CD56bright NK cell expansion correlated with EBV reactivation control post allogeneic hematopoietic stem cell transplantation.

Natural killer (NK) cells are equipped with anti-Epstein-Barr virus (EBV) function, however, whether EBV infection will affect NK cells reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To identify the characteristics of NK cells, we prospectively enrolled 11 patients who occurred EBV reactivation post allo-HSCT and 11 patients without EBV infection as control. We found that that EBV infection induced the expansion of CD56bright and NKG2A+KIR- NK subsets,and decreased the cytotoxicity function of NK cells. The frequency of NKG2A+KIR- NK cells were higher in patients who progressed into post-transplant lymphoproliferative disorder (PTLD) than EBV viremia patients, which also correlated with decreased proliferation and cytotoxic function. By screening the activation receptors of NK cells, we found the DNAM-1+CD56bright NK cells is significantly increased after EBV stimulation, further we demonstrated that DNAM-1 is essential for EBV induced NK cells activation as the cytokine release against EBV-transformed lymphoblastoid cell lines(EBV-LCLs) of CD56bright NK cells were significantly decreased after DNAM-1 blockade. NK cells infusion suppressed the progression of EBV-related tumor mice model. A prospective cohort indicated that old donor age was an independent risk factor for EBV infection. Rapid CD56bri expansion and high expression of DNAM-1 on CD56bri NK cells in response to EBV reactivation correlated with rapid EBV clearance post allo-HSCT in patients with younger donors. In summary, our data showed that high expression of DNAM-1 receptors on NK cell may participate protective CD56bri NK cells response to EBV infection after allo-HSCT.

Atlantoaxial intra-articular cage fusion by posterior intermuscular approach for treating reducible atlantoaxial dislocation: a technique note with case series.

PURPOSE: To evaluate the clinical feasibility of atlantoaxial intra-articular cage (AIC) fusion via intermuscular approach for treating reducible atlantoaxial dislocation (AAD). METHODS: An analysis was conducted on the data of 10 patients who underwent C1-C2 segmental fixation and AIC fusion for AAD by unilateral intermuscular approach and contralateral open approach. Outcome assessments included Japanese Orthopaedic Association score (JOA) and Visual Analog Scale Score for Neck Pain (VASSNP). The duration of surgical exposure, screw insertion and cage insertion, and postoperative drainage volume were also compared between two approaches. Bone fusion was evaluated through computed tomography (CT) reconstruction. Postoperative paravertebral tissue edema was evaluated by paravertebral tissue cross-sectional area (CSA) and signal intensity on T2 weighted sequence of magnetic resonance imaging (MRI) at 3 days postoperatively. RESULTS: The intermuscular approach exhibited a longer exposure time but lower drainage postoperatively compared to the open approach (P < 0.05). After operation, JOA scores significant improved (P < 0.05), while VASSNP scores significantly decreased (P < 0.05). There was no significant difference in preoperative CSA between two approaches (P > 0.05). However, compared to the open approach, the intermuscular approach exhibited less CSA (P < 0.05) and lower T2 signal intensity on MRI postoperatively, indicating less invasive to the paravertebral tissues. CONCLUSIONS: AIC fusion by intermuscular approach is an effective and safe technique in the treatment of reducible AAD. Intermuscular approach could reduce the postoperative drainage volume and the extent of paravertebral tissue edema compared to open approach.

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia: a multicenter, randomized, open-label, phase 3 trial.

Coinfusion of unrelated cord blood (UCB) units in haploidentical hematopoietic cell transplantation (haplo-HCT) (haplo-cord HCT) for hematopoietic malignancies showed promising results in previous reports, but the efficiency of haplo-cord HCT in acute myeloid leukemia (AML) still lacks sufficient evidence. This multicenter, randomized, phase 3 trial (ClinicalTrials.gov NCT03719534) aimed to assess the efficacy and safety of haplo-cord HCT in AML patients. A total of 268 eligible patients aged 18-60 years, diagnosed with measurable residual disease in AML (excluding acute promyelocytic leukemia), with available haploidentical donors and suitable for allotransplantation, were randomly allocated (1:1) to receive haplo-cord HCT (n = 134) or haplo-HCT (n = 134). The 3-year overall survival (OS) was the primary endpoint in this study. Overall median follow-up was 36.50 months (IQR 24.75-46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% confidence interval [CI]: 73.7-87.9 vs. 67.8% 95% CI 60.0-76.5, p = 0.013). Favorable progression-free survival (70.3%, 95% CI 62.6-78.8 vs. 57.6%, 95% CI 49.6-67.0, p = 0.012) and cumulative incidence of relapse (12.1%, 95% CI 12.0-12.2 vs. 30.3%, 95% CI 30.1-30.4, p = 0.024) were observed in haplo-cord HCT group. Grade 3-4 adverse events (AEs) within two years posttransplantation in the two groups were similar. Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery (p = 0.026) and increased T-cell reconstitution in the early period posttransplantation. Haplo-cord HCT can improve OS in AML patients without excessive AEs, which may exert additional benefits for recipients of haplo-HCT.

