Diagnostic role of the fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score as a noninvasive tool for liver fibrosis scoring.

Nonalcoholic fatty liver disease (NAFLD) is characterized by liver fibrosis, which serves as a crucial indicator of its progression and prognosis. Owing to the limitations of biopsy, which is the gold standard for measuring liver fibrosis, a reliable and noninvasive marker is required. We evaluated the diagnostic role of the fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease fibrosis score (NFS) in patients with NAFLD with varying severities of liver fibrosis. The FIB-4 index and NFS were calculated using laboratory data from 121 patients who underwent liver biopsies between January 2022 and December 2023. The results were compared with those of the Scheuer scoring system for liver biopsies (F0, F1 + F2, and F3 + F4) to determine the sensitivity and specificity of the FIB-4 index and the liver disease fibrosis score in detecting and staging liver fibrosis. Twenty-one patients had advanced fibrosis (F3-F4), and 100 had minimal or mild fibrosis (F0-F2). The degree of liver fibrosis increased with decreased albumin, alanine aminotransferase and platelet count levels, and increasing age. Receiver operating characteristic curve analysis for the FIB-4 index and NFS revealed that the areas under the curve for the FIB-4 index and NFS were 0.895 (95% confidence interval: 0.836-0.954) and 0.882 (95% confidence interval: 0.813-0.952), respectively. The FIB-4 indices showed 95.24% sensitivity at a cutoff point of 1.30, and 85% specificity at a cutoff point of 2.67, while the NFS indices showed 95.24% sensitivity at -1.455 cutoff point and 95% specificity at a cutoff point of 0.676. The FIB-4 index and NFS may replace biopsy for the detection of fibrosis in patients with NAFLD.

Association between metabolic syndrome and outcomes of large-artery atherosclerosis stroke treated with reperfusion therapy.

AIM: We aimed to investigate the impact of metabolic syndrome (MetS) on the outcomes of stroke patients with large-artery atherosclerosis who underwent reperfusion therapy. METHODS: A retrospective analysis was carried out on patients receiving reperfusion therapy for atherothrombotic stroke between January 2019 and May 2021. MetS was diagnosed according to the AHA/NHLBI criteria. The primary outcome was the composite outcome of disability (modified Rankin Scale [mRS] score 3-5), death or stroke recurrence within 3 months of stroke onset. Secondary outcomes included disability and death within 3 months as well as hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 hours after reperfusion treatment. The independent association of MetS with the above outcomes and the highly correlated components of MetS was examined using binary logistic regression analysis. RESULTS: A total of 174 patients were enrolled. MetS patients had a higher proportion of the composite outcome (p = 0.012), disability (p = 0.029) and HT (p = 0.049) than those without MetS, except for death (p = 0.375) and sICH (p = 0.306). Following adjustments, MetS remained independently associated with the composite outcome (adjusted OR, 3.011 [95 %CI 1.372-6.604]; p = 0.006) and disability (adjusted OR, 2.727 [95 %CI 1.220-6.098]; p = 0.015), but not HT (adjusted OR, 1.872 [95 %CI 0.854-4.104]; p = 0.117). Hypertriglyceridemia was remarkedly associated with the composite outcome (adjusted OR, 9.746 [95 % CI 2.402-39.536]; p = 0.001) and disability (adjusted OR, 6.966 [95 % CI 1.889-25.692]; p = 0.004). CONCLUSION: MetS is independently associated with an increased risk of composite outcome and disability in patients with large-artery atherosclerosis stroke receiving reperfusion therapy, and hypertriglyceridemia is the main component that drives the effect of MetS on outcomes.

Realization of Two-Dimensional Intrinsic Polar Metal in a Buckled Honeycomb Binary Lattice.

Structural topology and symmetry of a two-dimensional (2D) network play pivotal roles in defining its electrical properties and functionalities. Here, a binary buckled honeycomb lattice with C3v symmetry, which naturally hosts topological Dirac fermions and out-of-plane polarity, is proposed. It is successfully achieved in a group IV-V compound, namely monolayer SiP epitaxially grown on Ag(111) surface. Combining first-principles calculations with angle-resolved photoemission spectroscopy, the degeneration of the Dirac nodal lines to points due to the broken horizonal mirror symmetry is elucidated. More interesting, the SiP monolayer manifests metallic nature, which is mutually exclusive with polarity in conventional materials. It is further found that the out-of-plane polarity is strongly suppressed by the metallic substrate. This study not only represents a breakthrough of realizing intrinsic polarity in 2D metallic material via ingenious design but also provides a comprehensive understanding of the intricate interplay of many exotic low-dimensional quantum phenomena.

