Boosting electrocatalytic ammonia synthesis from nitrate by asymmetric chemical potential activated interfacial electric fields.

The electrocatalytic nitrate reduction reaction (NO3- RR) has immense potential to alleviate the problem of groundwater pollution and may also become a key route for the environmentally benign production of ammonia (NH3) products. Here, the unique effects of interfacial electric fields arising from asymmetric chemical potentials and local defects were integrated into the binary Bi2S3-Bi2O3 sublattices for enhancing electrocatalytic nitrate reduction reactions. The obtained binary system showed a superior Faraday efficiency (FE) for ammonia production of 94 % and an NH3 yield rate of 89.83 mg gcat-1h-1 at -0.4 V vs. RHE. Systematic experimental and computational results confirmed that the concerted interplay between interfacial electric fields and local defects not only promoted the accumulation and adsorption of NO3-, but also contributed to the destabilization of *NO and the subsequent deoxygenation hydrogenation reaction. This work will stimulate future designs of heterostructured catalysts for efficient electrocatalytic nitrate reduction reactions.

Hydrogenation Catalysis by Hydrogen Spillover on Platinum-Functionalized Heterogeneous Boronic Acid-Polyoxometalates.

The activation of molecular hydrogen is a key process in catalysis. Here, we demonstrate how polyoxometalate (POM)-based heterogeneous compounds functionalized with Platinum particles activate H2 by synergism between a hydrogen spillover mechanism and electron-proton transfer by the POM. This interplay facilitates the selective catalytic reduction of olefins and nitroarenes with high functional group tolerance. A family of polyoxotungstates covalently functionalized with boronic acids is reported. In the solid-state, the compounds are held together by non-covalent interactions (π-π stacking and hydrogen bonding). The resulting heterogeneous nanoscale particles form stable colloidal dispersions in acetonitrile and can be surface-functionalized with platinum nanoparticles by in situ photoreduction. The resulting materials show excellent catalytic activity in hydrogenation of olefins and nitrobenzene derivatives under mild conditions (1 bar H2 and room temperature).

POM@ZIF Derived Mixed Metal Oxide Catalysts for Sustained Electrocatalytic Oxygen Evolution.

The design of efficient and stable oxygen evolution reaction (OER) catalysts based on noble-metal-free materials is crucial for energy conversion and storage. In this work, it was demonstrated how polyoxometalate (POM)-doped ZIF-67 can be converted into a stable oxygen evolution electrocatalyst by chemical etching, cation exchange, and thermal annealing steps. Characterization by X-ray photoelectron spectroscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy and Raman spectroscopy indicate that POM-doped ZIF-67 derived carbon-supported metal oxides were synthesized. The resulting composite shows structural and compositional advantages which lead to low overpotential (306 mV at j=10 mA ⋅ cm-2 ) and long-term stability under harsh OER conditions (1.0 M aqueous KOH).

Management guideline for the off-label use of medicine in China (2021).

BACKGROUND: Off-label drug use embodies a thorough clinical diagnosis and evaluation of treatment needs and should not be confused with unreasonable drug use, but it also faces potential risks with drug safety and legal issues. RESEARCH DESIGN AND METHODS: We first established a guideline working group. Following the guideline development process recommended by the World Health Organization Handbook and the Chinese Medical Association, the key questions were determined through literature searches of PubMed, CNKI (Chinese National Knowledge Infrastructure) and other databases. Both the evidence and the clinicians' diagnosis and treatment workload were considered to formulate the initial recommendations. Finally, two rounds of Delphi surveys and one expert seminar were organized to determine the final recommendations of this guideline. Meanwhile, we graded the recommendations based on the body of evidence. RESULTS: We determined nine questions and proposed a total of 23 recommendations regarding the definition of off-label use of drugs, applicable circumstances, classification of evidence, informed consent, legal basis, adverse drug reaction monitoring and evaluation, management procedure, responsibilities and obligations of different stakeholders, medical insurance reimbursement, and the national approval system. CONCLUSIONS: This guideline standardized clinical off-label drug use and provided suggestions and references for the management of off-label drug use.

Molecular Iron Oxide Clusters Boost the Oxygen Reduction Reaction of Platinum Electrocatalysts at Near-Neutral pH.

The oxygen reduction reaction (ORR) is a key energy conversion process, which is critical for the efficient operation of fuel cells and metal-air batteries. Here, we report the significant enhancement of the ORR-performance of commercial platinum-on-carbon electrocatalysts when operated in aqueous electrolyte solutions (pH 5.6), containing the polyoxoanion [Fe28 (µ3 -O)8 (L-(-)-tart)16 (CH3 COO)24 ]20- . Mechanistic studies provide initial insights into the performance-improving role of the iron oxide cluster during ORR. Technological deployment of the system is demonstrated by incorporation into a direct formate microfluidic fuel cell (DFMFC), where major performance increases are observed when compared with reference electrolytes. The study provides the first examples of iron oxide clusters in electrochemical energy conversion and storage.

Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review.

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing ß-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

High Proton-Conductivity in Covalently Linked Polyoxometalate-Organoboronic Acid-Polymers.

The controlled bottom-up design of polymers with metal oxide backbones is a grand challenge in materials design, as it could give unique control over the resulting chemical properties. Herein, we report a 1D-organo-functionalized polyoxometalate polymer featuring a purely inorganic backbone. The polymer is self-assembled from two types of monomers, inorganic Wells-Dawson-type polyoxometalates, and aromatic organo-boronates. Their covalent linkage results in 1D polymer strands, which combine an inorganic oxide backbone (based on B-O and Nb-O linkages) with functional organic side-chains. The polymer shows high bulk proton conductivity of up to 1.59×10-1  S cm-1 at 90 °C and 98 % relative humidity. This synthetic approach could lead to a new class of organic-inorganic polymers where function can be designed by controlled tuning of the monomer units.

Electrocatalytic Oxygen Evolution by Hierarchically Structured Cobalt-Iron Composites.

The development of scalable routes to highly active and efficient oxygen evolution reaction (OER) electrocatalysts based on earth-abundant materials is crucial for post-fossil fuel energy schemes. Here, we demonstrate how commercial copper foam electrodes can be functionalized for water oxidation using a facile electrodeposition process. The resulting composite electrode features hierarchically structured cobalt-iron-based catalyst particles, which offer channel-like structures for the transport of electrolyte and release of oxygen gas bubbles. We report high electrocatalytic OER performance as demonstrated by high current densities at low overpotentials (293 mV at j = 50 mA cm-2) and long-term stability under technologically relevant alkaline conditions (>24 h in 1.0 M aqueous KOH).

Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women.

OBJECTIVES: Our aim was to investigate the prevalence and predictive variables of sarcopenia. METHODS: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. CONCLUSIONS: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.

Fournier Gangrene Associated with Sodium-Glucose Cotransporter-2 Inhibitors: A Pharmacovigilance Study with Data from the U.S. FDA Adverse Event Reporting System.

BACKGROUND: The U.S. Food and Drug Administration (FDA) released a safety warning of Fournier gangrene (FG), a rare but serious adverse effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors in August 2018. However, existing studies have focused mainly on individual FG case reports. Although several previous studies conducted reviews of cases, objective scientific analysis was not applied, and the prognosis data were inadequate. OBJECTIVE: This study is aimed at presenting data supplementary to existing studies by analysing postmarketing adverse event reports in the FDA Adverse Events Reporting System (FAERS) database. Multiple statistical analysis methods were applied to evaluate the potential association between SGLT2 inhibitors and FG, thus providing reliable and professionalized medication usage recommendations for SGLT2 inhibitors in clinical practice. METHODS: Disproportionality analysis and Bayesian analysis were applied for data mining among the suspected adverse event reports of FG associated with SGLT2 inhibitors recorded in the FAERS database during the period from January 2004 to September 2019. RESULTS: There were 542 FG cases identified in the FAERS database in patients receiving SGLT2 inhibitors. Among all SGLT2 inhibitor therapies, empagliflozin was associated with the highest number of FG reports (232 in total), while empagliflozin plus metformin had the strongest association with FG occurrence with the reporting odds ratio (ROR 54.79, 95% two-sided CI 31.56 to 95.12) and proportional reporting ratio (PRR 53.36, χ 2 666.70). There were 391 patients who underwent initial or prolonged hospitalization (72.14%), and 26 patients died (4.81%). Three new FG cases caused by ertugliflozin were found in 2019. CONCLUSION: The analysis of SGLT2 inhibitor-associated FG reports in the FAERS database identified signals between the drug and adverse events of interest. It also provides comprehensive information on the characteristics of FG onset and prognosis. Clinicians should pay more attention to this rare but severe adverse event when prescribing SGLT2 inhibitors in clinical practice.

Polyoxometalate-like sub-nanometer molybdenum(vi)-oxo clusters for sensitive, selective and stable H2O2 sensing.

Polyoxometalate-like molybdenum(vi)-oxo clusters ([Mo-oxo]n, n = 1-20) deposited on high surface-area carbon are developed as a biosensor for non-enzymatic electrochemical H2O2 detection. The sensor exhibits excellent electrocatalytic performance with a low detection limit, wide linear range, excellent sensitivity and stability. The composite can be stably deposited on screen-printed electrodes which combine microlitre analyses, long shelf-life and re-usability.

