Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice.

Premature ovarian insufficiency (POI) is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40. It represents a significant detriment to female fertility. However, the known POI-causative genes currently account for only a fraction of cases. To elucidate the genetic factors underlying POI, we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111. In a subsequent replication study involving 1,030 POI patients, this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants. These variants collectively account for eight cases, representing 0.78% of the study cohort. A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants. Notably, RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-ß/BMP signaling pathway. Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice, monkeys, and humans. To further investigate the functional implications of RNF111 variants, we generated two mouse models: one with a heterozygous missense mutation (Rnf111+/M) and another with a heterozygous null mutation (Rnf111+/-). Both mouse models exhibited impaired female fertility, characterized by reduced litter sizes and small ovarian reserve. Additionally, RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries. In conclusion, our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

Performance of 3D printed porous polyetheretherketone composite scaffolds combined with nano-hydroxyapatite/carbon fiber in bone tissue engineering: a biological evaluation.

Polyetheretherketone (PEEK) has been one of the most promising materials in bone tissue engineering in recent years, with characteristics such as biosafety, corrosion resistance, and wear resistance. However, the weak bioactivity of PEEK leads to its poor integration with bone tissues, restricting its application in biomedical fields. This research effectively fabricated composite porous scaffolds using a combination of PEEK, nano-hydroxyapatite (nHA), and carbon fiber (CF) by the process of fused deposition molding (FDM). The experimental study aimed to assess the impact of varying concentrations of nHA and CF on the biological performance of scaffolds. The incorporation of 10% CF has been shown to enhance the overall mechanical characteristics of composite PEEK scaffolds, including increased tensile strength and improved mechanical strength. Additionally, the addition of 20% nHA resulted in a significant increase in the surface roughness of the scaffolds. The high hydrophilicity of the PEEK composite scaffolds facilitated the in vitro inoculation of MC3T3-E1 cells. The findings of the study demonstrated that the inclusion of 20% nHA and 10% CF in the scaffolds resulted in improved cell attachment and proliferation compared to other scaffolds. This suggests that the incorporation of 20% nHA and 10% CF positively influenced the properties of the scaffolds, potentially facilitating bone regeneration. In vitro biocompatibility experiments showed that PEEK composite scaffolds have good biosafety. The investigation on osteoblast differentiation revealed that the intensity of calcium nodule staining intensified, along with an increase in the expression of osteoblast transcription factors and alkaline phosphatase activities. These findings suggest that scaffolds containing 20% nHA and 10% CF have favorable properties for bone induction. Hence, the integration of porous PEEK composite scaffolds with nHA and CF presents a promising avenue for the restoration of bone defects using materials in the field of bone tissue engineering.

An Analytical Thermal Buckling Model for Semiconductor Chips on a Substrate.

Semiconductor chips on a substrate have a wide range of applications in electronic devices. However, environmental temperature changes may cause mechanical buckling of the chips, resulting in an urgent demand to develop analytical models to study this issue with high efficiency and accuracy such that safety designs can be sought. In this paper, the thermal buckling of chips on a substrate is considered as that of plates on a Winkler elastic foundation and is studied by the symplectic superposition method (SSM) within the symplectic space-based Hamiltonian system. The solution procedure starts by converting the original problem into two subproblems, which are solved by using the separation of variables and the symplectic eigenvector expansion. Through the equivalence between the original problem and the superposition of subproblems, the final analytical thermal buckling solutions are obtained. The SSM does not require any assumptions of solution forms, which is a distinctive advantage compared with traditional analytical methods. Comprehensive numerical results by the SSM for both buckling temperatures and mode shapes are presented and are well validated through comparison with those using the finite element method. With the solutions obtained, the effects of the moduli of elastic foundations and geometric parameters on critical buckling temperatures and buckling mode shapes are investigated.

Chitosan-vancomycin hydrogel incorporated bone repair scaffold based on staggered orthogonal structure: a viable dually controlled drug delivery system.

