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Metal–metal bonding is crucial in chemistry for advancing our understanding of the fundamental aspects of chemical bonds. Metal–metal bonds based on alkaline-earth (Ae) elements, especially the heavier Ae elements (Ca, Sr, and Ba), are rarely reported due to their high electropositivity. Herein, we report two heteronuclear di-EMFs CaY@Cs(6)-C82and CaY@C2v(5)-C80, which contain unprecedented single-electron Ca–Y metal–metal bonds. These compounds were characterized by single-crystal X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and DFT calculations. The crystallographic study of CaY@Cs(6)-C82shows that Ca and Y are successfully encapsulated into the carbon cage with a Ca–Y distance of 3.691 Å. The CW-EPR study of both CaY@Cs(6)-C82and CaY@C2v(5)-C80exhibits a doublet, suggesting the presence of an unpaired electron located between Ca and Y. The combined experimental and theoretical results confirm the presence of a Ca–Y single-electron metal–metal bond with substantial covalent interaction, attributed to significant overlap between the 4s4p orbitals of Ca and the 5s5p4d orbitals of Y. Furthermore, pulse EPR spectroscopy was used to investigate the quantum coherence of the electron spin within this bond. The unpaired electron, characterized by its s orbital nature, is effectively protected by the carbon cage, resulting in efficient suppression of both spin–lattice relaxation and decoherence. CaY@Cs(6)-C82behaves as an electron spin qubit, displaying a maximum decoherence time of 7.74 μs at 40 K. This study reveals an unprecedented Ae–rare-earth metal–metal bond stabilized by the fullerene cages and elucidates the molecular qubit properties stemming from their unique bonding character, highlighting their potential in quantum information processing applications.

This paper studies the construction of constant $L_{1}$ -weight codes under $L_{\infty }$ -metric, which could be used to design codes addressing 0-indels (i.e., the insertion/deletion of 0’s only). Based on the patterns of small codes, we determine the maximum size for codes with distance 2 and length 3 for any constant weight, and several constructions and algorithms for suboptimal codes with general length $w+1$ are also provided. In general, for codes with distance D, length $w+1$ , and weight $tD+r$ , we derive the size of the largest code by using Hall’s theorem for integers $r=0$ , $t\in [{0,3}]$ and $w\geq t-1$ . When $r=\frac {D}{2}$ with D being even, codes with a cardinality that surpasses the known existing sizes by the additive term $\left \lceil{ \frac {1}{3}\binom {t+1}{2}}\right \rceil \left \lfloor{ \frac {w+1}{3}}\right \rfloor $ are constructed based on the structure of group divisible designs in combinatorics.

Metafibers, by integrating metasurface at the optical fiber tip, are emerging as the significant optical coupling platforms for nanophotonics and fiber-optic communities. Here, we propose a plasmonic metafiber for converting the fundamental mode to first-order mode in fiber, and as proof of device performance, demonstrate an all-fiber Q-switched cylindrical vector laser using the metafiber. Based on polarization-dependent plasmonic resonance, a polarization-independent mode conversion metasurface is designed theoretically and numerically, fabricated directly on fiber facet, and packaged as an all-fiber component with efficiency up to 21% at 1550-nm band. Using the metafiber in an all-fiber laser, Q-switched azimuthally polarized beam (APB) and radially polarized beam (RPB) are delivered at wavelength of 1548.5 nm with pulse durations from ∼7 to ∼2 μs when pump power increases from 30 to 120 mW. The mode purities of the APB and RPB are 86.5% and 90.7%, respectively. This work outlines a new strategy to integrate metasurfaces into “all-in-fiber” systems and offers a reliable route to construct next-generation laser sources, such as all-fiber ultrafast structured lasers.

The bound states (BSs) of solitons are found to have intriguing internal dynamics in ultrafast lasers. Here, we explore the binding mechanism and internal motions of asymmetric bound state (ABS) solitons constituted by unequal solitons at short-range with their tails directly overlapped. Experiments and simulations show that the periodic energy flux between two solitons, mediated by their overlapped tails, gives rise to a balanced separation and energy distribution across the ABS. The motion mechanisms of strong and weak solitons are discussed in detail. This work provides insights into the binding mechanism and internal dynamics of BSs.

