Genome sequencing of Coryphaenoides yaquinae reveals convergent and lineage-specific molecular evolution in deep-sea adaptation.

Abyssal (3501-6500 m) and hadal (>6500 m) fauna evolve under harsh abiotic stresses, characterized by high hydrostatic pressure, darkness and food shortage, providing unique opportunities to investigate mechanisms underlying environmental adaptation. Genomes of several hadal species have recently been reported. However, the genetic adaptation of deep sea species across a broad spectrum of ocean depths has yet to be thoroughly investigated, due to the challenges imposed by collecting the deep sea species. To elucidate the correlation between genetic innovation and vertical distribution, we generated a chromosome-level genome assembly of the macrourids Coryphaenoides yaquinae, which is widely distributed in the abyssal/hadal zone ranging from 3655 to 7259 m in depth. Genomic comparisons among shallow, abyssal and hadal-living species identified idiosyncratic and convergent genetic alterations underlying the extraordinary adaptations of deep-sea species including light perception, circadian regulation, hydrostatic pressure and hunger tolerance. The deep-sea fishes (Coryphaenoides Sp. and Pseudoliparis swirei) venturing into various ocean depths independently have undergone convergent amino acid substitutions in multiple proteins such as rhodopsin 1, pancreatic and duodenal homeobox 1 and melanocortin 4 receptor which are known or verified in zebrafish to be related with vision adaptation and energy expenditure. Convergent evolution events were also identified in heat shock protein 90 beta family member 1 and valosin-containing protein genes known to be related to hydrostatic pressure adaptation specifically in fishes found around the hadal range. The uncovering of the molecular convergence among the deep-sea species shed new light on the common genetic innovations required for deep-sea adaptation by the fishes.

Correlation Between C4/IgG with Macroproteinuria in Chronic Kidney Disease: A Pilot Study.

Background and Objectives: Loss of immunoglobulin G (IgG) is accompanied with proteinuria, especially macroproteinuria. The complement system participates kidney disease resulting in proteinuria. Whether the ratio of complement and IgG is associated with macroproteinuria remains unknown. Design Setting Participants and Measurements: A total of 1013 non-dialysis chronic kidney disease (CKD) patients were recruited according to the electrical case records system with 268 patients who endured kidney biopsy. Patients were grouped via the estimated glomerular filtration rate or the levels of proteinuria determination. Biomarkers in different CKD groups or proteinuria groups were compared by one-way ANOVA or independent samples t-test. Pearson or spearman analysis was employed to analyze correlation between clinical indexes. Further, influence factor of macroproteinuria was studied by using binary logistic regression. The ROC curve was performed to explore probable predictive biomarker for macroproteinuria. Results: No significant difference of complement C3 and C4 among CKD1 to CKD5 stages, while higher level of complement C4 in patients with macroproteinuria. Further, C4 had a positive correlation with proteinuria (r=0.255, p=0.006). After adjusted for age, IgA, IgM, triglyceride and HDL, a binary logistic regression model showed lnC4/IgG (OR=3.561, 95% CI 2.196-5.773, p<0.01), gender (OR=1.737, 95% CI 1.116-2.702, p=0.014), age (OR=0.983, 95% CI 0.969-0.997, p=0.014), and history of diabetes (OR=0.405, 95% CI 0.235-0.699, p<0.01) were independent influence factors of macroproteinuria. The area under the ROC curve was 0.77 (95% CI: 0.75-0.82, p<0.001) for C4/IgG. The analysis of ROC curves revealed a best cut-off for complement C4 was 0.024 and yielded a sensitivity of 71% and a specificity of 71%. The area under the ROC curve was 0.841 (95% CI: 0.735-0.946, p < 0.001) for C4/IgG in IgA nephropathy patients. The analysis of ROC curves revealed a best cut-off for complement C4/IgG was 0.026 and yielded a sensitivity of 75% and a specificity of 81.2%. The area under the ROC curve for C4/IgG in CKD1-5 stages were 0.772, 0.811, 0.785, 0.835, 0.674. Conclusion: Complement C4/IgG could be used to predict macroproteinuria.

Enhanced Carbon-Carbon Coupling at Interfaces with Abrupt Coordination Number Changes.

