Dysregulated proteasome activity and steroid hormone biosynthesis are associated with mortality among patients with acute COVID-19.

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1-3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.

Asymmetric Coordination of Bimetallic Fe-Co Single-Atom Pairs toward Enhanced Bifunctional Activity for Rechargeable Zinc-Air Batteries.

The advancement of rechargeable zinc-air batteries (RZABs) faces challenges from the pronounced polarization and sluggish kinetics of oxygen reduction and evolution reactions (ORR and OER). Single-atom catalysts offer an effective solution, yet their insufficient or singular catalytic activity hinders their development. In this work, a dual single-atom catalyst, FeCo-SAs, was fabricated, featuring atomically dispersed N3-Fe-Co-N4 sites on N-doped graphene nanosheets for bifunctional activity. Introducing Co into Fe single-atoms and secondary pyrolysis altered Fe coordination with N, creating an asymmetric environment that promoted charge transfer and increased the density of states near the Fermi level. This catalyst achieved a narrow potential gap of 0.616 V, with a half-wave potential of 0.884 V for ORR (vs the reversible hydrogen electrode) and a low OER overpotential of 270 mV at 10 mA cm-2. Owing to the superior activity of FeCo-SAs, RZABs exhibited a peak power density of 203.36 mW cm-2 and an extended cycle life of over 550 h, exceeding the commercial Pt/C + IrO2 catalyst. Furthermore, flexible RZABs with FeCo-SAs demonstrated the promising future of bimetallic pairs in wearable energy storage devices.

A multi-layer reduced graphene oxide catalyst encapsulating a high-entropy alloy for rechargeable zinc-air batteries.

A reduced graphene oxide encapsulating Fe6Ni20Co2Mn2Cu1.5@rGO catalyst is prepared using a Joule heating strategy. The graphene-coated layer with high crystallinity enhances the stability of the crystal structure, resulting in superior OER activity. Rechargeable zinc-air batteries with Fe6Ni20Co2Mn2Cu1.5@rGO demonstrate remarkable performance, boasting a high specific capacity of 800 mA h gZn-1, an impressive peak power density of 154.612 mW cm-2, and a cycle life of 300 hours at a current density of 10 mA cm-2.

Sedation and analgesia strategies for non-invasive mechanical ventilation: A systematic review and meta-analysis.

BACKGROUND: The use of sedative and analgesic drugs during non-invasive ventilation (NIV) in patients with acute respiratory failure (ARF) is controversial. OBJECTIVES: To assess the clinical effectiveness of sedative and analgesic medications used during NIV for patients with ARF to no sedation or analgesia. In addition, to investigate the characteristics of dexmedetomidine in comparison to other medications. METHODS: PubMed, Embase, Web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched. Mean differences (MDs) or pooled risk ratios (RRs) were computed using random-effects models. We applied the Cochrane risk-of-bias assessment tool 2.0 to assess the methodological quality of eligible studies and the GRADE approach to evaluate the evidence certainty. RESULTS: Twenty-one studies were selected. Whether in Group A (using sedative and analgesic drugs vs. nonuse) or Group B (using dexmedetomidine vs. other drugs), the rates of tracheal intubation and delirium, the length of NIV, and the length of stay in the intensive care unit (ICU LOS) all decreased in both experimental groups (P < 0.05). And there were no significant differences in all-cause mortality and the incidence of hypotension between the two groups (P > 0.05), while both Group A and Group B's experimental groups had greater incidences of bradycardia. CONCLUSIONS: Administering sedative and analgesic medications during NIV can reduce the risk of tracheal intubation and delirium. Additionally, dexmedetomidine outperformed other sedative medications in terms of these clinical outcomes, making it the better option when closely monitoring patients' vital signs.

Terselenophene Regioisomer Conjugated Polymer Materials for High-Performance Cancer Phototheranostics.

Molecular isomerization is a fundamental issue in the development of functional materials, with a crucial impact on photophysical properties. However, up to now, their effect on photothermal conversion is rarely investigated. Here, two near-infrared (NIR)-absorbing regioisomer conjugated polymers integrated with cis/trans-terselenophenes are designed and synthesized as efficient photothermal agents to enhance cancer phototheranostics. It is demonstrated that enhanced quinoidal resonance of trans-terselenophenes allows the resulting trans-CP to possess more planar backbone to further increase the effective conjugation length and result in the strong absorption spectra at 808 nm. Characterization of photophysical properties has proved that the photothermal conversion efficiency of trans-CP nanoparticles is up to 61.4%, and they are 210% as strong as cis-CP nanoparticles (29.4%). Further in vitro and in vivo works demonstrate efficient photothermal therapeutic effects with the guidance of photoacoustic imaging. This work affords a new understanding of the molecular isomerization into the development of conjugated materials for high-performance cancer phototheranostics.

