Realizing Ultrasensitive and Accurate Point-of-Care Profiling for ATP with a Triple-Mode Strategy Based on the ATP-Induced Reassembly of a Copper Coordination Polymer Nanoflower.

New strategies for accurate and reliable detection of adenosine triphosphate (ATP) with portable devices are significant for biochemical analysis, while most recently reported approaches cannot satisfy the detection accuracy and independent of large instruments simultaneously, which are unsuitable for fast, simple, and on-site ATP monitoring. Herein, a unique, convenient, and label-free point-of-care sensing strategy based on novel copper coordination polymer nanoflowers (CuCPNFs) was fabricated for multimode (UV-vis, photothermal, and RGB values) onsite ATP determination with high selectivity, sensitivity, and accuracy. The resulting CuCPNFs with a 3D hierarchical structure exhibit the ATP-triggered decomposition behavior because the competitive coordination between ATP and the copper ions of CuCPNFs can result in the formation of ATP-Cu, which reveals preeminent peroxidase mimics activity and can accelerate the oxidation of 3, 3', 5, 5'-tetramethylbenzidine (TMB) to form oxTMB. During this process, the detection system displayed not only color changes but also a strong NIR laser-driven photothermal effect. Thus, the photothermal and color signal variations are easily monitored by a portable thermometer and a smartphone. This multimode point-of-care platform can meet the requirements of onsite, without bulky equipment, accuracy, and reliability all at once, greatly enhancing its application in practice and paving a new way in ATP analysis.

Phosphorus-doped nickel cobalt oxide (NiCo2O4) wrapped in 3D hierarchical hollow N-doped carbon nanoflowers as highly efficient bifunctional electrocatalysts for overall water splitting.

Properly design and fabricate capable electrocatalysts with 3D hierarchical hollow framework to realize cost-effective and efficacious overall water splitting (OWS) are particularly meaningful for the large-scale arrangement of pivotal energy technology. In this study, P-doped NiCo2O4 nanoparticles encapsulated in N-doped carbon hierarchical hollow nanoflowers (P-NiCo2O4@NCHHNFs) were constructed using the hydrothermal-pyrolysis-phosphorization approach. This fascinating architecture can not merely serve as a conductive pathway for electron transfer, but at the same time effectively inhibited the aggregation and corrosion of the NiCo2O4 nanoparticles. Additionally, the P doping not only regulates electronic structure configuration to boost the intrinsic activity of the catalyst, but also enhance electrochemical surface areas to reveal more accessible active sites. Attributing to these characteristics, the as-prepared P-NiCo2O4@NCHHNFs exhibit preeminent electrocatalytic performance with low overpotentials of 283 mV and 162 mV for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) (at 10 mA cm-2), respectively. Specifically, by using the P-NiCo2O4@NCHHNFs as bifunctional catalysts, a low potential of 1.56 V (at 10 mA cm-2) is sufficient to drive overall water splitting with splendid durability. This study proposed an innovative strategy for the conceiving and fabricating high-performance catalysts via heteroatom-doping.

Coordination polymer and layered double hydroxide dual-precursors derived polymetallic phosphides confined in N-doped hierarchical porous carbon nanoflower as a highly efficient bifunctional electrocatalyst for overall water splitting.

Controllable construction of proficient electrocatalyst with 3D hierarchical architecture to achieve low cost and high efficient overall water splitting is of great significance to the sustainable development. Hereby, trimetallic phosphides confined in N-doped carbon nanoflowers (CoNiP/CoNiFeP@NCNFs) were fabricated using CoNi coordination polymer nanoflowers/CoNiFe layered double hydroxide (CoNi CPNFs/CoNiFe LDH) as precursors followed by phosphorization. Benefiting from the unique 3D hierarchical porous architecture, preeminent conductivity, high specific surface area, efficient mass/charge transfer and synergic effect of various transition metals, the well-designed CoNiP/CoNiFeP@NCNFs exhibit extraordinary electrocatalytic performance for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in alkaline media. Particularly, this novel material can work as a bifunctional catalyst in an integrated water-splitting electrolyzer, which only requires a low voltage of 1.55 V to realize the current density of 10 mA cm-2 with admirable durability (at least 28 h). This work certified the foreground of composites assembled by 3D hierarchical porous carbon and polymetallic phosphides for overall water splitting. It also provided a novel proposal for the rational designing and constructing highly active electrocatalysts by using coordination polymer and LDH as dual-precursors.

