Introduction: Orelabrutinib is a second-generation Bruton tyrosine kinase inhibitor (BTKi) with high kinase selectivity. Clinical studies have demonstrated that orelabrutinib achieved a high complete ...response rate of 26.3% in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), showing promising efficacy and acceptable safety profile. However, the real-world data of Orelabrutinib are not available. This study aimed to evaluate the effectiveness and safety of orelabrutinib-containing regimens for the treatment of patients (pts) with CLL/SLL in a real-world setting. Methods: This was a retrospective, multi-center, real-world study conducted. Pts (aged 18 years or older) with CLL/SLL who received at least 3 months of orelabrutinib-containing regimens between December 2020 and March 2023 were analyzed. Efficacy was evaluated by hematologic response rate (HRR), defined as the proportion of pts who met at least 1 of the following hematologic response criteria: hemoglobin response (pts having a recovery of hemoglobin value or ≥50% increase from baseline), platelet response (pts having a recovery of platelet count or ≥50% increase from baseline), or lymphocyte response (pts having a recovery of lymphocyte count or ≥50% reduction from baseline). Safety was assessed by adverse events (AEs) as per NCI-CTCAE 5.0. Results: 24 pts with CLL/SLL (12 males; 22 CLL) were included, with a median age of 62.5 years (range: 38-82). Most pts had an Eastern Cooperative Oncology Group score of 0-1 (17/24, 70.8%) and Rai stage III or IV disease (16/18, 88.9%). 7 pts with hypertension, of which 2 with very high-risk hypertension. 3 pts have previously received other BTKi. A total of 9 pts(37.5%) performed del(17p), TP53, or IGHV testing. Among them, pts received orelabrutinib 100 mg (2/24,) or 150 mg (22/24,) once daily. As of the cut-off date (July 13, 2023), the median follow-up was 10.67 (range, 2.73-25.77) months. 18 pts (16 CLL, 2 SLL) with abnormal hemoglobin value, platelet count, or lymphocyte count at baseline were evaluable for hematologic response. Hematologic response was achieved in 11 (61.1%) of 18 evaluable pts. Pts aged <65 years had a higher HRR versus pts aged ≥65 years (87.5% vs. 40.0%, p=0.040). HRR was 56.3% in CLL versus 100.0% in SLL pts, and 60.0% in pts with hypertension versus 61.5% without hypertension . Four of 11 responders had a hematologic response in at least two criteria (CLL, n=3; SLL, n=1), of which 3 pts had a hemoglobin response (Figure 1). The most commonly reported AEs included hemoglobin decreased (16.7%) and platelet count decreased (16.7%). Grade ≥3 AEs were white blood cell count decreased (4.2%), platelet count decreased (4.2%), and lymphocyte count decreased (4.2%). No pts experienced severe AEs. No cardiovascular AEs were reported during treatment in 7 pts with hypertension at baseline. Conclusions: This real-world study assessed the preliminary characteristics and clinical outcome of patients receiving orelabrutinib-containing regimens under routine clinical practice conditions in China. The orelabrutinib-containing regimens in this study furnished beneficial evidence for the treatment of CLL/SLL and is essential for determining the best treatment option, future data with a larger sample and longer follow-up will be updated.