Capillary electrophoretic assay for nitrate levels in the vitreous of proliferative diabetic retinopathy.

The determination of nitric oxide (NO) in human vitreous samples is complicated by the relatively short half-life of the analyte and the viscous, high salt and protein biological matrix. In this work, we developed a fast (<5min) and useful CE method to determine the stable metabolite, nitrate, from vitreous samples. This proposed method has been successfully applied to determine the nitrate levels from the vitreous humor of patients undergoing vitrectomy for a variety of conditions. A statistically significant increase (P=0.000001) of the mean level of nitrate was observed in vitreous humor of patients with proliferative diabetic retinopathy (41.17+/-4.09microM, n=27) versus controls (15.22+/-0.86microM, n=35). The elevated levels of nitrate in the vitreous of patients known to have diabetic retinopathy suggests that NO is involved with the pathology of this disease.

Multiplexed detection of nitrate and nitrite for capillary electrophoresis with an automated device for high injection efficiency.

A simple automated nanoliter scale injection device which allows for reproducible 5 nL sample injections from samples with a volume of <1 microL is successfully used for conventional capillary electrophoresis (CE) and Hadamard transform (HT) CE detection. Two standard fused silica capillaries are assembled axially through the device to function as an injection and a separation capillary. Sample solution is supplied to the injection capillary using pressure controlled with a solenoid valve. Buffer solution flows gravimetrically by the junction of the injection and separation capillaries and is also gated with a solenoid valve. Plugs of sample are pushed into the space between the injection and separation capillaries for electrokinectic injection. To evaluate the performance of the injection device, several optimizations are performed including the influence of flow rates, the injected sample volume and the control of the buffer transverse flow on the overall sensitivity. The system was then applied to HT-CE-UV detection for the signal-to-noise ratio (S/N) improvement of the nitric oxide (NO) metabolites, nitrite and nitrate. In addition, signal averaging was performed to explore the possibility of greater sensitivity enhancements compared to single injections.

Hadamard transform CE-UV detection for biological samples.

A Hadamard transform-capillary electrophoresis-UV (HT-CE-UV) detection technique is described for the analysis of biological samples. Pseudorandom injections of sample and buffer according to a simplex matrix obtained from the corresponding Hadamard matrix is performed with conventional capillaries. Alternating injections are achieved with a novel capillary "T" connector created by drilling conventional capillary dimensions through a 1-cm diameter polycarbonate disc. This connector design coupled with a switching system allows for rapid, electrokinetic injections of solution into alternating sample and buffer capillary arms for UV detection. The standard mixtures of nitric oxide (NO) metabolites, nitrite and nitrate, dissolved in physiological saline solution are injected into the separation capillary according to an 83-element injection sequence to obtain a signal-to-noise ratio (S/N) enhancement of ca. 4.5 over a single injection. Nitrite, being the less concentrated metabolite in NO detection and thereby more difficult to detect, was calibrated with the HT-CE-UV method and a limit of detection (LOD) of 0.56 microM was obtained. Rat blood plasma was analyzed with this detection system and demonstrated to be comparable with NO metabolite concentrations of previously published results. This HT-CE-UV method is described where a unique reservoir tube design that contains 8-microL standard nitrite sample volumes is placed over the end of the capillary arm to explore low volume limits for biological samples.

Determination of nitrate and nitrite in rat brain perfusates by capillary electrophoresis.

A fast and simple method for the direct, simultaneous detection of nitrite (NO(2) (-)) and nitrate (NO(3) (-)) in rat striatum has been developed using a capillary electrophoresis separation of low-flow push-pull perfusion samples. The method was optimized primarily for nitrite because nitrite is more important physiologically and is found at lower levels than nitrate. We obtained a complete separation of NO(2) (-) and NO(3) (-) in rat striatum within 1.5 min. Optimal CE separations were achieved with 20 mM phosphate, 2 mM cetyltrimethylammonium chloride (CTAC) buffer at pH 3.5. The samples were injected electrokinetically for 2 s into a 40 cm x 75 microm ID fused-silica capillary. The separation voltage was 10 kV (negative polarity), and the injection voltage was 16 kV (negative polarity). UV detection was performed at 214 nm. The limits of detection obtained at a signal-to-noise ratio (S/N) of 3 for nitrite and nitrate were 0.96 and 2.86 microM. This is one of the fastest separations of nitrite and nitrate of a biological sample ever reported. Interference produced by the high physiological level of chloride is successfully minimized by use of CTAC in the run buffer.