Efficacy and safety of KN046, a novel bispecific antibody against PD-L1 and CTLA-4, in patients with non-small cell lung cancer who failed platinum-based chemotherapy: a phase II study.

BACKGROUND: This study aimed to evaluate the efficacy and safety of KN046, a novel recombinant humanised antibody targeting PD-L1 and CTLA-4 in advanced non-small cell lung cancer (NSCLC) patients after failure or intolerance to platinum-based chemotherapy. METHODS: In this multi-centre, open-label phase II clinical trial, patients were enroled after failure or intolerance to platinum-based chemotherapy. KN046 at 3 mg/kg or 5 mg/kg was administered intravenously every 2weeks. The primary end-point was objective response rate (ORR) evaluated by a blinded independent review committee (BIRC). RESULTS: A total of 30 and 34 patients were included in the 3 mg/kg (cohort A) and 5 mg/kg (cohort B) cohorts. On 31st August 2021, the median follow-up duration was 24.08 months (interquartile [IQR], 22.28, 24.84) and 19.35months (IQR, 17.25, 20.90) in the 3 mg/kg and 5 mg/kg cohorts, respectively. BIRC-assessed ORRs were 13.3% and 14.7% in the 3 mg/kg and 5 mg/kg cohorts, respectively. Median progression-free survival was 3.68 (95% confidence interval [CI] 3.22-7.29) and 3.68 (95%CI 1.81-7.39) months, while overall survival was 19.70 (95.5%CI 15.44-not estimated [NE]) and 13.04 (95.5%CI 9.86-NE) months, respectively. The most common treatment-related adverse events (TRAEs) were anaemia (28.1%), hyperglycaemia (26.7%), and infusion-related reactions (26.7%). The incidence rates of grade ≥ 3 TRAEs and TRAEs leading to treatment discontinuation were 42.2% and 14.1%, respectively. CONCLUSIONS: Both 3 mg/kg and 5 mg/kg KN046 showed promising efficacy and favourable safety profile for advanced NSCLC after failure or intolerance to previous platinum-based chemotherapy. TRIAL REGISTRATION NUMBER: NCT03838848.

3D holey hierarchical nanoflowers assembled by cobalt phosphide embedded N-doped carbon nanosheets as bifunctional electrocatalyst for highly efficient overall water splitting.

With the increasing energy and environmental crisis, exploring convenient and general strategies for constructing of highly active, stable, and cost-effective bifunctional electrocatalysts for overall water splitting are exceedingly desirable yet still challenging. Herein, 3D hierarchical mesoporous cobalt phosphide embedded N-doped carbon nanoflowers (CoP@NCNFs) are successfully constructed with ultrathin nanosheets by phosphatingof the cobalt coordination polymer nanoflowers (CoCPNFs). By virtue of their unique architecture and particular composition, the obtained CoP@NCNFs reveal extraordinary performance with ultralow overpotentials and small Tafel slopes for both OER (291 mV at 10 mA cm-2; 75 mV dec-1) and HER (166 mV at 10 mA cm-2; 76 mV dec-1) in alkaline medium. In particular, CoP@NCNFs can act as both anode and cathode to perform overall water splitting, and the assembled device only needs a cell voltage as low as 1.59 V to achieve the current density of 10 mA cm-2. Simultaneously, the CoP@NCNFs also exhibit admirable durability (at least 15 h) throughout the water splitting process. These remarkable electrocatalytic performances could be attributed to the synergistic effect of highlyactive CoP NPs and conductive mesoporous N-doped carbon nanosheets, which effectively improved the surface contact between catalyst and electrolyte, mass diffusion, and stability.

Achieving Ultrasensitive Point-of-Care Assay for Mercury Ions with a Triple-Mode Strategy Based on the Mercury-Triggered Dual-Enzyme Mimetic Activities of Au/WO3 Hierarchical Hollow Nanoflowers.