In clinical practice, challenges remain in the treatment of large infected bone defects. Bone tissue engineering scaffolds with good mechanical properties and antibiotic-controlled release are powerful strategies for infection treatment. In this study, we prepared polylactic acid (PLA)/nano-hydroxyapatite (nHA) scaffolds with vertical orthogonal and staggered orthogonal structures by applying 3D printing technology. In addition, vancomycin (Van)-based chitosan (CS) hydrogel (Gel@Van) was loaded on the scaffold (PLA/nHA/CS-Van) to form a local antibiotic release system. The microstructure of the composite scaffold had high porosity with interconnected three-dimensional networks. The mechanical properties of the PLA/nHA/CS-Van composite scaffold were enhanced by the addition of CS-Van. The results of the water contact angle analysis showed that the hydrophilicity of the drug-loaded scaffold improved. In addition, the composite scaffold could produce sustained release in vitro for more than 8 weeks without adverse effects on the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1), which confirmed its good biocompatibility. During the in vitro antimicrobial study, the composite scaffold effectively inhibited the growth of Staphylococcus aureus (S. aureus). Therefore, our results suggest that the PLA/nHA/CS-Van composite scaffold is a promising strategy for treating infected bone defects.

Machine learning of pair-contact process with diffusion.

The pair-contact process with diffusion (PCPD), a generalized model of the ordinary pair-contact process (PCP) without diffusion, exhibits a continuous absorbing phase transition. Unlike the PCP, whose nature of phase transition is clearly classified into the directed percolation (DP) universality class, the model of PCPD has been controversially discussed since its infancy. To our best knowledge, there is so far no consensus on whether the phase transition of the PCPD falls into the unknown university classes or else conveys a new kind of non-equilibrium phase transition. In this paper, both unsupervised and supervised learning are employed to study the PCPD with scrutiny. Firstly, two unsupervised learning methods, principal component analysis (PCA) and autoencoder, are taken. Our results show that both methods can cluster the original configurations of the model and provide reasonable estimates of thresholds. Therefore, no matter whether the non-equilibrium lattice model is a random process of unitary (for instance the DP) or binary (for instance the PCP), or whether it contains the diffusion motion of particles, unsupervised learning can capture the essential, hidden information. Beyond that, supervised learning is also applied to learning the PCPD at different diffusion rates. We proposed a more accurate numerical method to determine the spatial correlation exponent [Formula: see text], which, to a large degree, avoids the uncertainty of data collapses through naked eyes.

Improvement of mechanical and antibacterial properties of porous nHA scaffolds by fluorinated graphene oxide.

Nano-hydroxyapatite (nHA) is widely used as a bio-scaffold material due to its good bioactivity and biocompatibility. In this study, fluorinated graphene oxide (FG) was added to nHA to improve its poor formability, weak mechanical properties, undesirable antimicrobial activity and other disadvantages that affect its clinical application. FG was synthesized by a simple hydrothermal method. Novel porous composite scaffolds were prepared by adding different weight ratios (0.1 wt%, 0.5 wt% and 1 wt%) of FG to nHA using the 3D printing technique. The morphology, phase composition and mechanical properties of the composite scaffolds were characterized. In addition, the degradation performance of the composite scaffolds, antibacterial activity against Staphylococcus aureus and Escherichia coli, and cytocompatibility were also investigated. The results showed that the nHA/FG composite scaffold was successfully prepared with a uniform distribution of FG on the scaffold. The mechanical properties showed that the compression strength of the nHA/FG composite scaffold was significantly higher than that of the nHA scaffold (7.22 ± 1.43 MPa). The porosity of all composite scaffolds was above 70%. The addition of FG significantly improved the mechanical properties of the nHA scaffold without affecting the porosity of the scaffold. In addition, the 0.5 wt% nHA/FG scaffold exhibited satisfactory cytocompatibility and antibacterial properties. Therefore, the constructed nHA/FG composite scaffold can be considered as a novel antimicrobial bone substitute material with good application prospects.

An Analytic Model of Transient Heat Conduction for Bi-Layered Flexible Electronic Heaters by Symplectic Superposition.