Connectome-based prediction of decreased trust propensity in older adults with mild cognitive impairment: A resting-state functional magnetic resonance imaging study.

Trust propensity (TP) relies more on social than economic rationality to transform the perceived probability of betrayal into positive reciprocity expectations in older adults with normal cognition. While deficits in social rationality have been observed in older adults with mild cognitive impairment (MCI), there is limited research on TP and its associated resting-state functional connectivity (RSFC) mechanisms in this population. To measure TP and related psychological functions (affect, motivation, executive cognition, and social cognition), MCI (n = 42) and normal healthy control (NHC, n = 115) groups completed a one-shot trust game and additional assessments of related psychological functions. RSFC associated with TP was analyzed using connectome-based predictive modeling (CPM) and lesion simulations. Our behavioral results showed that the MCI group trusted less (i.e., had lower TP) than the NHC group, with lower TP associated with higher sensitivity to the probability of betrayal in the MCI group. In the MCI group, only negative CPM models (RSFC negatively correlated with TP) significantly predicted TP, with a high salience network (SN) contribution. In contrast, in the NHC group, positive CPM models (RSFC positively correlated with TP) significantly predicted TP, with a high contribution from the default mode network (DMN). In addition, the total network strength of the NHC-specific positive network was lower in the MCI group than in the NHC group. Our findings demonstrated a decrease in TP in the MCI group compared to the NHC group, which is associated with deficits in social rationality (social cognition, associated with DMN) and increased sensitivity to betrayal (affect, associated with SN) in a trust dilemma. In conclusion, our study contributes to understanding MCI-related alterations in trust and their underlying neural mechanisms.

Linking fine root lifespan to root chemical and morphological traits-A global analysis.

Fine root lifespan is a critical trait associated with contrasting root strategies of resource acquisition and protection. Yet, its position within the multidimensional "root economics space" synthesizing global root economics strategies is largely uncertain, and it is rarely represented in frameworks integrating plant trait variations. Here, we compiled the most comprehensive dataset of absorptive median root lifespan (MRL) data including 98 observations from 79 woody species using (mini-)rhizotrons across 40 sites and linked MRL to other plant traits to address questions of the regulators of MRL at large spatial scales. We demonstrate that MRL not only decreases with plant investment in root nitrogen (associated with more metabolically active tissues) but also increases with construction of larger diameter roots which is often associated with greater plant reliance on mycorrhizal symbionts. Although theories linking organ structure and function suggest that root traits should play a role in modulating MRL, we found no correlation between root traits associated with structural defense (root tissue density and specific root length) and MRL. Moreover, fine root and leaf lifespan were globally unrelated, except among evergreen species, suggesting contrasting evolutionary selection between leaves and roots facing contrasting environmental influences above vs. belowground. At large geographic scales, MRL was typically longer at sites with lower mean annual temperature and higher mean annual precipitation. Overall, this synthesis uncovered several key ecophysiological covariates and environmental drivers of MRL, highlighting broad avenues for accurate parametrization of global biogeochemical models and the understanding of ecosystem response to global climate change.

Comparison of valganciclovir versus foscarnet for the treatment of cytomegalovirus viremia in adult acute leukemia patients after allogeneic hematopoietic cell transplantation.

Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.

High anisotropy in electrical and thermal conductivity through the design of aerogel-like superlattice (NaOH)0.5NbSe2.

