.

Long intergenic non-coding RNA 00839 (LINC00839) has been verified as a pro-metastasis factor in malignancies. However, the significance of LINC00839 in nasopharyngeal carcinoma (NPC) has yet to be illuminated, as well as its underlying mechanism. Here, we disclosed that LINC00839 is highly expressed in NPC. Deletion of LINC00839 suppresses NPC cells rapid growth, invasive capacity and EMT in vitro. Besides, LINC00839 is identified as a "sponge" for miR-454-3p, and upregulation of LINC00839 reverses miR-454-3p-mediated inhibition of aggressiveness in NPC cells. Furthermore, the expression of cellular-mesenchymal epithelial transition factor (c-Met), the downstream target of miR-454-3p, is downregulated by LINC00839 knockdown in NPC cells. In vivo, LINC00839 knockdown retards the tumor growth of NPC cells in the xenografted mice model. Collectively, attenuation of LINC00839 expression attenuates the aggressive properties of NPC cells via directly sponging the miR-454-3p and regulating c-Met expression.

Neuroprotective effects of oleanolic acid against cerebral ischemia-reperfusion injury in mice.

BACKGROUND/AIM: Stroke is among the most common causes of disability and death in highly developed countries and China. We sought to study the role of oleanolic acid in cerebral ischemia-reperfusion injury. METHODS: Middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemia-reperfusion injury in mice. For the short-term effects of oleanolic acid (OA) against MCAO, mice administrated with OA (6 mg/kg /d) for 3 days before the injury were evaluated the infarct volume, neurological scores, blood brain barrier permeability and oxidative stress level, while for the long-term effects, MCAO mice were injected daily with OA for 6 weeks, followed by assessments of motor function, behavior and cerebral infarction area. RESULTS: Pretreatment of oleanolic acid alleviated MCAO-induced ischemia-reperfusion injury as indicated by the significant decreases in cerebral infarction area and neurological symptom score at 24 h post injury, Evans blue leakage, expression of matrix metalloproteinase 9 (MMP9) and occludin, dihydroethidium fluorescence, and block malonaldehyde generation. In the long run, OA significantly reduced brain loss, enhanced the motor function, promoted the recovery of nerve function, and improved the learning and memory ability 9 weeks after the ischemia-reperfusion injury. OA also inhibited astrocytes proliferation and microglia activation, promoted the expression of synapse-related proteins, and increased the number of DCX+ cells in the hippocampus. CONCLUSIONS: OA exhibits both short-term and long-term protective effects against the cerebral ischemia-reperfusion injury in mice. The short-term protective mechanism is related to the anti-oxidation of blood-brain barrier, while the long-term protective effect lies in neuroglia modulation, promotion of synaptic connection and neuroregeneration.

How Emotional Interaction Affects Purchase Intention in Social Commerce: The Role of Perceived Usefulness and Product Type.

PURPOSE: On the basis of stimulus-organism-response (SOR) theory, this study extends the work of Lee and Kwon by examining the concept of perceived usefulness as a mediator between emotional interaction (familiarity and intimacy) and purchase intention. The consumer purchase decision model, in which product type plays a moderating role in the linking mechanism, is also explored. METHODS: We proposed a consumer purchase decision model, and empirically examined it by means of an online questionnaire survey. Confirmatory factor analysis and structural equation modeling with bootstrapping estimation were conducted using the data obtained from 269 social commerce users. RESULTS: Familiarity and intimacy positively affected the users' purchase intention in social commerce. Perceived usefulness mediated the relationship between emotional interaction and purchase intention. Moreover, product type moderated the following relationships: between familiarity and purchase intention, between intimacy and purchase intention, and between perceived usefulness and purchase intention. CONCLUSION: The results support this study's hypotheses and SOR theory. Purchase intention could be enhanced by improving emotional interaction and perceived usefulness.

Targeting DNA-PK overcomes acquired resistance to third-generation EGFR-TKI osimertinib in non-small-cell lung cancer.

The third-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), represented by osimertinib, has achieved remarkable clinical outcomes in the treatment of non-small-cell lung cancer (NSCLC) with EGFR mutation. However, resistance eventually emerges in most patients and the underlying molecular mechanisms remain to be fully understood. In this study, we generated an osimertinib-acquired resistant lung cancer model from a NSCLC cell line H1975 harboring EGFR L858R and T790M mutations. We found that the capacity of DNA damage repair was compromised in the osimertinib resistant cells, evidenced by increased levels of γH2AX and higher intensity of the comet tail after withdrawal from cisplatin. Pharmacological inhibiting the activity or genetic knockdown the expression of DNA-PK, a key kinase in DNA damage response (DDR), sensitized the resistant cells to osimertinib. Combination of osimertinib with the DNA-PK inhibitor, PI-103, or NU7441, synergistically suppressed the proliferation of the resistant cells. Mechanistically, we revealed that DNA-PK inhibitor in combination with osimertinib resulted in prolonged DNA damage and cell cycle arrest. These findings shed new light on the mechanisms of osimertinib resistance in the aspect of DNA repair, and provide a rationale for targeting DNA-PK as a therapeutic strategy to overcome osimertinib-acquired resistance in NSCLC.