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IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
In this paper, we describe the effects of different scanning speeds (600–900 mm/s) on the microstructure, mechanical properties and corrosion behavior of biodegradable bone-substitution alloys ...produced from 80:20 (by wt.) Fe:Mn powders using laser powder bed fusion (LPBF). Both the Mn content (18.9–15.1 wt% Mn) and density (7920–7730 kg/m3) of the LPBFed samples decreased slightly with increasing laser scanning speed, while the oxygen content increased (0.12–0.40 wt%). Increasing scanning speed also led to increased porosity (from 0.27% to 2.5%) and increased cracking. The specimen produced at the lowest scanning speed of 600 mm/s, which consisted of only the HCP ε-martensite phase, showed by far the highest yield strength (YS) at 644 MPa and the highest ultimate tensile strength (UTS) at 857 MPa, but the lowest elongation to failure (El) of only 13.7%. Specimens produced at higher scanning rates consisted of both BCC α′-martensite and ε-martensite phases. The sample fabricated at a scanning speed of 700 mm/s showed the best balance of mechanical properties with a YS of 330 MPa, a UTS of 839 MPa, and an El of 36.1%. Electrochemical testing showed corrosion rates from 0.09 mm/yr (600 mm/s specimen) to 0.22 mm/yr (700 mm/s specimen), which are higher than those of both pure Fe and most Fe–30Mn and Fe–35Mn alloys reported in the literature. The work demonstrates that the meso-/micro-scale structure, and, hence, the mechanical properties and corrosion rates of Fe–Mn alloys can be tailored by varying the scanning speed during LPBF processing. It also demonstrates the potential of LPBFed Fe–Mn alloys with low Mn content for use as biodegradable bone substitutes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We demonstrated the use of hydrated calcium vanadate (CaV6O16·3H2O, denoted as CaVO-2) as a cathode for aqueous zinc-ion batteries (AZIBs). Nanoribbons of hydrated calcium vanadate facilitated ...shortening of the Zn2+ transport distance and accelerated zinc-ion insertion. The introduction of interlayer structure water increased the interlayer spacing of calcium vanadate and as a “lubricant”. Ca2+ insertion also expanded the interlayer spacing and further stabilized the interlayer structure of vanadium-based oxide. The density functional theory results showed that the introduction of Ca2+ and structured water could effectively improve the diffusion kinetics, resulting in the rapid transport of zinc ions. As a result, AZIBs based on the CaVO-2 cathode offered high specific capacity (329.6 mAh g–1 at 200 mA g–1) and fast charge/discharge capability (147 mAh g–1 at 10 A g–1). Impressively, quasi-solid-state zinc-ion batteries based on the CaVO-2 cathode and polyacrylamide–cellulose nanofiber hydrogel electrolytes maintained an outstanding specific capacity and long cycle life (162 mAh g–1 over 10 000 cycles at 5 A g–1). This study provided a reliable strategy for metal-ion insertion and the structural water introduction of oxides to produce a high-quality cathode for ZIBs. Meanwhile, it provides ideas for the combination of vanadium-based materials and gel electrolytes to construct solid-state zinc-ion batteries.
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IJS, KILJ, NUK, PNG, UL, UM
The elastic modulus is a key factor influencing the applications of implant materials because of the weakening effect of stress shielding. Ti and its alloys are good potential implant materials ...thanks to their low elastic modulus and fine biocompatibility. The addition of alloying elements into pure Ti and Ti alloys is the basic way to further decrease the elastic modulus whilst simultaneously enhancing strength, wearability, and corrosion resistance, for example. Finding the relationship between the composition and elastic modulus can greatly promote the development of Ti alloys with a low modulus for implant applications. In the current work, we investigated the elastic modulus of TiZrTa alloys with scores of compositions by using the high-throughput diffusion couple method, nanoindentation, and an electron probe micro-analysis. The relationship between the elastic modulus and the composition of the TiZrTa alloys was obtained. The average valence electron theory was employed to make clear the variation between the elastic modulus and the composition. Finally, the composition range formulae of TiZrTa alloys likely to have a low modulus were established by combining our data and previous results. These findings are helpful in developing new Ti alloys with a low modulus and also help to further understand the alloying theory.
