Glutathione-triggered release of SO2 gas to augment oxidative stress for enhanced chemodynamic and sonodynamic therapy.

Recently, gas therapy has emerged as a promising alternative treatment for deep-seated tumors. However, some challenges regarding insufficient or uncontrolled gas generation as well as unclear therapeutic mechanisms restrict its further clinical application. Herein, a well-designed nanoreactor based on intracellular glutathione (GSH)-triggered generation of sulfur dioxide (SO2) gas to augment oxidative stress has been developed for synergistic chemodynamic therapy (CDT)/sonodynamic therapy (SDT)/SO2 gas therapy. The nanoreactor (designed as CCM@FH-DNs) is constructed by employing iron-doped hollow mesoporous silica nanoparticles as carriers, the surface of which was modified with the SO2 prodrug 2,4-dinitrobenzenesulfonyl (DNs) and further coated with cancer cell membranes for homologous targeting. The CCM@FH-DNs can not only serve as a Fenton-like agent for CDT, but also as a sonosensitizer for SDT. Importantly, CCM@FH-DNs can release SO2 for SO2-mediated gas therapy. Both in vitro and in vivo evaluations demonstrate that the CCM@FH-DNs nanoreactor performs well in augmenting oxidative stress for SO2 gas therapy-enhanced CDT/SDT via GSH depletion and glutathione peroxidase-4 enzyme deactivation as well as superoxide dismutase inhibition. Moreover, the doped iron ions ensure that the CCM@FH-DNs nanoreactors enable magnetic resonance imaging-guided therapy. Such a GSH-triggered SO2 gas therapy-enhanced CDT/SDT strategy provides an intelligent paradigm for developing efficient tumor microenvironment-responsive treatments.

Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF: not just ICSI failure.

ABSTRACT: Phospholipase C zeta (PLCζ) is a key sperm-borne oocyte-activating factor that triggers Ca2+ oscillations and the subsequent block to polyspermy following gamete fusion. Mutations in PLCZ1, the gene encoding PLCζ, cause male infertility and intracytoplasmic sperm injection (ICSI) fertilization failure; and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate (FR). However, in conventional in vitro fertilization (cIVF), whether and how sperm PLCζ affects fertilization remain unclear. Herein, we identified one previously reported and two novel PLCZ1 mutations associated with polyspermy in vitro that are characterized by excessive sperm-zona binding and a delay in pronuclei (PN) formation. Immunofluorescence staining and oocyte activation testing revealed that virtually all spermatozoa from patients lacked functional PLCζ and were thus unable to evoke Ca2+ oscillations. ICSI with an artificial oocyte activation treatment successfully rescued the polyspermic phenotype and resulted in a live birth. Furthermore, we analyzed PLCζ in an additional 58 males after cIVF treatment in the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between February 2019 and January 2022. We found that the proportion of spermatozoa that expressed PLCζ was positively correlated with both 2PN rate and total FR. The optimal cutoff value below which males were likely to experience low FR (total FR ≤30%) after cIVF was 56.7% for the proportion of spermatozoa expressing PLCζ. Our study expands the mutation and the phenotypic spectrum of PLCZ1 and further suggests that PLCζ constitutes a promising biomarker for identifying low FRs cases in cIVF due to sperm-related oocyte activation deficiency and that sperm PLCζ analysis may benefit the wider male population and not only men with ICSI failure.

Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against Wuhan-WT, delta and omicron BA1, BA2 spike trimers.

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of human angiotensin converting enzyme 2 (hACE-2) binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using Wuhan-WT (vaccine strain), delta (B.1.167.2), omicron BA1 and BA2 variant viral strains showed strong correlation with cell-based pseudovirus neutralization activity (PNA) and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta and omicron variant resistance to neutralization in samples with paired vaccine strain and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. Importantly, this completely automated assay can be performed in 4 h to measure neutralizing antibody titers for 16 samples over 8 serial dilutions or, 128 samples at a single dilution with replicates. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.

Effect of swab pooling on the Accula point-of-care RT-PCR for SARS-CoV-2 detection.

