Background and Aim
Remimazolam tosilate (RT) is a new short‐acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy ...and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy.
Methods
This positive‐controlled, non‐inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety.
Results
The success rate of sedation in the RT group was non‐inferior to that in the propofol group (97.34% vs 100.00%; difference in rate −2.66%, 95% CI −4.96 to −0.36, meeting criteria for non‐inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment‐related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001).
Conclusion
This trial established non‐inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.
We explore the tripartite entropic uncertainty and genuine tripartite quantumness of Dirac fields in the background of the Garfinkle–Horowitz–Strominger (GHS) dilation space-time. It is interesting ...to note that Hawking radiation leads to the decay of quantum nonlocality in the physically accessible region while preserving its total coherence. More importantly, it demonstrates an intrinsic trade-off relationship between the coherences of physically accessible and inaccessible regions. Moreover, we examine the effect of Hawking radiation on entropy-based measured uncertainty and find that stronger Hawking radiation causes the uncertainty in physically accessible regions to increase while decreasing the uncertainty in physically inaccessible regions. Therefore, our investigations may be beneficial to a better understanding of the system’s quantumness in a curved space-time. Combining relativity theory with quantum information science offers new avenues for comprehending the information paradoxes involving black holes.
Bone metastases occur in most advanced breast cancer patients and cause serious skeletal-related complications. The mechanisms by which bone metastasis seeds develop in primary tumors and ...specifically colonize the bone remain to be elucidated. Here, we show that forkhead box F2 (FOXF2) functions as a master transcription factor for reprogramming cancer cells into an osteomimetic phenotype by pleiotropic transactivation of the BMP4/SMAD1 signaling pathway and bone-related genes that are expressed at early stages of bone differentiation. The epithelial-to-osteomimicry transition regulated by FOXF2 confers a tendency on cancer cells to metastasize to bone which leads to osteolytic bone lesions. The BMP antagonist Noggin significantly inhibits FOXF2-driven osteolytic bone metastasis of breast cancer cells. Thus, targeting the FOXF2-BMP/SMAD axis might be a promising therapeutic strategy to manage bone metastasis. The role of FOXF2 in transactivating bone-related genes implies a biological function of FOXF2 in regulating bone development and remodeling.
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•The formation, function and implication of structural defects in MOF are presented.•Synthetic strategy and characterization of MOF-based membranes are ...described.•Structure-performance of MOF-based membranes in water reclamation are correlated.•Current challenges and potentials of MOF-based membranes are discussed.
Metal-organic framework (MOF), which is composed of metal ions and bridged organic ligands, are one of the most high-profile materials currently, because their regular and tunable pore structures confer unique properties. In particular, MOF materials have attracted widespread attention in the field of membrane separation, wherein water-stable MOF membranes stand out especially in the field of wastewater treatment and water regeneration. This review critically summarizes the various design and synthesis strategies of bare MOF membranes and MOF composite membranes. The formation and function of the structural defects in MOF play important roles in the performance of MOF-based membrane. Different characterization techniques are discussed systematically, and the applications of MOF membranes in membrane filtration, membrane distillation, and membrane pervaporation are described. In order to uncover the full potential of MOF-based membranes in wastewater treatment and water regeneration, current challenges are detailed and future research directions proposed.
Dendrite growth of alkali metal anodes limited their lifetime for charge/discharge cycling. Here, we report near-perfect anodes of lithium, sodium, and potassium metals achieved by electrochemical ...polishing, which removes microscopic defects and creates ultra-smooth ultra-thin solid-electrolyte interphase layers at metal surfaces for providing a homogeneous environment. Precise characterizations by AFM force probing with corroborative in-depth XPS profile analysis reveal that the ultra-smooth ultra-thin solid-electrolyte interphase can be designed to have alternating inorganic-rich and organic-rich/mixed multi-layered structure, which offers mechanical property of coupled rigidity and elasticity. The polished metal anodes exhibit significantly enhanced cycling stability, specifically the lithium anodes can cycle for over 200 times at a real current density of 2 mA cm
with 100% depth of discharge. Our work illustrates that an ultra-smooth ultra-thin solid-electrolyte interphase may be robust enough to suppress dendrite growth and thus serve as an initial layer for further improved protection of alkali metal anodes.
Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic ...malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases. CAR T cells were i.v. infused after lymphodepleting chemotherapy. Two delivery methods, three infusions versus one infusion of the total CAR T dose, were tested in, respectively, 8 and 9 cases. No response differences were noted among the two delivery subgroups. Together, after CAR T cell infusion, 10 cases experienced a mild cytokine release syndrome (CRS), 6 had severe but manageable CRS, and 1 died of a very severe toxic reaction. The abundance of BCMA and cytogenetic marker del(17p) and the elevation of IL-6 were the key indicators for severe CRS. Among 17 cases, the overall response rate was 88.2%, with 13 achieving stringent complete response (sCR) and 2 reaching very good partial response (VGPR), while 1 was a nonresponder. With a median follow-up of 417 days, 8 patients remained in sCR or VGPR, whereas 6 relapsed after sCR and 1 had progressive disease (PD) after VGPR. CAR T cells were high in most cases with stable response but low in 6 out of 7 relapse/PD cases. Notably, positive anti-CAR antibody constituted a high-risk factor for relapse/PD, and patients who received prior autologous hematopoietic stem cell transplantation had more durable response. Thus, biepitopic CAR T against BCMA represents a promising therapy for R/R MM, while most adverse effects are clinically manageable.
