Deciphering heterojunction layered double hydroxide-polyaniline-carbon nanotubes for phosphorus capture in capacitive deionization.

The capacitive deionization (CDI) has emerged as a robust technology due to its effective performance in removing and recovering phosphate in wastewater. However, there are still challenges in achieving fast charge transfer and high capacity phosphorus storage simultaneously. In this study, a layered double hydroxide-polyaniline-carbon nanotubes composite material (ZnFe-PANI/CNT) with heterojunction and pseudocapacitive characteristics was fabricated via a simple and effective precipitation strategy. The existence of heterojunction and pseudocapacitance of ZnFe-PANI/CNT was confirmed through material performance testing Moreover, with its fast charge transfer and high ion storage performance, it was achieved high phosphate adsorption efficiency (94 %) and sustainable electrode regeneration in low concentration phosphate wastewater. Ultraviolet photoelectron spectroscopy (UPS) and density functional theory revealed the ability to accelerate charge transfer, which was contributed by the heterojunction ZnFe-PANI/CNT. In addition, it was found that the synergies of electrostatic attraction, ligand exchange and surface complexation contributed to the high phosphate capture ability in the acidic environments. The binuclear bidentate or mononuclear bidentate structures dominated the surface configuration of phosphate adsorption at pH 4-9.

[Clinical analysis of resection and dura skull base reconstruction of cranionasal communication tumor in 31 cases].

Objective:To explore the methods of resection, dura and skull base repair and reconstruction of cranionasal communication tumor. Methods:Data of 31 patients with cranionasal communication tumor who underwent dura and skull base reconstruction after tumor resection from 2018 to 2022 were collected. Follow-up lasted for 3 to 41 months. Results:A total of 31 patients were enrolled, including 20 males and 11 females. The ages ranged from 19 to 74 years, with a median age of 57 years old. There were 17 benign lesions（one case of hemangioma, one case of Rathke cyst, one case of squamous papilloma, one case of craniopharyngioma, two cases of meningocele, two cases of varus papilloma, two cases of meningioma of grade Ⅰ, three cases of schwannoma, four cases of pituitary tumor） and 14 malignant lesions（one case of osteosarcoma, one case of poorly differentiated carcinoma, two cases of varus papilloma malignancy, two cases of olfactory neuroblastoma, two cases of adenocarcinoma, two cases of adenoid cystic carcinoma, four cases of squamous cell carcinoma） . Sixteen cases underwent nasal endoscopy combined with craniofacial incision and 15 cases underwent nasal endoscopy surgery alone. Complete resection of the mass and dura and skull base reconstruction were performed in all 31 patients, and free graft repair was performed in 8 cases（fascia lata in 5 cases and nasal mucosa in 3 cases）. Twenty-three cases were repaired with pedicled flaps（septal mucosal flap alone in 11 cases, septal mucosal flap combined with free graft in 6 cases, and cap aponeurosis combined with free graft in 6 cases）. Eight out of 31 patients underwent skull base bone repair. Postoperative cerebral hemorrhage occurred in 1 case, cerebrospinal fluid leakage in 1 case, intracranial infection in 2 cases. All patients were successfully treated without severe sequelae. Cerebrospinal fluid leakage and intracranial infection occurred in one patient after radiotherapy, who recovered after conservative treatment. All 17 patients with benign lesions survived. Thirteen out of 14 patients with malignant lesions received radiotherapy after surgery, nine survived without recurrence, five cases recurred, of which 2 survived with tumor, one underwent reoperation and 2 died. Conclusion:Cranionasal communication tumors are high-risk diseases of anterior and middle skull base, and various surgical repair methods could be selected after complete resection of the tumor. Successful reconstruction and multidisciplinary cooperation are crucial for treatment outcome.

Gene therapy for cross-correction of somatic organs and the CNS in mucopolysaccharidosis II in rodents and non-human primates.

Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by deficient activity of iduronate-2-sulfatase (I2S), leading to pathological accumulation of glycosaminoglycans (GAGs) in tissues. We used iduronate-2-sulfatase knockout (Ids KO) mice to investigate if liver-directed recombinant adeno-associated virus vectors (rAAV8-LSP-hIDSco) encoding human I2S (hI2S) could cross-correct I2S deficiency in Ids KO mouse tissues, and we then assessed the translation of mouse data to non-human primates (NHPs). Treated mice showed sustained hepatic hI2S production, accompanied by normalized GAG levels in somatic tissues (including critical tissues such as heart and lung), indicating systemic cross-correction from liver-secreted hI2S. Brain GAG levels in Ids KO mice were lowered but not normalized; higher doses were required to see improvements in brain histology and neurobehavioral testing. rAAV8-LSP-hIDSco administration in NHPs resulted in sustained hepatic hI2S production and therapeutic hI2S levels in cross-corrected somatic tissues but no hI2S exposure in the central nervous system, perhaps owing to lower levels of liver transduction in NHPs than in mice. Overall, we demonstrate the ability of rAAV8-LSP-hIDSco to cross-correct I2S deficiency in mouse somatic tissues and highlight the importance of showing translatability of gene therapy data from rodents to NHPs, which is critical for supporting translation to clinical development.

SRC-3 Knockout Attenuates Myocardial Injury Induced by Chronic Intermittent Hypoxia in Mice.

This study investigated the effects of chronic intermittent hypoxia (CIH), a model of sleep apnea syndrome (SAS), on cardiac function. SRC-3 was extremely lowly expressed in the adult mouse heart tissue, while SRC-3 was highly expressed in the adult mouse heart tissue after CIH, suggesting that SRC-3 is involved in CIH model. We further studied the role of SRC-3 in CIH-induced myocardial injury in mice. Twenty-four healthy Balb/c male mice (n = 16, wild type; n = 8, SRC-3 knockout (SRC3-KO)) were randomly divided into three groups: air control (Ctrl), CIH, and CIH+SRC3-KO. Mice were exposed to CIH for 12 weeks. qRT-PCR was used to evaluate cardiac expression of the following genes: 11HSD1, 11HSD2, GR, MR, COX-2, OPN, NOX2, HIF-1-α, IL-1ß, IL-6, iNOS, TNF-α, PC-1, and TGF-ß. Enzymatic levels of SOD, CAT, MDA, NOS, and NO in the mouse hearts were determined using commercially available kits. Immunohistochemistry (IHC) was used to evaluate NF-κB expression in cardiac tissues. A transmission electron microscope (TEM) was used to evaluate myocardial ultrastructure. TUNEL staining was used to assess myocardial cell apoptosis. CIH induced cardiac damage, which was ameliorated in the SRC-3 KO mice. CIH significantly increased the heart-to-body weight ratio, expression of all aforementioned genes except 11HSD1, GR, and MR, and increased the levels of MDA, NOS, NO, and NF-κB, which were attenuated in the SRC-3 KO mice. The CIH group had the lowest SOD and CAT levels, which were partially recovered in the CIH+SRC3-KO group. 11HSD2 gene expression was elevated in both the CIH and CIH+SRC3-KO groups compared to the Ctrl group. The CIH group had severe myocardial cell apoptosis and mitochondrial dysfunction, which were alleviated in the CIH+SRC3-KO group. CIH causes cardiac damage through inducing oxidative stress and inflammation. Knockout of SRC-3 ameliorates CIH-induced cardiac damage through antagonizing CIH-triggered molecular changes in cardiac tissue.

The different correlations between obesity and osteoporosis after adjustment of static mechanical loading from weight and fat free mass.

