iEssLnc: quantitative estimation of lncRNA gene essentialities with meta-path-guided random walks on the lncRNA-protein interaction network.

Gene essentiality is defined as the extent to which a gene is required for the survival and reproductive success of a living system. It can vary between genetic backgrounds and environments. Essential protein coding genes have been well studied. However, the essentiality of non-coding regions is rarely reported. Most regions of human genome do not encode proteins. Determining essentialities of non-coding genes is demanded. We developed iEssLnc models, which can assign essentiality scores to lncRNA genes. As far as we know, this is the first direct quantitative estimation to the essentiality of lncRNA genes. By taking the advantage of graph neural network with meta-path-guided random walks on the lncRNA-protein interaction network, iEssLnc models can perform genome-wide screenings for essential lncRNA genes in a quantitative manner. We carried out validations and whole genome screening in the context of human cancer cell-lines and mouse genome. In comparisons to other methods, which are transferred from protein-coding genes, iEssLnc achieved better performances. Enrichment analysis indicated that iEssLnc essentiality scores clustered essential lncRNA genes with high ranks. With the screening results of iEssLnc models, we estimated the number of essential lncRNA genes in human and mouse. We performed functional analysis to find that essential lncRNA genes interact with microRNAs and cytoskeletal proteins significantly, which may be of interest in experimental life sciences. All datasets and codes of iEssLnc models have been deposited in GitHub (https://github.com/yyZhang14/iEssLnc).

Altered counts and mitochondrial mass of peripheral blood leucocytes in patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.

Amide Proton Transfer-Weighted Magnetic Resonance Imaging for Application in Renal Fibrosis: A Radiological-Pathological-Based Analysis.

INTRODUCTION: Renal fibrosis (RF), being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer (APT) weighting to evaluate RF noninvasively. METHODS: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction, and sham operation, respectively. All rats underwent APT mapping on the 7th and 14th days after operation. Besides, 26 patients underwent renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. RESULTS: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of RF. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th days after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than in patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p < 0.1). CONCLUSION: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.

Enhancement of Synergistic Photocatalytic Performance by Anchoring Cadmium Sulfide on Nanosphere Structured Coordination Polymers.

Precisely tuning how and where a reaction occurs in a one-step selective system is important but challenging owing to the similar electronic environments in multiple active sites. In this work, highly selective and effective reaction sites were obtained by generating copper coordination polymers (Cu-CP) of a range of sizes and morphologies, from bulk solid crystals (1) to uniform nanosphere structures (1a), by controlling the amount of surfactant hexadecyl trimethylammonium bromide (CTAB). The results indicated that the morphology and size of the uniform nanosphere structures were affected by the proportion of CTAB; uniform distribution of nanosphere structures was achieved with a premade building carrier when the content of CTAB was 0.005 mmol, generating a well-established platform. Photocatalytic cadmium sulfide (CdS) was then immobilized on the surface of the premade platform unit 1a through an in situ process to generate CdS@1a composites with well-dispersed catalytic CdS active sites. Furthermore, the well-defined CdS@1a composite platform was utilized as photocatalysts to explore the selective one-step depolymerization reaction under blue-light irradiation. Notably, the CdS0.149@1a composite, which featured a unique structure with evenly dispersed, closely spaced catalytic sites, exhibiting remarkable photoelectrochemical behaviors for selective one-step depolymerization of lignin model substances to aromatic monomer phenol and acetophenone framework products. This work demonstrates the use of an inherently morphological process to construct outstanding photocatalysts that could enable a wide range of photocatalytic reactions.

The association of blood urea nitrogen to serum albumin ratio with short-term outcomes in Chinese patients with congestive heart failure: A retrospective cohort study.