Mitochondria-containing extracellular vesicles from mouse vs. human brain endothelial cells for ischemic stroke therapy.

Ischemic stroke-induced mitochondrial dysfunction in the blood-brain barrier-forming brain endothelial cells (BECs) results in long-term neurological dysfunction post-stroke. We previously reported data from a pilot study where intravenous administration of human BEC (hBEC)-derived mitochondria-containing extracellular vesicles (EVs) showed a potential efficacy signal in a mouse middle cerebral artery occlusion (MCAo) model of stroke. We hypothesized that EVs harvested from donor species homologous to the recipient species (e.g., mouse) may improve therapeutic efficacy, and therefore, use of mouse BEC (mBEC)-derived EVs may improve post-stroke outcomes in MCAo mice. We investigated potential differences in the mitochondria transfer of EVs derived from the same species as the recipient cell (mBEC-EVs and recipient mBECs or hBECs-EVs and recipient hBECs) vs. cross-species EVs and recipient cells (mBEC-EVs and recipient hBECs or vice versa). Our results showed that while both hBEC- and mBEC-EVs transferred EV mitochondria, mBEC-EVs outperformed hBEC-EVs in increasing ATP levels and improved recipient mBEC mitochondrial function via increasing oxygen consumption rates. mBEC-EVs significantly reduced brain infarct volume and neurological deficit scores compared to vehicle-injected MCAo mice. The superior therapeutic efficacy of mBEC-EVs in MCAo mice support the continued use of mBEC-EVs to optimize the therapeutic potential of mitochondria-containing EVs in preclinical mouse models.

Circ_0072088 promotes breast carcinoma progression via modulating miR-607/RNF2 axis.

OBJECTIVES: To explore how the circular non-coding RNA circ_0072088 influences the progression of breast carcinoma (BC) by affecting cell behavior. METHODS: We measured the levels of circ_0072088, microRNA-607 (miR-607), and ring finger protein 2 (RNF2) mRNA levels in BC tissues and cell lines using quantitative real-time PCR. We also conducted cell counting kit-8 (CCK-8), BrdU incorporation, and flow cytometry assays to assess cell viability, cell cycle, and apoptosis, respectively. RESULTS: We observed increased levels of circ_0072088 and RNF2, and decreased levels of miR-607 in BC tissues. Overexpressing circ_0072088 promoted BC cell proliferation and cell cycle progression while inhibiting apoptosis. Conversely, silencing circ_0072088 had the opposite effects. Our data suggest that circ_0072088 directly targets and downregulates miR-607, which in turn upregulates RNF2, a target of miR-607. Moreover, miR-607 overexpression could mitigate the pro-proliferative and anti-apoptotic effects of circ_0072088 on BC cells. CONCLUSION: Circ_0072088 drives BC progression by downregulating miR-607 and upregulating RNF2, thereby promoting cell proliferation and cycle progression while reducing apoptosis.

Association of the COL4A2 Gene Polymorphisms with Primary Intracerebral Hemorrhage Risk and Outcome in Chinese Han Population.