Ferroptosis: a promising target for cancer immunotherapy.

Ferroptosis is a recently recognized type of programmed cell death and emerges to play an important role in cancer biology and therapies. This unique form of cell death, characterized by iron-dependent lipid peroxidation, is exquisitely regulated by the cellular metabolic networks such as lipid, iron and amino acid metabolism. The sensitivity to ferroptosis varies among different tumors. Recent evidence reveals that triple-negative breast cancer (TNBC), a highly aggressive disease with limited effective targeted therapies is particularly vulnerable to ferroptosis inducers, suggesting this new form of non-apoptotic cell death as an attractive target for the treatment of the "difficult-to-treat" tumor. Intriguingly, ferroptosis has recently been implicated to be involved in T cell-mediated anti-tumor immunity and affect the efficacy of cancer immunotherapy. Better understanding of this ferroptotic cell death will shed light on the discovery of novel combination therapeutic strategies for cancer treatment. Herein, we provide an overview of the key hallmarks of ferroptosis, use TNBC as a model to characterize the regulation of ferroptosis in cancer, and highlight ferroptosis-modulating combination therapeutic strategies in the context of cancer immunotherapy.

Experimental evidence for long-term coexistence of copiotrophic and oligotrophic bacteria in pelagic surface seawater.

Most marine copiotrophic bacteria can produce extracellular enzymes to degrade biopolymers into bio-available smaller solutes, while oligotrophic bacteria usually cannot. Bacterial extracellular enzymes and enzymatic products can be a common resource that could be utilized by both copiotrophs and oligotrophs; when present, oligotrophs may outcompete the enzyme-producing copiotrophs. However, copiotrophs and oligotrophs consistently coexist in the ocean. How they maintain coexistence has still not been experimentally studied. In this study, the interaction and coexistence of a copiotroph and an oligotroph, isolated from the same surface seawater sample and utilizing the same proteinaceous substrate, were experimentally investigated. The copiotroph could secrete extracellular proteases to degrade and then utilize the proteinaceous substrate. The oligotroph was unable to utilize the proteinaceous substrate by itself, but could grow by using the hydrolysate amino acids. The copiotroph outcompeted the oligotroph by adsorbing the amino acids quickly and having a higher growth rate in the rich medium. The oligotroph survived by adapting to low concentration of nutrients. The copiotroph and oligotroph were able to maintain long-term (up to 142 days) coexistence in the laboratory. This study indicates that differences in the utilization of different concentrations of nutrients can drive the coexistence of marine copiotrophs and oligotrophs.

Effect of Redox Atmosphere on Contact Electrification of Polymers.

The Triboelectric Nanogenerator has demonstrated broad applications in energy, environmental, and electronic fields, as well as huge potential in the mechanism study of contact electrification, since 2012. Herein, we employed a Triboelectric Nanogenerator working in vertical contact-separation mode to study the electrification performance of the polymer under redox atmosphere. The results show that the electron-withdrawing ability of the polymer is weakened with increasing O3 concentration. Considering that O3 is typically one of the strongest oxidants, we further studied the electrification performance under H2, CO, and O2 atmosphere. It is found that the electron-withdrawing ability was predictably weakened under O2 atmosphere similar to the case of O3. On the contrary, the electron-withdrawing ability was enhanced under H2 and CO atmosphere. Accordingly, a theoretical mechanism involving the highest occupied surface state level is proposed to explain the effect of redox atmosphere on contact electrification. These results clarify that contact electrification can be varied by redox agents. Conversely, it also suggests the possibility to manipulate the redox reactions through the modification of contact electrification.

Interlayer quantum transport in Dirac semimetal BaGa2.