BACKGROUND AND AIMS: Limited evidence exists on the prognostic outcomes of the blood urea nitrogen to serum albumin ratio (B/A ratio) in congestive heart failure (CHF), particularly in developing countries with scarce heart failure epidemiological data. We aimed to investigate the association between B/A ratio and short-term outcomes in Chinese patients with CHF. METHODS AND RESULTS: We included 1761 CHF patients with available B/A ratio data from a cohort of 2008 patients. Patients were categorized into three groups based on B/A ratio (low to high). The primary endpoint was death or readmission within 28 days, and the secondary endpoint was death or readmission within 90 days. We employed restricted cubic spline analysis, Cox proportional hazards regression, and Kaplan-Meier curves to evaluate the relationship between B/A ratio at admission and the endpoints. Even after adjusting for other variables, higher B/A ratios were associated with increased rates of 28 days and 90 days mortality or readmission (HR: 2.4, 95% CI: 1.81-3.18 and HR: 1.74, 95% CI: 1.48-2.05). Significant differences in the risks of both primary and secondary endpoints were observed among the three B/A ratio groups. The association between B/A ratio and CHF was stable in the different subgroups (all P for interaction＞0.05). CONCLUSION: Higher B/A ratios are associated with an increased risk of short-term mortality or readmission in Chinese patients with CHF. The B/A ratio shows promise as a prognostic indicator for short-term outcomes in CHF patients.

Biphasic Rapid Culture in Differential Diagnosis of Tuberculosis.

Context: Early intervention and treatment are key measures for tuberculosis (TB) prevention and control, making early, rapid, and accurate diagnostic methods crucial. The Liquid-solid (Biphasic) rapid cultures is a novel tool for the differential diagnosis of tuberculosis. Objective: The study intended to evaluate the value of the biphasic cultures by comparing it to the acid-fast staining and liquid cultures, which have been the traditional gold-standard technology, to determine its value in the diagnosis of TB. Design: The research team conducted an experimental study. Setting: The study took place at the Affiliated Wuxi Fifth Hospital of Jiangnan University in Wuxi, China. Participants: Participants were 221 patients with suspected pulmonary tuberculosis who had been admitted to the hospital between July 2020 and December 2021. Outcome Measures: Using three methods-liquid-solid (biphasic) culture, acid-fast staining, and mycobacterial growth indicator tube (MGIT) 960 liquid culture, the research team tested participants' sputum samples: (1) for sensitivity; (2) for time to positive culture results, and (3) for differential diagnosis. Results: The biphasic culture's sensitivity was significantly higher than that of acid-fast staining, (P = .0003), and no significant difference existed between it and the MGIT 960 liquid cultures. The biphasic cultures's mean time to positivity was significantly shorter than that of the MGIT 960 liquid culture at the intervals 11-20 d (P < .0001) and 21-35 days (P = .0001). Moreover, the biphasic cultures could preliminarily differentiate nontuberculous mycobacteria (NTM) from mycobacterium tuberculosis (MTB), which is a significant advantage in tuberculosis diagnosis. Conclusions: This study highlights the potential of a biphasic culture as a reliable tool for the rapid differential diagnosis of tuberculosis, with a faster detection cycle and a higher sensitivity than conventional methods. The biphasic cultures is a valuable addition to the tuberculosis diagnostic armamentarium and can help improve patients' outcomes by enabling earlier diagnosis and treatments.

Tree-structured parzen estimator optimized-automated machine learning assisted by meta-analysis for predicting biochar-driven N2O mitigation effect in constructed wetlands.

Biochar is a carbon-neutral tool for combating climate change. Artificial intelligence applications to estimate the biochar mitigation effect on greenhouse gases (GHGs) can assist scientists in making more informed solutions. However, there is also evidence indicating that biochar promotes, rather than reduces, N2O emissions. Thus, the effect of biochar on N2O remains uncertain in constructed wetlands (CWs), and there is not a characterization metric for this effect, which increases the difficulty and inaccuracy of biochar-driven alleviation effect projections. Here, we provide new insight by utilizing machine learning-based, tree-structured Parzen Estimator (TPE) optimization assisted by a meta-analysis to estimate the potency of biochar-driven N2O mitigation. We first synthesized datasets that contained 80 studies on global biochar-amended CWs. The mitigation effect size was then calculated and further introduced as a new metric. TPE optimization was then applied to automatically tune the hyperparameters of the built extreme gradient boosting (XGBoost) and random forest (RF), and the optimum TPE-XGBoost obtained adequately achieved a satisfactory prediction accuracy for N2O flux (R2 = 91.90%, RPD = 3.57) and the effect size (R2 = 92.61%, RPD = 3.59). Results indicated that a high influent chemical oxygen demand/total nitrogen (COD/TN) ratio and the COD removal efficiency interpreted by the Shapley value significantly enhanced the effect size contribution. COD/TN ratio made the most and the second greatest positive contributions among 22 input variables to N2O flux and to the effect size that were up to 18% and 14%, respectively. By combining with a structural equation model analysis, NH4+-N removal rate had significant negative direct effects on the N2O flux. This study implied that the application of granulated biochar derived from C-rich feedstocks would maximize the net climate benefit of N2O mitigation driven by biochar for future biochar-based CWs.