OBJECTIVES: To explore complex correlations between obesity (OB) and osteoporosis (OP) after adjustment of static mechanical loading from weight and fat free mass (FFM). METHODS: A total of 3749 Chinese aged ≥65 years were selected from our ongoing cohort study. OB indices and bone mineral density (BMD) were measured for each subject. Linear regression analyses were performed to explore the correlations between OB indices and OP under three adjustment models (unadjusted, adjusted with weight and adjusted with FFM). RESULTS: Under no adjustment, three general obesity indices (body mass index: BMI, fat mass: FM, and percentage FM: PFM) were positively associated with BMD at three skeletal sites (P<0.001) in the regression analyses. However, after the adjustment with weight, these associations were mostly significant but reverse i.e., negatively in direction. After adjustment with FFM, the three indices were still positively and significantly (P<0.001) associated with BMD but regression coefficients were smaller compared to the unadjusted associations. Similar associations were observed for central adiposity and lower limb adiposity indices. CONCLUSIONS: The combined relation of OB to OP due to the physiological factors secreted from adipose tissues and the static mechanical loading from FM is positive in direction.

An overview of surface-enhanced Raman scattering substrates by pulsed laser deposition technique: fundamentals and applications.

Metallic nanoparticles (NPs), as an efficient substrate for surface-enhanced Raman scattering (SERS), attract much interests because of their various shapes and sizes. The appropriate size and morphology of metallic NPs are critical to serve as the substrate for achieving an efficient SERS. Pulsed laser deposition (PLD) is one of the feasible physical methods employed to synthesize metallic NPs with controllable sizes and surface characteristics. It has been recognized to be a successful tool for the deposition of SERS substrates due to its good controllability and high reproducibility in the manufacture of metallic NPs. This review provides an overview about the recent advances for the preparation of SERS substrates by PLD technique. The influences of parameters on the sizes and morphologies of metallic NPs during the deposition processes in PLD technique including laser output parameters, gas medium, liquid medium, substrate temperature, and properties of 3D substrate are presented. The applications of SERS substrates produced by PLD in the environmental monitoring and biomedical analysis are summarized. This knowledge could serve as a guideline for the researchers in exploring further applications of PLD technique in the production of SERS substrate.

Adjustable magnetoresistance in semiconducting carbonized phthalonitrile resin.

Herein, we report the first example of controllable magnetoresistance in a semiconducting carbonized phthalonitrile resin. This special phenomenon is explained using the different ratios of graphite-like (sp2) and diamond-like (sp3) bonds and localization length (a0) as well as the density of states at the Fermi-level (N(EF)).

Solvent-free nanoalumina loaded nanocellulose aerogel for efficient oil and organic solvent adsorption.

HYPOTHESIS: Cellulose-based aerogel, due to its rich reserves, environmental friendliness and porous structure, is considered as a new type of adsorbents for treating oil and water pollution. However, the functionalization of cellulose aerogel is still required for the efficient increase of its adsorption performance in wide applications. The combination of nanomaterials could significantly improve the adsorption capability of nanocellulose aerogel. EXPERIMENTS: In this work, nanocomposite aerogels comprising of nanocellulose and nanoalumina (NC/Al2O3) are produced via a solvent-free method and the effect of weight ratios between nanocellulose and nanoalumina on the adsorption properties of NC/Al2O3 aerogels has been studied. FINDINGS: The results reveal that the NC/Al2O3 aerogel with a low density of 5.1 mg cm-3 could obtain the optimal pore microstructures and the highest oil and organic solvent adsorption capacities with the preparation condition under the nanocellulose/nanoalumina weight ratio of 1:0.25 and 0.4 wt% of nanocellulose in aqueous solution. The presence of nanoalumina facilitates the change of microstructure morphologies, the increase of BET specific surface area and the adsorption capacities of NC aerogel. Compared with pure NC aerogel (74.07 ± 1.67, 69.87 ± 1.01, 81.21 ± 3.20, 52.07 ± 1.70, 48.49 ± 1.01, 75.45 ± 3.58 and 87.03 ± 0.46 g g-1 for thiophene, anhydrous ethanol, ethyl acetate, cyclohexane, sesame oil, acetone and dichloromethane, respectively), the NC/Al2O3 aerogel manifests an outstanding adsorption capacity (108.07 ± 0.37, 89.91 ± 4.83, 93.93 ± 3.81, 71.13 ± 2.48, 64.83 ± 2.25, 85.19 ± 3.87 and 117.65 ± 5.68 g g-1, accordingly). By considering the desirable performance features and the convenient fabrication approach, this nanocellulose nanocomposite aerogel might be a feasible alternative for oily waste water recovery and conservation of environment.