Cu-catalyzed electrochemical CO2 reduction reaction (CO2RR) produces multi-carbon (C2+) chemicals with considerable selectivities and activities, yet required high overpotentials impede its practical application. Here, we design interfaces with abrupt coordination number (CN) changes that greatly reduce the applied potential for achieving high C2+ Faradaic efficiency (FE). Encouraged by the mechanistic finding that the coupling between *CO and *CO(H) is the most probable C-C bond formation path, we use Cu2O- and Cu-phthalocyanine-derived Cu (OD-Cu and PD-Cu) to build the interface. Using operando X-ray absorption spectroscopy (XAS), we find that the Cu CN of OD-Cu is ~11, favoring CO* adsorption, while the PD-Cu has a COH*-favorable CN of ~4. Operando Raman spectroscopy revealed that the interfaces with abrupt CN changes promote *OCCOH formation. As a result, the designed catalyst achieves a C2+ FE of 85±2 % at 220 mA cm-2 in a zero-gap CO2 electrolyzer. An improvement of C2+ FE by 3 times is confirmed at the low potential regime where the current density is 60-140 mA cm-2, compared to bare OD-Cu. We report a 45-h stable CO2RR operation at 220 mA cm-2, producing a C2+ product FE of ~80 %.

Immobilized Tetraalkylammonium Cations Enable Metal-free CO2 Electroreduction in Acid and Pure Water.

Carbon dioxide reduction reaction (CO2 RR) provides an efficient pathway to convert CO2 into desirable products, yet its commercialization is greatly hindered by the huge energy cost due to CO2 loss and regeneration. Performing CO2 RR under acidic conditions containing alkali cations can potentially address the issue, but still causes (bi)carbonate deposition at high current densities, compromising product Faradaic efficiencies (FEs) in present-day acid-fed membrane electrode assemblies. Herein, we present a strategy using a positively charged polyelectrolyte-poly(diallyldimethylammonium) immobilized on graphene oxide via electrostatic interactions to displace alkali cations. This enables a FE of 85 %, a carbon efficiency of 93 %, and an energy efficiency (EE) of 35 % for CO at 100 mA cm-2 on modified Ag catalysts in acid. In a pure-water-fed reactor, we obtained a 78 % CO FE with a 30 % EE at 100 mA cm-2 at 40 °C. All the performance metrics are comparable to or even exceed those attained in the presence of alkali metal cations.

Site-Specific Anchoring a Luminescent Tag in a Protein with Non-Emissive Iridium(III) Complex.

Site-specific modification of proteins with synthetic fluorescent tag effectively improves the resolution of imaging, and such a labeling method with negligible three-dimensional structural perturbations and minimal impact on the biological functions of proteins is of high interest to dissect the high-resolution activities of biomolecules in complex systems. To this end, several non-emissive iridium(III) complexes [Ir(C-N)2 (H2 O)2 ]+ OTF- (C-N denotes various cyclometalated ligands) were designed and synthesized. These complexes were tested for attaching a protein by coordinating to H/X (HisMet, HisHis, and HisCys) that are separated by i and i+4 in α-helix. Replacement of the two labile water ligands in the iridium(III) complex by a protein HisHis pair increases the luminescent intensity up to over 100 folds. This labeling approach has been demonstrated in a highly specific and efficient manner in a number of proteins, and it is also feasible for labeling target proteins in cell lysates.

The arrival ward requiring help by wheelchair or medical cart, arterial oxygenation index, age, albumin and neutrophil count score: Predicting in-hospital mortality in Chinese patients with acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: In this study, we will derive and validate a prognostic tool to predict in-hospital death based on Chinese acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. METHODS: Independent predictors of in-hospital death were identified by logistic regression analysis and incorporated into a clinical prediction tool. RESULTS: The clinical prediction model was developed with data from 1121 patients and validated with data from 245 patients. The five predictors of in-hospital death from the development cohort (Arrival ward requiring help by wheelchair or medical cart, Arterial oxygenation index, Age, Albumin and Neutrophil count) were combined to form the AAAAN Score. The AAAAN Score achieved good discrimination (AUC = 0.85, 95% CI 0.81-0.89) and calibration (Hosmer-Lemeshow chi-square value was 3.33, p = 0.65). The AAAAN Score, which underwent internal bootstrap validation, also showed excellent discrimination for mortality (AUC = 0.85, 95% CI 0.81 to 0.89) and performed more strongly than other clinical prediction tools. Patients were categorized into 3 risk groups based on the scores: low risk (0-2 points, 0.7% in-hospital mortality), intermediate risk (3-4 points, 4.1% in-hospital mortality), and high risk (5-7 points, 23.4% in-hospital mortality). Predictive performance was confirmed by external validation. CONCLUSIONS: The AAAAN Score is a prognostic tool to predict in-hospital death in Chinese AECOPD patients.