The relationship of single nucleotide polymorphisms (SNPs) in COL4A2 gene with risk and outcome of primary intracerebral hemorrhage (ICH) in the Chinese Han population remains unclear, which was investigated in this study. Primary ICH patients and non-stroke controls of Chinese Han ethnicity were enrolled. The genotypes of 8 tag-SNPs were determined using a custom-by-design 48-Plex SNPscan Kit. Poor 3-month outcome was defined as modified Rankin Scale score 4-6. Logistic regression was employed to examine association between COL4A2 variants and risk and poor outcome of primary ICH. 323 patients with primary ICH and 376 stroke-free controls were included. Compared to controls, the rs1049931 G and rs1049906 C alleles were associated with increased ICH risk (p = 0.027 and 0.033), and these two allele counts increased this risk after adjustments respectively (additive model: adjusted OR [aOR] 1.41, 95% CI 1.03-1.94, corrected p = 0.043; aOR 1.37, 95% CI 1.01-1.86, corrected p = 0.043). The rs1049931 AG/GG and rs1049906 CT/CC genotypes showed increased susceptibility to non-lobar hemorrhage (aOR 1.63, 95% CI 1.06-2.50, p = 0.025; aOR 1.63, 95% CI 1.07-2.47, p = 0.022). Haplotype analysis revealed an association between rs1049906-rs1049931 haplotype CG and ICH risk (OR 1.36, 95% CI 1.05-1.78, p = 0.021). Regarding clinical outcome, the rs3803230 C allele (dominant model: aOR 1.94, 95% CI 1.04-3.63, p = 0.037) and haplotype AC of rs7990214-rs3803230 (OR 1.98, 95% CI 1.13-3.46, p = 0.015) contributed to 3-month poor outcome. The COL4A2 polymorphisms are associated with an increased risk of primary ICH, mainly non-lobar hemorrhage, and with long-term poor outcome after ICH in Chinese Han population.

Serum heme oxygenase-1 level predicts clinical outcome after acute ischemic stroke.

AIMS: The relationship between heme oxygenase-1 (HO-1) and human ischemic stroke outcome remains unclear, which was investigated in this study. METHODS: Acute ischemic stroke patients admitted within 24 h were enrolled. Serum HO-1 levels at baseline were measured via ELISA. Poor 3-month functional outcome was defined as modified Rankin Scale (mRS) score 3-6. Multivariable-adjusted binary logistic regression and restricted cubic spline models were employed to examine association between serum HO-1 and functional outcome. HO-1's additive prognostic utility was assessed by net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: Of 194 eligible patients, 79 (40.7%) developed poor functional outcomes at 3-month follow-up. The highest quartile of serum HO-1 was independently associated with a lower risk of poor functional outcome (adjusted OR 0.13, 95% CI 0.04-0.45; p = 0.001) compared with the lowest HO-1 category. The relationship between higher HO-1 levels and reduced risk of poor functional outcome was linear and dose responsive (p = 0.002 for linearity). Incorporating HO-1 into the analysis with conventional factors significantly improved reclassification for poor functional outcomes (NRI = 41.2%, p = 0.004; IDI = 5.0%, p = 0.004). CONCLUSIONS: Elevated serum HO-1 levels at baseline were independently associated with improved 3-month functional outcomes post-ischemic stroke. Serum HO-1 measurement may enhance outcome prediction beyond conventional clinical factors.

Mitochondria-containing extracellular vesicles from mouse vs . human brain endothelial cells for ischemic stroke therapy.

Ischemic stroke-induced mitochondrial dysfunction in the blood-brain barrier-forming brain endothelial cells ( BECs ) results in long-term neurological dysfunction post-stroke. We previously data from a pilot study where intravenous administration of human BEC ( hBEC )-derived mitochondria-containing extracellular vesicles ( EVs ) showed a potential efficacy signal in a mouse middle cerebral artery occlusion ( MCAo ) model of stroke. We hypothesized that EVs harvested from donor species homologous to the recipient species ( e.g., mouse) may improve therapeutic efficacy, and therefore, use of mouse BEC ( mBEC )-derived EVs may improve post-stroke outcomes in MCAo mice. We investigated potential differences in the mitochondria transfer of EVs derived from the same species as the recipient cell (mBEC-EVs and recipient mBECs or hBECs-EVs and recipient hBECs) vs . cross-species EVs and recipient cells (mBEC-EVs and recipient hBECs or vice versa ). Our results showed that while both hBEC- and mBEC-EVs transferred EV mitochondria, mBEC-EVs outperformed hBEC-EVs in increasing ATP levels and improved recipient mBEC mitochondrial function via increasing oxygen consumption rates. mBEC-EVs significantly reduced brain infarct volume and neurological deficit scores compared to vehicle-injected MCAo mice. The superior therapeutic efficacy of mBEC-EVs in a mouse MCAo stroke support the continued use of mBEC-EVs to optimize the therapeutic potential of mitochondria-containing EVs in preclinical mouse models.