Introduction: Swab pooling may allow for more efficient use of point-of-care assays for SARS-CoV-2 detection in settings where widespread testing is warranted, but the effects of pooling on assay performance are not well described. Methods: We tested the Thermo-Fisher Accula rapid point-of-care RT-PCR platform with contrived pooled nasal swab specimens. Results: We observed a higher limit of detection of 3,750 copies/swab in pooled specimens compared to 2,250 copies/swab in individual specimens. Assay performance appeared worse in a specimen with visible nasal mucous and debris, although performance was improved when using a standard laboratory mechanical pipette compared to the transfer pipette included in the assay kit. Conclusion: Clinicians and public health officials overseeing mass testing efforts must understand limitations and benefits of swab or sample pooling, including reduced assay performance from pooled specimens. We conclude that the Accula RT-PCR platform remains an attractive candidate assay for pooling strategies owing to the superior analytical sensitivity compared to most home use and point-of-care tests despite the inhibitory effects of pooled specimens we characterized.

Novel biallelic ASTL variants are associated with polyspermy and female infertility: A successful live birth following ICSI treatment.

Fertilization of the egg by the sperm is the first vital stage of embryogenesis. In mammals, only one sperm is incorporated into the oocyte. Polyspermy is a key anomaly of fertilization that is generally lethal to the embryo. To date, only a few causative genes for polyspermy have been reported. In a recent study, a homozygous variant in astacin-like metalloendopeptidase (ASTL), which encodes the ovastacin enzyme that cleaves ZP2 to prevent polyspermy, was found to be associated with female infertility characterized by polyspermy in vitro. Herein, we identified two ASTL variants in a Chinese woman likely responsible for her primary infertility and polyspermy in in vitro fertilization. Both variants were located within the key catalytic domain and predicted to alter hydrogen bonds, potentially impairing protein stability. Moreover, expression and immunoblot analyses in CHO-K1 cells indicated abnormal ovastacin zymogen activation or decreased enzyme stability. Intracytoplasmic sperm injection treatment successfully bypassed the defect in polyspermy blocking and resulted in a live birth. Our study associates ASTL variants with human infertility and further supports the contribution of this gene to blocking polyspermy in humans. Our findings expand the spectrum of ASTL mutations and should facilitate the diagnosis of oocyte-borne polyspermy.

Supplementing a specific synbiotic suppressed the incidence of AOM/DSS-induced colorectal cancer in mice.

In this study, we evaluated the effect of a specific synbiotic on CAC (AOM/DSS-induced colitis-associated cancer). We confirmed that the synbiotic intervention was able to protect the intestinal barrier and inhibit CAC occurrence via upregulating tight junction proteins and anti-inflammatory cytokines, and downregulating pro-inflammatory cytokines. Moreover, the synbiotic significantly improved the disorder of the colonic microbiota of CAC mice, promoted the formation of SCFAs and the production of secondary bile acids, and alleviated the accumulation of primary bile acids in the CAC mice. Meanwhile, the synbiotic could significantly inhibit the abnormal activation of the intestinal Wnt/ß-catenin signaling pathway significantly related to IL-23. In a word, the synbiotic can inhibit the occurrence and development of colorectal tumors and it may be a functional food to prevent inflammation-related colon tumors, and the research also provided a theoretical basis for improving the intestinal microecological environment through diet therapy.

Reactive oxygen species nanoamplifiers with multi-enzymatic activities for enhanced tumor therapy.

The ingenious combination of nano-enzymes with multi-enzyme activities and therapeutic drugs that can promote reactive oxygen species (ROS) production in cancer cells will enhance the therapeutic efficacy of nanomedicines on malignant tumors by amplifying oxidative stress. Herein, PEGylated Ce-doped hollow mesoporous silica nanoparticles (Ce-HMSN-PEG) loaded with saikosaponin A (SSA) are elaborately constructed as a smart nanoplatform for improving the efficiency of tumor therapy. The carrier Ce-HMSN-PEG showed multi-enzyme activities due to the presence of mixed Ce3+/Ce4+ ions. In the tumor microenvironment, peroxidase-like Ce3+ ions convert endogenous H2O2 into highly toxic ˙OH for chemodynamic therapy, while Ce4+ ions not only show catalase-like activity to reduce tumor hypoxia but also exhibit glutathione (GSH) peroxidase-mimicking properties to effectively deplete GSH in tumor cells. Moreover, the loaded SSA can cause the enrichment of superoxide anions (˙O2-) and H2O2 within tumor cells by disrupting mitochondrial functions. By integrating the respective advantages of Ce-HMSN-PEG and SSA, the as-prepared SSA@Ce-HMSN-PEG nanoplatform can efficiently trigger cancer cell death and inhibit tumor growth via significantly enhanced ROS production. Therefore, this positive combination therapy strategy has a good application prospect for enhancing antitumor efficacy.