[Ferroptosis:Mechanisms and Application in Tumor Treatment].

Ferroptosis is a form of regulated cell death that depends on iron and reactive oxygen species.Different from apoptosis,necrosis,and autophagy,ferroptosis is characterized by the accumulation of lipid peroxides in cells.Studies have discovered that ferroptosis is closely associated with the occurrence and development of tumors and inducing ferroptosis in tumor cells can enhance the therapeutic effects of drugs on tumors.This article summarizes the latest research progress in ferroptosis regarding its mechanisms and associations with tumors,aiming to provide a reference for further understanding the interaction mechanisms between ferroptosis and tumors and offering new insights and targets for the treatment of tumors.

[Modular pharmacology: research progress and development of analysis platform].

Based on the systematic deconstruction of multi-dimensional and multi-target biological networks, modular pharmacology explains the complex mechanism of diseases and the interactions of multi-target drugs. It has made progress in the fields of pathogenesis of disease, biological basis of disease and traditional Chinese medicine(TCM) syndrome, pharmacological mechanism of multi-target herbs, compatibility of formulas, and discovery of new drug of TCM compound. However, the complexity of multi-omics data and biological networks brings challenges to the modular deconstruction and analysis of the drug networks. Here, we constructed the "Computing Platform for Modular Pharmacology" online analysis system, which can implement the function of network construction, module identification, module discriminant analysis, hub-module analysis, intra-module and inter-module relationship analysis, and topological visualization of network based on quantitative expression profiles and protein-protein interaction(PPI) data. This tool provides a powerful tool for the research on complex diseases and multi-target drug mechanisms by means of modular pharmacology. The platform may have broad range of application in disease modular identification and correlation mechanism, interpretation of scientific principles of TCM, analysis of complex mechanisms of TCM and formulas, and discovery of multi-target drugs.

Triboelectric Nanogenerators Assembled by Cobalt(II) Coordination Polymer Incorporated Composite Films and their Application for Self-Powered Anticorrosion.

A friction layer with stability and durability is important to promote the practical application of triboelectric nanogenerators (TENGs). In this work, a two-dimensional cobalt coordination polymer (Co-CP) was successfully synthesized using cobalt nitrate, 4,4',4''-tricarboxyltriphenylamine and 2,2'-bipyridine. To clearly clarify the effect of the doping proportions of Co-CP and the types of composite polymers on the output performance of the TENG, Co-CP was combined with two organic polymers having different polarities (polyvinylidene fluoride (PVDF) and ethyl cellulose (EC)) to form a series of composite films, which were used as the friction electrode materials to fabricate TENGs. Electrical characterizations indicated that a high output current and voltage were obtained from the TENG based on 15 wt.% Co-CP incorporated in PVDF (Co-CP@PVDF), which could be further improved by the Co-CP@EC composite film at the same doping ratio. Furthermore, the optimally fabricated TENG was demonstrated to prevent electrochemical corrosion of carbon steel.

The inhibition of p38 MAPK blocked inflammation to restore the functions of rat meibomian gland epithelial cells.