In a flexible electronic heater (FEH), periodic metal wires are often encapsulated into the soft elastic substrate as heat sources. It is of great significance to develop analytic models on transient heat conduction of such an FEH in order to provide a rapid analysis and preliminary designs based on a rapid parameter analysis. In this study, an analytic model of transient heat conduction for bi-layered FEHs is proposed, which is solved by a novel symplectic superposition method (SSM). In the Laplace transform domain, the Hamiltonian system-based governing equation for transient heat conduction is introduced, and the mathematical techniques incorporating the separation of variables and symplectic eigen expansion are manipulated to yield the temperature solutions of two subproblems, which is followed by superposition for the temperature solution of the general problem. The Laplace inversion gives the eventual temperature solution in the time domain. Comprehensive time-dependent temperatures by the SSM are presented in tables and figures for benchmark use, which agree well with their counterparts by the finite element method. A parameter analysis on the influence of the thermal conductivity ratio is also studied. The exceptional merit of the SSM is on a direct rigorous derivation without any assumption/predetermination of solution forms, and thus, the method may be extended to more heat conduction problems of FEHs with more complex structures.

Nano-silica particles synergistically IgE-mediated mast cell activation exacerbating allergic inflammation in mice.

Background: Allergic respiratory diseases have increased dramatically due to air pollution over the past few decades. However, studies are limited on the effects of inorganic components and particulate matter with different particle sizes in smog on allergic diseases, and the possible molecular mechanism of inducing allergies has not been thoroughly studied. Methods: Four common mineral elements with different particle sizes in smog particles were selected, including Al2O3, TiO2, Fe2O3, and SiO2. We studied the relationship and molecular mechanism of smog particle composition, particle size, and allergic reactions using mast cells, immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis (PCA) model, and an ovalbumin (OVA)-induced asthmatic mouse model in vitro and in vivo, combined with transmission electron microscopy, scanning transmission X-ray microscopy analysis, and transcriptome sequencing. Results: Only 20 nm SiO2 particles significantly increased ß-hexosaminidase release, based on dinitrophenol (DNP)-human serum albumin (HSA) stimulation, from IgE-sensitized mast cells, while other particles did not. Meanwhile, the PCA model showed that Evan's blue extravasation in mice was increased after treatment with nano-SiO2 particles. Nano-SiO2 particles exposure in the asthmatic mouse model caused an enhancement of allergic airway inflammation as manifested by OVA-specific serum IgE, airway hyperresponsiveness, lung inflammation injury, mucous cell metaplasia, cytokine expression, mast cell activation, and histamine secretion, which were significantly increased. Nano-SiO2 particles exposure did not affect the expression of FcϵRI or the ability of mast cells to bind IgE but synergistically activated mast cells by enhancing the mitogen-activated protein kinase (MAPK) signaling pathway, especially the phosphorylation levels of the extracellular signal-regulated kinase (ERK)1/2. The ERK inhibitors showed a significant inhibitory effect in reducing ß-hexosaminidase release. Conclusion: Our results indicated that nano-SiO2 particles stimulation might synergistically activate IgE-sensitized mast cells by enhancing the MAPK signaling pathway and that nano-SiO2 particles exposure could exacerbate allergic inflammation. Our experimental results provide useful information for preventing and treating allergic diseases.

Transfer learning of phase transitions in percolation and directed percolation.

The latest advances of statistical physics have shown remarkable performance of machine learning in identifying phase transitions. In this paper, we apply domain adversarial neural network (DANN) based on transfer learning to studying nonequilibrium and equilibrium phase transition models, which are percolation model and directed percolation (DP) model, respectively. With the DANN, only a small fraction of input configurations (two-dimensional images) needs to be labeled, which is automatically chosen, to capture the critical point. To learn the DP model, the method is refined by an iterative procedure in determining the critical point, which is a prerequisite for the data collapse in calculating the critical exponent ν_{⊥}. We then apply the DANN to a two-dimensional site percolation with configurations filtered to include only the largest cluster which may contain the information related to the order parameter. The DANN learning of both models yields reliable results which are comparable to the ones from Monte Carlo simulations. Our study also shows that the DANN can achieve quite high accuracy at much lower cost, compared to the supervised learning.

Investigation of urine metabolome of BALB/c mouse infected with an avirulent strain of Toxoplasma gondii.

