Nondefective Vacancy Enhanced Resistive Switching Reliability in Emergent van der Waals Metal Phosphorus Trisulfide-Based Memristive In-Memory Computing Hardware.

Two-dimensional-material-based memristors are emerging as promising enablers of new computing systems beyond von Neumann computers. However, the most studied anion-vacancy-enabled transition metal dichalcogenide memristors show many undesirable performances, e.g., high leakage currents, limited memory windows, high programming currents, and limited endurance. Here, we demonstrate that the emergent van der Waals metal phosphorus trisulfides with unconventional nondefective vacancy provide a promising paradigm for high-performance memristors. The different vacancy types (i.e., defective and nondefective vacancies) induced memristive discrepancies are uncovered. The nondefective vacancies can provide an ultralow diffusion barrier and good memristive structure stability giving rise to many desirable memristive performances, including high off-state resistance of 1012 Ω, pA-level programming currents, large memory window up to 109, more than 7-bit conductance states, and good endurance. Furthermore, a high-yield (94%) memristor crossbar array is fabricated and implements multiple image processing successfully, manifesting the potential for in-memory computing hardware.

Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study.

Bruton tyrosine kinase (BTK) inhibitor is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Zanubrutinib, a highly selective BTK inhibitor, is approved for patients with MCL who have received ≥1 prior therapy. We report the long-term safety and efficacy results from the multicenter, open-label, phase 2 registration trial of zanubrutinib. Patients (n = 86) received oral zanubrutinib 160 mg twice daily. The primary endpoint was the overall response rate (ORR), assessed per Lugano 2014. After a median follow-up of 35.3 months, the ORR was 83.7%, with 77.9% achieving complete response (CR); the median duration of response was not reached. Median progression-free survival (PFS) was 33.0 months (95% confidence interval [CI], 19.4-NE). The 36-month PFS and overall survival (OS) rates were 47.6% (95% CI, 36.2-58.1) and 74.8% (95% CI, 63.7-83.0), respectively. The safety profile was largely unchanged with extended follow-up. Most common (≥20%) all-grade adverse events (AEs) were neutrophil count decreased (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), white blood cell count decreased (33.7%), and platelet count decreased (32.6%); most were grade 1/2 events. Most common (≥10%) grade ≥3 AEs were neutrophil count decreased (18.6%) and pneumonia (12.8%). Rates of infection, neutropenia, and bleeding were highest in the first 6 months of therapy and decreased thereafter. No cases of atrial fibrillation/flutter, grade ≥3 cardiac AEs, second primary malignancies, or tumor lysis syndrome were reported. After extended follow-up, zanubrutinib demonstrated durable responses and a favorable safety profile in R/R MCL. The trial is registered at ClinicalTrials.gov as NCT03206970.

Enhanced light-matter interaction in two-dimensional transition metal dichalcogenides.

Two-dimensional (2D) transition metal dichalcogenide (TMDC) materials, such as MoS2, WS2, MoSe2, and WSe2, have received extensive attention in the past decade due to their extraordinary electronic, optical and thermal properties. They evolve from indirect bandgap semiconductors to direct bandgap semiconductors while their layer number is reduced from a few layers to a monolayer limit. Consequently, there is strong photoluminescence in a monolayer (1L) TMDC due to the large quantum yield. Moreover, such monolayer semiconductors have two other exciting properties: large binding energy of excitons and valley polarization. These properties make them become ideal materials for various electronic, photonic and optoelectronic devices. However, their performance is limited by the relatively weak light-matter interactions due to their atomically thin form factor. Resonant nanophotonic structures provide a viable way to address this issue and enhance light-matter interactions in 2D TMDCs. Here, we provide an overview of this research area, showcasing relevant applications, including exotic light emission, absorption and scattering features. We start by overviewing the concept of excitons in 1L-TMDC and the fundamental theory of cavity-enhanced emission, followed by a discussion on the recent progress of enhanced light emission, strong coupling and valleytronics. The atomically thin nature of 1L-TMDC enables a broad range of ways to tune its electric and optical properties. Thus, we continue by reviewing advances in TMDC-based tunable photonic devices. Next, we survey the recent progress in enhanced light absorption over narrow and broad bandwidths using 1L or few-layer TMDCs, and their applications for photovoltaics and photodetectors. We also review recent efforts of engineering light scattering, e.g., inducing Fano resonances, wavefront engineering in 1L or few-layer TMDCs by either integrating resonant structures, such as plasmonic/Mie resonant metasurfaces, or directly patterning monolayer/few layers TMDCs. We then overview the intriguing physical properties of different van der Waals heterostructures, and their applications in optoelectronic and photonic devices. Finally, we draw our opinion on potential opportunities and challenges in this rapidly developing field of research.