Northwest China is one of the most arid regions in the world and has experienced intriguing climate warming and humidification. Nonetheless, future climate conditions in Northwest China still remain ...uncertain. In this study, we applied an ensemble of the 12 latest model simulations of the Coupled Model Intercomparison Project Phase 6 (CMIP6) to assess future drought conditions until 2099 in Northwest China, as inferred from the Palmer Drought Severity Index (PDSI). Future drought conditions were projected under three climate change scenarios through the combination of shared socioeconomic pathways (SSPs) and representative concentration pathways (RCPs), namely, SSP126 (SSP1 + RCP2.6, a green development pathway), SSP245 (SSP2 + RCP4.5, an intermediate development pathway), and SSP585 (SSP5 + RCP8.5, a high development pathway). For 2015-2099, drought severity showed no trend under SSP126, in contrast, for the SSP245 and SSP585 scenarios, a rapid increase during 2015-2099 was observed, especially under SSP585. We also found that the drought frequency in Northwest China under SSP585 was generally lower than that under SSP126 and SSP245, although the drought duration under SSP585 tended to be longer. These findings suggest the green development pathway in drought mitigation and adaptation strategies in Northwest China, an arid and agricultural region along the Silk Road.
A Kagome structure covalent organic framework (COF) film with three‐state NIR electrochromic properties was designed and synthesized. The COFTPDA‐PDA film is composed of hexagonal nanosheets with ...high crystallinity and has three reversible color states at different applied potentials. It has high absorption spectra changes in the NIR region, ascribed to the strong intervalence charge transfer (IVCT) interaction of the Class III mixed‐valence systems of the conjugated triphenylamine species. The film showed sub‐second response time (1.3 s for coloring and 0.7 s for bleaching at 1050 nm) and long retention time in the NIR region. COFTPDA‐PDA film shows superior NIR electrochromic properties in term of response time and stability, attributed to the highly ordered porous structure and the π–π stacking structure of the COFTPDA‐PDA architecture. The COFTPDA‐PDA film was applied in mimicking a flip‐flop logic gate with optical memory function.
A Kagome structure covalent organic framework (COF) film was synthesized and exhibited three‐state electrochromic properties with sub‐second response time and long retention time in the near‐infrared region. Taking potential and absorbance as input and output signal, respectively, a mimicking logic gate with optical memory functions was demonstrated based on the COFTPDA‐PDA film.
Photodynamic therapy (PDT) shows unique selectivity and irreversible destruction toward treated tissues or cells, but still has several problems in clinical practice. One is limited therapeutic ...efficiency, which is attributed to hypoxia in tumor sites. Another is the limited treatment depth because traditional photosensitizes are excited by short wavelength light (<700 nm). An assembled nano‐complex system composed of oxygen donor, two‐photon absorption (TPA) species, and photosensitizer (PS) was synthesized to address both problems. The photosensitizer is excited indirectly by two‐photon laser through intraparticle FRET mechanism for improving treatment depth. The oxygen donor, hemoglobin, can supply extra oxygen into tumor location through targeting effect for enhanced PDT efficiency. The mechanism and PDT effect were verified through both in vitro and in vivo experiments. The simple system is promising to promote two‐photon PDT for clinical applications.
A nanocomplex system composed of oxygen donor, two‐photon absorption (TPA) species, and photosensitizer (PS) was synthesized. The photosensitizer is excited indirectly by two‐photon laser through intraparticle FRET mechanism for improving treatment depth. The oxygen donor, hemoglobin, can supply extra oxygen into tumor location through targeting effect for enhanced photodynamic therapy efficiency.
The selective separation of structurally similar aliphatic/aromatic hydrocarbons is an essential goal in industrial processes. In this study, we report the synthesis of a water-soluble (Tr2M3)4L4 (Tr ...= cycloheptatrienyl ring; M = metal; L = organosulfur ligand) molecular cage (1) via self-assembly of the water-soluble acceptor tripalladium sandwich species (Tr2Pd3)(CH3CN)NO32 and the attachment onto L of solubilizing methoxyethoxy appendants to be utilized in an energy-friendly alternative approach to the separation of structurally similar molecules under ambient conditions. Cage 1, comprising a hydrophobic inner cavity, exhibited good solubility and stability in aqueous media. It also demonstrated excellent performance in the sequential separation of alkanes (C6–C9), xylene, and other disubstituted benzene isomers and cis/trans-decalin.
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