A novel explainable online calculator for contrast-induced AKI in diabetics: a multi-centre validation and prospective evaluation study.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients. METHODS: 3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used. RESULTS: In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777-0.853)) and external validation (AUC: 0.816 (95% CI 0.770-0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783-0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755-0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688-0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator. CONCLUSION: We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions.

Perovskite-Derived Bismuth with I- and Cs+ Dual Modification for High-Efficiency CO2 -to-Formate Electrosynthesis and Al-CO2 Batteries.

Bi-based materials are one of the most promising candidates for electrochemical CO2 reduction reaction (CO2 RR) to formate; however, the majority of them still suffer from low current density and stability that essentially constrain their potential applications at the industrial scale. Surface modification represents an effective approach to modulate the electrode microenvironment and the relative binding strength of key intermediates. Herein, it is demonstrated that the surface comodification with halides and alkali metal ions from the conversion of Bi-based halide perovskite nanocrystals is a viable strategy to boost the CO2 RR performance of Bi for formate electrosynthesis. Cs3 Bi2 I9 nanocrystals are prepared by a hot-injection method. The as-prepared products feature well-defined hexagonal shape and uniform size distribution. When used as the precatalyst, Cs3 Bi2 I9 nanocrystals are converted to Cs+ and I- comodified Bi. The resultant catalyst exhibits high formate Faradaic efficiency close to 100%, and remarkable partial current density up to 44 mA cm-2 in an H-cell and up to 276 mA cm-2 in a flow cell. Moreover, Cs3 Bi2 I9 is used as the cathode catalyst and paired with an Al anode in an Al-CO2 battery for simultaneous CO2 valorization and power generation.

In-situ spectroscopic probe of the intrinsic structure feature of single-atom center in electrochemical CO/CO2 reduction to methanol.

While exploring the process of CO/CO2 electroreduction (COxRR) is of great significance to achieve carbon recycling, deciphering reaction mechanisms so as to further design catalytic systems able to overcome sluggish kinetics remains challenging. In this work, a model single-Co-atom catalyst with well-defined coordination structure is developed and employed as a platform to unravel the underlying reaction mechanism of COxRR. The as-prepared single-Co-atom catalyst exhibits a maximum methanol Faradaic efficiency as high as 65% at 30 mA/cm2 in a membrane electrode assembly electrolyzer, while on the contrary, the reduction pathway of CO2 to methanol is strongly decreased in CO2RR. In-situ X-ray absorption and Fourier-transform infrared spectroscopies point to a different adsorption configuration of *CO intermediate in CORR as compared to that in CO2RR, with a weaker stretching vibration of the C-O bond in the former case. Theoretical calculations further evidence the low energy barrier for the formation of a H-CoPc-CO- species, which is a critical factor in promoting the electrochemical reduction of CO to methanol.

Correlation of ACR and TcPO2 in diabetic kidney disease patients: A pilot study.

OBJECTIVE: Transcutaneous oxygen pressure (TcPO2) is used to assess microcirculation clinically; however, it is not widely available especially in rural hospital. The study was designed to explore potential alternatively biomarkers to assess microcirculation in diabetic kidney disease (DKD). METHODS: A total of 404 patients from Xuzhou first hospital were recruited according to the case records system. Patients were grouped via the ratio of albuminuria and creatinine (ACR; <30 mg/g, 30-300 mg/g, >300 mg/g). Biomarkers in different ACR groups were compared by analysis of variance. Correlation analysis was determined by Pearson or Spearman analysis and binary logistic regression. The receiver operating characteristics (ROC) curve was performed to elucidate the prediction effect of ACR on TcPO2. RESULTS: A total of 404 diabetic patients were recruited with 248 patients diagnosed as DKD and 156 non-DKDs. Age and cystatin C were significantly higher in the ACR3 group compared with those in the ACR1 group, whereas glomerular filtration rate, low-density lipoprotein cholesterol, and TcPO2 were markedly decreased in the ACR3 group (p < .05). Frequency of low TcPO2 (<40 mm Hg) was markedly increased as increment of ACR stages with 30.2% in the ACR3 group (p < .01). There was a negative correlation between TcPO2 and age, ACR, chronic kidney disease (CKD), fast blood glucose, diabetes mellitus (DM) duration, and diabetic neuropathy. Further, binary logistic regression showed ACR was an independent influence factor for low TcPO2. After adjusting for age, gender, hypertension, DM duration, body mass index, glycated hemoglobin, diabetic neuropathy, and CKD, ACR was still an independent influence factor for TcPO2 (odds ratio = 2.464, p < .01). The area under the ROC curve was 0.768 (95% confidence interval: 0.700-0.836, p < .001) for ACR. The analysis of ROC curves revealed a best cutoff for ACR was 75.25 mg/g and yielded a sensitivity of 71.7% and a specificity of 71.7%. CONCLUSIONS: ACR could be used as an alternative biomarker for assessing microcirculation in DKD patients.