A two-part, single-arm, multicentre, phase I study of zanubrutinib, a selective Bruton tyrosine kinase inhibitor, in Chinese patients with relapsed/refractory B-cell malignancies.

This single-arm, multicentre, phase I study is the first study of zanubrutinib, a potent, specific, irreversible Bruton tyrosine kinase (BTK) inhibitor, in Chinese patients with relapsed/refractory B-cell malignancies. The objectives were to evaluate safety and preliminary anti-tumour activity. Forty-four patients received zanubrutinib 320 mg once daily (QD) (n = 10) or 160 mg twice daily (BID) (n = 34) until disease progression or unacceptable toxicity. 29.5% of patients received zanubrutinib for at least two years. The most common adverse event (AE) and the most common grade 3 or higher AE was neutrophil count decreased (54.5% and 25.0% respectively). Two patients (4.5%) discontinued treatment due to AEs and one treatment-emergent AE led to death. All haemorrhagic events were grade 1-2 (except for one non-serious grade 3 purpura). No second primary malignancies, tumour lysis syndrome, or atrial fibrillation/flutter occurred. The overall response rate was 52.3% (complete response rate, 18.2%). Patients with all cancer subtypes benefited from treatment. BTK C481S/R or L528W mutations were found in zanubrutinib-progressive patients. The safety/efficacy profiles of patients treated with 320 mg QD and 160 mg BID were comparable and similar daily area under the curve (AUC) was achieved. Overall, zanubrutinib was well tolerated and either of these two regimens is clinically practical. Registered at ClinicalTrials.gov (NCT03189524, on 16 June 2017, https://clinicaltrials.gov/ct2/show/NCT03189524).

Distinguishing Ultrafast Energy Transfer in Atomically Thin MoS2 /WS2 Heterostructures.

Van der Waals semiconducting heterostructures, known as stacks of atomically thin transition-metal dichalcogenide (TMD) layers, have recently been reported as new quantum materials with fascinating optoelectronic properties and novel functionalities. These discoveries are significantly related to the interfacial carrier dynamics of the excited states. Carrier dynamics have been reported to be predominantly driven by the ultrafast charge transfer (CT) process; however, the energy transfer (ET) process remains elusive. Herein, the ET process in MoS2 /WS2 heterostructures via transient absorption microscopy is reported. By analyzing the ultrafast dynamics using various MoS2 /WS2 interfaces, an ET rate of ≈240 fs is obtain, which is not trivial to the CT process. This study elucidates the role of the ET process in interfacial carrier dynamics and provides guidance for engineering interfaces for optoelectronic and quantum applications of TMD heterostructures.

Zanubrutinib for the treatment of patients with Waldenström macroglobulinemia: 3 years of follow-up.

Inhibitors of Bruton's tyrosine kinase (BTK) have established therapeutic activity in patients with Waldenström macroglobulinemia (WM). Zanubrutinib, a potent and selective BTK inhibitor, was evaluated in a phase 1/2 study in patients with WM who were either treatment-naïve (TN) or had relapsed/refractory (R/R) disease. Patients had disease requiring treatment per International Workshop on Waldenström Macroglobulinemia (IWWM) criteria. Treatment was 160 mg of oral zanubrutinib twice daily (n = 50) or 320 mg once daily (n = 23). Efficacy endpoints included overall response rate (ORR) and very good partial response/complete response (VGPR/CR) rates per IWWM-6 criteria (with modification of VGPR definition published previously). Between September 2014 and March 2018, 77 patients (24 TN and 53 R/R) began treatment. At a median follow-up of 36.0 months for patients with R/R disease and 23.5 months for TN, 72.7% remained on treatment. Reasons for treatment discontinuation included any adverse events in 13.0% of patients (1 treatment related), disease progression (10.4%), and other (3.9%). The ORR was 95.9%, and the VGPR/CR rate was 45.2%, which increased over time: 20.5% at 6 months, 32.9% at 12 months, and 43.8% at 24 months. Estimated 3-year progression-free survival rate was 80.5%, and overall survival rate was 84.8%. Adverse events of interest included contusion (32.5%, all grade 1), neutropenia (18.2%), major hemorrhage (3.9%), atrial fibrillation/flutter (5.2%), and grade 3 diarrhea (2.6%). Long-term treatment with single-agent zanubrutinib resulted in deep and durable responses in some patients with WM. The safety profile of long-term zanubrutinib therapy in these patients was acceptable. This trial was registered at www.clinicaltrials.gov as #NCT02343120.

Excitonic Dynamics in Janus MoSSe and WSSe Monolayers.

