Search

A novel lithium-impregnated hollow MOFs as the electrolyte to assemble solid-state battery, presenting excellent ionic conductivity and high Li+ transference number.

Neurospora crassa protein QDE-1, a member of the two-barrel polymerase superfamily, possesses both DNA- and RNA-dependent RNA polymerase (DdRP and RdRP) activities. The dual activities are essential for the production of double-stranded RNAs (dsRNAs), the precursors of small interfering RNAs (siRNAs) in N. crassa. Here, we report five complex structures of N-terminal truncated QDE-1 (QDE-1ΔN), representing four different reaction states: DNA/RNA-templated elongation, the de novo initiation of RNA synthesis, the first step of nucleotide condensation during de novo initiation and initial NTP loading. The template strand is aligned by a bridge-helix and double-psi beta-barrels 2 (DPBB2), the RNA product is held by DPBB1 and the slab domain. The DNA template unpairs with the RNA product at position –7, but the RNA template remains paired. The NTP analog coordinates with cations and is precisely positioned at the addition site by a rigid trigger loop and a proline-containing loop in the active center. The unique C-terminal tail from the QDE-1 dimer partner inserts into the substrate-binding cleft and plays regulatory roles in RNA synthesis. Collectively, this work elucidates the conserved mechanisms for DNA/RNA-dependent dual activities by QDE-1 and other two-barrel polymerase superfamily members.

Owing to their characteristic structures, metal-organic frameworks (MOFs) are considered as the leading candidate for drug-delivery materials. However, controlling the synthesis of MOFs with uniform morphology and high drug-loading/release efficiencies is still challenging, which greatly limits their applications and promotion. Herein, a multifunctional MOF-based drug-delivery system (DDS) with a controlled pore size of 100-200 nm for both therapeutic and bioimaging purposes was successfully synthesized in one step. Fe-MOF-based microcapsules were synthesized through a competitive coordination method, which was profited from the intrinsic coordination characteristics of the Fe element and the host-guest supramolecular interactions between Fe3+ and polyoxometalates anions. This as-synthesized macroporous DDS could greatly increase the drug-loading/release rate (77%; 83%) and serve as a magnetic resonance (MR) contrast agent. Because an Fe-containing macroporous DDS presents ultrahigh drug loading/release, the obtained 5-FU/Fe-MOF-based microcapsules displayed good biocompatibility, extremely powerful inhibition of tumor growth, and satisfactory MR imaging capability. Given all these advantages, this study integrates high therapeutic effect and diagnostic capability via a simple and effective morphology-controlling strategy, aiming at further facilitating the applications of MOFs in multifunctional drug delivery.

Nanocatalytic cancer therapy based on chemodynamic therapy, which converts hydrogen peroxide (H2O2) into toxic reactive oxygen species via the Fenton-like reaction, is regarded as a promising therapeutic strategy due to its specific response toward the tumor microenvironment (TME). However, the H2O2 concentration in TME (100 μM to 1 mM) is insufficient and introducing enough H2O2 or H2O2-generating agents is challenging. In view of this, we report a drug delivery system, CaO2/DOX@Cu/ZIF-8@HA (CDZH), which is capable of targeted H2O2 self-supply and exhibits outstanding chemo/chemodynamic synergetic therapy capability. CaO2/DOX@Cu/ZIF-8@HA is synthesized by fabricating biodegradable Cu/ZIF-8 shell-encapsulated CaO2 nanoparticles, loading chemotherapy drug doxorubicin, and coating a hyaluronic acid shell. In an acidic tumor microenvironment, the CDZH nanostructures targeted the release of doxorubicin, Cu2+, and CaO2. Doxorubicin affects chemotherapy and bioimaging, and CaO2 supplies H2O2 through a Cu-Fenton-like reaction to generate hydroxyl radicals with high oxidation activity for chemodynamic therapy. In brief, the drug delivery system combined targeted H2O2 self-supply and targeted bioimaging possess the potential of an efficient synergistic strategy for chemodynamic therapy and chemotherapy.