Serum Cystatin C within 24 hours after admission: a potential predictor for acute kidney injury in Chinese patients with community acquired pneumonia.

BACKGROUND: Acute kidney injury (AKI) is common in patients with community-acquired pneumonia (CAP), and is associated with poor prognosis. Therefore, in this study, we evaluated whether AKI in Chinese patients with CAP could be well predicted by serum Cystatin C within 24 h after admission. METHODS: Univariate and multivariate logistic regression analyses were used to investigate independent factors of AKI in patients with CAP. RESULTS: Totally, 2716 patients with CAP were included in this study. 766 (28%) patients developed AKI. After multivariate logistic regression analysis, serum Cystatin C (odds ratio [OR] 4.27, 95% confidence interval [CI] 3.36-5.44; p < 0.001) was an independent factor for AKI in patients with CAP. Serum Cystatin C had an area under the receiver operating characteristic curve (AUC) of 0.81 for predicting AKI, with an optimal cutoff value of 1.37 mg/L, computing 68% sensitivity, 80% specificity. Furthermore, serum Cystatin C within 24 h after admission still had a good and stable prediction efficiency for AKI in various subgroups (age, gender, hypertension, diabetes, coronary artery disease, cardiac insufficiency, cerebrovascular disease, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, and tumor, albumin, anemia, platelet count, white blood cell count, and uric acid, confusion, uremia, respiratory rate, blood pressure, and age 65 years or older [CURB-65] score, acute respiratory failure, intensive care unit admission, and mechanical ventilation) of patients with CAP (AUCs: 0.69-0.84). CONCLUSION: Serum Cystatin C within 24 h after admission appears to be a good biomarker for predicting AKI in Chinese patients with CAP.

Shared responsibility of carbon emission for international trade based on carbon emission embodied between developing and developed countries.

Traditional Production-Based Accounting (PBA) principle does not consider the embodied carbon emissions in export and import trade. A multiregional input-output (MRIO) model is constructed to estimate the embodied carbon dioxide emissions of 41 countries and regions worldwide, based on the PBA and shared responsibility approach in this paper. The results indicate that the embodied carbon emissions in 2018 in China's export trade were 1326 million tons higher than that of import trade. China, India, and the USA have a different carbon coefficient in the 35 sectors, but electricity, gas, and water supply sectors are the largest coefficient for them. A reduction in carbon emission coefficient would contribute to a decrease in imports and exports. Through the empirical analysis of the embodied carbon emissions in China's import and export trade, it can be seen that China is a major producer of carbon emissions, not a consumer country, and has taken more carbon emissions responsibility for the world. The developed countries should take more shared carbon emission responsibility than the PBA. And it is more reasonable and impartial to assign developed and developing countries carbon emissions responsibility in the light of the shared responsibility method.

IKKα aggravates renal fibrogenesis by positively regulating the Wnt/ß-catenin pathway.

AKI (acute kidney injury) with maladaptive repair plays exacerbated role in renal fibrosis characterized by tubulointerstitial fibrosis. Previously, we reported that IKKα contributed to kidney regeneration and inhibited inflammation. Here, we first identified the role and mechanism of IKKα on TGF-ß1-induced fibrosis in human tubular epithelial cells and fibrotic kidneys. IKKα was up-regulated in kidney tubular epithelium in unilateral ureteral obstruction (UUO) and unilateral ischemic reperfusion injury (UIRI) mice. Immunohistochemical staining showed that IKKα was positively correlated with the extent of kidney fibrosis in tissue biopsies from chronic kidney disease (CKD) patients. Compared with wild-type controls, Ksp-IKKα-/- mice exhibited inactivated Wnt/ß-catenin pathway, decreased serum creatinine and interstitial fibrosis in the kidney after IRI. In TGF-ß1-stimulated human tubular epithelial cells, IKKα overexpression enhanced ß-catenin nuclear translocation. Blocking IKKα by siRNA specifically suppressed ß-catenin activation and downstream profibrotic genes such as fibronectin and α-smooth muscle actin (α-SMA). Taken together, our study demonstrated that IKKα aggravated renal fibrogenesis by activating Wnt/ß-catenin signalling pathway, providing a new target for the treatment of kidney fibrosis.