The quantum limit is quite easy to achieve once the band crossing exists exactly at the Fermi level (EF) in topological semimetals. In multilayered Dirac fermion systems, the density of Dirac fermions on the zeroth Landau levels (LLs) increases in proportion to the magnetic field, resulting in intriguing angle- and field-dependent interlayer tunneling conductivity near the quantum limit. BaGa2 is an example of a multilayered Dirac semimetal with its quasi-2D Dirac cone located at EF, providing a good platform to study its interlayer transport properties. In this paper, we report the negative interlayer magnetoresistance induced by the tunneling of Dirac fermions between the zeroth LLs of neighboring Ga layers in BaGa2. When the field deviates from the c-axis, the interlayer resistivity ρzz(θ) increases and finally results in a peak with the applied field perpendicular to the c-axis. These unusual interlayer transport properties are observed together in the Dirac semimetal under ambient pressure and are well explained by the model of tunneling between Dirac fermions in the quantum limit.

Extracellular Enzyme Activity and Its Implications for Organic Matter Cycling in Northern Chinese Marginal Seas.

Extracellular enzymes, initiating the degradation of organic macromolecules, are important functional components of marine ecosystems. Measuring in situ seawater extracellular enzyme activity (EEA) can provide fundamental information for understanding the biogeochemical cycling of organic matter in the ocean. Here we investigate the patterns of EEA and the major factors affecting the seawater EEA of Chinese marginal seas. The geographic distribution of EEA along a latitudinal transect was examined and found to be associated with dissolved organic carbon. Compared with offshore waters, inshore waters had higher enzyme activity. All the tested substrates were hydrolyzed at different rates and phosphatase, ß-glucosidase and protease contributed greatly to summed hydrolysis rates. For any particular enzyme activity, the contribution of dissolved to total EEA was strongly heterogenous between stations. Comparisons of hydrolysis rates of the polymers and their corresponding oligomers suggest that molecule size does not necessarily limit the turnover of marine organic matter. In addition, several typical enzyme-producing clades, such as Bacteroidetes, Planctomycetes, Chloroflexi, Roseobacter, Alteromonas, and Pseudoalteromonas, were detected in the in situ environments. These enzyme-producing clades may be responsible for the production of different enzymes. Overall, each enzyme was found to flexibly respond to environmental conditions and were linked to microbial community composition. It is likely that this activity will profoundly affect organic matter cycling in the Chinese marginal seas.

Parvularcula marina sp. nov., isolated from surface water of the South China Sea, and emended description of the genus Parvularcula.

A Gram-stain-negative, aerobic, flagellated, rod-shaped bacterial strain, SM1705T, was isolated from a surface seawater sample collected from the South China Sea. The strain grew at 10-40 °C and with 0.5-13.0 % (w/v) NaCl. It hydrolysed Tweens 20, 40 and 60, but did not hydrolyse starch or Tween 80 nor reduce nitrate to nitrite. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain SM1705T was affiliated with the genus Parvularcula, sharing the highest sequence similarity (96.0 %) with type strain of Parvularcula bermudensis and forming a coherent branch together with the latter within the clade of Parvularcula. The major cellular fatty acids were identified as summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0 and C18 : 0. Polar lipids included three unidentified glycolipids and one unidentified lipid. The major respiratory quinone of strain SM1705T was Q10. The genomic DNA G+C content of strain SM1705T was 59.3 mol%. Based on the polyphasic evidence presented in this paper, strain SM1705T represents a novel Parvularcula species, for which the name Parvularcula marina sp. nov. is proposed. The type strain is SM1705T (=KCTC 62795T=MCCC 1K03505T=CCTCC AB 2018345T).

Muricauda nanhaiensis sp. nov., isolated from seawater of the South China Sea.

A Gram-stain-negative, aerobic, oxidase- and catalase-positive, non-flagellated, non-gliding, yellow-pigmented, and rod-shaped bacterium with appendages, designated strain SM1704T, was isolated from surface seawater collected from the South China Sea. The strain grew at 15-42 °C and with 1-10 % NaCl. It hydrolysed aesculin, but did not hydrolyse gelatin and Tween 80 nor reduce nitrate to nitrite. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SM1704T was affiliated with the genus Muricauda, sharing 94.1-95.9 % sequence similarities with type strains of recognized Muricauda species. The major fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH and the main polar lipids were phosphatidylethanolamine, three unidentified lipids and three unidentified aminolipids. The major respiratory quinone was menaquinone-6. The genomic DNA G+C content of strain SM1704T was 40.7 mol%. On the basis of results from polyphasic analysis of strain SM1704T, it is considered to represent a novel species within the genus Muricauda, for which the name Muricaudananhaiensis sp. nov. is proposed. The type strain is SM1704T (=KCTC 62797T=MCCC 1K03557T).

Trophic Specialization Results in Genomic Reduction in Free-Living Marine Idiomarina Bacteria.