Background Understanding the characteristics of intrinsic connectivity networks (ICNs) in terms of both glucose metabolism and functional connectivity (FC) is important for revealing cognitive aging and neurodegeneration, but the relationships between these two aspects during aging has not been well established in older adults. Objective This study is to assess the relationship between age-related glucose metabolism and FC in key ICNs, and their direct or indirect effects on cognitive deficits in older adults. Methods We estimated the individual-level standard uptake value ratio (SUVr) and FC of eleven ICNs in 59 cognitively unimpaired older adults, then analyzed the associations of SUVr and FC of each ICN and their relationships with cognitive performance. Results The results showed both the SUVr and FC in the posterior default mode network (pDMN) had a significant decline with age, and the association between them was also significant. Moreover, both decline of metabolism and FC in the pDMN were significantly correlated with executive function decline. Finally, mediation analysis revealed the glucose metabolism mediated the FC decline with age and FC mediated the executive function deficits. Conclusions Our findings indicated that covariance between glucose metabolism and FC in the pDMN is one of the main routes that contributes to age-related executive function decline.

Nanocatalytic cancer therapy based on chemodynamic therapy, which converts hydrogen peroxide (H

A 55-year-old man and a 52-year-old man presenting with neurological symptoms were referred for F-FDG PET/CT for the underlying malignancy. In both cases, extensive intraspinal hypermetabolism was observed in F-FDG PET/CT. The cerebrospinal fluid culture finally confirmed infection of Brucella. This report illustrates that neurobrucellosis may present as intraspinal hypermetabolism on F-FDG PET/CT, and thus it should be added to the differential diagnosis.

Combined administration of different drugs is a widely acknowledged approach for effective cancer therapy. However, the limited targeting, as well as inferior drug loading capacities of current drug delivery systems (DDS), are still the bottleneck for better performance in cancer treatment. Herein, we successfully developed a cancer cell membrane (CM) decorated calcium carbonate (CC) hybrid nanoparticles (HN) for the co-delivery of cisplatin (CDDP) and oleanolic acid (OA). The physicochemical property of HN/CDDP/OA was evaluated, which revealed that the as-prepared DDS was core-shell structured and well-dispersed nanoparticles with size around 100 nm. The HN/CDDP/OA showed high stability and biocompatibility with pH-responsive drug release. Moreover, the CM modification in HN also demonstrated highly elevated tumor-homing nature than bare CC. Finally, the feasibility of HN/CDDP/OA in the treatment of gastric cancer (MGC-803 cell line) was assessed. HN/CDDP/OA showed better performance than mono systems with enhanced apoptosis and capable of reversing multidrug resistance (MDR) of cancer cells.

A 23-year-old man with drug-resistant epilepsy was admitted for presurgical evaluation. The epileptogenic zone could not be derived from seizure semiology and scalp electroencephalographic monitoring definitely. MRI showed periventricular nodular heterotopia in occipital horn of left lateral ventricle with high FDG uptake on interictal 18 F-FDG PET scan, whereas the hypometabolic zone in the left medial temporal lobe was also found on PET with no abnormality on MRI. Stereoelectroencephalographic implantation was performed to identify the seizure-onset zone. Two independent epileptogenic foci located in periventricular nodular heterotopia and left hippocampus were validated by stereoelectroencephalographic monitoring and the outcome of subsequent thermocoagulation.

A 63-year-old woman presented with abdominal pain and hematochezia was referred for 18 F-FDG PET/CT for the underlying malignancy. PET/CT detected diffuse thickening of the bowel walls with intense radioactivity in the colons. She was later diagnosed with multiple myeloma and secondary gastrointestinal amyloidosis, and achieved complete response of myeloma and amyloidosis after 9 cycles of chemotherapy. This case highlighted that gastrointestinal abnormality caused by amyloidosis might be the only presenting symptoms and findings in 18 F-FDG PET/CT in patients with multiple myeloma.

Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

Normal aging is accompanied by structural degeneration and glucose hypometabolism in the human brain. However, the relationship between structural network disconnections and hypometabolism in normal aging remains largely unknown. In the present study, by combining MRI and PET techniques, we investigated the metabolic mechanism of the structural brain connectome and its relationship with normal aging in a cross-sectional, community-based cohort of 42 cognitively normal elderly individuals aged 57–84 years. The structural connectome was constructed based on diffusion MRI tractography, and the network efficiency metrics were quantified using graph theory analyses. FDG-PET scanning was performed to evaluate the glucose metabolic level in the cortical regions of the individuals. The results of this study demonstrated that both network efficiency and cortical metabolism decrease with age (both p

Additional file 1: Supplementary figures and tables.

Facing considerable challenges associated with aging and dementia, China urgently needs an evidence-based health-care system for prevention and management of dementia. The Beijing Aging Brain Rejuvenation Initiative (BABRI) is a community-based cohort study initiated in 2008 that focuses on asymptomatic stages of dementia, aims to develop community-based prevention strategies for cognitive impairment, and provides a platform for scientific research and clinical trials. Thus far, BABRI has recruited 10,255 participants (aged 50 and over, 60.3% female), 2021 of whom have been followed up at least once at a 2- or 3-year interval. This article presents aims and study design of BABRI; summarizes preliminary behavioral and neuroimaging findings on mild cognitive impairment (MCI) and results of clinical trials on MCI; and discusses issues concerning early prevention in community, MCI diagnosis methods, and applications of database of aging and dementia. BABRI is proposed to build a systematic framework on brain health in old age.

Background: New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide which reconstitutes gut microbiota, reduces neuroinflammation, decreases amyloid deposition, and improves cognition in AD animal models. The first phase 3 clinical trial of GV-971 has been completed in China. Methods: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results: 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time-point, measurable at the week 4 visit and continuing throughout the trial. The difference between groups in change from baseline was −2.15 points (95% confidence interval, −3.07 to −1.23; PConclusions: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well tolerated. Trial registration: ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014.

Metal–organic frameworks (MOFs) are emerging as a novel class of conductive materials for the lithium-ion transport. However, developing MOFs with high-performance of lithium ion conductivity is largely limited due to the lack of capability of lithium ion storage in the rigid lattice of the MOF crystals. Herein, an advanced hollow metal–organic framework (ZIF-67@ZIF-8), which can store more lithium ions and transmit them by the wall of the cavity, has been designed and fabricated for the first time. Due to its special hollow structure and high lithium ion loading capability, the hollow ZIF-67@ZIF-8 exhibits superior ionic conductivity. Consequently, our strategy provides a new perspective for the development of solid electrolytes with excellent ionic conductivity.

Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, is an uncommon histiocytic disorder, which is rare and typically occurs in lymph nodes. However, one third of the cases manifest as extranodal disease. The cardiac involvement of this disease is extremely rare. We reported here the FDG PET/CT findings of a pathologically confirmed Rosai-Dorfman disease occurring in the right atrium in a 60-year-old man.

Bolometers for infrared detection by thermally induced resistance changes are indispensable components for extensive applications, in particular for security purposes. Microminiaturization is the direction of developing bolometers with a high performance and high resolution. However, the current micro-bolometers based on VOx are still subject to low responsivity and low response speed. Further development of high-performance micro-bolometers requires new designs of both materials and structures. Herein, we developed helical-shaped micro-bolometers based on the composites of vanadium dioxide (VO2) and carbon nanocoils (CNCs). It was shown that in the composite, the helical structure greatly enhanced the light absorption efficiency, the nanoscale diameter guaranteed small thermal capacitance, and the reversible phase transition of VO2 led to a large resistance change. More importantly, VO2/CNC bolometers showed a non-hysteretic response working in the phase-transition region. Due to the synergistic effect, the VO2/CNC bolometers had a very high temperature coefficient of resistance up to 35%/K, ultrahigh responsivity of 3.3 × 105 V W−1, a short response time lower than 2 ms, and a long lifetime of more than 1 000 000 cycles, all of which were superior to those of VOx-based bolometers. Our work reveals an inspiring strategy to prepare high-performance micro-bolometers, which will find potential applications in ultrasensitive thermal imaging and thermo-sensitive sensors.