Material stock analysis of urban road from nighttime light data based on a bottom-up approach.

In recent years, there has been an increasing focus on the dynamics of material stock, that is, the basis of material flow in the entire ecosystem. With the gradual improvement of the global road network encryption project, the uncontrolled extraction, processing, and transportation of raw materials impose serious resource concerns and environmental pressure. Quantifying material stocks enable governments to formulate scientific policies because socio-economic metabolism, including resource allocation, use, and waste recovery, can be systematically assessed. In this study, OpenStreetMap road network data were used to extract the urban road skeleton, and nighttime light images were divided by watershed to construct regression equations based on geographical location attributes. Resultantly, a generic road material stock estimation model was developed and applied to Kunming. We concluded that (1) the top three stocks are stone chips, macadam, and grit (total weight is 380 million tons), (2) the proportion of asphalt, mineral powder, lime, and fly ash is correspondingly similar, and (3) the unit area stock decreases as the road grade declines; therefore, the branch road has the lowest unit stock.

A 1-kb human CDCA8 promoter directs the spermatogonia-specific luciferase expression in adult testis.

Cell division cycle associated 8 (CDCA8) is a component of the chromosomal passenger complex and plays an essential role in mitosis, meiosis, cancer growth, and undifferentiated state of embryonic stem cells. However, its expression and role in adult tissues remain largely uncharacterized. Here, we studied the CDCA8 transcription in adult tissues by generating a transgenic mouse model, in which the luciferase was driven by a 1-kb human CDCA8 promoter. Our previous study showed that this 1-kb promoter was active enough to dictate reporter expression faithfully reflecting endogenous CDCA8 expression. Two founder mice carrying the transgene were identified. In vivo imaging and luciferase assays in tissue lysates revealed that CDCA8 promoter was highly activated and drove robust luciferase expression in testes. Subsequently, immunohistochemical and immunofluorescent staining showed that in adult transgenic testes, the expression of luciferase was restricted to a subset of spermatogonia that were located along the basement membrane and positive for the expression of GFRA1, a consensus marker for early undifferentiated spermatogonia. These findings for the first time indicate that the CDCA8 was transcriptionally activated in testis and thus may play a role in adult spermatogenesis. Moreover, the 1-kb CDCA8 promoter could be used for spermatogonia-specific gene expression in vivo and the transgenic lines constructed here could also be used for recovery of spermatogonia from adult testes.

Modulation of hypoxia and redox in the solid tumor microenvironment with a catalytic nanoplatform to enhance combinational chemodynamic/sonodynamic therapy.

The efficacy of reactive oxygen species-mediated therapy is generally limited by hypoxia and overexpressed glutathione (GSH) in the tumor microenvironment (TME). To address these issues, herein, a smart Mn3O4/OCN-PpIX@BSA nanoplatform is rationally developed to enhance the combinational therapeutic efficacy of chemodynamic therapy (CDT) and sonodynamic therapy (SDT) through TME modulation. For constructing the catalytic nanoplatform (Mn3O4/OCN-PpIX@BSA), Mn3O4 nanoparticles were grown in situ on oxidized g-C3N4 (OCN) nanosheets, and the as-prepared Mn3O4/OCN nano-hybrids were then successively loaded with protoporphyrin (PpIX) and coated with bovine serum albumin (BSA). The catalase-like Mn3O4 nanoparticles are able to effectively catalyze the overexpressed endogenous H2O2 to produce O2, which could relieve hypoxia and improve the therapeutic effect of combinational CDT/SDT. The decomposition of Mn3O4 by GSH enables the release of Mn2+ ions, which not only facilitates good T1/T2 dual-modal magnetic resonance imaging for tumor localization but also results in the depletion of GSH and the Mn2+-driven Fenton-like reaction, thus further amplifying the oxidative stress and achieving improved therapeutic efficacy. It is worth noting that the Mn3O4/OCN-PpIX@BSA nanocomposites exhibit minimal toxicity to normal tissues at therapeutic doses. These positive findings provide a new strategy for the convenient construction of TME-regulating smart theranostic nanoagents to improve the therapeutic outcomes towards malignant tumors effectively.