Hawthorn, one of the widely‐used traditional Chinese medicines, has been used to treat dyspepsia, hyperlipidemia, and cardiovascular disease in the clinic. Our previous study revealed that gallic ...acid, neochlorogenic acid, cryptochlorogenic acid, vitexin, and quercetin were active components of hawthorn. In this study, a simple, precise, and reliable liquid chromatography‐mass spectrometry method was developed for the simultaneous quantification of five components in rat serums. The separation was achieved on the Hypersil GOLD C18 column, and the mobile phases consisted of 0.1% acetic acid water and methanol at a flow rate of 0.3 mL/min. The mass spectrometry data acquisition was performed on Q‐Extractive‐Orbitrap mass spectrometry with an electrospray ionization source in negative ion mode. The proposed liquid chromatography‐mass spectrometry method was validated in terms of linearity, intra‐ and inter‐precision, accuracy, recoveries, matrix effects, and stability. Then this newly proposed liquid chromatography‐mass spectrometry method was successfully applied to a pharmacokinetic study on rats after oral administration of hawthorn aqueous extracts. This study provided relevant information on the pharmacokinetics of active components of hawthorn and explained the underlying mechanism of their bioactivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The use of a dual-interference channels static Fourier transform imaging spectrometer based on stepped micro-mirror (D-SIFTS) for environmental gas monitoring has the advantages of high throughput, a ...compact structure, and a stable performance. It also has the characteristics of both a broad spectral range and high spectral resolution. However, its unique structural features also bring many problems for subsequent data processing, mainly including the complex distribution of the interference data, the low signal-to-noise ratio (SNR) of infrared scene images, and a unique inversion process of material information. To this end, this paper proposes a method of image and spectra information processing and gas concentration inversion. A multiscale enhancement algorithm for infrared images incorporating wavelet denoising is used to obtain high-quality remote sensing scene images, and spectral reconstruction optimization algorithms, such as interference intensity sequence resampling, are used to obtain accurate spectral information; the quantitative calibration model of the detected gas concentration is established to achieve high-precision inversion of gas concentration, and its distribution is visualized in combination with the scene image. Finally, the effectiveness and accuracy of the data processing algorithm are verified through the use of several experiments, which provide essential theoretical guidance and technical support for the practical applications of D-SIFTS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
is an important bacterial genus containing many pathogenic species. Although more and more
phages were isolated, the genome, ecology and evolution of
phages and their roles in bacteriophage therapy, ...have not been fully revealed.
Novel
phage vB_ValR_NF infecting
was isolated from the coastal waters of Qingdao during the
blooms, Characterization and genomic feature of phage vB_ValR_NF has been analysed using phage isolation, sequencing and metagenome method.
Phage vB_ValR_NF has a siphoviral morphology (icosahedral head 114±1 nm in diameter; a tail length of 231±1 nm), a short latent period (30 minutes) and a large burst size (113 virions per cell), and the thermal/pH stability study showed that phage vB_ValR_NF was highly tolerant to a range of pHs (4-12) and temperatures (-20 - 45 °C), respectively. Host range analysis suggests that phage vB_ValR_NF not only has a high inhibitory ability against the host strain
, but also can infect 7 other
strains. In addition, the phage vB_ValR_NF has a double-stranded 44, 507 bp DNA genome, with 43.10 % GC content and 75 open reading frames. Three auxiliary metabolic genes associated with aldehyde dehydrogenase, serine/threonine protein phosphatase and calcineurin-like phosphoesterase were predicted, might help the host
occupy the survival advantage, thus improving the survival chance of phage vB_ValR_NF under harsh conditions. This point can be supported by the higher abundance of phage vB_ValR_NF during the
blooms than in other marine environments. Further phylogenetic and genomic analysis shows that the viral group represented by
phage vB_ValR_NF is different from other well-defined reference viruses, and can be classified into a new family, named
. In general, as a new marine phage infecting
, phage vB_ValR_NF provides basic information for further molecular research on phage-host interactions and evolution, and may unravel a novel insight into changes in the community structure of organisms during the
blooms. At the same time, its high tolerance to extreme conditions and excellent bactericidal ability will become important reference factors when evaluating the potential of phage vB_ValR_NF in bacteriophage therapy in the future.