Enhanced recovery after surgery (ERAS) pathway comprises a set of comprehensive elements which have been reported to enhance patient postoperative prognosis. In the current study, we aimed to evaluate the effectiveness of the ERAS in patients undergoing laparoscopic adrenal resection. A retrospective review was performed to compare the outcomes of patients undergoing adrenalectomy for primary aldosteronism between the pre-ERAS period and the ERAS era. Data was generated from the traditional surgical period (September 1, 2019, to December 31, 2019) and the ERAS period (September 1, 2020, to December 31, 2020), respectively. Forty-seven adrenalectomy patients were enrolled (pre-ERAS, n= 21; ERAS, n= 26) in analysis. The results revealed that both total length of hospital stay and postoperative length of stay decreased in the ERAS period compared with the pre-ERAS period (14.19 ± 4.96 vs 11.27 ± 4.37, p= 0.015; 5.43 ± 1.08 vs 3.31 ± 0.97, p< 0.001). The medical expenses decreased significantly in the ERAS group (p< 0.05). While, the surgery-related complications, including urinary retention, retroperitoneal effusion and gastrointestinal discomfort, possessed no statistical difference. The ERAS pathway was safe and feasible for adrenalectomy in patients with primary aldosteronism. The ERAS could promote patients to quickly recover from the postoperative status to a physiological state, and decrease the length of hospitalization and medical cost after surgery.

Lead selenide (PbSe) is a new emerging semiconductor with layer-dependent bandgap that has attracted much interest due to its high infrared response and good environmental stability. We have prepared large-scale PbSe films with the area of 7 cm2and thickness of 25 nm based on physical vapor deposition approach at 160°C. The PbSe films exhibit saturable absorption property at 1.55 μm and a polarization-sensitive saturable absorber is obtained by growing PbSe on D-shaped fiber. Single-pulse with the duration of 490 fs is generated at the pump of 12 mW and the mode-locking operation is maintained at the pump of 1500 mW, indicating the high damage threshold of the D-shaped fiber based saturable absorber. Two polarization-insensitive saturable absorbers are achieved by depositing PbSe on fiber facet and polyvinyl alcohol film, respectively. For fiber facet (polyvinyl alcohol film) based saturable absorber, the repetition rate of Q-switched pulses increases from 8.6 (16.3) kHz to 45.4 (59.2) kHz while the duration decreases from 7.92 (12) μs to 2.06 (3.12) μs by tuning the pump from 15 mW to 90 (60) mW. Such large-scale PbSe films possess features of low cost and high modulation ability, and can find important applications in infrared optical modulators and detectors.

We demonstrate a mode converter with an insertion loss of 0.36 dB based on mode coupling of tapered single-mode and two-mode fibers, and realize all-fiber flexible cylindrical vector lasers at 1550 nm. Attributing to the continuous distribution of a tangential electric field at taper boundaries, the laser is switchable between the radially and azimuthally polarized states by adjusting the input polarization. In the temporal domain, the operation is controllable among continuous-wave, Q-switched, and mode-locked statuses by changing the saturable absorber or pump strength. The duration of Q-switched radially/azimuthally polarized laser spans from 10.4/10.8 to 6/6.4 μs at the pump range of 38 to 58 mW, while that of the mode-locked pulse varies from 39.2/31.9 to 5.6/5.2 ps by controlling the laser bandwidth. The proposed laser combines the features of a cylindrical vector beam, a fiber laser, and an ultrafast pulse, providing a special and cost-effective source for practical applications.

As a universal phenomenon in nonlinear optical systems, intermittency is usually accompanied by the coherence loss such as soliton explosions in fiber lasers. Based on real-time spectroscopy, we revealed the coherent dissipative soliton intermittency in normal-dispersion fiber lasers. By increasing the pump strength, the intermittency transforms from the transient pulsation to the bi-stable soliton. It is demonstrated that the slow-gain effect dominates such coherent intermittency. Our results provide novel insights into laser physics, offering a promising approach for studying the bi-stable dissipative soliton.

Shp2 tyrosine phosphatase plays a critical role in hematopoiesis, and dominant active mutations have been detected in the human gene PTPN11, encoding Shp2, in child leukemia patients. We report here that although no such mutations were detected in 44 adult leukemia patients screened, Shp2 expression levels were significantly elevated in primary leukemia cells and leukemia cell lines, as compared with normal hematopoietic progenitor cells. The Shp2 protein amounts correlated well with the hyperproliferative capacity but were inversely associated with the differentiation degree of leukemia cells. Suppression of Shp2 expression induced apoptosis and inhibition of leukemic cell clonogenic growth. Notably, the majority of Shp2 was preferentially localized to the plasma membrane and was constitutively phosphorylated on tyrosine in leukemia cells, and also in normal hematopoietic cells following mitogenic stimulation. Based on these results, we propose that aberrantly increased expression of Shp2 may contribute, collaboratively with other factors, to leukemogenesis.