An Ultrasound-Triggered Nanoplatform for Synergistic Sonodynamic-Nitric Oxide Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) has aroused intensive interest as a powerful alternative for cancer treatment in recent years due to its non-invasiveness and deep tissue penetration. However, the therapeutic effect of SDT alone is still limited by intrinsic hypoxia in solid tumors. Combined synergistic therapy strategies are highly desired for improving therapeutic efficiency. Herein, a rationally designed intelligent theranostic nanoplatform is developed for the enhancement of cancer treatment through synergistic SDT and nitric oxide (NO) therapy. This US-triggered nanoplatform is fabricated by integrating a sonosensitizer Rose Bengal (RB) and a NO donor (SNO) into manganese-doped hollow mesoporous silica nanoparticles (MH-SNO@RB). Impressively, the acidic and reducing tumor microenvironment accelerates the sustainable release of Mn ions from the framework, which facilitates the MH-SNO@RB to be used as a contrast agent for magnetic resonance imaging. More importantly, the reactive oxygen species (ROS) generated by RB and NO molecules released from SNO, which are simultaneously triggered by US, can react with each other to yield highly reactive peroxynitrite (ONOO-) ions for effective tumor inhibition both in vitro and in vivo. Furthermore, the nanoplatform demonstrates good hemocompatibility and histocompatibility. This study opens a new strategy for the full utilization of US and intelligent design avenues for high-performance cancer treatment.

Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against native-like vaccine and delta variant spike trimers.

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of hACE-2 binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using vaccine and delta variant viral strains showed strong correlation with cell-based pseudovirus and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta variant resistance to neutralization in samples with paired vaccine and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.

Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against native-like vaccine and delta variant spike trimers.

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of hACE-2 binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using vaccine and delta variant viral strains showed strong correlation with cell-based pseudovirus and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta variant resistance to neutralization in samples with paired vaccine and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.

Sulourea-coordinated Pd nanocubes for NIR-responsive photothermal/H2S therapy of cancer.

BACKGROUND: Photothermal therapy (PTT) frequently cause thermal resistance in tumor cells by inducing the heat shock response, limiting its therapeutic effect. Hydrogen sulfide (H2S) with appropriate concentration can reverse the Warburg effect in cancer cells. The combination of PTT with H2S gas therapy is expected to achieve synergistic tumor treatment. METHODS: Here, sulourea (Su) is developed as a thermosensitive/hydrolysable H2S donor to be loaded into Pd nanocubes through in-depth coordination for construction of the Pd-Su nanomedicine for the first time to achieve photo-controlled H2S release, realizing the effective combination of photothermal therapy and H2S gas therapy. RESULTS: The Pd-Su nanomedicine shows a high Su loading capacity (85 mg g-1), a high near-infrared (NIR) photothermal conversion efficiency (69.4%), and NIR-controlled H2S release by the photothermal-triggered hydrolysis of Su. The combination of photothermal heating and H2S produces a strong synergetic effect by H2S-induced inhibition of heat shock response, thereby effectively inhibiting tumor growth. Moreover, high intratumoral accumulation of the Pd-Su nanomedicine after intravenous injection also enables photothermal/photoacoustic dual-mode imaging-guided tumor treatment. CONCLUSIONS: The proposed NIR-responsive heat/H2S release strategy provides a new approach for effective cancer therapy.

Gadolinium-doped hollow silica nanospheres loaded with curcumin for magnetic resonance imaging-guided synergistic cancer sonodynamic-chemotherapy.