A 3d-printed composite electrode for sustained electrocatalytic oxygen evolution.

We report the facile design and fabrication of 3D-printed microstructured electrodes for electrocatalytic oxygen evolution. ABS polymer-based mesh scaffolds are chemically functionalized to enable electroless nickel metal deposition and subsequent catalyst (nickel iron hydroxide) immobilization. The resulting composites show sustained oxygen evolution with low overpotentials and high stability. The modular approach reported enables the scalable on-demand fabrication of microstructured composite electrodes.

Efficient Tetra-Functional Electrocatalyst with Synergetic Effect of Different Active Sites for Multi-Model Energy Conversion and Storage.

Energy crisis and global warming due to excessive CO2 emissions are the two major challenges of the world. Conversion of CO2 into useful fuels along with rechargeable metal air batteries and water splitting is one way to combat the energy crisis, which is bottlenecked due to the lack of multifunctional electrocatalyst. Herein simple but multifunctional electrocatalyst, which combined CoNi nanoalloy, N-doped carbon nanotubes, and single atomic Ni sites together is reported. The prepared electrocatalyst has shown remarkable performance for CO2RR, ORR, OER, and HER. The practical utilization of the catalyst is mansifested by a dual model metal CO2/air battery and water electrolyzer. An excellent CO2RR with FE of 99% is achieved in 0.5 M KHCO3 medium. The catalyst exhibits more positive onset (0.98 V) and half wave potential (0.86 V) than Pt/C for ORR, extremely low overpotential (η10) of 250 mV for OER, and thus the lowest ORR/OER potential gap of 0.62 V. In alkaline medium, the catalyst also shows excellent HER performance with η10 of 49 mV, resulting in the smallest cell bias of 1.57 V for overall water splitting to date. This work provides a new pathway to design more stellar multifunctional electrocatalyst for sustainable and clean renewable energy technology.

Polyoxometalates on Functional Substrates: Concepts, Synergies, and Future Perspectives.

Polyoxometalates (POMs) are molecular metal oxide clusters that feature a broad range of structures and functionalities, making them one of the most versatile classes of inorganic molecular materials. They have attracted widespread attention in homogeneous catalysis. Due to the challenges associated with their aggregation, precipitation, and degradation under operational conditions and to extend their scope of applications, various strategies of depositing POMs on heterogeneous substrates have been developed. Recent ground-breaking developments in the materials chemistry of supported POM composites are summarized and links between molecular-level understanding of POM-support interactions and macroscopic effects including new or optimized reactivities, improved stability, and novel function are established. Current limitations and future challenges in studying these complex composite materials are highlighted, and cutting-edge experimental and theoretical methods that will lead to an improved understanding of synergisms between POM and support material from the molecular through to the nano- and micrometer level are discussed. Future development in this fast-moving field is explored and emerging fields of research in POM heterogenization are identified.

Bulk Nanostructuring of Janus-Type Metal Electrodes.

The stable deposition of reactive nanostructures on metal electrodes is a key process for modern technologies including energy conversion/ storage, electrocatalysis or sensing. Here a facile, scalable route is reported, which allows the bulk nanostructuring of copper foam electrodes with metal, metal oxide or metal hydroxide nanostructures. A concentration-gradient driven synthetic approach enables the fabrication of Janus-type electrodes where one face features Cu(OH)2 nanowires, while the other face features CuO nanoflowers. Thermal or chemical conversion of the nanostructured surfaces into copper oxide or copper metal is possible whilst retaining the respective nanostructure morphologies. As proof of concept, the functionalized electrodes are promising in electrocatalytic water oxidation and water reduction reactions.

Bottom-up Design of Bimetallic Cobalt-Molybdenum Carbides/Oxides for Overall Water Splitting.

Earth-abundant transition-metal-based catalysts for electrochemical water splitting are critical for sustainable energy schemes. In this work, we use a rational design method for the synthesis of ultrasmall and highly dispersed bimetallic CoMo carbide/oxide particles deposited on graphene oxide. Thermal conversion of the molecular precursors [H3 PMo12 O40 ], Co(OAc)2 ⋅4 H2 O and melamine in the presence of graphene oxide gives the mixed carbide/oxide (Co6 Mo6 C2 /Co2 Mo3 O8 ) nanoparticle composite deposited on highly dispersed, N,P-doped carbon. The resulting composite shows outstanding electrocatalytic water-splitting activity for both the oxygen evolution and hydrogen evolution reaction, and superior performance to reference samples including commercial 20 % Pt/C & IrO2 . Electrochemical and other materials analyses indicate that Co6 Mo6 C2 is the main active phase in the composite, and the N,P-doping of the carbon matrix increases the catalytic activity. The facile design could in principle be extended to multiple bimetallic catalyst classes by tuning of the molecular metal oxide precursor.