Prognostic value of the systemic inflammatory index (SII) and systemic inflammatory response index (SIRI) in patients with traumatic spinal cord injury.

PURPOSE: The overwhelming inflammatory response plays a critical role in the secondary injury cascade of traumatic spinal cord injury (tSCI). The systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are two novel inflammatory biomarkers. The SII was calculated based on lymphocyte, neutrophil, and platelet counts, while the SIRI was calculated based on lymphocyte, neutrophil, and monocyte counts. Their prognostic value in patients with tSCI remains unclear. METHODS: Patients with tSCI admitted within 24 h of trauma were retrospectively and consecutively enrolled. Peripheral blood samples were collected on admission. The primary outcome was American Spinal Injury Association Impairment Scale (AIS) grade conversion at discharge. Multivariable logistic regression analysis was performed to determine the relationship between SII and SIRI and AIS grade conversion. We performed receiver operating characteristic curve (ROC) analysis to assess the discriminative ability of SII, and SIRI in predicting AIS grade conversion. RESULTS: Among 280 included patients, 77 (27.5%) had improved AIS grade conversion at discharge. After adjustment for confounders, SII was independently associated with AIS grade conversion (per SD, odds ratio [OR], 0.68; 95% confidence interval [CI] 0.47-0.98, p = 0.040), while the association between SIRI and AIS grade conversion was insignificant (per 1 SD, OR, 0.77; 95% CI 0.55-1.08, p = 0.130). The ROC analysis revealed that the SII had the best predictive value for AIS grade conversion (area under curve: 0.608, 95% CI 0.536-0.678). CONCLUSIONS: Increased SII was independently associated with a decreased likelihood of improved AIS grade conversion.

The Change in Fibrinogen is Associated with Outcome in Patients with Acute Ischemic Stroke Treated with Endovascular Thrombectomy.

BACKGROUND: Fibrinogen has been identified as a modulator of the coagulation and inflammatory process. There is uncertainty about the relationship between the dynamic profile of fibrinogen levels and its impact on clinical outcomes in patients with acute ischemic stroke treated with endovascular thrombectomy. METHODS: We consecutively enrolled patients with acute ischemic stroke who underwent endovascular thrombectomy. Fibrinogen was measured on admission and during hospitalization. The change in fibrinogen (Δfibrinogen) was calculated as the highest follow-up fibrinogen minus admission fibrinogen, with a positive Δfibrinogen indicating an increase in fibrinogen level. Functional outcome was assessed by the modified Rankin Scale at 3 months. Poor outcome was defined as modified Rankin Scale > 2. RESULTS: A total of 346 patients were included (mean age 67.4 ± 13.6 years, 52.31% men). The median fibrinogen on admission was 2.77 g/L (interquartile range 2.30-3.39 g/L). The median Δfibrinogen was 1.38 g/L (interquartile range 0.27-2.79 g/L). Hyperfibrinogenemia (> 4.5 g/L) on admission was associated with an increased risk of poor outcome [odds ratio (OR) 5.93, 95% confidence interval (CI) 1.44-24.41, p = 0.014]. There was a possible U-shaped association of Δfibrinogen with outcomes, with an inflection point of - 0.43 g/L (p = 0.04). When Δfibrinogen was < - 0.43 g/L, a higher decrease in fibrinogen (lower Δfibrinogen value) was associated with a higher risk of poor outcome (OR 0.22, 95% CI 0.02-2.48, p = 0.219). When Δfibrinogen was > - 0.43 g/L, the risk of poor outcome increased with increasing fibrinogen (OR 1.27, 95% CI 1.04-1.54, p = 0.016). CONCLUSIONS: In patients with endovascular thrombectomy, hyperfibrinogenemia on admission was associated with poor functional outcomes at 3 months, whereas Δfibrinogen was associated with poor 3-month outcomes in a possible U-shaped manner.

Comparison of Characteristics and Outcomes Between Acute Ischemic Stroke Patients with Different Types of Heart Failure.

