Derivation and validation of a novel score for early prediction of severe CRS after CAR-T therapy in haematological malignancy patients: A multi-centre study.

Chimeric antigen receptor T (CAR-T) cell therapy is highly effective in inducing complete remission in haematological malignancies. Severe cytokine release syndrome (CRS) is the most significant and life-threatening adverse effect of this therapy. This multi-centre study was conducted at six hospitals in China. The training cohort included 87 patients with multiple myeloma (MM), an external validation cohort of 59 patients with MM and another external validation cohort of 68 patients with acute lymphoblastic leukaemia (ALL) or non-Hodgkin lymphoma (NHL). The levels of 45 cytokines on days 1-2 after CAR-T cell infusion and clinical characteristics of patients were used to develop the nomogram. A nomogram was developed, including CX3CL1, GZMB, IL4, IL6 and PDGFAA. Based on the training cohort, the nomogram had a bias-corrected AUC of 0.876 (95% CI = 0.871-0.882) for predicting severe CRS. The AUC was stable in both external validation cohorts (MM, AUC = 0.907, 95% CI = 0.899-0.916; ALL/NHL, AUC = 0.908, 95% CI = 0.903-0.913). The calibration plots (apparent and bias-corrected) overlapped with the ideal line in all cohorts. We developed a nomogram that can predict which patients are likely to develop severe CRS before they become critically ill, improving our understanding of CRS biology, and may guide future cytokine-directed therapies.

Secondary Raman and Brillouin mode suppression in two- and three-mirror-cavity diamond Raman lasers.

We report an investigation into secondary mode suppression in single longitudinal mode (SLM) 1240 nm diamond Raman lasers. For a three-mirror V-shape standing-wave cavity incorporating an intra-cavity LBO crystal to suppress secondary modes, we achieved stable SLM output with a maximum output power of 11.7 W and a slope efficiency 34.9%. We quantify the level of χ(2) coupling necessary to suppress secondary modes including those generated by stimulated Brillouin scattering (SBS). It is found that SBS-generated modes often coincide with higher-order spatial modes in the beam profile and can be suppressed using an intracavity aperture. Using numerical calculations, it is shown that the probability for such higher-order spatial modes is higher for an apertureless V-cavity than in two-mirror cavities due its contrasting longitudinal mode-structure.

Efficient single-frequency 972†nm Yb-doped fiber amplifier with core pumping and elevated temperature.

In this work, we present a monolithic single-frequency, single-mode and polarization maintaining Yb-doped fiber (YDF) amplifier delivering up to 6.9 W at 972 nm with a high efficiency of 53.6%. Core pumping at 915 nm and elevated temperature of 300 °C were applied to suppress the unwanted 977 nm and 1030 nm ASE in YDF, so as to improve the 972 nm laser efficiency. In addition, the amplifier was further used to generate a single-frequency 486 nm blue laser with 590 mW of output power by single-pass frequency doubling.

Generation of 1.3†µm femtosecond pulses by cascaded nonlinear optical gain modulation in phosphosilicate fiber.

Nonlinear optical gain modulation (NOGM) is a simple and effective approach to generate highly coherent ultrafast pulses with a flexible wavelength. In this work, we demonstrate 34 nJ, 170 fs pulse generation at 1319 nm through a piece of phosphorus-doped fiber by two-stage cascaded NOGM with a 1064 nm pulsed pump. Beyond the experiment, numerical results show that 668 nJ, 391 fs pulses at 1.3 µm can be produced with up to 67% conversion efficiency by increasing the pump pulse energy and optimizing the pump pulse duration. This would offer an efficient method to obtain high-energy sub-picosecond laser sources for applications such as multiphoton microscopy.

Generation of 978†nm dispersion-managed solitons from a polarization-maintaining Yb-doped figure-of-9 fiber laser.

Restricted by the narrow gain bandwidth of Yb3+ near 980 nm, it is challenging to generate dispersion-managed (DM) solitons at this wavelength. In this work, we demonstrate the generation of DM solitons at 978 nm in a polarization-maintaining (PM) figure-of-9 fiber laser. Highly coherent pulses with 14.4 nm spectral bandwidth and 175 fs pulse duration are experimentally obtained. To the best of our knowledge, this is the shortest ∼980 nm pulse ever reported in an Yb-doped mode-locked fiber laser. Numerical simulations are performed to reveal the DM solitons' temporal and spectral evolution inside the figure-of-9 cavity under the condition of a narrow gain bandwidth. This robust and cost-effective 978 nm femtosecond laser is a promising light source for applications such as underwater communication and biophotonics.