Cobalt Nanoparticles and Atomic Sites in Nitrogen-Doped Carbon Frameworks for Highly Sensitive Sensing of Hydrogen Peroxide.

In situ monitoring of hydrogen peroxide (H2 O2 ) during its production process is needed. Here, an electrochemical H2 O2 sensor with a wide linear current response range (concentration: 5 × 10-8 to 5 × 10-2 m), a low detection limit (32.4 × 10-9 m), and a high sensitivity (568.47 µA mm-1 cm-2 ) is developed. The electrocatalyst of the sensor consists of cobalt nanoparticles and atomic Co-Nx moieties anchored on nitrogen doped carbon nanotube arrays (Co-N/CNT), which is obtained through the pyrolysis of the sandwich-like urea@ZIF-67 complex. More cobalt nanoparticles and atomic Co-Nx as active sites are exposed during pyrolysis, contributing to higher electrocatalytic activity. Moreover, a portable screen-printed electrode sensor is constructed and demonstrated for rapidly detecting (cost ≈40 s) H2 O2 produced in microbial fuel cells with only 50 µL solution. Both the synthesis strategy and sensor design can be applied to other energy and environmental fields.

Breast milk concentration of hydroxychloroquine in Chinese lactating women with connective tissue diseases.

PURPOSE: Considering the very limited while varying information about the excretion of hydroxychloroquine (HCQ) into human milk, we sought to determine the breast milk concentrations of HCQ in Chinese lactating patients with connective tissue diseases to assess the safety of HCQ in infants of this population. METHODS: Breastfeeding women who had been on HCQ for at least 1 year were recruited. Milk samples were collected at five time points over 12 h. Breast milk HCQ levels were measured by a validated high-performance liquid chromatography (HPLC) assay. According to the general daily milk consumption of 0.15 L/kg for an infant, the dose of HCQ received by the infants via breastfeeding was calculated. RESULTS: Thirty-three patients completed the study who received HCQ treatment with the following regimens: 0.1 g bid (n = 3), 0.2 g qd (n = 8), 0.2 g bid (n = 21), and 0.2 g qod (n = 1). The mean breast milk HCQ levels (µg/mL) over the 12-h sampling period for each dosage regimen group were 0.4, 0.7, 1.4, and 0.4, respectively. The dose of HCQ (mg) received by the infants via breastfeeding would be 0.4, 0.4, 0.9, and 0.2, which were 0.26%, 0.26%, 0.29%, and 0.26% of the daily maternal doses, respectively. The infant's weight-adjusted relative dose (mg/kg) was 0.1, 0.1, 0.2, and 0.1, respectively, equivalent to 1.9%, 3.0%, 3.0%, and 3.2% of the maternal dose per kilogram body weight, respectively. CONCLUSION: Our study found that HCQ has very low concentrations in breast milk. It is probably safe for the patients to give breastfeeding during HCQ therapy period.

Transition-Metal Oxides/Carbides@Carbon Nanotube Composites as Multifunctional Electrocatalysts for Challenging Oxidations and Reductions.

The rapid development of renewable-energy technologies such as water splitting, rechargeable metal-air batteries, and fuel cells requires highly efficient electrocatalysts capable of the oxygen-reduction reaction (ORR) and the oxygen-evolution reaction (OER). Herein, we report a facile sonication-driven synthesis to deposit the molecular manganese vanadium oxide precursor [Mn4 V4 O17 (OAc)3 ]3- on multiwalled carbon nanotubes (MWCNTs). Thermal conversion of this composite at 900 °C gives nanostructured manganese vanadium oxides/carbides, which are stably linked to the MWCNTs. The resulting composites show excellent electrochemical reactivity for ORR and OER, and significant reactivity enhancements compared with the precursors and a Pt/C reference are reported. Notably, even under harsh acidic conditions, long-term OER activity at low overpotential is reported. In addition, we report exceptional activity of the composites for the industrially important Cl2 evolution from an aqueous HCl electrolyte. The new composite material shows how molecular deposition routes leading to highly active and stable multifunctional electrocatalysts can be developed. The facile design could in principle be extended to multiple catalyst classes by tuning of the molecular metal oxide precursor employed.

Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention.

BACKGROUND: Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing-related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. METHODS: A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non-sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty-two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre-intensive and post-intensive lifestyle interventions, were measured. RESULTS: The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non-sarcopenic subjects, serum interleukin (IL)-6, IL-18, tumour necrosis factor-α (TNF-α), TNF-like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF-α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6-fold and 14.3-fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4-fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF-α, IL-18, insulin, and adiponectin (all P < 0.05). CONCLUSIONS: High levels of the inflammatory cytokines TWEAK and TNF-α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.