Interlayer decoupling plays an essential role in realizing unprecedented properties in atomically thin materials, but it remains relatively unexplored in the bulk. It is unclear how to realize a large crystal that behaves as its monolayer counterpart by artificial manipulation. Here, we construct a superlattice consisting of alternating layers of NbSe2 and highly porous hydroxide, as a proof of principle for realizing interlayer decoupling in bulk materials. In (NaOH)0.5NbSe2, the electric decoupling is manifested by an ideal 1D insulating state along the interlayer direction. Vibration decoupling is demonstrated through the absence of interlayer models in the Raman spectrum, dominant local modes in heat capacity, low interlayer coupling energy and out-of-plane thermal conductivity (0.28 W/mK at RT) that are reduced to a few percent of NbSe2's. Consequently, a drastic enhancement of CDW transition temperature (>110 K) and Pauling-breaking 2D superconductivity is observed, suggesting that the bulk crystal behaves similarly to an exfoliated NbSe2 monolayer. Our findings provide a route to achieve intrinsic 2D properties on a large-scale without exfoliation.

Temporal dynamics of soil dissolved organic carbon in temperate forest managed by prescribed burning in Northeast China.

Dissolved organic carbon (DOC) is an important function of soil organic carbon and sensitive to environmental disturbance. Few studies have explored the variations in soil DOC dynamics and effects on soil physicochemical properties following prescribed burnings. In this study, Pinus koraiensis plantation forests in Northeast China were selected and subjected to prescribed burning in early November 2018. Soil DOC and different soil physicochemical and biological properties in the 0-10 cm and 10-20 cm soil layers were sampled six times within two years after a prescribed burning. In this study, some soil physicochemical (SOC, TN, and ST) and microbial biomass properties (MBC) recovered within two years after a prescribed burning. Compared to the unburned control stands, the post-fire soil DOC concentrations in the upper and lower soil layers increased by 16% and 12%, respectively. Soil DOC concentrations varied with sampling time, and peaked one year after the prescribed burning. Our results showed that soil chemical properties (NH4+-N and pH) rather than biological properties (microbial biomass) were the main driving factors for changes in post-fire soil DOC concentrations. Current study provides an important reference for post-fire and seasonal soil C cycling in plantation forests of Northeast China.

Insufficiency of collagenases in establishment of primary chondrocyte culture from cartilage of elderly patients receiving total joint replacement.

Background Collagenases are frequently used in chondrocyte isolation from articular cartilage. However, the sufficiency of this enzyme in establishing primary human chondrocyte culture remains unknown. Methods Cartilage slices shaved from femoral head or tibial plateau of patients receiving total joint replacement surgery (16 hips, 8 knees) were subjected to 0.02% collagenase IA digestion for 16 h with (N = 19) or without (N = 5) the pre-treatment of 0.4% pronase E for 1.5 h. Chondrocyte yield and viability were compared between two groups. Chondrocyte phenotype was determined by the expression ratio of collagen type II to I. The morphology of cultured chondrocytes was monitored with a light microscope.Results Cartilage with pronase E pre-treatment yielded significantly higher chondrocytes than that without the pre-treatment (3,399 ± 1,637 cells/mg wet cartilage vs. 1,895 ± 688 cells/mg wet cartilage; P = 0.0067). Cell viability in the former group was also significantly higher than that in the latter (94% ± 2% vs. 86% ± 6%; P = 0.03). When cultured in monolayers, cells from cartilage with pronase E pre-treatment grew in a single plane showing rounded shape while cells from the other group grew in multi-planes and exhibited irregular shape. The mRNA expression ratio of collagen type II to I was 13.2 ± 7.5 in cells isolated from cartilage pre-treated with pronase E, indicating a typical chondrocyte phenotype. Conclusions Collagenase IA was not sufficient in establishing primary human chondrocyte culture. Cartilage must be treated with pronase E prior to collagenase IA application.

Fucosylation Promotes Cytolytic Function and Accumulation of NK Cells in B Cell Lymphoma.

Natural killer (NK) cells have been demonstrated as a promising cellular therapy as they exert potent anti-tumor immune responses. However, applications of NK cells to tumor immunotherapy, especially in the treatment of advanced hematopoietic and solid malignancies, are still limited due to the compromised survival and short persistence of the transferred NK cells in vivo. Here, we observed that fucosyltransferase (FUT) 7 and 8 were highly expressed on NK cells, and the expression of CLA was positively correlated with the accumulation of NK cells in clinical B cell lymphoma development. Via enzyme-mediated ex vivo cell-surface fucosylation, the cytolytic effect of NK cells against B cell lymphoma was significantly augmented. Fucosylation also promoted NK cell accumulation in B cell lymphoma-targeted tissues by enhancing their binding to E-selectin. Moreover, fucosylation of NK cells also facilitated stronger T cell anti-tumor immune responses. These findings suggest that ex vivo fucosylation contributes to enhancing the effector functions of NK cells and may serve as a novel strategy for tumor immunotherapy.