Self-Assembly of Helical Nanofibrous Chiral Covalent Organic Frameworks.

Despite significant progress on the design and synthesis of covalent organic frameworks (COFs), precise control over microstructures of such materials remains challenging. Herein, two chiral COFs with well-defined one-handed double-helical nanofibrous morphologies were constructed via an unprecedented template-free method, capitalizing on the diastereoselective formation of aminal linkages. Detailed time-dependent experiments reveal the spontaneous transformation of initial rod-like aggregates into the double-helical microstructures. We have further demonstrated that the helical chirality and circular dichroism signal can be facilely inversed by simply adjusting the amount of acetic acid during synthesis. Moreover, by transferring chirality to achiral fluorescent molecular adsorbents, the helical COF nanostructures can effectively induce circularly polarized luminescence with the highest luminescent asymmetric factor (glum ) up to ≈0.01.

Cascaded nonlinear optical gain modulation for coherent femtosecond pulse generation.

Nonlinear optical gain modulation (NOGM) is a method to generate high performance ultrafast pulses with wavelength versatility. Here we demonstrate coherent femtosecond Raman pulse generation through cascaded NOGM process experimentally. Two single-frequency seed lasers (1121 and 1178 nm) are gain-modulated by 117 nJ 1064 nm picosecond pulses in a Raman fiber amplifier. Second-order (1178 nm) Stokes pulses are generated, which have a pulse energy of 76 nJ (corresponding to an optical conversion efficiency of 65%) with a pulse duration of 621 fs (after compression). Dynamic evolution of both pump and cascaded Stokes pulses within the Raman amplifier are investigated by numerical simulations. The influences of pump pulse duration and energy are studied in detail numerically. Moreover, the simulations reveal that NOGM pulses with higher energy and shorter pulse duration could be obtained by limiting the impact of walk-off effect between pump and Raman pulses. This approach can offer a high energy and wavelength-agile ultrafast source for various applications such as optical metrology and biomedical imagining.

Robust single-frequency 589 nm fiber laser based on phase modulation and passive demodulation.

A robust 20-W continuous-wave single frequency 589 nm laser is developed to aim for sodium guide star in astronomy. The source is based on applying π-depth binary phase modulation to a single frequency seed laser along with 3 steps of strain in the gain fiber to suppress the stimulated Brillouin scattering in the high power 1178 nm amplifier and realizing the recovery of single frequency after frequency doubling in a periodically poled LiTaO3 crystal. The efficiency of frequency doubling reaches up to 41.6%. To the best of our knowledge, it is the highest power reported for continuous-wave 589 nm laser generation by single-pass frequency doubling. The approach significantly simplifies the sodium guide star laser design and improves robustness.

Numerical simulation of nonlinear optical gain modulation in a Raman fiber amplifier.

Nonlinear optical gain modulation (NOGM) in a Raman fiber amplifier is numerically simulated with the generalized nonlinear Schrödinger equation. In the NOGM setup, a single frequency continuous wave seed laser is gain modulated into femtosecond pulses by an ultrafast pump, which can induce strong stimulated Raman scattering in a piece of single mode optical fiber. Different parameters regarding seed, pump and nonlinear gain medium (Raman fiber) are investigated in detail to find the best condition for higher Raman conversion efficiency. Simulated results reveal that the walk-off between pump and Raman pulses due to dispersion is one of the most important factors affecting the NOGM pulse's performance. Only when the speed of walk-off matches with the one of Raman conversion process can the conversion efficiency be optimized. This work offers a guild-line for the design of a fiber-based NOGM laser, which is able to produce wavelength-agile, femtosecond laser pulses with µJ-level pulse energy under more than 85% efficiency.

Formation of Stable NiIII N-Confused Porphyrins Aided by a 3-Ethoxy Group.

We report the synthesis, characterization, and reactivities of two stable NiIII N-confused porphyrin (NCP) complexes. Metalation of 3-OEt NCP 1 with NiCl2 ⋅ 6H2 O in CHCl3 /EtOH gave 3-OEt NiII NCP 3 initially, which was easily oxidized in air to form the NiIII complex of NCP inner C-oxide 4. Bis-ethoxy-modified NiIII complex 5 was synthesized by oxidation of 3 with PIFA in ethanol and CHCl3 . The structures of 4 and 5 were determined by single-crystal X-ray diffraction analysis. An unusually long NiIII -C bond (2.170(9) Å) was observed in 4. The g-factor (g>2.1) observed in the EPR spectra of 4 and 5 further confirmed that they are paramagnetic NiIII complexes. Comparative experiments showed that the 3-ethoxy group plays an important role in the formation of 4 and 5. Reduction of 4 and 5 with NaBH4 regenerated complex 3.

