The outcomes of 293 patients with leukemia undergoing HLA-identical sibling (n ‫؍‬ 158) or related HLA-mismatched (n ‫؍‬ 135) hematopoietic cell transplantation (HCT) performed during the same time period were compared. Patients received BUCY2 in HLA-identical sibling HCT or BUCY2 ؉ ATG in mismatched HCT as conditioning regimens, followed by unmanipulated marrow and/or peripheral blood (PB) transplantation. All patients achieved full engraftment. The cumulative incidences of grades II to IV acute graft-versus-host disease (aGVHD) in the matched and mismatched cohorts were 32% (CI, 25%-39%) versus 40% (CI, 32%-48%, P ‫؍‬ .13), respectively, with the relative risk (RR) ‫؍‬ 0.64 (95% CI, 0.43-0.94), P ‫؍‬ .02. The incidence of chronic GVHD did not differ significantly between the cohorts (P ‫؍‬ .97). Two-year incidences of treatment-related mortality and relapse for matched versus mismatched were 14% (range, 9%-20%) versus 22% (range, 15%-29%) with P ‫؍‬ .10 and 13% (range, 8%-19%) versus 18% (range, 10%-27%) with P ‫؍‬ .40, respectively. Two-year adjusted leukemia-free survival (LFS) and overall survival were 71% (range, 63%-78%) versus 64% (range, 54%-73%) with P ‫؍‬ .27 and 72% (range, 64%-79%) versus 71% (range, 62%-77%) with P ‫؍‬ .72, respectively. Multivariate analyses showed that only advanced disease stage and a diagnosis of acute leukemia had increased risk of relapse, treatment failure, and overall mortality. In summary, HCT performed with related HLA-mismatched donors is a feasible approach with acceptable outcomes. (Blood. 2006;107:3065-3073)

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Immune checkpoint blockades, such as inhibitors against programmed death 1 (PD-1) and its ligand (PD-L1), have received extensive attention in the past decade because of their dramatic clinical outcomes in advanced malignancies. However, both primary and acquired resistance becomes one of the major obstacles, which greatly limits the long-lasting effects and wide application of PD-1/PD-L1 blockade therapy. PD-1/PD-L1 both regulates and is regulated by cellular signaling pathways and epigenetic modification, thus inhibiting the proliferation and effector function of T and B cells. The lack of tumor antigens and effective antigen presentation, aberrant activation of oncogenic pathways, mutations in IFN-γ signaling, immunosuppressive tumor microenvironment such as regulatory T cells, myeloid-derived suppressor cells, M2 macrophages, and immunoinhibitory cytokines can lead to resistance to PD-1/PD-L1 blockade. In this review, we describe PD-1 related signaling pathways, essential factors contributing to the resistance of PD-1 blockade, and discuss strategies to increase the efficacy of immunotherapy. Furthermore, we discuss the possibility of combined epigenetic therapy with PD-1 blockade as a potential promising approach for cancer treatment.

Although collisions between atoms and molecules are largely understood, collisions between two molecules have proven much harder to study. In both experiment and theory, our ability to determine quantum-state-resolved bimolecular cross-sections lags behind their atom-molecule counterparts by decades. For many bimolecular systems, even rules of thumb-much less intuitive understanding-of scattering cross sections are lacking. Here, we report the measurement of state-to-state differential cross sections on the collision of state-selected and velocity-controlled nitric oxide (NO) radicals and oxygen (O) molecules. Using velocity map imaging of the scattered NO radicals, the full product-pair correlations of rotational excitation that occurs in both collision partners from individual encounters are revealed. The correlated cross sections show surprisingly good agreement with quantum scattering calculations using ab initio NO-O potential energy surfaces. The observations show that the well-known energy-gap law that governs atom-molecule collisions does not generally apply to bimolecular excitation processes, and reveal a propensity rule for the vector correlation of product angular momenta.

Rotational product-pair correlations have been observed, while ND3 was rotationally excited, D2 was simultaneously rotationally excited and de-excited.

PreS deletion mutations of genotype C HBV might play a role in HBV-related hepatocarcinogenesis.

Breast cancer is the most common malignancy for women worldwide, while Triple Negative Breast Cancer (TNBC) accounts for 20% in all patients. Compared with estrogen receptor positive breast cancer, which could be effectively controlled via endocrine therapy, TNBC is more aggressive and worse in prognosis. It is therefore urgent and necessary to develop a novel therapeutic strategy for TNBC treatment. Recent studies identified Hippo signaling is highly activated in TNBC, which could be a driving pathway for TNBC progression. In our study, we determine RNF187 as a negative regulator for Hippo signaling activation. RNF187 depletion significantly decreases cell migration and invasion capacity in TNBC. These effects could be rescued by further YAP depletion. Depletion of RNF187 increases the YAP protein level and Hippo signaling target genes, such as CTGF and CYR61 in TNBC. Immuno-precipitation assay shows that RNF187 associates with YAP, promoting its degradation possibly via inducing YAP K48-dependent polyubiquitination. Interestingly, Our clinical data reveals that RNF187 reversely correlates with YAP protein level and Hippo target genes. RNF187 tends to correlate with good prognosis in TNBC patients. Our study provides evidence to establish a proteolytic mechanism in regulation Hippo signaling activation in TNBC.

We present the first crossed beam scattering experiment using a Zeeman decelerated molecular beam. The narrow velocity spreads of Zeeman decelerated NO (X 2 Π 3/2 , j = 3/2) radicals result in high-resolution scattering images, thereby fully resolving quantum diffraction oscillations in the angular scattering distribution for inelastic NO-Ne collisions, and product-pair correlations in the radial scattering distribution for inelastic NO-O2 collisions. These measurements demonstrate similar resolution and sensitivity as in experiments using Stark decelerators, opening up possibilities for controlled and low-energy scattering experiments using chemically relevant species such as H and O atoms, O2 molecules or NH radicals.Establishing experimental tools to study molecular collisions with the highest possible level of detail has been an important goal in molecular physics for decades [1]. The sensitivity and resolution of the experiment depends on the control over the particles before the collision, and how they are detected afterwards. In recent years, the combination of Stark deceleration and velocity map imaging (VMI) to both control and probe the quantum state and velocity of molecules, has greatly enhanced the possibilities to investigate molecular collisions in crossed beam experiments [2]. The narrow velocity and angular spreads of Stark-decelerated beams result in scattering images with unprecedented radial and angular resolution, that can be exploited to resolve structure in the scattering images -and thus the differential cross section (DCS) of the scattering process -that would have been washed out using conventional molecular beams. Recent examples include the direct imaging of quantum diffraction oscillations [3][4][5], the measurement of correlated excitations in bimolecular collisions [6], and the probing of scattering resonances at low collision energies [7,8].Despite these successes and further prospects to unravel fine details of collision processes, the Stark deceleration technique has a major limitation. As the method relies on the interaction of neutral molecules with electric fields, it can only be applied to species with a sufficiently large electric dipole moment. Although these include important molecules for scattering studies [9, 10], many chemically relevant species like H, O and F atoms, O 2 molecules or ground state NH radicals exclusively have a magnetic dipole moment, rendering the Stark deceleration technique useless. Yet, these species are of paramount importance to molecular reaction dynamics [11], surface scattering [12], and the emerging fields of cold and ultracold molecules alike [13].Recently, various types of Zeeman decelerators -the magnetic analogue of a Stark decelerator -have been realized, and the successful deceleration [14-24] and subsequent trapping [25-30] of a variety of atomic and molecular species has been reported. Yet, the application of molecular decelerators in crossed beam experiments poses specific requirements on density, state purity, and velocity control o...