A unique metal-organic framework with the formula [Cd4(H2L)2(L)·H2O]·3H2O (H4L = 5,5'-(1H-1,2,4-triazole-3,5-diyl)diisophthalic acid) was successfully constructed under solvothermal conditions. The frameworks with multiple free Lewis base sites and Lewis acid sites exhibited easily sensitized properties. After the encapsulation of Tb3+ cations, the as-synthesized Tb3+@Cd-MOF demonstrated strong luminescence induced by the efficient energy transfer from the bridging ligands to the Tb3+ cations, with the potential to serve as a chemical sensor. Interestingly, Tb3+@Cd-MOF was proven to be a very promising and highly selective and sensitive luminescent platform for the quantitative detection of arginine, which is the biomarker of cystinuria. The fluorescent probe presented high selectivity to arginine in urine with strong luminescence quenching. Furthermore, a convenient fluorescence-based test paper for the visual detection of arginine in applications was prepared. For the first time, arginine was quantified and monitored in urine by a highly efficient recyclable fluorescent sensor based on Tb3+-functionalized MOF hybrids, which may be a potential candidate for the further development of clinical diagnostic tools.

Metal-organic frameworks (MOFs) are attractive in designing drug delivery systems for the treatment of cancer because of their unique porous properties. However, the search for multifunctional MOFs with high drug loading and magnetic resonance/fluorescence imaging capacities is still a challenge and they have rarely been reported. In this article, using the intrinsic advantages of MOFs, hollow Fe-MOFs with biomolecular grafting were fabricated and shown to be capable of loading much more drugs and exhibiting targeted drug delivery, pH-controlled drug release and magnetic resonance/fluorescence imaging. Benefiting from their hollow structures, the drug loading capacity is as high as 35%. Due to post-modification with folic acid (FA) and the fluorescent reagent (5-FAM) and the existence of Fe(iii), in vitro experiments indicate that Fe-MOF-5-NH2-FA-5-FAM/5-FU can target cancer cells HepG-2 and display excellent magnetic resonance/fluorescence imaging. Furthermore, in vivo biodistribution indicates that Fe-MOF-5-NH2-FA-5-FAM/5-FU can accumulate in the tumor. Taken together, our work integrates high drug loading and bioimaging into a single MOF successfully and reveals the enormous potential of the functionalized MOF for drug delivery and bioimaging.

With the aging of the population, diseases related to cognitive impairment have caused great harm to society and families. Objective evaluation of the level of cognitive aging and clarification of the process and neural mechanism of cognitive aging would provide a basis for forewarning and treatment in the early stages of disease. Thus, there is a necessity to establish large-scale, high-standard community-based elderly brain health cohorts. Detailed in this paper, the Beijing Aging Brain Rejuvenation Initiative (BABRI) project, which launched in 2008 by Beijing Normal University and aimed to build a database focusing on cognitive aging and brain health, encompasses 10000 samples from elderly individuals in local communities and over 5000 multimodal neuroimaging cases. After ten years of unremitting efforts, the BABRI database has taken shape with more than 7000 community-based cases for individuals above 50 years of age. Ever since, BABRI has been used to preliminarily establish cognitive aging norms for native Chinese senior citizens, revealing the incidence and risk factors for mild cognitive impairment and systematically identifying their specific neural characteristics that may potentially serve as biomarkers for early detection before the onset of disease. Based on social needs and international trends in neuroscience, the implementation of large community-based elderly brain health cohort studies and the establishment of a multidimensional database to document the patterns of cognitive aging would provide high quality and innovative resources for elderly brain health promotion, major brain disease prevention and development of related researches, and play a key role in the implementation of new projects related to brain science in China.