Magnetic nanocellulose-magnetite aerogel for easy oil adsorption.

HYPOTHESIS: Cellulose aerogels are a new category of high-efficiency adsorbents for treating oil spills and water pollution. However, the hydrophilic properties and recyclability of aerogels after adsorption hamper developments and applications. Combining both hydrophobic and magnetic properties are expected to improve their adsorption capacity and functionality. EXPERIMENTS: In this study, the effect of oleic acid (OA) and nanomagnetite on the preparation of magnetic nanocellulose aerogels (called as NCA/OA/Fe3O4) by a mechanical mixing combined with freeze-drying method have been investigated. FINDINGS: It has been found that the optimal condition for fabricating this NCA/OA/Fe3O4 aerogel is 0.4 wt% nanocellulose, 3 mg mL-1 OA and 0.5 wt% Fe3O4 in the aqueous solution. This aerogel has a very low density of 9.2 mg cm-3 and demonstrates a high adsorption capacity of 68.06 g g-1 for cyclohexane. In addition, this aerogel adsorbent demonstrates an excellent magnetic responsivity and can be easily recycled by a permanent magnet after adsorption. As a consequence, this hydrophobic magnetic NCA/OA/Fe3O4 aerogel is promising not only for easy oil and organic solvent adsorption but also potentially for other magnetic related applications.

Constructing interconnected spherical hollow conductive networks in silver platelets/reduced graphene oxide foam/epoxy nanocomposites for superior electromagnetic interference shielding effectiveness.

How to significantly increase electromagnetic interference (EMI) shielding performances by improving electrical conductivities is still a serious challenge. Herein, we have explored and prepared a 3D silver platelets/reduced graphene oxide foam (AgPs/rGF) with numerous regular spherical hollow structures, which ingeniously achieved uniform dispersion of the AgPs along the 3D rGO network via the sol-gel template method. Combining AgPs/rGF with epoxy resin (EP), 3D AgPs/rGF/EP nanocomposites with highly regular segregated structures were successfully fabricated. Due to interconnected spherical hollow conductive networks of the AgPs/rGF and the interfacial synergy between AgPs/rGF and EP, the 3D AgPs/rGF/EP nanocomposites containing 0.44 vol% rGF and 0.94 vol% AgPs show the maximum EMI shielding effectiveness (SE) value of 58 dB in the X-band (shielding 99.9998% of incident electromagnetic waves), 274% improvement in comparison with that of 3D rGF/EP nanocomposites (∼21 dB). The corresponding electrical conductivity improves from 0.1 to 45.3 S m-1, and the dielectric loss increases from ∼0.6 to ∼0.8. In addition, the theoretical minimum skin depth of the 3D AgPs/rGF/EP nanocomposites is calculated by analyzing the skin effect. It provides a guideline for fabricating lightweight, thin and multi-functional shielding nanocomposites in the key fields of spacecraft and high precision electronics.

Characteristics and prognosis of idiopathic sudden sensorineural hearing loss in aged people: a retrospective study.

Background: Few studies focused on the prognosis of sudden sensorineural hearing loss (ISSHL) of aged people. Objectives: The aim of this study is to analyze the characteristics, treatment, and prognostic factors of ISSHL in aged people. Material and methods: A total of 278 patients diagnosed of ISSHL in aged people from 2014 to 2019 were retrospectively analyzed. Univariates were analyzed by univariate and multivariate logistic analysis. Results: Among the 13 univariates, the patients' age was younger in the overall recovery group ORG (p = .018), while onset days was shorter in ORG (p = .000). The percentage of DM and HTN comorbidities were higher in ORG (p = .026 and .038). Meanwhile differences were significant in audiogram configurations (p = .037), the degree of hearing loss (p = .033), and types of lipid treatment (p = .020). Then these seven independent risk factors were included in the multivariate analysis, final results indicated that hypertension (p = .028), lipid control groups (p = .009), age (p = .000), and onset days (p = .001) were related to the treatment outcome of ISSHL. Conclusions: The prognosis of ISSHL in aged patients was closely related to age, the onset days of treatment, and good control of complications such as hypertension and hyperlipidemia, so vascular factors were considered as the main causes of morbidity.