Meibomian glands (MGs) are vital for ocular surface health. However, the roles of inflammation in the progression of meibomian gland dysfunction (MGD) are largely unknown. In this study, the roles of the inflammation factor interleukin-1ß (IL-1ß) via the p38 mitogen-activated protein kinases (MAPK) signaling pathway on rat meibomian gland epithelial cells (RMGECs) were explored. Eyelids from adult rat mice at 2 months and 2 years of age were stained with specific antibodies against IL-1ß to identify inflammation levels. RMGECs were exposed to IL-1ß and/or SB203580, a specific inhibitor of p38 MAPK signaling pathway, for 3 days. Cell proliferation, keratinization, lipid accumulation, and matrix metalloproteinases 9 (MMP9) expression were evaluated by MTT assay, polymerase chain reaction (PCR), immunofluorescence staining, apoptosis assay, lipid staining, and Western blot analyses. We found that IL-1ß was significantly higher in the terminal ducts of MGs in rats with age-related MGD than in young rats. IL-1ß inhibited cell proliferation, suppressed lipid accumulation and peroxisome proliferator activator receptor γ (PPARγ) expression, and promoted apoptosis while activating the p38 MAPK signaling pathway. Cytokeratin 1 (CK1), a marker for complete keratinization, and MMP9 in RMGECs were also up-regulated by IL-1ß. SB203580 effectively diminished the effects of IL-1ß on differentiation, keratinization, and MMP9 expression by blocking IL-1ß-induced p38 MAPK activation, although it also inhibited cell proliferation. The inhibition of the p38 MAPK signaling pathway blocked IL-1ß-induced differentiation reduction, hyperkeratinization, and MMP9 overexpression of RMGECs, which provides a potential therapy for MGD.

Erectile dysfunction, depression, and anxiety in patients with functional anorectal pain: a case-control study.

BACKGROUND: Men with functional anorectal pain (FARP) report having erectile dysfunction (ED) and significant changes in psychological status. AIM: The study sought to investigate the risk factors associated with FARP among male Chinese outpatients, alongside the impact of FARP on patients' ED, depression, and anxiety. METHODS: This case-control study included 406 male participants, divided into FARP (n = 323) and healthy control (n = 73) groups. Demographic and disease characteristics were collected from the patients, and the 5-item International Index of Erectile Function, Patient Health Questionnaire-9, and Generalized Anxiety Disorder 7 were used to assess erectile function, depression, and anxiety symptoms. Baseline characteristics were described using descriptive statistics, logistic regression analysis identified factors influencing FARP, and its association with ED, depression, and anxiety were analyzed using linear and ordinal logistic regression analyses. Validity was ensured through subgroup and sensitivity analyses. OUTCOMES: The primary outcome was the association between FARP and ED, depression, and anxiety; the secondary outcome was the influencing factors of FARP such as lifestyle and work habits. RESULTS: Men with FARP were likely to have more serious ED (59.8% vs 32.9%), depression (20.7% vs 4.1%), and anxiety(31.5% vs 12.3%); have lower 5-item International Index of Erectile Function scores; or have higher Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7 scores compared with unaffected participants. Alcohol intake, family relationship, high work pressure, and prolonged bowel movements were significantly associated with FARP severity. The association between FARP with ED, depression, and anxiety was statistically significant in both crude and adjusted models. FARP was associated with 2.47, 2.73, and 2.67 times higher risk for ED, depression, and anxiety, respectively. An increase pain severity increased the incidence of ED (moderate pain: 4.80 times, P < .000; severe pain: 3.49 times, P < .004), depression (moderate pain: 1.85 times, P < .017; severe pain: 2.04 times, P < .037), and anxiety (moderate pain: 1.86 times, P < .014).Clinical Implications: Changes in lifestyle and work habits can help prevent pain symptom exacerbation. Attention to erection and psychological issues in patients with FARP and interdisciplinary comprehensive treatment may improve the efficacy. STRENGTHS AND LIMITATIONS: The study highlights a correlation between FARP and ED, depression, and anxiety, with pain severity being a contributing factor. However, the study's limitations include a small sample size and potential recall bias, and other sexual functions were not thoroughly explored. CONCLUSION: Patients with FARP have a higher prevalence of ED, depression, and anxiety, which increase with pain severity. Factors such as alcohol intake, work pressure, prolonged sitting, and longer defecation times are significantly correlated with FARP pain severity.