The exploration of new strategies for portable detection of mercury ions with high sensitivity and selectivity is of great value for biochemical and environmental analyses. Herein, a straightforward, convenient, label-free, and portable sensing platform based on a Au nanoparticle (NP)-decorated WO3 hollow nanoflower was constructed for the sensitive and selective detection of Hg(II) with a pressure, temperature, and colorimetric triple-signal readout. The resulting Au/WO3 hollow nanoflowers (Au/WO3 HNFs) could efficaciously impede the aggregation of Au NPs, thus significantly improving their catalytic activity and stability. The sensing mechanism of this new strategy using pressure as a signal readout was based on the mercury-triggered catalase mimetic activity of Au/WO3 HNFs. In the presence of the model analyte Hg(II), H2O2 in the detection system was decomposed to O2 fleetly, resulting in a detectable pressure signal. Accordingly, the quantification of Hg(II) was facilely realized based on the pressure changes, and the detection limit could reach as low as 0.224 nM. In addition, colorimetric and photothermal detection of Hg(II) using the Au/WO3 HNFs based on their mercury-stimulated peroxidase mimetic activity was also investigated, and the detection limits were calculated to be 78 nM and 0.22 µM for colorimetric and photothermal methods, respectively. Hence, this nanosensor can even achieve multimode determination of Hg(II) with the concept of point-of-care testing (POCT). Furthermore, the proposed multimode sensing platform also displayed satisfactory sensing performance for the Hg(II) assay in actual water samples. This promising strategy may provide novel insights on the fabrication of a multimode POCT platform for sensitive, selective, and accurate detection of heavy metal ions.

Running an Internet Hospital in China: Perspective Based on a Case Study.

Internet hospitals, as a new forum for doctors to conduct diagnosis and treatment activities based on the internet, are emerging in China and have become integral to the development of the medical field in conjunction with increasing reforms and policies in China's medical and health system. Here, we take the Internet Hospital of the First Affiliated Hospital, Zhejiang University (FAHZU Internet Hospital) as an example to discuss the operations and functional positioning of developing internet hospital medical services in relation to physical hospitals. This viewpoint considers the platform operation, management, and network security of FAHZU Internet Hospital, and summarizes the advantages and limitations in the operation to provide a reference for other areas with interest in developing internet hospitals.

Controlled growth of AgI nanoparticles on hollow WO3 hierarchical structures to act as Z-scheme photocatalyst for visible-light photocatalysis.

Controllable fabrication of nanomaterials with hierarchical architecture have received much attention in the field of photocatalysis due to their enhanced light-harvesting efficiency. Moreover, fabricating direct Z-scheme heterojunctions havebeenproven to be effective way to enhance the photocatalytic performance of photocatalysts. Herein, hierarchically hollow WO3 nanoflower was successfully synthesized by a simple hydrothermal treatment of tungsten chloride (WCl6) in ethanol solution. Decoration of the obtained WO3 with AgI nanoparticles in situ can form the Z-scheme AgI/WO3 hollow hierarchical nanoflowers (AgI/WO3 HHNFs). The AgI/WO3 HHNFs exhibited excellent photocatalytic activity and remarkable stability for the degradation of tetracycline hydrochloride (TC-HCl) and Eosin B (EB) under the irradiation of a low energy consume light (LED lamp, 5 W). Interestingly, compared to pure AgI nanoparticles, 3D hollow WO3 nanoflowers and AgI/WO3 nanosheets, the AgI/WO3 HHNFs revealed conspicuously enhanced photocatalytic activity. Thisphenomenon could be associated to three aspects, namely the high light-harvesting efficiency, increased light trapping and scattering capability and strongly coupled Z-scheme heterointerface, which effectively improved the photoelectron-hole sepreation efficiency. Our work therefore provide a novel insight for the fabrication of 3D hollow hierarchical structures.

Pyrolysis of metal-organic framework (CuBTC) decorated filter paper as a low-cost and highly active catalyst for the reduction of 4-nitrophenol.