Controllable organic magnetoresistance in polyaniline coated poly(p-phenylene-2,6-benzobisoxazole) short fibers.

Herein, we first report a tunable organic magnetoresistance (OMAR) effect in polyaniline (PANI) coated acid treated poly(p-phenylene-2,6-benzobisoxazole) (t-PBO) short fibers. This unique OMAR is interpreted using the paramagnetic nature of PBO molecules combined with the localization length a0 calculated from the wave-function shrinkage model and forward interference model.

Phosphoproteome Analysis of Cells Infected with Adapted and Nonadapted Influenza A Virus Reveals Novel Pro- and Antiviral Signaling Networks.

Influenza A viruses (IAVs) quickly adapt to new environments and are well known to cross species barriers. To reveal a molecular basis for these phenomena, we compared the Ser/Thr and Tyr phosphoproteomes of murine lung epithelial cells early and late after infection with mouse-adapted SC35M virus or its nonadapted SC35 counterpart. With this analysis we identified a large set of upregulated Ser/Thr phosphorylations common to both viral genotypes, while Tyr phosphorylations showed little overlap. Most of the proteins undergoing massive changes of phosphorylation in response to both viruses regulate chromatin structure, RNA metabolism, and cell adhesion, including a focal adhesion kinase (FAK)-regulated network mediating the regulation of actin dynamics. IAV also affected phosphorylation of activation loops of 37 protein kinases, including FAK and several phosphatases, many of which were not previously implicated in influenza virus infection. Inhibition of FAK proved its contribution to IAV infection. Novel phosphorylation sites were found on IAV-encoded proteins, and the functional analysis of selected phosphorylation sites showed that they either support (NA Ser178) or inhibit (PB1 Thr223) virus propagation. Together, these data allow novel insights into IAV-triggered regulatory phosphorylation circuits and signaling networks.IMPORTANCE Infection with IAVs leads to the induction of complex signaling cascades, which apparently serve two opposing functions. On the one hand, the virus highjacks cellular signaling cascades in order to support its propagation; on the other hand, the host cell triggers antiviral signaling networks. Here we focused on IAV-triggered phosphorylation events in a systematic fashion by deep sequencing of the phosphoproteomes. This study revealed a plethora of newly phosphorylated proteins. We also identified 37 protein kinases and a range of phosphatases that are activated or inactivated following IAV infection. Moreover, we identified new phosphorylation sites on IAV-encoded proteins. Some of these phosphorylations support the enzymatic function of viral components, while other phosphorylations are inhibitory, as exemplified by PB1 Thr223 modification. Our global characterization of IAV-triggered patterns of phospho-proteins provides a rich resource to further understand host responses to infection at the level of phosphorylation-dependent signaling networks.

Super light 3D hierarchical nanocellulose aerogel foam with superior oil adsorption.

In this work, the concentration effect of both nanocellulose and sodium dodecylsulfate (SDS) on the fabrication of a super light 3D hierarchical framework adsorbent nanocellulose aerogel foam (NAF) is exploited through a high speed mechanical foaming and solvent-free method by adding SDS. The results show that the optimal concentration of nanocellulose and SDS for preparation of this 3D NAF/SDS is 0.4 and 0.2 wt%, accordingly. By utilizing unique gridding framework of NAF/SDS, a low density of 1.50 mg cm-3 and high adsorption capacity of 206.79, 194.75 and 145.20 g g-1 towards cyclohexane, ethyl acetate, and vacuum pump oil, accordingly, are achieved in the as-prepared NAF/SDS, which is much higher than that of conventional nanocellulose aerogel (NA) (52.07, 81.12 and 34.52 g g-1, respectively). The results illustrate that this NAF/SDS is a promising candidate for preparing 3D hierarchical network structure from natural polymer cellulose in an environmental control for oil adsorption.