BACKGROUND: The protozoan parasite Toxoplasma gondii is a major concern for human and animal health. Although the metabolic understanding of toxoplasmosis has increased in recent years, the analysis of metabolic alterations through noninvasive methodologies in biofluids remains limited. METHODS: Here, we applied liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics and multivariate statistical analysis to analyze BALB/c mouse urine collected from acutely infected, chronically infected and control subjects. RESULTS: In total, we identified 2065 and 1409 metabolites in the positive electrospray ionization (ESI +) mode and ESI - mode, respectively. Metabolomic patterns generated from principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) score plots clearly separated T. gondii-infected from uninfected urine samples. Metabolites with altered levels in urine from T. gondii-infected mice revealed changes in pathways related to amino acid metabolism, fatty acid metabolism, and nicotinate and nicotinamide metabolism. CONCLUSIONS: This is the first study to our knowledge on urine metabolic profiling of BALB/c mouse with T. gondii infection. The urine metabolome of infected mouse is distinctive and has value in the understanding of Toxoplasmosis pathogenesis and improvement of treatment.

Improvement of the mechanical properties and osteogenic activity of 3D-printed polylactic acid porous scaffolds by nano-hydroxyapatite and nano-magnesium oxide.

Porous bone scaffolds based on high-precision 3D printing technology gave recently been developed for use in bone defect repair. However, conventional scaffold materials have poor mechanical properties and low osteogenic activity, limiting their clinical use. In this study, a porous composite tissue-engineered bone scaffold was prepared using polylactic acid, nano-hydroxyapatite, and nano-magnesium oxide as raw materials for high-precision 3D printing. The composite scaffold takes full advantage of the personalized manufacturing features of 3D printers and can be used to repair complex bone defects in clinical settings. The composite scaffold combines the advantages of nano-hydroxyapatite, which improves the formability of scaffold printing, and of nano-magnesium oxide, which regulates pH during degradation and provide a good environment for cell growth. Additionally, nano-magnesium oxide and nano-hydroxyapatite have a bidirectional effect on promoting the compressive strength and osteogenic activity of the scaffolds. The prepared composite porous scaffolds based on 3D printing technology show promise for bone defect repair.

circFAM120B functions as a tumor suppressor in esophageal squamous cell carcinoma via the miR-661/PPM1L axis and the PKR/p38 MAPK/EMT pathway.

Extensive changes of circRNA expression underscore their essential contributions to multiple hallmarks of cancers; however, their functions and mechanisms of action in esophageal squamous cell carcinoma (ESCC) remain undetermined. Here, we adopted a three-stage approach by first screening for significantly differentially expressed circRNAs in ESCC and performing an external validation study, followed by the functional analyses. The properties of circRNAs were evaluated using Sanger sequencing, RNase R digestion, actinomycin D treatment, subcellular localization analysis, and fluorescence in situ hybridization. Target transcripts were predicted using online tools and verified by dual-luciferase, RNA immunoprecipitation, qRT-PCR, and western blot. Biotin-labeled RNA-protein pull-down, mass spectrometry, and RNA immunoprecipitation were employed to identify proteins interacting with circRNAs. Gain- and loss-of-function experiments were performed to uncover the roles of circRNAs, their target genes, and binding proteins in the proliferation, metastasis, and invasion. We observed that circFAM120B (hsa_circ_0001666) was frequently downregulated in cancer tissues and patient plasma, and its expression level was related to overall survival in ESCC patients. Overexpression of circFAM120B inhibited the proliferation, metastasis, and invasion of ESCC while silencing it enhanced malignant phenotypes. Mechanistically, circFAM120B was predominantly located in the cytoplasm, guarantying its sponging for miR-661 to restore the expression of PPM1L, a tumor suppressor. We observed that circFAM120B could reduce the stability of RNA-dependent protein kinase (PKR) by promoting its ubiquitination-dependent degradation and subsequently regulating the p38 MAPK signaling pathway, resulting in the repression of EMTs in ESCC cells. Our findings suggest that circFAM120B is a promising biomarker of ESCC, which acts as a tumor suppressor via the circFAM120B/miR-661/PPM1L axis and PKR/p38 MAPK/EMT pathway, supporting its significance as a candidate therapeutic target.