Curcumin is a kind of anti-cancer chemotherapeutic drug and has been demonstrated to be able to produce reactive oxygen species (ROS) under the stimuli of ultrasound (US). Herein, gadolinium-doped hollow mesoporous silica nanospheres (Gd-HMSNs) loaded with curcumin (Cur) and conjugated with carboxymethyl dextran (CMD) have been facilely fabricated and applied for magnetic resonance imaging (MRI)-guided synergistic cancer sonodynamic-chemotherapy. The as-prepared multifunctional theranostic nanoplatform (Cur@Gd-HMSNs-CMD) shows high drug loading capacity, satisfactory biocompatibility, pH-responsive degradation, and US-triggered drug release. Due to the release of Gd3+ ions or oligomers during degradation, the nanoplatform Cur@Gd-HMSNs-CMD could serve as an effective contrast agent for T1-weighted MRI to guide cancer treatment. More significantly, in vivo experiments show that the Cur@Gd-HMSNs-CMD can efficiently inhibit the tumor growth by a high inhibition rate of ~85.6% under US irradiation, mainly resulting from the synergistic effect of sonodynamic-chemotherapy. This innovative "two-in-one" theranostic nanoplatform using a single drug provides a new strategy for developing "all-in-one" nanomaterials for combined cancer treatment.

Functionalized g-C3N4 nanosheets for potential use in magnetic resonance imaging-guided sonodynamic and nitric oxide combination therapy.

The oxygen consumption-induced hypoxia and the high concentration of glutathione in tumor microenvironment limit the treatment outcomes of sonodynamic therapy (SDT). SDT needs to be combined with other treatment modalities to achieve the desired therapeutic efficiency. In this study, an oxidized g-C3N4 (OCN) nanosheet-based theranostic nanoplatform is developed for sonodynamic and nitric oxide (NO) combination therapy of cancer. The OCN nanosheets are successively modified with amino-terminated 6-armed polyethylene glycol, chlorin e6, and Gd3+ ions, and then the as-prepared OCN-PEG-(Ce6-Gd3+) nanosheets are loaded with the NO donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6). Upon ultrasound (US) irradiation, the OCN-PEG-(Ce6-Gd3+)/BNN6 nanocomposite can induce the generation of reactive oxygen species (ROS) and simultaneously release NO molecules to effectively kill the cancer cells, thereby significantly suppressing the tumor growth. Moreover, a good in vivo T1-weighted magnetic resonance imaging (MRI) contrast effect is achieved after intravenous injection of OCN-PEG-(Ce6-Gd3+)/BNN6 due to remarkably enhanced contrast performance of the nanocomposite. Therefore, the OCN-PEG-(Ce6-Gd3+)/BNN6 formulation can serve as a promising theranostic agent for MRI-guided sonodynamic-NO combination therapy.

Using Eco-Friendly Recycled Powder from CDW to Prepare Strain Hardening Cementitious Composites (SHCC) and Properties Determination.

Using eco-friendly recycled brick powder (RBP) derived from waste brick to prepare strain hardening cementitious composites (SHCC) provides a new way of recycling the construction and demolition waste (CDW), and the dosage of cement in SHCC can be decreased. This paper investigated the micro-properties and mechanical properties of SHCC containing RBP by a series of experiments. The results showed that RBP had typical characteristics of supplementary cementitious material (SCM). The addition of RBP increased the SiO2 content and decreased the hydration products in cementitious materials; in this case, the mechanical properties of mortar decreased with increasing RBP replacements, and a linear relationship was observed between them. It was noticed that the adverse effect of RBP on the mechanical properties decreased with increasing PVA fiber content in mortar. For SHCC containing various RBP replacements, the ultimate load increased, and the ultimate displacement decreased with increasing curing days. When using RBP to replace cement by weight, the ultimate displacement increased with the addition of RBP. Meanwhile, there was no significant reduction in the ultimate load of SHCC. When using RBP to replace fly ash (FA) by weight, the incorporation of RBP decreased the ultimate displacement of SHCC, whereas the ultimate load was improved. For example, the ultimate load and displacement of SHCC with 54%RBP were 17.6% higher and 16.4% lower, respectively, than those of SHCC with 54% FA.

Tumor pH-Responsive Albumin/Polyaniline Assemblies for Amplified Photoacoustic Imaging and Augmented Photothermal Therapy.