Progress on the Photocatalytic Reduction Removal of Chromium Contamination.

Rapid industrialization leads to increased wastewater discharge encompassing hexavalent chromium (Cr(VI)), which leads to serious environmental problems of toxicity and potential carcinogenicity. Removal of these species is normally carried out by ion-exchange, precipitation, membrane filtration, sorption, photocatalytic reduction, etc. This review mainly focuses on the photocatalytic and photoelectrocatalytic (PEC) reduction of Cr (VI), because of their advantages over other methods such as reduced risk of secondary pollution by non-reduced Cr (VI), no sludge formation, no need for a large amount of chemical reagents, clean and easy installation. The main factors influencing the photocatalytic reduction efficiency of Cr (VI) such as catalyst activity, solution pH, Cr adsorption on the catalyst and additives, are briefly discussed. Finally, a special emphasis is provided to the photoelectrocatalytic (PEC) reduction of Cr (VI).

X-linked Alport syndrome: pathogenic variant features and further auditory genotype-phenotype correlations in males.

OBJECTIVE: To analyze the clinical audiological characteristics of X-Linked Alport syndrome (XLAS) in males and their relationships with genotypes. METHODS: The clinical data of 87 male patients with AS were reviewed. Hearing levels were evaluated using pure tone audiometry (PTA) testing, acoustic immittance, and otoacoustic emissions (OAE) testing. The genotypes of COL4A5 and the pathogenic variants were analyzed. The relationships between auditory phenotypes and genotypes were analyzed. RESULTS: Among the 87 patients, the number of patients with normal hearing and hearing loss were 32 and 55, respectively. In all cases, the hearing loss was characterized as bilateral symmetrical sensorineural deafness. Majority of the patients had mild-to-moderate hearing loss. Hearing loss usually started in the middle frequency range and gradually affected high frequencies, at school age and gradually increased with increasing age. However, it maintained a relatively steady level of 50-60 dB HL during the teenage years. The audiometric curves included groove-type in 51 cases (92.73%). Patients were identified to have 60 different COL4A5 pathogenic variants. Of the 49 patients who were followed-up for more than 2 years, 28 cases presented a decreasing trend in the hearing level of about 5 dB per year. The degree of hearing loss was positively correlated with gene mutation type and renal function. CONCLUSIONS: Hearing loss in males with XLAS is symmetrical sensorineural, and progressive with increasing age. There is a significant correlation between the degree of hearing loss and genotype, renal function, and age.

A superfast hexavalent chromium scavenger: Magnetic nanocarbon bridged nanomagnetite network with excellent recyclability.

In this work, a nanocarbon bridged nanomagnetite network (NC-NMN) is developed through the electrospinning of epichlorohydrin functionalized polystyrene (f-PS), followed by the direct calcination of f-PS and ferric nitrate, which is capable of superfast removing hexavalent chromium (Cr(VI)) from polluted water within only 15 s benefiting from its gridding framework, with an adsorption rate constant of 1.64 g mg-1 min-1 according to the pseudo-second-order kinetics. The well-fitted Langmuir isotherm model indicates a monolayer adsorption for Cr(VI) on NC-NMN. The thermodynamic parameters including negative ΔG° and positive ΔH° demonstrate that the Cr(VI) adsorption on NC-NMN is spontaneous and endothermic. The Cr(VI) adsorption retention, which is only 3.8%, is achieved for NC-NMN after five cycles, exhibiting a prominent stability and an excellent recyclability. X-ray photoelectron spectroscopy (XPS), zeta potential and energy-filter transmission electron spectroscopy (EFTEM) results illustrate that both the electrostatic attraction and the network structure of NC-NMN are responsible for the superior Cr(VI) adsorption performance. This work intends to provide a new method for designing the novel structure materials for polluted water treatment.

Association of Plasma Irisin with Bone Mineral Density in a Large Chinese Population Using an Extreme Sampling Design.