The fabrication of multifunctional sodium alginate scaffold incorporating ibuprofen-loaded modified PLLA microspheres based on cryogenic 3D printing.

A strategy to develop a multifunctional sodium alginate personalized scaffold with enhanced mechanical stability, osteogenesis activity and excellent anti-inflammatory activity by cryogenic 3 D printing combined with subsequent crosslinking with Sr2+ is proposed in this study. The ink for 3 D printing was prepared by dispersing modified PLLA droplets containing ibuprofen into sodium alginate aqueous solution using lecithin as stabilizer. The results showed that the drug-loaded microspheres formed from the low-temperature solidifying of the modified PLLA droplets were homogeneously dispersed in sodium alginate substrate, and the scaffold displayed a sustained drug release performance toward ibuprofen which endowed the scaffold with persistent anti-inflammatory effects. In vitro cell culture indicated that the lecithin not only acted as the stabilizer, but also stimulated the proliferation and mineralization of osteoblastic cells on the scaffold. Sr2+-crosslinking improved the mechanical properties and osteogenic activity of the scaffold.

Cryogenic 3D printing of modified polylactic acid scaffolds with biomimetic nanofibrous architecture for bone tissue engineering.

The individualized polylactic acid (PLA) scaffolds fabricated by 3D printing technique have a good application prospect in the bone tissue engineering field. However, 3D printed PLA scaffold mainly manufactured by using a Fused Deposition Modelling fabrication technique (FDM) has some disadvantages, such as having smooth surface, strong hydrophobicity, poor cell adhesion, undesirable bioactivity, the degradation and deterioration at a high temperature triggering an inflammatory response. In this work, the aminated modified polylactic acid nanofibrous scaffold prepared by cryogenic 3D printing technology is designed to provide a feasible countermeasure to solve the key problems existing at present. The prepared scaffolds were fully characterized in terms of physico-chemical and morphological analyses, and the collected results revealed that the using of the cryogenic 3D printing technology can effectively avoid the degradation and deterioration of PLA at a high temperature required by FDM technique and promote the formation of nanofibrous structures. The in vitro tests with MC3T3-E1 cells confirmed that the cell-responsive biomimetic fibrous architecture and improved hydrophilicity due to the introduction of hydrophilic active amino groups provided a bioactive interface for cell adhesion and growth. Meanwhile, the active amino groups introduced by ammonolysis reaction can act as active sites for biomineralization. Thus, the as-prepared scaffolds may hold great potential for bone tissue engineering applications.

Inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer: a systematic review and meta-analysis.

BACKGROUND: Accumulating literature has shown the predictive values of inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer but with inconsistent findings. METHOD: We performed a meta-analysis to systematically evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C reactive protein-to-albumin ratio (CAR), systemic inflammation index (SII), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS) and modified Glasgow Prognostic Score (mGPS) in oesophageal cancer. The outcome indicators include the overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). We applied pooled HR, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve together with 95% CI to estimate the predictive accuracy. RESULTS: A total of 72 studies, including 22 260 patients, were included in the meta-analysis. Elevated NLR, PLR CAR, SII, GPS, mGPS and decreased LMR and PNI were associated with poor OS of oesophageal cancer. A high level of NLR, PLR and GPS was related to poor DFS. A high level of NLR and GPS was related to poor CSS. The summarised AUC of CAR (0.72, 95% CI: 0.68 to 0.75) and mGPS (0.75, 95% CI: 0.71 to 0.78) surpassed any other indicators. CONCLUSIONS: Clinical indicators such as NLR, PLR, LMR, PNI, SII, CAR, GPS and mGPS have the moderate predictive ability in OS, DFS and CSS of oesophageal cancer. The pretreatment level of CAR and mGPS showed an outstanding prediction value in 5-year OS for oesophageal cancer.

Critical roles of cytokine storm and secondary bacterial infection in acute kidney injury development in COVID-19: A multi-center retrospective cohort study.