Tree organ growth and carbon allocation dynamics impact the magnitude and δ13C signal of stem and soil CO2 fluxes.

Incomplete knowledge of carbon (C) allocation dynamics in trees hinders accurate modeling and future predictions of tree growth. We studied C allocation dynamics in a mature Pinus sylvestris L. dominated forest with a novel analytical approach, allowing the first comparison of: (i) magnitude and δ13C of shoot, stem and soil CO2 fluxes (Ashoot, Rstem and Rsoil), (ii) concentration and δ13C of compound-specific and/or bulk non-structural carbohydrates (NSCs) in phloem and roots and (iii) growth of stem and fine roots. Results showed a significant effect of phloem NSC concentrations on tracheid growth, and both variables significantly impacted Rstem. Also, concentrations of root NSCs, especially starch, had a significant effect on fine root growth, although no effect of root NSC concentrations or root growth was detected on Rsoil. Time series analysis between δ13C of Ashoot and δ13C of Rstem or δ13C of Rsoil revealed strengthened C allocation to stem or roots under high C demands. Furthermore, we detected a significant correlation between δ13C of Rstem and δ13C of phloem sucrose and glucose, but not for starch or water-soluble carbohydrates. Our results indicate the need to include C allocation dynamics into tree growth models. We recommend using compound-specific concentration and δ13C analysis to reveal C allocation processes that may not be detected by the conventional approach that utilizes bulk organic matter.

Features of Epstein-Barr Virus and Cytomegalovirus Reactivation in Acute Leukemia Patients After Haplo-HCT With Myeloablative ATG-Containing Conditioning Regimen.

Background: Haploidentical donor hematopoietic cell transplantation (haplo-HCT) has become a preferred option for patients without HLA-matched donors, but it increases the risk of viral reactivations. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are common viruses post-HCT, but limited data have been reported in the setting of haplo-HCT. Methods: We conducted a retrospective study enrolling acute leukemia patients who received haplo-HCT with myeloablative conditioning regimen employing ATG in our center from July 2014 to July 2017. All the patients enrolled were EBV-IgM and EBV-DNA negative but EBV-IgG positive, and so were their donors. The same went for CMV as well. Results: In total, 602 patients were recruited consisting of 331 with acute myeloid leukemia (AML) and 271 with acute lymphoblastic leukemia (ALL). One-year cumulative incidences of EBV (22.9% ± 2.4% vs. 27.4% ± 2.8%, P = 0.169) and CMV (24.7% ± 2.4% vs. 29.4% ± 2.8%, P = 0.190) reactivation were comparable between AML and ALL. EBV and CMV were independent risk factors for each other. In the AML group, male recipients [HR = 1.275, 95% CI (1.001-1.624), P = 0.049] and acute graft-versus-host disease [HR = 1.592, 95% CI (1.001-2.533), P = 0.049] were independent risk factors for EBV reactivation and CMV reactivation, respectively. CMV rather than EBV reactivation was related to a trend of worsened treatment-related mortality (TRM) (15.6% ± 0.1% vs. 10.2% ± 0.0%, P = 0.067) and progression-free survival (PFS) (60.6% ± 4.1% vs. 70.3% ± 2.3%, P = 0.073), while significant impacts were revealed only in the subgroup analysis. CMV reactivation resulted in a remarkable inferior 2-year overall survival (OS) (64.2% ± 5.7% vs. 77.6% ± 3.2%, P = 0.038) and PFS (55.0% ± 5.9% vs. 71.9% ± 3.4%, P = 0.042) in ALL patients. On the other hand, in the EBV+/CMV- subgroup, relapse was lower in ALL patients (8.2% ± 0.2% vs. 32.4% ± 0.8%, P = 0.010) compared with AML patients, which led to a superior 2-year OS (82.0% ± 6.2% vs. 60.3% ± 8.8%, P = 0.016) and PFS (74.5% ± 7.0% vs. 57.5% ± 8.4%, P = 0.036). Conclusion: We concluded that EBV and CMV reactivations were frequent in acute leukemia patients after haplo-HCT, with possibly distinctive risk factors from HLA-matched HCT. There could be a potential interaction between EBV and CMV, but impacts on transplant outcomes remained complex.