The fabrication of noble metal free catalysts with excellent performance and high stability by a simple, efficient, general and low-cost approach remains an urgent task for solving the problem of resource shortage. Herein, Cu-based metal organic frameworks (MOFs) immobilized on commercial filter papers were used as pyrolysis precursors to synthesize CuxO@C at various calcination temperatures. Notably, the resultant CuxO@C-400 exhibits an excellent catalytic performance toward the reaction of reducing 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). By virtue of the large specific surface area, well-developed porosity, good stability and high dispersity of CuxO nanoparticles, the obtained CuxO@C-400 could complete the reduction reaction within 11 min with a large apparent rate constant κapp value (4.8 × 10-3 s-1). Our strategy therefore opens a new avenue for the preparation of low-cost and high-performance noble metal free catalysts.

Photocatalysis-Based Nanoprobes Using Noble Metal-Semiconductor Heterostructure for Visible Light-Driven in Vivo Detection of Mercury.

The development of sensitive and reliable methods to monitor the presence of mercuric ions in cells and organisms is of great importance to biological research and biomedical applications. In this work, we propose a strategy to construct a solar-driven nanoprobe using a 3D Au@MoS2 heterostructure as a photocatalyst and rhodamine B (RB) as a fluorescent and color change reporter molecule for monitoring Hg2+ in living cells and animals. The sensing mechanism is based on the photoinduced electron formation of gold amalgam in the 3D Au@MoS2 heterostructure under visible light illumination. This formation is able to remarkably inhibit the photocatalytic activity of the heterostructure toward RB decomposition. As a result, "OFF-ON" fluorescence and color change are produced. Such characteristics enable this new sensing platform to sensitively and selectively detect Hg2+ in water by fluorescence and colorimetric methods. The detection limits of the fluorescence assay and colorimetric assay are 0.22 and 0.038 nM for Hg2+, respectively; these values are well below the acceptable limits in drinking water standards (10 nM). For the first time, such photocatalysis-based sensing platform is successfully used to monitor Hg2+ in live cells and mice. Our work therefore opens a promising photocatalysis-based analysis methodology for highly sensitive and selective in vivo Hg2+ bioimaging studies.

Medication use patterns, health care resource utilization, and economic burden for patients with major depressive disorder in Beijing, People's Republic of China.

OBJECTIVE: The objective of the study was to investigate medication usage patterns, health care resource utilization, and direct medical costs of patients with major depressive disorder (MDD) in Beijing, People's Republic of China. METHODS: Data were extracted from a random sample of the Beijing Urban Employee Basic Medical Insurance database. Patients aged ≥18 years, with ≥1 primary diagnosis of MDD and 12-month continuous enrollment after their first observed MDD diagnosis between 2012 and 2013 were identified. Those with a diagnosis of schizophrenia, bipolar disorder, or cancer during the analysis period were excluded. RESULTS: In total 8,484 patients, with a mean age of 57.2 years, were included and 63% were female. The top three commonly observed comorbidities were hypertension (70.9%), anxiety disorder (68.6%), and coronary heart disease (65.1%). Furthermore, 71.4% of patients were treated with antidepressant medications, including 60.5% of patients treated with selective serotonin reuptake inhibitors, followed by noradrenergic and specific serotonergic antidepressants (9.0%) and serotonin-norepinephrine reuptake inhibitors (8.3%). The proportions of patients who discontinued their initial antidepressant within the first and second months after the index date were 45.4% and 77.0%, respectively. Concomitant medications were prescribed for 76.8% of patients. Only 0.42% of patients experienced ≥1 MDD-related hospitalization(s) during the 1-year follow-up, and the average annual number of hospitalization was 1.2 for those hospitalized. The mean length of stay was 33.4 days per hospitalization. All patients had ≥1 MDD-related outpatient visit(s). The mean annual number of outpatient visits per patient was 3.1. The mean annual direct medical costs per patient with MDD was RMB ¥1,694.1 (48.5% for antidepressant medications), and that for hospitalized patients was RMB ¥21,291.0 (15.0% for antidepressant medications). CONCLUSION: In Beijing, the majority of patients with MDD were treated in the outpatient setting only and they received antidepressants. Selective serotonin reuptake inhibitors were the most commonly used antidepressants. However, the duration to antidepressant medication was short, and persistence was low. The economic burden of MDD-related hospitalization was considerable.