We report here details of steady-state and time-resolved spectroscopy of excitonic dynamics for Janus transition metal dichalcogenide monolayers, including MoSSe and WSSe, which were synthesized by low-energy implantation of Se into transition metal disulfides. Absorbance and photoluminescence spectroscopic measurements determined the room-temperature exciton resonances for MoSSe and WSSe monolayers. Transient absorption measurements revealed that the excitons in Janus structures form faster than those in pristine transition metal dichalcogenides by about 30% due to their enhanced electron-phonon interaction by the built-in dipole moment. By combining steady-state photoluminescence quantum yield and time-resolved transient absorption measurements, we find that the exciton radiative recombination lifetime in Janus structures is significantly longer than in their pristine samples, supporting the predicted spatial separation of the electron and hole wave functions due to the built-in dipole moment. These results provide fundamental insight in the optical properties of Janus transition metal dichalcogenides.

Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL.

Zanubrutinib is a potent and highly selective inhibitor of Bruton tyrosine kinase (BTK). In this first-in-human, open-label, multicenter, phase 1 study, patients in part 1 (3 + 3 dose escalation) had relapsed/refractory B-cell malignancies and received zanubrutinib 40, 80, 160, or 320 mg once daily or 160 mg twice daily. Part 2 (expansion) consisted of disease-specific cohorts, including treatment-naive or relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The primary end points were safety and tolerability, and definition of the maximum tolerated dose (part 1). Additional end points included pharmacokinetics/pharmacodynamics and preliminary efficacy. Reported herein are results from 144 patients enrolled in the dose-finding and CLL/SLL cohorts. No dose-limiting toxicities occurred in dose escalation. Median BTK occupancy in peripheral blood mononuclear cells was >95% at all doses. Sustained complete (>95%) BTK occupancy in lymph node biopsy specimens was more frequent with 160 mg twice daily than 320 mg once daily (89% vs 50%; P = .0342). Consequently, 160 mg twice daily was selected for further investigation. With median follow-up of 13.7 months (range, 0.4-30.5 months), 89 CLL/SLL patients (94.7%) remain on study. Most toxicities were grade 1/2; neutropenia was the only grade 3/4 toxicity observed in >2 patients. One patient experienced a grade 3 subcutaneous hemorrhage. Among 78 efficacy-evaluable CLL/SLL patients, the overall response rate was 96.2% (95% confidence interval, 89.2-99.2). Estimated progression-free survival at 12 months was 100%. Zanubrutinib demonstrated encouraging activity in CLL/SLL patients, with a low incidence of major toxicities. This trial was registered at www.clinicaltrials.gov as #NCT02343120.

Dense Electron-Hole Plasma Formation and Ultralong Charge Lifetime in Monolayer MoS2 via Material Tuning.

Many-body interactions in photoexcited semiconductors can bring about strongly interacting electronic states, culminating in the fully ionized matter of electron-hole plasma (EHP) and electron-hole liquid (EHL). These exotic phases exhibit unique electronic properties, such as metallic conductivity and metastable high photoexcitation density, which can be the basis for future transformative applications. However, the cryogenic condition required for its formation has limited the study of dense plasma phases to a purely academic pursuit in a restricted parameter space. This paradigm can potentially change with the recent experimental observation of these phases in atomically thin MoS2 and MoTe2 at room temperature. A fundamental understanding of EHP and EHL dynamics is critical for developing novel applications on this versatile layered platform. In this work, we studied the formation and dissipation of EHP in monolayer MoS2. Unlike previous results in bulk semiconductors, our results reveal that electromechanical material changes in monolayer MoS2 during photoexcitation play a significant role in dense EHP formation. Within the free-standing geometry, photoexcitation is accompanied by an unconstrained thermal expansion, resulting in a direct-to-indirect gap electronic transition at a critical lattice spacing and fluence. This dramatic altering of the material's energetic landscape extends carrier lifetimes by 2 orders of magnitude and allows the density required for EHP formation. The result is a stable dense plasma state that is sustained with modest optical photoexcitation. Our findings pave the way for novel applications based on dense plasma states in two-dimensional semiconductors.

Surface-enhanced Raman scattering of monolayer transition metal dichalcogenides on Ag nanorod arrays.

In this work, we studied surface-enhanced Raman scattering (SERS) of MS2 (M=Mo, W) monolayers that were transferred onto Ag nanorod arrays. Compared to the suspended monolayers, the Raman intensity of monolayers on an Ag nanorod substrate was strongly enhanced for both in-plane and out-of-plane vibration modes: up to 8 (5) for E2g and 20 (23) for A1g in MoS2 (WS2). This finding reveals a promising SERS substrate for achieving uniform and strong enhancement for two-dimensional materials in the applications of optical detecting and sensing.