Tumor-microenvironment-responsive theranostics have great potential for precision diagnosis and effective treatment of cancer. Polyaniline (PANI) is the first reported pH-responsive organic photothermal agent and is widely used as a theranostic agent. However, tumor pH-responsive PANI-based theranostic agents are not explored, mainly because the conversion from the emeraldine base (EB) to emeraldine salt (ES) state of PANI requires pH < 4, which is lower than tumor acidic microenvironment. Herein, a tumor pH-responsive PANI-based theranostic agent is designed and prepared for amplified photoacoustic imaging guided augmented photothermal therapy (PTT), through intermolecular acid-base reactions between carboxyl groups of bovine serum albumin (BSA) and imine moieties of PANI. The albumin/PANI assemblies (BSA-PANI) can convert from the EB to ES state at pH < 7, accompanied by the absorbance redshift from visible to near-infrared region. Both in vitro and in vivo results demonstrate that tumor acidic microenvironment can trigger both the photoacoustic imaging (PAI) signal amplification and the PTT efficacy enhancement of BSA-PANI assemblies. This work not only highlights that BSA-PANI assemblies overcome the limitation of low-pH protonation, but also provides a facile assembly strategy for a tumor pH-responsive PANI-based nanoplatform for cancer theranostics.

Altered body composition and increased visceral adipose tissue in premenopausal and late postmenopausal patients with SLE.

OBJECTIVE: Visceral adipose tissue (VAT) is becoming a recognized cardiovascular (CV) risk factor. This study aimed to evaluate body composition, especially VAT, in systemic lupus erythematosus (SLE) and to explore the association between VAT and SLE disease-related factors. METHOD: Ninety-eight inpatients with SLE and 108 age- and body mass index (BMI)-matched healthy controls were included. Demographic and clinical parameters were recorded. The VAT was measured by dual-energy x-ray absorptiometry. RESULT: The mean age and disease duration of patients were 46.4 ± 13.0 years and 8.0 ± 7.0 years, respectively. Patients with SLE had higher VAT volume (p = 0.0015) and mass (p = 0.0017) than controls, especially in premenopausal and postmenopausal groups. The subanalysis of subjects with BMI less than 25 kg/m2 indicated that patients had lower lean mass (p = 0.0005), fat-free mass (p = 0.0005), and fat-free mass index (p = 0.0001), but increased adiposity distribution than controls, including VAT volume and mass. However, overweight/obese patients had similar body composition with controls. The VAT volume correlated with BMI, age, menopausal status, hypertension, uric acid, creatinine, non-high-density lipoprotein cholesterol, and triglyceride in both groups. In the patient group, the VAT volume correlated with disease duration, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI), and low serum complement, but not with SLEDAI and glucocorticoid dose. CONCLUSION: This study suggested that SLE patients had some traditional CV risk factors such as altered body composition and increased VAT. The higher VAT in patients with SLE was associated with traditional cardiometabolic risks, which may contribute to CV events in SLE populations. Key Points • Patients with SLE had increased VAT volume and mass than controls. • The VAT volume correlated with traditional cardiometabolic risk factors. • In SLE patient group, the VAT volume correlated with disease duration, SLICC/ACR-DI, and low serum complementC3/C4, but not with SLEDAI and glucocorticoid dose.

Electrophoretically Sheathed Carbon Fiber Microelectrodes with Metal/Nitrogen/Carbon Electrocatalyst for Electrochemical Monitoring of Oxygen in Vivo.

Metal/nitrogen/carbon (M/N/C, M = Co or Fe) nanomaterials have been demonstrated to catalyze oxygen reduction reaction (ORR) with implication in fuel cell studies; however, their potential application as sensing materials for in vivo monitoring of oxygen (O2) in the central nervous system has never been reported. This study reports a first demonstration that M/N/C nanomaterials can be used as sensing materials to form an electrochemical assay for in vivo O2 monitoring. To demonstrate this application, the M/N/C nanocomposites prepared by pyrolysis of zeolitic imidazolate framework (ZIF-67) are used as an example and is electrophoretically deposited onto carbon fiber microelectrodes (CFEs) to catalyze a four-electron reduction of O2 without producing cell-toxic hydrogen peroxide intermediate. The M/N/C-sheathed CFEs have high catalytic performance toward ORR in a neutral solution, selectivity toward O2 sensing in the presence of ascorbic acid (AA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), uric acid (UA), and 5-hydroxytryptamine (5-HT) at their physiological levels in rat brain, and capability to real-time monitor O2 fluctuation during respiring gases. This study offers a new electrochemical approach to in vivo O2 monitoring with nonplatinum catalyst for ORR.