Programmable Thermo-Responsive Actuation of Hydrogels via Light-Guided Surface Growth of Active Layers on Shape Memory Substrates.

Hydrogel shape memory and actuating functionalities are heavily pursued and have found great potential in various application fields. However, their combination for more flexible and complicated morphing behaviors is still challenging. Herein, it is reported that by controlling the light-initiated polymerization of active hydrogel layers on shape memory hydrogel substrates, advanced morphing behaviors based on programmable hydrogel shapes and actuating trajectories are realized. The formation and photo-reduction-induced dissociation of Fe3+ -carboxylate coordination endow the hydrogel substrates with the shape memory functionality. The photo-reduced Fe2+ ions can diffuse from the substrates into the monomer solutions to initiate the polymerization of the thermally responsive active layers, whose actuating temperatures and amplitudes can be facially tuned by controlling their thicknesses and compositions. One potential application, a shape-programmable 3D hook that can lift an object with a specific shape, is also unveiled. The demonstrated strategy is extendable to other hydrogel systems to realize more versatile and complicated actuating behaviors.

COX17 restricts renal fibrosis development by maintaining mitochondrial copper homeostasis and restoring complex IV activity.

Renal fibrosis relies on multiple proteins and cofactors in its gradual development. Copper is a cofactor of many enzymes involved in renal microenvironment homeostasis. We previously reported that intracellular copper imbalance occurred during renal fibrosis development and was correlated with fibrosis intensity. In this study, we investigated the molecular mechanisms of how copper affected renal fibrosis development. Unilateral ureteral obstruction (UUO) mice were used for in vivo study; rat renal tubular epithelial cells (NRK-52E) treated with TGF-ß1 were adapted as an in vitro fibrotic model. We revealed that the accumulation of copper in mitochondria, rather than cytosol, was responsible for mitochondrial dysfunction, cell apoptosis and renal fibrosis in both in vivo and in vitro fibrotic models. Furthermore, we showed that mitochondrial copper overload directly disrupted the activity of respiratory chain complex IV (cytochrome c oxidase), but not complex I, II and III, which hampered respiratory chain and disrupted mitochondrial functions, eventually leading to fibrosis development. Meanwhile, we showed that COX17, the copper chaperone protein, was significantly upregulated in the mitochondria of fibrotic kidneys and NRK-52E cells. Knockdown of COX17 aggravated mitochondrial copper accumulation, inhibited complex IV activity, augmented mitochondrial dysfunction and led to cell apoptosis and renal fibrosis, whereas overexpression of COX17 could discharge copper from mitochondria and protect mitochondrial function, alleviating renal fibrosis. In conclusion, copper accumulation in mitochondria blocks complex IV activity and induces mitochondrial dysfunction. COX17 plays a pivotal role in maintaining mitochondrial copper homeostasis, restoring complex IV activity, and ameliorating renal fibrosis.

Neural transcription factor Pou4f1 promotes renal fibrosis via macrophage-myofibroblast transition.

Unresolved inflammation can lead to tissue fibrosis and impaired organ function. Macrophage-myofibroblast transition (MMT) is one newly identified mechanism by which ongoing chronic inflammation causes progressive fibrosis in different forms of kidney disease. However, the mechanisms underlying MMT are still largely unknown. Here, we discovered a brain-specific homeobox/POU domain protein Pou4f1 (Brn3a) as a specific regulator of MMT. Interestingly, we found that Pou4f1 is highly expressed by macrophages undergoing MMT in sites of fibrosis in human and experimental kidney disease, identified by coexpression of the myofibroblast marker, α-SMA. Unexpectedly, Pou4f1 expression peaked in the early stage in renal fibrogenesis in vivo and during MMT of bone marrow-derived macrophages (BMDMs) in vitro. Mechanistically, chromatin immunoprecipitation (ChIP) assay identified that Pou4f1 is a Smad3 target and the key downstream regulator of MMT, while microarray analysis defined a Pou4f1-dependent fibrogenic gene network for promoting TGF-ß1/Smad3-driven MMT in BMDMs at the transcriptional level. More importantly, using two mouse models of progressive renal interstitial fibrosis featuring the MMT process, we demonstrated that adoptive transfer of TGF-ß1-stimulated BMDMs restored both MMT and renal fibrosis in macrophage-depleted mice, which was prevented by silencing Pou4f1 in transferred BMDMs. These findings establish a role for Pou4f1 in MMT and renal fibrosis and suggest that Pou4f1 may be a therapeutic target for chronic kidney disease with progressive renal fibrosis.