Irisin, a myokine produced by skeletal muscle in response to physical exercise, promotes trans-differentiation of white adipose tissue into brown adipose tissue. Recent evidences suggested that irisin also plays an important role in the control of bone metabolism. This study aimed to ascertain the relationship between plasma irisin and bone mineral density (BMD) in Chinese population by adoption of an extreme sampling method. Based on a large and screened Chinese elderly population (N = 6308), two subgroups with extremely high and low hip BMD were selected for discovery (N = 80, high vs. low BMD = 44:36) and validation (N = 60, high vs. low BMD = 30:30), respectively. Plasma irisin, P1NP, and ß-CTx were measured using commercially available ELISA kits. Other metabolic parameters (e.g., blood glucose, total cholesterol and triglycerides) were collected. Student's t test and Spearman correlation analyses were conducted in SPSS. Significant difference was discovered for plasma irisin between females and age-matched males (N = 80, male vs. female = 42:38, P = 0.002). The plasma irisin levels were significantly higher in high BMD subjects than in low BMD subjects, which was observed in both discovery (P = 0.012) and validation samples (P = 0.022). However, such observation was limited to males only. Further correlation analyses in males showed that plasma irisin was correlated with BMD (r = 0.362, P = 0.025) and triglyceride (r = - 0.354, P = 0.032). Plasma irisin levels were associated with hip BMD in Chinese elderly men. This study represented the first effort of investigating the relationship of plasma irisin and BMD in elderly population. The positive correlation between plasma irisin and BMD hints intrinsic communication between muscle and bone.

Site-specific identification and quantitation of endogenous SUMO modifications under native conditions.

Small ubiquitin-like modifier (SUMO) modification regulates numerous cellular processes. Unlike ubiquitin, detection of endogenous SUMOylated proteins is limited by the lack of naturally occurring protease sites in the C-terminal tail of SUMO proteins. Proteome-wide detection of SUMOylation sites on target proteins typically requires ectopic expression of mutant SUMOs with introduced tryptic sites. Here, we report a method for proteome-wide, site-level detection of endogenous SUMOylation that uses α-lytic protease, WaLP. WaLP digestion of SUMOylated proteins generates peptides containing SUMO-remnant diglycyl-lysine (KGG) at the site of SUMO modification. Using previously developed immuno-affinity isolation of KGG-containing peptides followed by mass spectrometry, we identified 1209 unique endogenous SUMO modification sites. We also demonstrate the impact of proteasome inhibition on ubiquitin and SUMO-modified proteomes using parallel quantitation of ubiquitylated and SUMOylated peptides. This methodological advancement enables determination of endogenous SUMOylated proteins under completely native conditions.

Sirtuin 5 is required for mouse survival in response to cardiac pressure overload.

In mitochondria, the sirtuin SIRT5 is an NAD+-dependent protein deacylase that controls several metabolic pathways. Although a wide range of SIRT5 targets have been identified, the overall function of SIRT5 in organismal metabolic homeostasis remains unclear. Given that SIRT5 expression is highest in the heart and that sirtuins are commonly stress-response proteins, we used an established model of pressure overload-induced heart muscle hypertrophy caused by transverse aortic constriction (TAC) to determine SIRT5's role in cardiac stress responses. Remarkably, SIRT5KO mice had reduced survival upon TAC compared with wild-type mice but exhibited no mortality when undergoing a sham control operation. The increased mortality with TAC was associated with increased pathological hypertrophy and with key abnormalities in both cardiac performance and ventricular compliance. By combining high-resolution MS-based metabolomic and proteomic analyses of cardiac tissues from wild-type and SIRT5KO mice, we found several biochemical abnormalities exacerbated in the SIRT5KO mice, including apparent decreases in fatty acid oxidation and glucose oxidation as well as an overall decrease in mitochondrial NAD+/NADH. Together, these abnormalities suggest that SIRT5 deacylates protein substrates involved in cellular oxidative metabolism to maintain mitochondrial energy production. Overall, the functional and metabolic results presented here suggest an accelerated development of cardiac dysfunction in SIRT5KO mice in response to TAC, explaining increased mortality upon cardiac stress. Our findings reveal a key role for SIRT5 in maintaining cardiac oxidative metabolism under pressure overload to ensure survival.