This work evaluated the use of the positron emission tomography (PET)/computed tomography (CT) technique to assess the early therapeutic response and predict the prognosis of patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) who underwent apatinib therapy. Standardised uptake value (SUV), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), derived from18F-FDG PET/CT and SUV from68Ga-NOTA-PRGD2 PET/CT were evaluated. Tumour response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Sixteen of 20 patients achieved partial response (PR) and four of 20 had stable disease (SD) after apatinib therapy. Six progression-free survival (PFS) events occurred. A strong correlation was observed between the best change in the sum of the longest diameters of target lesions (ΔCT%) and18F-FDG PET/CT indices after the completion of the first treatment cycle (ΔMTV% (P = 0.0019), ΔTLG% (P = 0.0021) and ΔSUVmax% (P = 0.0443)). A significant difference in PFS was observed between patients with ΔMTV% P = 0.0019) and between patients with ΔTLG% P = 0.0065). Ten of 11 patients presented a decrease in SUVmax on68Ga-NOTA-PRGD2 PET/CT after two cycles of apatinib therapy and showed PR, whereas one patient presenting an increase in SUVmax only showed SD as the best response. When a cut-off value of the target/background ratio at −20% was used, two PFS curves showed a significant difference (P = 0.0016). Hence, early assessment by18F-FDG and68Ga-NOTA-PRGD2 PET/CT was effective in the prediction and evaluation of RAIR-DTC treated with apatinib.

For electrochemical carbon dioxide reduction (CO2RR), metal–N sites exhibit promising catalytic activity, yet the structure–activity relationship remains largely unclear. Here we synthesize well-defined homogeneous catalysts containing four coordinating pyridine N atoms, regulate the coordination metal centers in immobilized molecular complexes, and investigate their catalytic performances in CO2RR. The resulting Co(qpy)/CNTs composite exhibit the highest efficiency. Its Faradaic efficiency for CO reaches >98% over the broad range from −0.5 V to −0.9 V (vs. RHE), with long-term stability over 100 h. Density functional theory calculations reveal that the larger electronic overlap between the catalytic site and intermediate can decrease the free energy change for *COOH formation. The calculation results are experimentally verified by changing the metal centers (Fe(qpy), Ni(qpy) and Cu(qpy)). This work unveils the relationship between metal–ligand coordination and CO2RR performance, and offers a strategy for the design and synthesis of high-performance catalysts for practical applications.

Metal–organic frameworks (MOFs) have attracted significant interest for drug delivery. However, MOFs usually have micropores smaller than 2 nm, restraining larger drug molecules from entering into the pores of MOFs, restricting their practical application as drug carriers. Here we demonstrate a novel one-step approach to synthesize a fluorescent hierarchical-pore metal–organic framework (H-MOF), which is realized by assembling a MOF in an aqueous solution containing rhodamine b (RhB) as a modulator and a fluorescent imaging reagent. The as-synthesized fluorescent H-MOF can not only serve as a substrate to in situ load micromolecule and macromolecular drugs simultaneously, but can also efficiently deliver the drugs into cells. The red fluorescence of RhB remains in the H-MOF, avoiding the interference of auto-fluorescence in vivo imaging and realizing high quantum yield and low-background imaging. The low cytotoxicity, good biocompatibility and high imaging efficiency of the fluorescence H-MOF are confirmed using murine gastric cancer 803 (MGC-803) cells and human airway smooth muscle cell (HASMC) as modes. Good stability and distribution in vivo are confirmed using naked mouse as modes. Taken together, we demonstrate the possibility of using one-step method to obtain fluorescent H-MOF, aiming for loading various drug molecules and bioimaging, which probably is useful for some specific requirements of pharmaceuticals.