Development of a Strategy for L-Lactic Acid Production by Rhizopus oryzae Using Zizania latifolia Waste and Cane Molasses as Carbon Sources.

As a biodegradable and renewable material, polylactic acid is considered a major environmentally friendly alternative to petrochemical plastics. Microbial fermentation is the traditional method for lactic acid production, but it is still too expensive to compete with the petrochemical industry. Agro-industrial wastes are generated from the food and agricultural industries and agricultural practices. The utilization of agro-industrial wastes is an important way to reduce costs, save energy and achieve sustainable development. The present study aimed to develop a method for the valorization of Zizania latifolia waste and cane molasses as carbon sources for L-lactic acid fermentation using Rhizopus oryzae LA-UN-1. The results showed that xylose derived from the acid hydrolysis of Z. latifolia waste was beneficial for cell growth, while glucose from the acid hydrolysis of Z. latifolia waste and mixed sugars (glucose and fructose) from the acid hydrolysis of cane molasses were suitable for the accumulation of lactic acid. Thus, a three-stage carbon source utilization strategy was developed, which markedly improved lactic acid production and productivity, respectively reaching 129.47 g/L and 1.51 g/L·h after 86 h of fermentation. This work demonstrates that inexpensive Z. latifolia waste and cane molasses can be suitable carbon sources for lactic acid production, offering an efficient utilization strategy for agro-industrial wastes.

Modular networks and genomic variation during progression from stable angina pectoris through ischemic cardiomyopathy to chronic heart failure.

BACKGROUND: Analyzing disease-disease relationships plays an important role for understanding etiology, disease classification, and drug repositioning. However, as cardiovascular diseases with causative links, the molecular relationship among stable angina pectoris (SAP), ischemic cardiomyopathy (ICM) and chronic heart failure (CHF) is not clear. METHODS: In this study, by integrating the multi-database data, we constructed paired disease progression modules (PDPMs) to identified relationship among SAP, ICM and CHF based on module reconstruction pairs (MRPs) of K-value calculation (a Euclidean distance optimization by integrating module topology parameters and their weights) methods. Finally, enrichment analysis, literature validation and structural variation (SV) were performed to verify the relationship between the three diseases in PDPMs. RESULTS: Total 16 PDPMs were found with K > 0.3777 among SAP, ICM and CHF, in which 6 pairs in SAP-ICM, 5 pairs for both ICM-CHF and SAP-CHF. SAP-ICM was the most closely related by having the smallest average K-value (K = 0.3899) while the maximum is SAP-CHF (K = 0.4006). According to the function of the validation gene, inflammatory response were through each stage of SAP-ICM-CHF, while SAP-ICM was uniquely involved in fibrosis, and genes were related in affecting the upstream of PI3K-Akt signaling pathway. 4 of the 11 genes (FLT1, KDR, ANGPT2 and PGF) in SAP-ICM-CHF related to angiogenesis in HIF-1 signaling pathway. Furthermore, we identified 62.96% SVs were protein deletion in SAP-ICM-CHF, and 53.85% SVs were defined as protein replication in SAP-ICM, while ICM-CHF genes were mainly affected by protein deletion. CONCLUSION: The PDPMs analysis approach combined with genomic structural variation provides a new avenue for determining target associations contributing to disease progression and reveals that inflammation and angiogenesis may be important links among SAP, ICM and CHF progression.

Role of dietary resistant starch in the regulation of broiler immunological characteristics.