Acute ischemic stroke (AIS) can be complicated by heart failure involving preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), and whether or not the prognosis differs between the 2 types of patients remains unclear. We compared the clinical characteristics and outcomes of the 2 types of patients at 3 months after the stroke.We retrospectively analyzed patients who, between 1 January 2018 and 1 January 2021, experienced AIS that was complicated by HFrEF or HFpEF. All patients had been prospectively registered in the Chengdu Stroke Registry. Poor outcome was defined as a modified Rankin Scale (mRS) score of 2-6 at 3 months. Univariate and binary logistic regression was used to assess whether HFpEF was associated with a significantly worse prognosis than HFrEF.Among the final sample of 108 patients (60.2% men; mean age, 73.08 ± 10.82 years), 75 (69.4%) had HFpEF. Compared to HFrEF patients, those with HFpEF were older (P = 0.002), were more likely to have chronic kidney disease (P = 0.033), and were more likely to experience a poor outcome (P = 0.022). After adjustments, HFpEF was associated with significantly greater risk of poor outcome than HFrEF (OR 4.13, 95%CI 1.20-15.79, P = 0.029). However, rates of hemorrhagic transformation or mortality at 3 months after AIS did not differ significantly between the 2 types of heart failure (all P > 0.05).Patients with AIS involving HFpEF experience worse outcomes than those with HFrEF and therefore may require special monitoring and management. Our findings need to be verified in large prospective studies.

Sublimation-based wafer-scale monolayer WS2 formation via self-limited thinning of few-layer WS2.

Atomically-thin monolayer WS2 is a promising channel material for next-generation Moore's nanoelectronics owing to its high theoretical room temperature electron mobility and immunity to short channel effect. The high photoluminescence (PL) quantum yield of the monolayer WS2 also makes it highly promising for future high-performance optoelectronics. However, the difficulty in strictly growing monolayer WS2, due to its non-self-limiting growth mechanism, may hinder its industrial development because of the uncontrollable growth kinetics in attaining the high uniformity in thickness and property on the wafer-scale. In this study, we report a scalable process to achieve a 4 inch wafer-scale fully-covered strictly monolayer WS2 by applying the in situ self-limited thinning of multilayer WS2 formed by sulfurization of WOx films. Through a pulsed supply of sulfur precursor vapor under a continuous H2 flow, the self-limited thinning process can effectively trim down the overgrown multilayer WS2 to the monolayer limit without damaging the remaining bottom WS2 monolayer. Density functional theory (DFT) calculations reveal that the self-limited thinning arises from the thermodynamic instability of the WS2 top layers as opposed to a stable bottom monolayer WS2 on sapphire above a vacuum sublimation temperature of WS2. The self-limited thinning approach overcomes the intrinsic limitation of conventional vapor-based growth methods in preventing the 2nd layer WS2 domain nucleation/growth. It also offers additional advantages, such as scalability, simplicity, and possibility for batch processing, thus opening up a new avenue to develop a manufacturing-viable growth technology for the preparation of a strictly-monolayer WS2 on the wafer-scale.

Integration of Single-Atom Catalyst with Z-Scheme Heterojunction for Cascade Charge Transfer Enabling Highly Efficient Piezo-Photocatalysis.

Piezo-assisted photocatalysis (namely, piezo-photocatalysis), which utilizes mechanical energy to modulate spatial and energy distribution of photogenerated charge carriers, presents a promising strategy for molecule activation and reactive oxygen species (ROS) generation toward applications such as environmental remediation. However, similarly to photocatalysis, piezo-photocatalysis also suffers from inferior charge separation and utilization efficiency. Herein, a Z-scheme heterojunction composed of single Ag atoms-anchored polymeric carbon nitride (Ag-PCN) and SnO2- x is developed for efficient charge carrier transfer/separation both within the catalyst and between the catalyst and surface oxygen molecules (O2 ). As revealed by charge dynamics analysis and theoretical simulations, the synergy between the single Ag atoms and the Z-scheme heterojunction initiates a cascade electron transfer from SnO2- x to Ag-PCN and then to O2 adsorbed on Ag. With ultrasound irradiation, the polarization field generated within the piezoelectric hybrid further accelerates charge transfer and regulates the O2 activation pathway. As a result, the Ag-PCN/SnO2- x catalyst efficiently activates O2 into ·O2 - , ·OH, and H2 O2 under co-excitation of visible light and ultrasound, which are consequently utilized to trigger aerobic degradation of refractory antibiotic pollutants. This work provides a promising strategy to maneuver charge transfer dynamics for efficient piezo-photocatalysis by integrating single-atom catalysts (SACs) with Z-scheme heterojunction.