Morphological and molecular evolution of hadal amphipod's eggs provides insights into embryogenesis under high hydrostatic pressure.

Hadal zones are unique habitats characterized by high hydrostatic pressure (HHP) and scarce food supplies. The ability of eggs of species dwelling in hadal zones to develop into normal embryo under high hydrostatic pressure is an important evolutionary and developmental trait. However, the mechanisms underlying the development of eggs of hadal-dwelling species remain unknown due to the difficulty of sampling ovigerous females. Here, morphological and transcriptome analyses of eggs of the "supergiant" amphipod Alicella gigantea collected from the New Britain Trench were conducted. The morphology of A. gigantea eggs, including size, was assessed and the ultrastructure of the eggshell was investigated by scanning electron microscopy. Transcriptome sequencing and molecular adaptive evolution analysis of A. gigantea eggs showed that, as compared with shallow-water Gammarus species, genes exhibiting accelerated evolution and the positively selected genes were mostly related to pathways associated with "mitosis" and "chitin-based embryonic cuticle biosynthetic process", suggesting that "normal mitosis maintenance" and "cuticle development and protection" are the two main adaptation strategies for survival of eggs in hadal environments. In addition, the concentration of trimethylamine oxide (TMAO), an important osmotic regulator, was significantly higher in the eggs of hadal amphipods as compared to those of shallow-water species, which might promote the eggs' adaptation abilities. Morphological identification, evolutionary analysis, and the trimethylamine oxide concentration of A. gigantea eggs will facilitate a comprehensive overview of the piezophilic adaptation of embryos in hadal environments and provide a strategy to analyze embryogenesis under high hydrostatic pressure.

Efficient Protein-Protein Couplings Mediated by Small Molecules under Mild Conditions.

Protein-protein coupling reactions under physiological conditions that do not impact the three-dimensional structures of the proteins are in high demand. Owing to the combination of phenylsulfonyl and aldehyde groups in 5-fluoro-4-(phenylsulfonyl)picolinaldehyde (FPPA), the fluorine substituent shows high reactivity toward free thiols. In FPPA, the fluorine is more reactive than phenylsulfonyl for free thiols. Thus the first quantitative nucleophilic substitution can be followed by selective substitution of phenylsulfonyl by an additional thiol or cyclization of aldehyde with a 1,2-aminothiol molecule. The FPPA mediated protein-protein coupling proceeds efficiently under mild conditions, resulting in stable protein conjugates. This coupling method has negligible 3D structural perturbations on the target proteins, and it produces overall intact, nearly traceless, and native structural folds of proteins. It is highly suitable for reconstruction of proteins that are difficult to make and segmental isotopic labeling of multidomain proteins.

Tailoring a Nanochaperone to Regulate α-Synuclein Assembly.

Protein misassembly leads to the formation of dysfunctional and toxic molecular species relating to neurodegeneration in Parkinson's disease and Alzheimer's disease. Here, we tailored a nanochaperone (αS-nChap) for α-synuclein to regulate its assembly. The αS-nChap is capable of i) specifically recognizing α-synuclein; ii) dynamically capturing and stabilizing monomeric α-synuclein and retarding oligomerization; iii) tightly capturing oligomeric α-synuclein to prevent fibrillization; and iv) transporting α-synuclein oligomers to the lysosomal degradation system. The regulation of α-synuclein assembly by αS-nChap was studied in vitro. Moreover, the role of αS-nChap preventing α-synuclein pathology in cells and protecting neurons from apoptosis was investigated. The strategy of tailoring a nanochaperone to regulate aberrant assembly of pathogenic proteins provides important insights into protein misfolding diseases. We foresee that αS-nChap has therapeutic value for Parkinson's disease.

Gut Microbial Divergence Between Three Hadal Amphipod Species from the Isolated Hadal Trenches.