Shp2 tyrosine phosphatase plays a critical role in hematopoiesis, and dominant active mutations have been detected in the human gene PTPN11, encoding Shp2, in child leukemia patients. We report here that although no such mutations were detected in 44 adult leukemia patients screened, Shp2 expression levels were significantly elevated in primary leukemia cells and leukemia cell lines, as compared with normal hematopoietic progenitor cells. The Shp2 protein amounts correlated well with the hyperproliferative capacity but were inversely associated with the differentiation degree of leukemia cells. Suppression of Shp2 expression induced apoptosis and inhibition of leukemic cell clonogenic growth. Notably, the majority of Shp2 was preferentially localized to the plasma membrane and was constitutively phosphorylated on tyrosine in leukemia cells, and also in normal hematopoietic cells following mitogenic stimulation. Based on these results, we propose that aberrantly increased expression of Shp2 may contribute, collaboratively with other factors, to leukemogenesis.

We demonstrate an all-fiber Q-switched cylindrical vector laser based on a black phosphorus saturable absorber and a transverse mode converter. The saturable absorber is prepared by incorporating the polyvinyl alcohol with anti-oxidized black phosphorus nanosheets exfoliated in aqueous poly(dimethyldiallyl ammonium chloride) solution. The mode converter is composed of a tapered two-mode fiber and a single-mode fiber, and it can excite switchable azimuthally and radially polarized beams by modulating the input polarization. By enhancing the pump power from 64.68 to 174.82 mW, the repetition rate of the Q-switched azimuthally/radially polarized laser enlarges from 16.72/19.25 to 30.71/37.82 kHz.

Multiple myeloma (MM) is the second most common hematologic malignancy in the United States. Chromosome 13 deletions are found in approximately one half (50%) of all patient samples and is associated with worse outcomes. The retinoblastoma gene (Rb1) has been implicated as a candidate tumor suppressor at 13q14, however, unmutated Rb1 remains expressed from retained alleles in the majority of cases. We sought to explore the role of Rb1 in plasma cells by generating mice with deficiency of Rb1 targeted to late B-cell development.The Rb family member p107 can compensate for Rb1 function, so we crossed Rb1Flox/Flox and P107−/−mouse strains with Cγ1-Cre knock-in mice that express the Cre recombinase specifically in germinal center (GC) B-cells to generate mice with tissue-specific deletion of Rb in germinal center cells (Cg1-Rb-KO), and we aged these mice to assess disease development.In Cg1-Rb-KO mice, we demonstrated the Rb1 locus was successfully recombined in splenic germinal center cells (B220+, GL7+ and IgG1+), as well as in post-germinal center cells (B220-, CD138+). Recombination was also detectable in bone marrow B-cell but not myeloid cell progenitors. Cg1-Rb-KO mice developed normally but became ill starting at 40 weeks of age. Sick mice demonstrated weight loss, hypoplastic spleens, osteopenia and significant lymphopenia. Thorough analysis of bone marrow and spleen hematopoietic progenitor cell subsets by multi-parameter flow cytometry at the time of death revealed dramatic reductions in marrow B-cell (Hardy fractions C-D, from 3.18×103to 40 cells and from 1.4×106 to 7.5×104cells respectively), suggesting an effective collapse of the B-cell lineage in mice lacking Rb. Examination of Cg1-Rb-KO mice prior to becoming sick (age 30–35 weeks) demonstrated increased numbers of B-cell progenitors in the bone marrow, consistent with Rb's known role in cell cycle regulation. Together, our results suggest Cg1-Rb-KO mice develop benign B-cell hyperplasia followed by a lethal collapse of the B-cell lineage. To help explain this B-cell exhaustion phenotype, we measured reactive oxygen species (ROS) in the B-cell of young Cg1-Rb-KO mice. We observed significantly increased ROS in Cg1-Rb-KO mice at baseline and following LPS stimulation ex vivo and in vivo compared to p107-KO control mice, suggesting that B-cells from Cg1-Rb-KO mice have elevated levels of oxidative stress.Rb1 is important for maintenance of B-cell homeostasis and protects B-lineage progenitor cells from oxidative stress and exhaustion. Rb1 deletion was not sufficient for B-cell transformation and additional mutations are likely required for MM development in the context of complete RB1 loss.Vij: Millennium: Speakers Bureau.