Alloying Matters for Ordering: Synthesis of Highly Ordered PtCo Intermetallic Catalysts for Fuel Cells.

Porous carbon-supported atomically ordered intermetallic compounds (IMCs) are promising electrocatalysts in boosting oxygen reduction reaction (ORR) for fuel cell applications. However, the formation mechanism of IMC structures under high temperatures is poorly understood, which hampers the synthesis of highly ordered IMC catalysts with promoted ORR performance. Here, we employ high-temperature X-ray diffraction and energy-dispersive spectroscopic elemental mapping techniques to study the formation process of IMCs, by taking PtCo for example, in an industry-relevant impregnation synthesis. We find that high-temperature annealing is crucial in promoting the formation of alloy particles with a stoichiometric Co/Pt ratio, which in turn is the precondition for transforming the disordered alloys to ordered intermetallic structures at a relatively low temperature. Based on the findings, we accordingly synthesize highly ordered L10-type PtCo catalysts with a remarkable ORR performance in fuel cells.

Non-iridium-based electrocatalyst for durable acidic oxygen evolution reaction in proton exchange membrane water electrolysis.

Iridium-based electrocatalysts remain the only practical anode catalysts for proton exchange membrane (PEM) water electrolysis, due to their excellent stability under acidic oxygen evolution reaction (OER), but are greatly limited by their high cost and low reserves. Here, we report a nickel-stabilized, ruthenium dioxide (Ni-RuO2) catalyst, a promising alternative to iridium, with high activity and durability in acidic OER for PEM water electrolysis. While pristine RuO2 showed poor acidic OER stability and degraded within a short period of continuous operation, the incorporation of Ni greatly stabilized the RuO2 lattice and extended its durability by more than one order of magnitude. When applied to the anode of a PEM water electrolyser, our Ni-RuO2 catalyst demonstrated >1,000 h stability under a water-splitting current of 200 mA cm-2, suggesting potential for practical applications. Density functional theory studies, coupled with operando differential electrochemical mass spectroscopy analysis, confirmed the adsorbate-evolving mechanism on Ni-RuO2, as well as the critical role of Ni dopants in stabilization of surface Ru and subsurface oxygen for improved OER durability.

Anthracene Single-Crystal Scintillators for Computer Tomography Scanning.

X-ray imaging and computed tomography (CT) technology, as the important non-destructive measurements, can observe internal structures without destroying the detected sample, which are always used in biological diagnosis to detect tumors, pathologies, and bone damages. It is always a challenge to find materials with a low detection limit, a short exposure time, and high resolution to reduce X-ray damage and acquire high-contrast images. Here, we described a low-cost and high-efficient method to prepare centimeter-sized anthracene crystals, which exhibited intense X-ray radioluminescence with a detection limit of ∼0.108 µGy s-1, which is only one-fifth of the dose typically used for X-ray diagnostics. Additionally, the low absorption reduced the damage in radiation and ensured superior cycle performance. X-ray detectors based on anthracene crystals also exhibited an extremely high resolution of 40 lp mm-1. The CT scanning and reconstruction of a foam sample were then achieved, and the detailed internal structure could be clearly observed. These indicated that organic crystals are expecting to be leading candidate low-cost materials for low-dose and highly sensitive X-ray detection and CT scanning.

Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study.