The streamlining hypothesis is generally used to explain the genomic reduction events related to the small genome size of free-living bacteria like marine bacteria SAR11. However, our current understanding of the correlation between bacterial genome size and environmental adaptation relies on too few species. It is still unclear whether there are other paths leading to genomic reduction in free-living bacteria. The genome size of marine free-living bacteria of the genus Idiomarina belonging to the order Alteromonadales (Gammaproteobacteria) is much smaller than the size of related genomes from bacteria in the same order. Comparative genomic and physiological analyses showed that the genomic reduction pattern in this genus is different from that of the classical SAR11 lineage. Genomic reduction reconstruction and substrate utilization profile showed that Idiomarina spp. lost a large number of genes related to carbohydrate utilization, and instead they specialized on using proteinaceous resources. Here we propose a new hypothesis to explain genomic reduction in this genus; we propose that trophic specialization increasing the metabolic efficiency for using one kind of substrate but reducing the substrate utilization spectrum could result in bacterial genomic reduction, which would be not uncommon in nature. This hypothesis was further tested in another free-living genus, Kangiella, which also shows dramatic genomic reduction. These findings highlight that trophic specialization is potentially an important path leading to genomic reduction in some marine free-living bacteria, which is distinct from the classical lineages like SAR11.IMPORTANCE The streamlining hypothesis is usually used to explain the genomic reduction events in free-living bacteria like SAR11. However, we find that the genomic reduction phenomenon in the bacterial genus Idiomarina is different from that in SAR11. Therefore, we propose a new hypothesis to explain genomic reduction in this genus based on trophic specialization that could result in genomic reduction, which would be not uncommon in nature. Not only can the trophic specialization hypothesis explain the genomic reduction in the genus Idiomarina, but it also sheds new light on our understanding of the genomic reduction processes in other free-living bacterial lineages.

EA15, MIR22, LINC00472 as diagnostic markers for diabetic kidney disease.

This study aimed to investigate the molecular mechanisms of diabetic kidney disease (DKD) and to explore new potential therapeutic strategies and biomarkers for DKD. First we analyzed the differentially expressed changes between patients with DKD and the control group using the chip data in Gene Expression Omnibus (GEO) database. Then the gene chip was subjected to be annotated again, so as to screen long noncoding RNAs (lncRNAs) and study expression differences of these lncRNAs in DKD and controlled samples. At last, the function of the differential lncRNAs was analyzed. A total of 252 lncRNAs were identified, and 14 were differentially expressed. In addition, there were 1,629 differentially expressed messenger RNAs (mRNAs) genes, and proliferation and apoptosis adapter protein 15 (PEA15), MIR22, and long intergenic nonprotein coding RNA 472 ( LINC00472) were significantly differentially expressed in DKD samples. Through functional analysis of the encoding genes coexpressed by the three lncRNAs, we found these genes were mainly enriched in type 1 diabetes and autoimmune thyroid disease pathways, whereas in Gene Ontology (GO) function classification, they were also mainly enriched in the immune response, type I interferon signaling pathways, interferon-γ mediated signaling pathways, and so forth. To summary, we identified EA15, MIR22, and LINC00472 may serve as the potential diagnostic markers of DKD.

Molecular differences in Alzheimer's disease between male and female patients determined by integrative network analysis.

Alzheimer's disease (AD) is a complex neurodegenerative disease and the most common cause of dementia among the elderly. There has been increasing recognition of sex differences in AD prevalence, clinical manifestation, disease course and prognosis. However, there have been few studies on the molecular mechanism underlying these differences. To address this issue, we carried out global gene expression and integrative network analyses based on expression profiles (GSE84422) across 17 cortical regions of 125 individuals with AD. There were few genes that were differentially expressed across the 17 regions between the two sexes, with only four (encoding glutamate metabotropic receptor 2, oestrogen-related receptor beta, kinesin family member 26B, and aspartoacylase) that were differentially expressed in three regions. A pan-cortical brain region co-expression network analysis identified pathways and genes (eg, glycogen synthase kinase 3ß) that were significantly associated with clinical characteristics of AD (such as neurofibrillary score) in males only. Similarity analyses between region-specific networks indicated that male patients exhibited greater variability, especially in the superior parietal lobule, dorsolateral prefrontal cortex and occipital visual cortex. A network module analysis revealed an association between clinical traits and crosstalk of sex-specific modules. An examination of temporal and spatial patterns of sex differences in AD showed that molecular networks were more conserved in females than in males in different cortical regions and at different AD stages. These findings provide insight into critical molecular pathways governing sex differences in AD pathology.