The remarkably reversible thermochromic luminescence behavior and the rare nonlinear optical (NLO) properties of the Ag
55
(MoO
4
)
6
(C&z.tbd;C
t
Bu)
24
(CH
3
COO)
18
(CH
3
COO)·2H
2
O ({Ag
55
Mo
6
...} for short) nanocluster reported were investigated experimentally. The important contributions of Ag
+
, C&z.tbd;C
−
ions and MoO
4
2−
groups to the NLO properties were proved by further density functional theory (DFT) calculations.
The reversible thermochromic luminescence and rare third-order NLO properties of the {Ag
55
Mo
6
} nanocluster reported were studied experimentally, and the contributions of Ag
+
, C&z.tbd;C
−
and MoO
4
2−
groups to NLO properties were proved by DFT calculations.
Summary
Licensed natural killer (NK) cells have been demonstrated to have anti‐cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor‐recipient pairs ...and the killer cell immunoglobulin–like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post‐T‐cell‐replete haploidentical stem cell transplantation. Multivariate analysis showed that donor‐recipient KIR ligand graft‐versus‐host or host‐versus‐graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377–4·744, P = 0·003) post‐transplantation. Donor‐recipient KIR ligand matching decreased CMV reactivation 51·65% (46·67, 56·62%) vs. 75·28% (70·87, 79·69%), P = 0·012, refractory CMV infection 17·58% (13·77, 21·40%) vs. 35·96% (31·09, 40·82%), P = 0·004 and CMV disease 3·30% (1·51, 5·08%) vs. 11·24% (8·04, 14·43%), P = 0·024 by day 100 post‐transplantation. In addition, the percentage of γ‐interferon expression on donor‐derived NK cells was significantly higher in the recipients among the recipient‐donor pairs with a KIR ligand match compared with that in the recipients among the pairs with a KIR ligand graft‐versus‐host or host‐versus‐graft direction mismatch on days 30 and 100 post‐transplantation (P = 0·036 and 0·047, respectively). These findings have suggested that donor‐recipient KIR ligand matching might promote the NK cell licensing process, thereby increasing NK cell‐mediated protection against CMV reactivation.
The interaction of inhibitory receptors with self-MHC class I (MHC-I) molecules is responsible for NK cell education. The intensity of DNAM-1 expression correlates with NK cell education. However, ...whether DNAM-1 expression directly influences the functional competence of NK cells via the KIR/MHC-I interaction remains unclear. Based on allogeneic haploidentical hematopoietic stem cell transplantation, we investigated the intensity of DNAM-1 expression on reconstituted NK cells via the interaction of KIR with both donor HLA and recipient HLA at days 30, 90, and 180 after hematopoietic stem cell transplantation. The reconstituted NK cells educated by donor and recipient HLA molecules showed the highest DNAM-1 expression, whereas DNAM-1 expression on educated NK cells with only recipient HLA molecules was higher than that on educated NK cells with only donor HLA molecules, indicating that NK cells with donor or recipient HLA molecules regulate DNAM-1 expression and thereby affect NK cell education. Additionally, the effects of recipient cells on NK cell education were greater than those of donor cells. However, only when the DNAM-1, NKP30, and NKG2D receptors were blocked simultaneously was the function of educated and uneducated NK cells similar. Therefore, activating receptors may collaborate with DNAM-1 to induce educated NK cell hyperresponsiveness. Our data, based on in vitro and in vivo studies, demonstrate that the functional competence of NK cells via the KIR/MHC-I interaction correlates with DNAM-1 expression in human NK cells.
Dual catalysis has become a desirable alternative because of the synergetic effect of two distinct catalysts, but little is known about the mechanism of dual catalysis and its effect on the high ...reactivity and selectivity. Here, a novel Ullmann C-C cross-coupling of bromobenzene and 4-methoxyphenyltriflate via nickel/palladium dual catalysis has been investigated using density functional theory. The orthogonal reactivity of NiI/Pd0 combination is the precondition and foundation of achieving such a Ullmann cross-coupling reaction. In the present dual catalysis, the NiI complex acts as the primary catalyst, while the Pd0 catalyst plays a decisive role in the cross-selectivity.
A novel oxidation state modulation mechanism, merging oxidative quenching (IrIII–*IrIII–IrIV–IrIII) and nickel catalytic (NiII–NiI–NiIII–NiI–NiII) cycles, has been illuminated unambiguously for ...photoredox-mediated iridium(iii)/nickel(ii) dual catalyzed C–O cross-coupling of aryl bromide and alcohol. Quinuclidine participates in a crucial proton-coupled electron transfer process to accelerate the reaction and regulate C–O coupling selectivity.
The prognosis of
11q23/KMT2A
-rearranged (
KMT2A
-r) acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. Minimal residual disease (MRD) is an important ...prognostic factor for relapse. Thus, we aimed to identify the evolution of
KMT2A
before and after allo-HSCT and the efficacy of preemptive immunotherapies for
KMT2A
-r AL patients receiving allo-HSCT.