Resistant starch (RS) has received increased attention due to its potential health benefits. This study was aimed to investigate the effects of dietary corn RS on immunological characteristics of broilers. A total of 320 broiler chicks were randomly allocated to five dietary treatments: normal corn-soyabean (NC) diet group, corn starch diet group, 4 %, 8 % and 12 % RS diet groups. This trial lasted for 42 d. The relative weights of spleen, thymus and bursa, the concentrations of nitric oxide (NO) and IL-4 in plasma at 21 d of age, as well as the activities of total nitric oxide synthase (TNOS) and inducible nitric oxide synthase (iNOS) in plasma at 21 and 42 d of age showed positive linear responses (P < 0·05) to the increasing dietary RS level. Meanwhile, compared with the birds from the NC group at 21 d of age, birds fed 4 % RS, 8 % RS and 12 % RS diets exhibited higher (P < 0·05) relative weight of bursa and concentrations of NO and interferon-γ in plasma. Birds fed 4 % RS and 8 % RS diets showed higher (P < 0·05) number of IgA-producing cells in the jejunum. While compared with birds from the NC group at 42 d of age, birds fed 12 % RS diet showed higher (P < 0·05) relative weight of spleen and activities of TNOS and iNOS in plasma. These findings suggested that dietary corn RS supplementation can improve immune function in broilers.

Output Enhancement of Triboelectric Nanogenerators Based on Hierarchically Regular Cadmium Coordination Polymers for Photocycloaddition.

Exploiting the well-arranged and tunable frameworks of crystalline materials, we herein report coordination polymers (CPs) with modulated hierarchical structures as triboelectric materials to construct and extend the application scope of triboelectric nanogenerators (TENGs). Different lengths and shapes of bridging ligands [4,4'-bpa = 1,2-bis(4-pyridyl)ethane, 4,4'-bpe = 1,2-bis(4-pyridyl)ethene, and 4,4'-bpp = 1,3-di(2-pyridyl)propane for 1, 2, and 3, respectively] were used to construct Cd-CP-based hierarchical frameworks. These compounds were used as triboelectric materials, and their electronic structure contributions were determined by the output of the corresponding TENGs. The results indicated that 2-TENG with the 4,4'-bpe ligand had the highest output, attributed to the improvement in the electron activity due to the π-conjugation group in the bridging ligand, which was further verified by density functional theory calculations. Furthermore, 2@PVDF (PVDF = polyvinylidene fluoride) composite films with different concentrations of Cd-CP were prepared. Detailed electrical characterizations revealed that the arrangement of 12% active constituents of Cd-CP-2 effectively enhanced the output performance of 2@PVDF-TENG, which could light up an ultraviolet lamp plate to successfully execute the [2 + 2] photocycloaddition.

DPP4/CD32b/NF-κB Circuit: A Novel Druggable Target for Inhibiting CRP-Driven Diabetic Nephropathy.

Diabetic nephropathy (DN) is a major cause of end-stage renal disease, but treatment remains ineffective. C-reactive protein (CRP) is pathogenic in DN, which significantly correlated with dipeptidyl peptidase-4 (DPP4) expression in diabetic patients with unknown reason. Here, using our unique CRPtg-db/db mice, we observed human CRP markedly induced renal DPP4 associated with enhanced kidney injury compared with db/db mice. Interestingly, linagliptin, a US Food and Drug Administration (FDA)-approved specific DPP4 inhibitor, effectively blocked this CRP-driven DN in the CRPtg-db/db mice. Mechanistically, CRP evoked DPP4 in cultured renal tubular epithelial cells, where CD32b/nuclear factor κB (NF-κB) signaling markedly enriched p65 binding on the DPP4 promoter region to increase its transcription. Unexpectedly, we further discovered that CRP triggers dimerization of DPP4 with CD32b at protein level, forming a novel DPP4/CD32b/NF-κB signaling circuit for promoting CRP-mediated DN. More importantly, linagliptin effectively blocked the circuit, thereby inhibiting the CRP/CD32b/NF-κB-driven renal inflammation and fibrosis. Thus, DPP4 may represent a precise druggable target for CRP-driven DN.