Tuning the Circumference of Six-Porphyrin Nanorings.

Most macrocycles are made from a simple repeat unit, resulting in high symmetry. Breaking this symmetry allows fine-tuning of the circumference, providing better control of the host-guest behavior and electronic structure. Here, we present the template-directed synthesis of two unsymmetrical cyclic porphyrin hexamers with both ethyne (C2) and butadiyne (C4) links, and we compare these nanorings with the symmetrical analogues with six ethyne or six butadiyne links. Inserting two extra carbon atoms into the smaller nanoring causes a spectacular change in binding behavior: the template affinity increases by a factor of 3 × 109, to a value of ca. 1038 M-1, and the mean effective molarity is ca. 830 M. In contrast, removing two carbon atoms from the largest nanoring results in almost no change in its template-affinity. The strain in these nanorings is 90-130 kJ mol-1, as estimated both from DFT calculation of homodesmotic reactions and from comparing template affinities of linear and cyclic oligomers. Breaking the symmetry has little effect on the absorption and fluorescence behavior of the nanorings: the low radiative rates that are characteristic of a circular delocalized S1 excited state are preserved in the low-symmetry macrocycles.

Detecting Mechanochemical Atropisomerization within an STM Break Junction.

We have employed the scanning tunneling microscope break-junction technique to investigate the single-molecule conductance of a family of 5,15-diaryl porphyrins bearing thioacetyl (SAc) or methylsulfide (SMe) binding groups at the ortho position of the phenyl rings (S2 compounds). These ortho substituents lead to two atropisomers, cis and trans, for each compound, which do not interconvert in solution under ambient conditions; even at high temperatures, isomerization takes several hours (half-life 15 h at 140 °C for SAc in C2Cl4D2). All the S2 compounds exhibit two conductance groups, and comparison with a monothiolated (S1) compound shows the higher group arises from a direct Au-porphyrin interaction. The lower conductance group is associated with the S-to-S pathway. When the binding group is SMe, the difference in junction length distribution reflects the difference in S-S distance (0.3 nm) between the two isomers. In the case of SAc, there are no significant differences between the plateau length distributions of the two isomers, and both show maximal stretching distances well exceeding their calculated junction lengths. Contact deformation accounts for part of the extra length, but the results indicate that cis-to-trans conversion takes place in the junction for the cis isomer. The barrier to atropisomerization is lower than the strength of the thiolate Au-S and Au-Au bonds, but higher than that of the Au-SMe bond, which explains why the strain in the junction only induces isomerization in the SAc compound.

High order cascaded Raman random fiber laser with high spectral purity.

An up to 8th order cascaded Raman random fiber laser with high spectral purity is achieved with the pumping of a narrow linewidth amplified spontaneous emission source. The spectral purity is over 90% for all the 8 Stokes orders. The highest output power is 6.9 W at 1691.6 nm with an optical conversion efficiency of 21% from 1062.0 nm. As a comparison, with conventional FBG-based fiber oscillator as pump source, only 47% spectral purity is achieved at 8th order. The temporal stability of the pump laser is proved to play a key role, because the time fluctuation of pump laser is transferred directly to Raman outputs and results in power distribution among different Stokes orders.

Solid-state 589 nm seed laser based on Raman fiber amplifier for sodium wind/temperature lidar in Tibet, China.

A narrowband sodium lidar for measuring mesospheric temperature and wind has been established at YangBaJing, Tibet (90°E, 30°N, 4300 m a.s.l), China. The system is designed and optimized based on important upgrades using new technology. In the lidar system, single-mode 589 nm seed laser is produced by frequency doubling of 1178 nm diode laser with a periodically poled lithium niobate (PPLN) waveguide. The output power of 589 nm continuous-wave laser is up to 1.5 W with the help of a seed-injected Raman fiber amplifier. Furthermore, fast three-frequency switcher is designed with a couple of fiber magneto optical switches (FMOS) for measuring wind and temperature, simultaneously, which greatly reduces the system maintenance. These improvements greatly simplify the lidar system, thus, achieve robust operation with minimum maintenance requirements.

2 W single-frequency, low-noise 509 nm laser via single-pass frequency doubling of an ECDL-seeded Yb fiber amplifier.

A single-frequency low-noise green laser at 509 nm is developed for the study of cesium Rydberg atoms. The laser is generated by single-pass second-harmonic generation of a Yb fiber amplifier seeded with an external cavity diode laser (ECDL) at 1018 nm in a periodically poled MgO-doped lithium-niobate crystal. An up to 2.03 W, 509 nm laser is obtained from a 10.04 W incident 1018 nm laser with a conversion efficiency of 20.2%. The linewidth of the 509 nm laser is estimated to be 40 kHz according to the measured linewidth of 20 kHz of the 1018 nm fundamental laser. The relative intensity noise is 0.038% rms integrated from 10 Hz to 10 MHz.