KMT2A
expression was determined through TaqMan-based RQ-PCR technology. Preemptive immunotherapies included interferon-α and donor lymphocyte infusion. We collected 1751 bone marrow samples from 177 consecutive
KMT2A
-r AL patients. Pre-HSCT
KMT2A
positivity was correlated with post-HSCT
KMT2A
positivity (correlation coefficient=0.371,
P
<0.001). The rates of achieving
KMT2A
negativity after allo-HSCT were 96.6%, 92.9%, and 68.8% in the pre-HSCT low-level group (>0, <0.1%), intermediate-level group (≥ 0.1%, <1%), and high-level group (≥1%), respectively. The rates of regaining
KMT2A
positivity after allo-HSCT were 7.7%, 35.7%, 38.5%, and 45.5% for the pre-HSCT
KMT2A
-negative, low-level, intermediate-level, and high-level groups, respectively (
P
<0.001). The 4-year cumulative incidence of relapse after allo-HSCT was as high as 53.7% in the pre-HSCT
KMT2A
expression ≥ 0.1% group, which was compared to the
KMT2A
-negative group (15.1%) and
KMT2A
<0.1% group (31.2%). The clinical outcomes of patients with post-HSCT
KMT2A
positivity were poorer than those of patients with persistent
KMT2A
negativity. Although post-HSCT preemptive immunotherapies might help to achieve
KMT2A
negativity, the long-term efficacy was unsatisfactory. Thus, pre-HSCT
KMT2A
positivity was significantly associated with post-HSCT
KMT2A
positivity. The clinical outcomes of patients with post-HSCT
KMT2A
positivity were poor, which might not be overcome by commonly used immunotherapies.
To evaluate the efficacy of interferon-α (IFN-α) as maintenance therapy in patients with favorable-risk acute myeloid leukemia (AML), this retrospective study enrolled 84 patients with favorable-risk ...AML: 42 patients who received IFN-α maintenance therapy and 42 patients who did not (control). The median follow-up time and duration of IFN-α treatment was 26 (6-54) months and 18 (2-24) months, respectively. The 4-year estimated relapse-free survival (RFS) after the last consolidation chemotherapy was 86.8% (95% confidence interval (CI), 75.8-97.8%) in the IFN-α group and 55.7% (95% CI, 37.2-74.3%) in the control group (p=.007). The 4-year estimated overall survival was 94.4% (95% CI, 86.8-102%) and 76.4% (95% CI, 61.9-90.9%) in IFN-α and control groups, respectively (p=.040). The Cox regression analysis showed that IFN-α treatment was the only independent factor affecting RFS (p=.004). Maintenance therapy with IFN-α may prevent relapse in favorable-risk AML after consolidation chemotherapy.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of ...traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the
Protease-activated receptor 2 activation is critical to induction of neuronal hyperexcitability and cAMP-PKA activation after nerve injury.
Chronic compression (CCD) or dissociation of dorsal root ...ganglion (DRG) can induce cyclic adenosine monophosphate (cAMP)-dependent DRG neuronal hyperexcitability and behaviorally expressed hyperalgesia. Here, we report that protease-activated receptor 2 (PAR2) activation after CCD or dissociation mediates the increase of cAMP activity and protein kinase A (PKA) and cAMP-dependent hyperexcitability and hyperalgesia in rats. CCD and dissociation, as well as trypsin (a PAR2 activator) treatment, increased level of cAMP concentration, mRNA, and protein expression for PKA subunits PKA-RII and PKA-c and protein expression of PAR2, in addition to producing neuronal hyperexcitability and, in CCD rats, thermal hyperalgesia. The increased expression of PAR2 was colocalized with PKA-c subunit. A PAR2 antagonistic peptide applied before and/or during the treatment, prevented or largely diminished the increased activity of cAMP and PKA, neuronal hyperexcitability, and thermal hyperalgesia. However, posttreatment with the PAR2 antagonistic peptide failed to alter either hyperexcitability or hyperalgesia. In contrast, an adenylyl cyclase inhibitor, SQ22536, administrated after dissociation or CCD, successfully suppressed hyperexcitability and hyperalgesia, in vitro and/or in vivo. Trypsin-induced increase of the intracellular calcium Ca2+i was prevented in CCD or dissociation DRG neurons. These alterations were further confirmed by knockdown of PAR2 with siRNA. In addition, trypsin and PAR2 agonistic peptide-induced increase of cAMP was prevented by inhibition of PKC, but not Gαs. These findings suggest that PAR2 activation is critical to induction of nerve injury-induced neuronal hyperexcitability and cAMP-PKA activation. Inhibiting PAR2 activation may be a potential target for preventing/suppressing development of neuropathic pain.
Novel recurrent fusion gene types such as zinc finger protein 384 (
) fusions have been identified in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with the application of next-generation ...sequencing technologies. However, the comprehensive large-scale clinical cohort study for clarifying their prognostic significance remains scarce to date. A total of 242 consecutive adult Ph-negative BCP-ALL patients treated in our institute were retrospectively screened
fusions at diagnosis by multiplex real time quantitative PCR.
fusions were identified in 47 patients (19.4%) and all belonged to B-other ALL (having no high hyperdiploid karyotype,
-
,
-
,
-
, or
rearrangement). In the whole cohort, patients with
fusions had significantly higher 3-year relapse-free-survival (RFS) and tended to have a higher 3-year overall survival (OS) than those with no
fusions (80.1%
52.5%,
= 0.013; 67.6%
54.0%,
= 0.10). For patients receiving chemotherapy alone and received allogeneic-hematologic stem cell transplantation (allo-HSCT) were censored at the time of transplantation, patients with
fusions had both similar RFS and similar OS to B-other ALL patients with no
fusions (RFS: P =0.94 and 0.30; OS: P =0.94 and 0.51). For patients receiving transplantation, those with
fusions had significantly higher 3-year RFS than B-other ALL patients with no
fusions and their OS were similar (P = 0.022 and 0.24). Only two of 31 patients with
fusions and receiving allo-HSCT relapsed, individually occurred 66.8 and 69.8 months after transplantation. Therefore,
fusion is common in adult BCP-ALL, which may define a new group from BCP-ALL containing no classical fusion transcript with better prognosis through receiving allo-HSCT.
PDF