Epstein-Barr virus and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation in patients with non-Hodgkin lymphoma: the prevalence and impacts on outcomes : EBV and CMV reactivation post allo-HCT in NHL.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivations are common complications after allogeneic hematopoietic cell transplantation (allo-HCT), but data focusing on non-Hodgkin lymphoma (NHL) are limited. We retrospectively analyzed the prevalence of EBV and CMV reactivation post-allo-HCT and the impacts on transplant outcomes in 160 NHL patients. The 1-year incidences of EBV and CMV reactivation were 22.58% and 25.55%, respectively. Independent impactors for EBV reactivation were more than 6 lines of chemotherapy (P = 0.030), use of rituximab (P = 0.004), and neutrophil recovery within 30 days post-HCT (P = 0.022). For T-cell lymphoblastic lymphoma patients, the International Prognostic Index (IPI) (P = 0.015) and chronic GVHD (P = 0.001) increased the risk of CMV reactivation. CMV reactivation was independently related to a lower risk of relapse (P = 0.027) but higher transplant-related mortality (TRM) (P = 0.038). Although viral reactivation had no significant impact on overall survival (OS) in the whole cohort, it led to an inferior 2-year OS (67.6% versus 92.5%, P = 0.005) and TRM (20.1% versus 4.7%, P = 0.020) in recipients surviving for more than 180 days. We concluded that EBV and CMV reactivation post-allotransplant still deserved concern particularly in NHL patients with high-risk factors, since it is generally related to a deteriorated prognosis. Large-scale studies are warranted to validate our findings.

Epstein-Barr virus reactivation after allogeneic hematopoietic stem cell transplantation: multifactorial impact on transplant outcomes.

Epstein-Barr virus (EBV) reactivation after allogeneic hematopoietic cell transplantation (allo-HCT) is one of the major concerns that may lead to fatal EBV diseases. However, updated data are needed because of the remarkable evolution of the HCT protocol and donor selection. We conducted a retrospective study that enrolled 890 allo-HCT recipients. Independent risk factors for EBV reactivation were use of antithymocyte globulin, haploidentical donor, and the presence of chronic graft-versus-host disease. The cumulative incidence of EBV reactivation was 2.9%, 11.7%, 27.3%, and 41.9% for patients with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). Posttransplant lymphoproliferative disorders (PTLDs) occurred in seven patients. EBV reactivation was associated with inferior survival in recipients who survived more than 2 years post-HCT (P < 0.001) but might time-dependently benefit those patients with malignancies by decreasing relapse incidence (P = 0.046). A decreased relapse incidence was observed 1 year after HCT for recipients at first or second remission (P = 0.042) and in the first year post-HCT for recipients with advanced diseases (P = 0.032). We concluded that with current management, PTLDs were efficiently controlled, but EBV reactivation still had a multifactorial impact on transplant outcomes. Multicenter prospective studies are warranted to validate these findings.

Temperature and moisture dependence of daily growth of Scots pine (Pinus sylvestris L.) roots in Southern Finland.

Scots pine (Pinus sylvestris L.) is one of the most important conifers in Northern Europe. In boreal forests, over one-third of net primary production is allocated to roots. Pioneer roots expand the horizontal and vertical root systems and transport nutrients and water from belowground to aboveground. Fibrous roots, often colonized by mycorrhiza, emerge from the pioneer roots and absorb water and nutrients from the soil. In this study, we installed three flatbed scanners to detect the daily growth of both pioneer and fibrous roots of Scots pine during the growing season of 2018, a year with an unexpected summer drought in Southern Finland. The growth rate of both types of roots had a positive relationship with temperature. However, the relations between root elongation rate and soil moisture differed significantly between scanners and between root types indicating spatial heterogeneity in soil moisture. The pioneer roots were more tolerant to severe environmental conditions than the fibrous roots. The pioneer roots initiated elongation earlier and ceased it later than the fibrous roots. Elongation ended when the temperature dropped below the threshold temperature of 4 °C for pioneer roots and 6 °C for fibrous roots. During the summer drought, the fibrous roots halted root surface area growth at the beginning of the drought, but there was no drought effect on the pioneer roots over the same period. To compare the timing of root production and the aboveground organs' production, we used the CASSIA model, which estimates the aboveground tree carbon dynamics. In this study, root growth started and ceased later than growth of aboveground organs. Pioneer roots accounted for 87% of total root productivity. We suggest that future carbon allocation models should separate the roots by root types (pioneer and fibrous), as their growth patterns are different and they have different reactions to changes in the soil environment.