Seawater electrolysis is a potentially cost-effective approach to green hydrogen production, but it currently faces substantial challenges for its high energy consumption and the interference of ...chlorine evolution reaction (ClER). Replacing the energy-demanding oxygen evolution reaction with methanol oxidation reaction (MOR) represents a promising alternative, as MOR occurs at a significantly low anodic potential, which cannot only reduce the voltage needed for electrolysis but also completely circumvents ClER. To this end, developing high-performance MOR catalysts is a key. Herein, a novel quaternary Pt
Pd
CuGa/C intermetallic nanoparticle (i-NP) catalyst is reported, which shows a high mass activity (11.13 A mg
), a large specific activity (18.13 mA cm
), and outstanding stability toward alkaline MOR. Advanced characterization and density functional theory calculations reveal that the introduction of atomically distributed Pd in Pt
CuGa intermetallic markedly promotes the oxidation of key reaction intermediates by enriching electron concentration around Pt sites, resulting in weak adsorption of carbon-containing intermediates and favorable adsorption of synergistic OH
groups near Pd sites. MOR-assisted seawater electrolysis is demonstrated, which continuously operates under 1.23 V for 240 h in simulated seawater and 120 h in natural seawater without notable degradation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Seawater electrolysis is a potentially cost‐effective approach to green hydrogen production, but it currently faces substantial challenges for its high energy consumption and the interference of ...chlorine evolution reaction (ClER). Replacing the energy‐demanding oxygen evolution reaction with methanol oxidation reaction (MOR) represents a promising alternative, as MOR occurs at a significantly low anodic potential, which cannot only reduce the voltage needed for electrolysis but also completely circumvents ClER. To this end, developing high‐performance MOR catalysts is a key. Herein, a novel quaternary Pt1.8Pd0.2CuGa/C intermetallic nanoparticle (i‐NP) catalyst is reported, which shows a high mass activity (11.13 A mgPGM−1), a large specific activity (18.13 mA cmPGM−2), and outstanding stability toward alkaline MOR. Advanced characterization and density functional theory calculations reveal that the introduction of atomically distributed Pd in Pt2CuGa intermetallic markedly promotes the oxidation of key reaction intermediates by enriching electron concentration around Pt sites, resulting in weak adsorption of carbon‐containing intermediates and favorable adsorption of synergistic OH− groups near Pd sites. MOR‐assisted seawater electrolysis is demonstrated, which continuously operates under 1.23 V for 240 h in simulated seawater and 120 h in natural seawater without notable degradation.
A novel quaternary Pt1.8Pd0.2CuGa intermetallic nanoparticle electrocatalyst is designed, which shows outstanding performance for the methanol oxidation reaction in alkaline–saline water. Stable energy‐saving hybrid seawater electrolysis is further demonstrated, using the prepared Pt1.8Pd0.2CuGa nanoparticles to catalyze the anodic methanol oxidation coupled with the cathodic hydrogen evolution, which completely circumvents the interfering chlorine evolution.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Metal–halide perovskites are promising light-emitting materials due to their continually tunable emission peak, high color purity, high emission efficiency, and low cost. Incorporating some ...two-dimensional (2D) perovskites into the three-dimensional (3D) perovskite can facilitate carrier localization to the emitting area and reduce nonradiative recombination. However, the incorporated 2D perovskites typically contain diverse phases with different bandgaps and random distribution, which significantly limits the performance of perovskite light emitting diodes (PeLEDs). Furthermore, the morphology of the quasi-2D perovskite film is also a key issue to the device performance. Herein, through replacing part of FA+ with Cs+, the phase distribution and morphology of perovskite film can be tailored simultaneously. When 20% of FA+ is replaced by Cs+ in the perovskite film, the charge transfer efficiency is enhanced and the current leakage is suppressed. Eventually, the efficiency of PeLED is almost doubled and the stability is also significantly improved.
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IJS, KILJ, NUK, PNG, UL, UM