Acute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID-19) and is associated with in-hospital death. We investigated the incidence of AKI in 223 hospitalized COVID-19 patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically confirmed COVID-19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020, and April 8, 2020. We included 124 patients with moderate COVID-19 and 99 with severe COVID-19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID-19 and 4.0% for moderate COVID-19 (p < 0.001). Furthermore, cytokine storm was found in 30 (13.5%) patients and only found in the severe group. Kidney injury at admission (odds ratio [OR]: 3.132, 95% confidence interval [CI]: 1.150-8.527; p = 0.025), cytokine storm (OR: 4.234, 95% CI: 1.361-13.171; p = 0.013), and acute respiratory distress syndrome (ARDS) (OR: 7.684, 95% CI: 2.622-22.523; p < 0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% of AKI patients with cytokine storms may develop a secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than in those without (13.0 × 109/L, interquartile range [IQR] 11.3 vs. 8.3 × 109/L, IQR 7.5, p = 0.005). Approximately 1/6 patients with COVID-19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID-19 patients.

Effects of different positive end-expiratory pressure titrating strategies on oxygenation and respiratory mechanics during one- lung ventilation: a randomized controlled trial.

BACKGROUND: Positive end-expiratory pressure (PEEP) is widely used to reduce the risk of hypoxemia and atelectasis during one-lung ventilation (OLV); however, the optimal strategy for PEEP titrating remains unclear.The purpose of the study was to investigate the effects of different PEEP titrating strategies on oxygenation and respiratory mechanics during OLV. METHODS: Patients undergoing thoracic surgery with general anesthesia were randomly allocated into five groups. In P0 group, PEEP was set to zero; in PLIP2 group, PEEP was set to 2 cmH2O plus the pressure of lower inflection point (LIP) of pressure-volume (P-V) curve; in PLIPS group, PEEP was titrated to achieve maximum static compliance from the averaged LIP pressure value; in groups PSTAT and PDYN, the incremental PEEP values were titrated to achieve maximum static compliance or maximum dynamic compliance from 4 cmH2O. Hemodynamic measurements, respiratory mechanics, and blood gas analyses were recorded at the beginning of OLV, OLV 15 min, OLV 30 min, OLV 45 min, and OLV 60 min. Also, the intrapulmonary shunt (Qs/Qt), physiological dead space to tidal volume ratio (VD/VT), and oxygenation index (OI) were calculated and compared. RESULTS: Seventy-five patients consented to participate in this study. Dynamic compliance, peak inspiratory pressure (PIP), and plateau inspiratory pressure (Pplat) increased after PEEP titration during OLV. PIP, Qs/ Qt, and OI showed no differences among groups. Group PDYN showed lower Pplat, lower driving pressure, and higher dynamic compliance when compared with zero PEEP group. CONCLUSIONS: The PEEP titrating strategy according to dynamic compliance can improve respiratory mechanics, whereas it has no significant effects on oxygenation, dead space ratio, and intrapulmonary shunt, suggesting that it is better during OLV for thoracic surgery.

Evaluation of cytokines as a biomarker to distinguish active tuberculosis from latent tuberculosis infection: a diagnostic meta-analysis.

OBJECTIVES: With a marginally effective vaccine and no significant breakthroughs in new treatments, a sensitive and specific method to distinguish active tuberculosis from latent tuberculosis infection (LTBI) would allow for early diagnosis and limit the spread of the pathogen. The analysis of multiple cytokine profiles provides the possibility to differentiate the two diseases. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library, Clinical Key and EMBASE databases were searched on 31 December 2019. ELIGIBILITY CRITERIA: We included case-control studies, cohort studies and randomised controlled trials considering IFN-γ, TNF-α, IP-10, IL-2, IL-10, IL-12 and VEGF as biomarkers to distinguish active tuberculosis and LTBI. DATA EXTRACTION AND SYNTHESIS: Two students independently extracted data and assessed the risk of bias. Diagnostic OR, sensitivity, specificity, positive and negative likelihood ratios and area under the curve (AUC) together with 95% CI were used to estimate the diagnostic value. RESULTS: Of 1315 records identified, 14 studies were considered eligible. IL-2 had the highest sensitivity (0.84, 95% CI: 0.72 to 0.92), while VEGF had the highest specificity (0.87, 95% CI: 0.73 to 0.94). The highest AUC was observed for VEGF (0.85, 95% CI: 0.81 to 0.88), followed by IFN-γ (0.84, 95% CI: 0.80 to 0.87) and IL-2 (0.84, 95% CI: 0.81 to 0.87). CONCLUSION: Cytokines, such as IL-2, IFN-γ and VEGF, can be utilised as promising biomarkers to distinguish active tuberculosis from LTBI. PROSPERO REGISTRATION NUMBER: CRD42020170725.