Abstract 1315

Chronic myeloid leukemia (CML) is a pluripotent hematopoietic stem cell disorder characterized by accumulation of mature and immature granulocytes in peripheral blood and bone marrow due to uncontrolled growth and resistance to apoptosis. The dysregulated activity of the bcr/abl oncoprotein tyrosine kinase, which is encoded by the bcr-abl fusion gene generated from the chromosomal translocation of t(9; 22) and present in approximately 95% of CML patients, has been shown to be responsible for these malignant phenotypes. Numerous studies have demonstrated that only being phosphorylated that p210bcr/abl oncoprotein can promote cell proliferation and survival, and block apoptosis of tumor cells. Bcr/abl tyrosine kinase has chaperone association with heat shock protein 90 (Hsp90), which plays an essential role in stabilization of bcr/abl protein. Here we describe the activity of a natural small molecular compound, berbamine from plant Berberis amurensis that can selectively induce cell death of both Gleevecsensitive and -resistant Ph+ CML cells, but little is known about its exact mechanisms. We investigated the the expression levels of phosphorylated p210bcr/abl protein and Hsp90 protein in apoptosis induced by berbamine in K562 cells by means of various technologies, including cell culture system, flow cytomerty, western blot and immunoprecipitation (IP). Methods: Human Ph+ CML leukemia K562 cells, which express endogenous p210bcr/abl protein, were cultured in RPMI 1640 and treated with berbamine as indicated time and dose. Flow cytometry (FCM) and Annexin V-FLUOS/PI staining kit were used to evaluate apoptosis of leukemic cells; FCM and cytoperm/cytofix plus Caspase-3-McAb-PE were employed to measure leukemic cells with activated Caspase-3. Phosphorylation of p210bcr/abl protein in leukemic cells were assessed by a combination of immunoprecipitation (IP) with c-abl antibody and Western blot with p-Tyr(pY99)antibody. The protein levels of P210bcr/abl, Hsp90 and Hsp70 in leukemic cells were determined by Western blot with antibodies to c-abl, Hsp90 and Hsp70, respectively. Results: After treatment with berbamine at 8 µg/ml for 48 h, the percentages of leukemic cells expressing activated caspase-3 and apoptotic cells were 45.69% and 48.43%, respectively. IP and WB results showed that berbamine at low concentration markedly inhibited phosphorylation of p210bcr/abl protein in leukemia cells, and the amount of phosphorylated p210bcr/abl in leukemia cells exposured to berbamine at 8 µg/ml for 6 h were only 8.41% of that of untreated leukemia cells without the protein levels of P210bcr/abl down-regulated. Berbamine also down-regulated chaperone Hsp90 protein, and the amount of Hsp90 protein in leukemia cells treated with berbamine at 8 µg/ml for 48 h accounted for 18.37% of that of untreated leukemia cells. Interestingly, berbamine at 8 µg/ml had no obvious effects on chaperone Hsp70 protein expression associated with the resistance of leukemia cells to apoptosis. Conclusions: Berbamine could induce caspase-3-mediated apoptosis of Ph+ leukemia cells through inhibiting phosphorylation of p210bcr/abl protein and down-regulating its chaperone Hsp90 protein. Unlike Hsp90 inhibitor GA that could upregulate Hsp70, berbamine had no obvious effects on chaperone Hsp70 protein expression in leukemia cells, suggesting that berbamine may be a novel class of Hsp90 inhibitor, and further study is required.