Chimeric antigen receptor (CAR)-T cell therapy against T cell malignancies faces major challenges including fratricide between CAR-T cells and product contamination from the blasts. Allogeneic CAR-T cells, generated from healthy donor T cells, can provide ready-to-use, blast-free therapeutic products, but their application could be complicated by graft-versus-host disease (GvHD) and host rejection. Here we developed healthy donor-derived, CD7-targeting CAR-T cells (RD13-01) with genetic modifications to resist fratricide, GvHD and allogeneic rejection, as well as to potentiate antitumor function. A phase I clinical trial (NCT04538599) was conducted with twelve patients recruited (eleven with T cell leukemia/lymphoma, and one with CD7-expressing acute myeloid leukemia). All patients achieved pre-set end points and eleven proceeded to efficacy evaluation. No dose-limiting toxicity, GvHD, immune effector cell-associated neurotoxicity or severe cytokine release syndrome (grade ≥ 3) were observed. 28 days post infusion, 81.8% of patients (9/11) showed objective responses and the complete response rate was 63.6% (7/11, including the patient with AML). 3 of the responding patients were bridged to allogeneic hematopoietic stem cell transplantation. With a median follow-up of 10.5 months, 4 patients remained in complete remission. Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) reactivation was observed in several patients, and one died from EBV-associated diffuse large B-cell lymphoma (DLBCL). Expansion of CD7-negative normal T cells was detected post infusion. In summary, we present the first report of a Phase I clinical trial using healthy donor-derived CD7-targeting allogeneic CAR-T cells to treat CD7+ hematological malignancies. Our results demonstrated the encouraging safety and efficacy profiles of the RD13-01 allogeneic CAR-T cells for CD7+ tumors.

Intermetallic PtFe Electrocatalysts for the Oxygen Reduction Reaction: Ordering Degree-Dependent Performance.

Platinum-based atomically ordered alloys (i.e., intermetallic compounds) have distinct advantages over disordered solid solution counterparts in boosting the cathodic oxygen-reduction reaction (ORR) in proton-exchange-membrane fuel cells. Nevertheless, the pivotal role of ordering degree of intermetallic catalysts in promoting ORR performance has been ignored heavily so far, probably owing to the lack of synthetic routes for controlling the ordering degree, especially for preparing highly ordered intermetallic catalysts. Herein, a family of intermetallic PtFe catalysts with similar particle size of 3-4 nm but varied ordering degree in a wide range of 10-70% are prepared. After constructing the PtFe/Pt core/shell structure with around 3 Pt-layer skin, a positive correlation between the ordering degree of the intermetallic catalysts and their ORR activity and durability is identified. Notably, the highly ordered PtFe/Pt catalyst exhibits a high mass activity of 0.92 A mgPt -1 at 0.9 ViR-corrected as cathode catalyst in H2 -O2 fuel cell, with only 24% loss after accelerated durability tests. The ordering degree-dependent performance can be ascribed to the compressive strain effect induced by the intermetallic PtFe core with smaller lattice parameters, and the more thermodynamically stable intermetallic structure compared to disordered alloys.

Ordering Degree-Dependent Activity of Pt3M (M = Fe, Mn) Intermetallic Nanoparticles for Electrocatalytic Methanol Oxidation.

Atomically ordered intermetallic alloys with unique electronic and geometrical structures are highly attractive for heterogeneous catalysis and electrocatalysis. However, the formation of intermetallic phases generally requires high-temperature annealing to overcome the kinetic energy barrier of atom ordering, which unfortunately causes high material heterogeneity and thus makes it challenging to identify the exact contribution of ordered structures to the improved performance. Here, we prepared a family of small-sized intermetallic core/shell Pt3M@Pt (M = Mn or Fe) catalysts with varied ordering degree by a high-temperature sulfur-confined method. We identified a strong correlation between the ordering degree of the intermetallic Pt3M core of the catalysts and their electrocatalytic activity for the methanol oxidation reaction. Density functional theory calculations show that the intermetallic Pt3M core induces a compressive strain on the Pt-skin, which weakens the CO* binding, lowers the free energy change from CO* to COOH*, and therefore promotes electrocatalytic methanol oxidation.

Leakages suppression by isolating the desired quantum levels for high-temperature terahertz quantum cascade lasers.

The key challenge for terahertz quantum cascade lasers (THz-QCLs) is to make it operating at room-temperature. The suppression of thermally activated leakages via high lying quantum levels is emphasized recently. In this study, we employ the advanced self-consistent method of non-equilibrium Green's function, aiming to reveal those kinds of leakages in the commonly used THz-QCL designs based on 2-, 3- and 4-quantum well. At the high temperature of 300 K, if all the confined high lying quantum levels and also the continuums are included within three neighboring periods, leakages indeed possess high fraction of the total current (21%, 30%, 50% for 2-, 3- and 4-quantum well designs, respectively). Ministep concept is introduced to weaken those leakage channels by isolating the desired levels from high lying ones, thus the leakages are well suppressed, with corresponding fractions less than 5% for all three designs.