Construction of a circRNA-Related ceRNA Prognostic Regulatory Network in Breast Cancer.

PURPOSE: Accumulating evidence has indicated that circRNAs are closely involved in tumorigenesis and progression of human cancers. However, the molecular mechanism underlying function of circRNAs in breast cancer has not been thoroughly elucidated. Currently, we aimed to characterize the circRNA-related competing endogenous RNA (ceRNA) regulatory network in breast cancer and to construct prognostic model. MATERIALS AND METHODS: First, we constructed circRNA expression profiles for paired breast cancer in a Chinese population using a human circRNA microarray. Expression profiles of circRNAs, miRNAs, and mRNAs were retrieved from our circRNA dataset, the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We applied the limma and edgeR packages to identify differentially expressed RNAs. Weighted gene correlation network analysis (WGCNA) was used to identify critical modules of mRNAs. Next, a ceRNA network was established based on circRNA-miRNA and miRNA-mRNA intersections. Both Cox regression analysis and ROC curve analysis were performed to generate prognostic model. Additionally, we performed Gene Set Enrichment Analysis (GSEA) on prognostic signatures. RESULTS: Total of 59 circRNAs, 98 miRNAs and 3966 mRNAs were identified as differentially expressed RNAs. We first identified 38 miRNA-mRNA pairs and 38 circRNA-miRNA pairs to construct the circRNA-miRNA-mRNA regulatory network and then generated a prognostic model based on 7 signatures (MMD, SLC29A4, CREB5, FOS, ANKRD29, MYOCD, and PIGR), and patients with high-risk scores presented poor prognosis. Several cancer-related pathways were enriched, including the TGF-ß pathway, the focal adhesion pathway, and the JAK-STAT signaling pathway, and 20 prognostic ceRNA regulatory networks were subsequently identified. CONCLUSION: In all, we screened a series of dysregulated circRNAs, miRNAs, and mRNAs, and constructed circRNA-related ceRNA network in breast cancer. Our findings may help to deepen the understanding of circRNA-related regulatory mechanisms. Moreover, we generated a prognostic model that provided new insight into postoperative management for breast cancer.

The YTH Domain Family of N6-Methyladenosine "Readers" in the Diagnosis and Prognosis of Colonic Adenocarcinoma.

To profile the landscape of methylation N6 adenosine (m6A) RNA regulators in colonic adenocarcinoma (COAD) and to explore potential diagnostic and prognostic biomarkers, we assessed the differential expression patterns of m6A RNA methylation regulators between 418 COAD patients and 41 controls based on profiling from The Cancer Genome Atlas (TCGA) database. We plotted the receiver operating characteristic (ROC) curves and calculated the area under the curve (AUC) values to estimate the discrimination ability. The relationship between the expression of m6A RNA methylation regulators and clinicopathological characteristics was explored. Kaplan-Meier plotter, log-rank test, and Cox regression were used and a nomogram was created to explore the prognostic significance of m6A-related genes in overall survival at the mRNA level. Pathway analysis was performed by gene set enrichment analysis (GSEA) using TCGA dataset, and a coexpression network was built based on the STRING database. We observed that YTHDF1, METTL3, and KIAA1429 were significantly upregulated, while YTHDF3, YTHDC2, METTL14, and ALKBH5 were significantly downregulated in COAD samples compared to normal samples. YTHDF1 had the highest diagnostic value. Low expression of YTHDF3 predicted a poor survival rate in COAD patients. YTHDC2 was related to sex and showed a downward trend as clinical stage increased. Our results indicate that the YT521-B homology (YTH) domain family ("readers"), especially YTHDF1, YTHDF3, and YTHDC2, might play a significant role in the detection, progression, and prognosis of COAD, indicating that they are promising cancer biomarkers.