Chronic myeloid leukemia (CML) is a pluripotent hematopoietic stem cell disorder characterized by accumulation of mature and immature granulocytes in peripheral blood and bone marrow due to uncontrolled growth and resistance to apoptosis. The dysregulated activity of the bcr/abl oncoprotein tyrosine kinase, which is encoded by the bcr-abl fusion gene generated from the chromosomal translocation of t(9; 22) and present in approximately 95% of CML patients, has been shown to be responsible for these malignant phenotypes. Numerous studies have demonstrated that only being phosphorylated that p210bcr/abl oncoprotein can promote cell proliferation and survival, and block apoptosis of tumor cells. Bcr/abl tyrosine kinase has chaperone association with heat shock protein 90 (Hsp90), which plays an essential role in stabilization of bcr/abl protein. Here we describe the activity of a natural small molecular compound, berbamine from plant Berberis amurensisthat can selectively induce cell death of both Gleevecsensitive and -resistant Ph+ CML cells, but little is known about its exact mechanisms. We investigated the the expression levels of phosphorylated p210bcr/abl protein and Hsp90 protein in apoptosis induced by berbamine in K562 cells by means of various technologies, including cell culture system, flow cytomerty, western blot and immunoprecipitation (IP).

Our previous studies have indicated a stringent requirement of SHP-2 tyrosine phosphatase for normal hematopoiesis, but little is known whether SHP-2 plays a role in human leukemogenesis. Here, we show that SHP-2 plays a pivotal role in regulating the proliferating potential of human leukemia cells. We identified three types of SHP-2 proteins: m-, n- and c-SHP-2 proteins from both leukemic and normal hematopoietic cells. The m- and n-SHP-2 proteins (termed as active SHP-2) are derived from the c-SHP-2 protein (inactive SHP-2), and highly expressed on the internal membrane of rapidly proliferating cells at S/G2 phase, and in nucleus of mitotic cells at prophase and prometaphase, respectively, whereas the c-SHP-2 protein is ubiquitously expressed in the cytoplasm of both proliferating and resting cells. Intriguingly, we found that both active SHP-2 protein and its mRNA were constitutively overexpressed in leukemic blasts from various human leukemia cell lines and nearly all cases of various subtypes of human leukemia tested, relative to normal hematopoietic progenitors. Moreover, the expression level of active SHP-2 protein is positively correlated with the hyperproliferative phenotype of leukemia patients, and inversely associated with differentiation degree of hematopoietic cells. Most importantly, block of SHP-2 expression induces apoptosis and growth inhibition of leukemic clonogenic cells both in vitro and in vivo. In addition, we found that both PI3k/Akt and Ras/Erk signaling pathways are constitutively activated in human leukemias. Finally, we identified no mutation in PTPN11 among all tested leukemia patients. Based on these findings, we propose that SHP-2 tyrosine phosphatase plays an essential role in human leukemogenesis in which it may directly controls the proliferative potential of neoplastic cells of human leukemia via regulating signaling pathways involved in survival, growth and apoptosis of leukemia cells such as PI3k/Akt and Ras/Erk signaling pathways.

Our previous studies have indicated a stringent requirement of SHP-2 tyrosine phosphatase for normal hematopoiesis, but little is known whether SHP-2 plays a role in human leukemogenesis. Here, we show that SHP-2 plays a pivotal role in regulating the proliferating potential of human leukemia cells. We identified three types of SHP-2 proteins: m-, n- and c-SHP-2 proteins from both leukemic and normal hematopoietic cells. The m- and n-SHP-2 proteins (termed as active SHP-2) are derived from the c-SHP-2 protein (inactive SHP-2), and highly expressed on the internal membrane of rapidly proliferating cells at S/G2 phase, and in nucleus of mitotic cells at prophase and prometaphase, respectively, whereas the c-SHP-2 protein is ubiquitously expressed in the cytoplasm of both proliferating and resting cells. Intriguingly, we found that both active SHP-2 protein and its mRNA were constitutively overexpressed in leukemic blasts from various human leukemia cell lines and nearly all cases of various subtypes of human leukemia tested, relative to normal hematopoietic progenitors. Moreover, the expression level of active SHP-2 protein is positively correlated with the hyperproliferative phenotype of leukemia patients, and inversely associated with differentiation degree of hematopoietic cells. Most importantly, block of SHP-2 expression induces apoptosis and growth inhibition of leukemic clonogenic cells both in vitro and in vivo. In addition, we found that both PI3k/Akt and Ras/Erk signaling pathways are constitutively activated in human leukemias. Finally, we identified no mutation in PTPN11 among all tested leukemia patients. Based on these findings, we propose that SHP-2 tyrosine phosphatase plays an essential role in human leukemogenesis in which it may directly controls the proliferative potential of neoplastic cells of human leukemia via regulating signaling pathways involved in survival, growth and apoptosis of leukemia cells such as PI3k/Akt and Ras/Erk signaling pathways.