Amphipods are the dominant scavenging metazoan species in the hadal trenches at water depths below 6,000 m. The gut microbiota have been considered to be contribution to the adaptation of deep-sea organisms; however, few comparative analyses of animal gut microbiota between different isolated hadal environments have been done so far. Here, we employed high-throughput 16S rRNA sequencing to compare the gut microbial taxonomic composition and functional potential diversity of three hadal amphipod species, Hirondellea gigas, Bathycallisoma schellenbergi, and Alicella gigantea, collected from the Mariana Trench, Marceau Trench, and New Britain Trench in the Pacific Ocean, respectively. Results showed that different community compositions were detected across all the amphipod specimens based on the analyses of alpha-diversity, hierarchical cluster tree, and PCoA (principal coordinate analysis). Moreover, almost no correlation was observed between genera overrepresented in different amphipods by microbe-microbe correlations analysis, which suggested that the colonization of symbionts were host-specific. At genus level, Psychromonas was dominant in H. gigas, and Candidatus Hepatoplasma was overall dominant in A. gigantea and B. schellenbergi. Comparison of the functional potential showed that, though three hadal amphipod species shared the same predominant functional pathways, the abundances of those most shared pathways showed distinct differences across all the specimens. These findings pointed to the enrichment of particular functional pathways in the gut microbiota of the different isolated trench amphipods. Moreover, in terms of species relative abundance, alpha-diversity and beta-diversity, there was high similarity of gut microbiota between the two A. gigantea populations, which dwelled in two different localities of the same hadal trench. Altogether, this study provides an initial investigation into the gut-microbial interactions and evolution at the hadal depths within amphipod. Each of these three amphipod species would be a model taxa for future studies investigating the influence habitat difference and geography on gut-microbial communities.

Deficiency of IKKα in Macrophages Mitigates Fibrosis Progression in the Kidney after Renal Ischemia-Reperfusion Injury.

Aims. Acute kidney injury (AKI) can lead to chronic kidney disease (CKD), and macrophages play a key role in this process. The aim of this study was to discover the role of IκB kinase α (IKKα) in macrophages in the process of AKI-to-CKD transition. Main Methods. We crossed lyz2-Cre mice with IKKα-floxed mice to generate mice with IKKα ablation in macrophages (Mac IKKα-/-). A mouse renal ischemia/reperfusion injury (IRI) model was induced by clamping the renal artery for 45 minutes. Treated mice were evaluated for blood biochemistry, tissue histopathology, and fibrosis markers. Macrophages were isolated from the peritoneal cavity for coculturing with tubular epithelial cells (TECs) and flow cytometry analysis. Key Findings. We found that fibrosis and kidney function loss after IRI were significantly alleviated in Mac IKKα-/- mice compared with wild-type (WT) mice. The expression of fibrosis markers and the infiltration of M2 macrophages were decreased in the kidneys of Mac IKKα-/- mice after IRI. The in vitro experiment showed that the IRI TECs cocultured with IKKα-/- macrophages (KO MΦs) downregulated the fibrosis markers accompanied by a downregulation of Wnt/ß-catenin signaling. Significance. These data support the hypothesis that IKKα is involved in mediating macrophage polarization and increasing the expression of fibrosis-promoting inflammatory factors in macrophages. Therefore, knockdown of IKKα in macrophages may be a potential method that can be used to alleviate the AKI-to-CKD transition after IRI.

SIX1 Activation Is Involved in Cell Proliferation, Migration, and Anti-inflammation of Acute Ischemia/Reperfusion Injury in Mice.

Nephrogenic proteins are re-expressed after ischemia/reperfusion (I/R) injury; however, the role of these proteins is still unknown. We found that sine oculis homeobox 1 (SIX1), a developmentally regulated homeoprotein, is reactivated in tubular epithelial cells after I/R injury associated with cell proliferation/migration and anti-inflammation. We demonstrated that SIX1 promoted cell proliferation by upregulating cyclin and glycolytic genes, and might increase cell migration by upregulating the expression of matrix metalloproteinase 9 (MMP9) directly or indirectly in the cell model. Notably, SIX1 targeted the promoters of the amino-terminal enhancer of split (AES) and fused in sarcoma (FUS), which are cofactors of nuclear factor-κB (NF-κB) subunit RELA, and then inhibited the transactivation function of RELA. The expression of monocyte chemotactic protein-1 (MCP-1) was decreased by the SIX1-mediated NF-κB pathway. Our results showed that the expression of cyclin, glycolytic genes, and MMP9 were significantly increased, and the infiltration of monocytes/macrophages (Mophs) was suppressed in SIX1 overexpression kidney at 1, 2, and 3 days after reperfusion. The overexpression of SIX1 resulted in reducing kidney damage from I/R injury in mice by promoting cell proliferation and migration and by inhibiting inflammation. Our study provides evidence that SIX1 involved in cell proliferation, migration, and anti-inflammation in the I/R model, which might be a potential therapeutic target that could be used to ameliorate kidney damage.