Unexpected Interactions between Alkyl Straps and Pyridine Ligands in Sulfur-Strapped Porphyrin Nanorings.

Strapped or "basket-handle" porphyrins have been investigated previously as hemoglobin mimics and catalysts. The facial selectivity of their interactions with axial ligands is a sensitive test for noncovalent bonding. Here the binding of pyridyl ligands to zinc porphyrins with thioester-linked alkyl straps is investigated in solution by NMR spectroscopy and UV-vis titration, and in the solid state by X-ray crystallography. We expected that coordination of the axial ligand would occur on the less hindered face of the porphyrin, away from the strap. Surprisingly, attractive interactions between the strap and the ligand direct axial coordination to the strapped face of the porphyrin, except when the strap is short and tight. The strapped porphyrins were incorporated into π-conjugated cyclic porphyrin hexamers using template-directed synthesis. The strap and the sulfur substituents are located either inside or outside the porphyrin nanoring, depending on the length of the strap. Six-porphyrin nanorings with outwardly pointing sulfur anchors were prepared for exploring quantum interference effects in single-molecule charge transport.

A meso-meso ß-ß ß-ß Triply Linked Subporphyrin Dimer.

A meso-meso ß-ß ß-ß triply linked subporphyrin dimer 6 was synthesized by stepwise reductive elimination of ß-to-ß doubly PtII -bridged subporphyrin dimer 9. Dimer 6 was characterized by spectroscopic and electrochemical measurements, theoretical calculations, and picosecond time-resolved transient absorption spectroscopy. X-ray diffraction analysis reveals that 6 has a bowl-shaped structure with a positive Gaussian curvature. Despite the curved structure, 6 exhibits a remarkably red-shifted absorption band at 942 nm and a small electrochemical HOMO-LUMO gap (1.35 eV), indicating an effectively conjugated π-electronic network.

Ultra-wide wavelength tuning of a cascaded Raman random fiber laser.

An ultra-broadband tunable cascaded Raman random fiber laser pumped by a tunable (1020-1080 nm) ytterbium-doped fiber laser is investigated. By continuously adjusting the pump laser wavelength, the Raman random laser tunes accordingly due to the Raman gain competition. By increasing the pump power, up to the 5th order Raman random laser is achieved. As a result, 300 nm of continuous wavelength tuning from 1070 to 1370 nm is achieved by adjusting the pump wavelength and power altogether. The highest output power is 1.8 W at 1360 nm with an optical efficiency of 15% from 1080 nm. To the best of our knowledge, this is the widest wavelength tuning range reported for a random fiber laser so far.

Directly 2,12- and 2,8-Linked Zn(II) Porphyrin Oligomers: Synthesis, Optical Properties, and Coherence Lengths.

Directly 2,12- and 2,8-linked Zn(II) porphyrin oligomers were prepared from 2,12- and 2,8-diborylated Zn(II) porphyrin by a cross platinum-induced coupling with a 2-borylated Zn(II) porphyrin end unit followed by a triphenylphosphine (PPh3 )-mediated reductive elimination. Comparative studies on the steady-state absorption and fluorescence spectra and the fluorescence lifetimes led to a conclusion that the exciton in the S1 state is delocalized over approximately four and two Zn(II) porphyrin units for 2,12- and 2,8-linked Zn(II) porphyrin arrays, respectively.

Exciton coupling dynamics in syn- and anti-type ß-ß linked Zn(ii) porphyrin linear arrays.

The photophysical properties of molecular arrays are strongly dependent on a variety of structural factors: the constituent chromophores, dihedral angle, linkage length, linkage position, the center-to-center distance between chromophores, and the linker itself. Here, we investigated the exciton coupling dynamics of syn- and anti-type ß-ß directly linked Zn(ii) porphyrin linear arrays. Focusing on the relationship between the origin of the lowest excited electronic state and the linkage position, we evaluated the exciton coupling strength and carried out time-dependent density functional theory (TDDFT) calculations on model compounds as well as femtosecond transient absorption anisotropy (fs-TAA) measurements. Based on our experiments and calculations, we propose that a different origin of the lowest excited state leads to linkage-position-dependent exciton coupling. In short, compared with syn-type porphyrin arrays, anti-type arrays induce distinct and stronger exciton coupling in the lowest excited state.