Interface coassembly of mesoporous MoS2 based-frameworks for enhanced near-infrared light driven photocatalysis.

The three-dimensional porous Fe3O4@Cu2-xS-MoS2 framework is reported for the first time. The as-prepared 3D framework exhibits good structural stability, high surface area, enhanced adsorption capacity to substrates, and strong absorption in the NIR range. As a result, such hybrid frameworks exhibit excellent NIR-light photocatalytic activity and stable cycling for the direct arylation of heteroaromatics at room temperature.

White emission magnetic nanoparticles as chemosensors for sensitive colorimetric and ratiometric detection, and degradation of ClO⁻ and SCN⁻ in aqueous solutions based on a logic gate approach.

Fluorescent chemosensors for detecting single anions have been largely synthesized. However, the simultaneous detection and degradation of multiple anions remain a major challenge. Herein we report the synthesis of a white emission nanoprobe on the basis of a Coumarin-Rhodamine CR1-Eu complex coordinated to dipicolinic acid (dpa)-PEG-Fe3O4 nanoparticles for the selective detection of ClO(-) and SCN(-) ions on controlling by a logic gate. The obtained nanoprobe exhibits three individual primary colors (blue, green, and red) as well as white emission at different excitation energies. Interestingly, this nanoprobe shows a marked rose red to violet emission color change in response to ClO(-), a reversible violet to rose red emission color change in response to SCN(-), and high ClO(-) and SCN(-) selectivity and sensitivity with a detection limit of 0.037 and 0.250 nM, respectively. Furthermore, the SCN(-) and ClO(-) can degrade simultaneously through the redox reaction between ClO(-) and SCN(-).

Multifunctional Fe3O4 nanoparticles for highly sensitive detection and removal of Al(III) in aqueous solution.

Fe(3)O(4) nanoparticles (NPs) decorated with rhodamine 6G Schiff base, which exhibit high selectivity and sensitivity toward Al(3+) over other common metal ions in aqueous media under a physiological pH window via a 1:1 binding mode, have been synthesized and characterized. The resulting conjugate renders the rhodamine 6G Schiff base unit more water soluble, and the detection limit reaches 0.3 ppb in water. Moreover, can detect Al(3+) in a wide pH span (5.0-11.0) and enrich/remove excess Al(3+) in water via an external magnetic field, which indicates that it has more potential and further practical applications for biology and toxicology. Furthermore, provides good fluorescent imaging of Al(3+) in living cells.

3-Methyl-1-phenyl-4-[(Z)-phen-yl(4-acetamido-anilino)methyl-idene]-1H-pyrazol-5(4H)-one.

In the title compound, C(25)H(22)N(4)O(2), the dihedral angles between the central pyrazole ring and the phenyl and benzene rings are 37.01 (3), 75.58 (7) and 49.67 (8)°. An intra-molecular N-H⋯O hydrogen bond generates an S(6) motif. In the crystal, N-H⋯O hydrogen bonds link mol-ecules into a zigzag chain extended along the b axis.

2-(3-Hy-droxy-benzyl-amino)-acetic acid.

There are two independent 2-(3-hy-droxy-benzyl-amino)-acetic acid mol-ecules, C(9)H(11)NO(3), in the asymmetric unit of the title compound. The dihedral angle between the benzene rings of the two independent mol-ecules is 58.12 (4)°. The crystal packing is stablized by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds.

N-Methyl-N-phenyl-2-(quinolin-8-yl-oxy)acetamide monohydrate.

In the title compound, C(18)H(16)N(2)O(2)·H(2)O, the dihedral angle between the quinoline ring system and the benzene ring is 87.19 (8)°. In the crystal, water mol-ecules are linked to acetamide mol-ecules via inter-molecular O-H⋯N and O-H⋯O hydrogen bonds.

2-Chloro-N-methyl-N-phenyl-acetamide.

In the title compound, C(9)H(10)ClNO, the non-H atoms, excluding the phenyl group, are almost coplanar (r.m.s. deviation of the non-H atoms = 0.1015 Å). The dihedral angle formed between this plane and the benzene ring is 87.07 (5)°. Weak inter-molecular C-H⋯O inter-actions help to stabilize the packing.