First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study.

BACKGROUND: Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy. METHODS: This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov, NCT03191786. FINDINGS: Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4-11·9] vs 9·2 months [5·9-11·2]; stratified hazard ratio 0·78 [0·63-0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3-29·4) with atezolizumab compared with 12% (6·7-18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3-4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]). INTERPRETATION: First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy. FUNDING: F Hoffmann-La Roche and Genentech Inc, a member of the Roche group.

A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04).

OBJECTIVE: To evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer. METHODS: In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial (NCT04300647), patients with PD-L1-positive (SP263 tumor area positivity ≥5%) recurrent/persistent cervical cancer after 1-2 chemotherapy lines (≥1 platinum-based) were randomized 3:1 to atezolizumab 1200 mg with/without tiragolumab 600 mg every 3 weeks until disease progression or unacceptable toxicity. Stratification factors were performance status, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee-assessed confirmed objective response rate per RECIST v1.1 in patients receiving tiragolumab plus atezolizumab. An objective response rate ≥21% (one-sample z-test p≤0.0245) was required for statistical significance versus a historical reference. RESULTS: Protocol-defined independent review committee-assessed objective response rates were 19.0% (95% CI 12.6 to 27.0) in 126 patients receiving tiragolumab plus atezolizumab (p=0.0787 vs historical reference) and 15.6% (95% CI 6.5 to 29.5) in 45 atezolizumab-treated patients. Response rates were higher in PD-L1high (tumor area positivity ≥10%) than PD-L1low (tumor area positivity 5%-9%) subgroups with both regimens. At 8.5 months' median follow-up, independent review committee-assessed progression-free survival was 2.8 months (95% CI 1.7 to 4.1) with tiragolumab plus atezolizumab and 1.9 months (95% CI 1.5 to 3.0) with atezolizumab. In post hoc analyses (10.4 months' median follow-up), median overall survival was 11.1 months (95% CI 9.6 to 14.5) with the combination and 10.6 months (95% CI 6.9 to 13.8) with atezolizumab (crossover permitted). In the combination group, 3% of patients had adverse events requiring treatment discontinuation and 8% had grade ≥3 adverse events of special interest; corresponding values in the single-agent arm were 4% and 11%. There were no treatment-related deaths or new safety findings. CONCLUSION: The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

Generation and propagation properties of Bessel-Gaussian beams with a rotationally symmetric power-exponent-phase vortex.

In this paper, the generation and propagation properties of Bessel-Gaussian (BG) rotationally symmetric power-exponent-phase vortex beam (RSPEPVBs) were demonstrated and discussed. The results showed that the BG-RSPEPVBs can be directly generated based on the spatial light modulator, of which the phase singularities were verified by the interference patterns with the plane wave. It can be found that the intensity distributions of the BG-RSPEPVBs, with different topological charges (TCs) and power orders, were fan-shaped and polycyclic, which possessed the characteristics of BG beams and RSPEPVBs, simultaneously. Thus, the propagation invariance of the BG-RSPEPVBs is better than that of Laguerre-Gaussian RSPEPVBs and RSPEPVBs. Moreover, the focusing spot of the BG-RSPEPVBs would evolve into a bright ring with the same ring radius at the focal plane, which is independent of the TC and more suitable for the applications of optical coupling, optical communication, optical trapping, and so on.

Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study.

BACKGROUND: Targeted therapy and immunotherapy have shown intracranial activity in melanoma with CNS metastases, but there remains an unmet need, particularly for patients with symptomatic CNS metastases. We aimed to evaluate atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastases. METHODS: TRICOTEL was a multicentre, open-label, single-arm, phase 2 study done in two cohorts: a BRAFV600 wild-type cohort and a BRAFV600 mutation-positive cohort, recruited at 21 hospitals and oncology centres in Brazil, France, Germany, Hungary, Italy, Spain, and Switzerland. Eligible patients were aged 18 years or older with previously untreated metastatic melanoma, brain metastases of 5 mm or larger in at least one dimension, and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients in the BRAFV600 wild-type cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21). Patients in the BRAFV600 mutation-positive cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab was withheld in cycle 1. Treatment was continued until progression, toxicity, or death. The primary outcome was intracranial objective response rate confirmed by assessments at least 4 weeks apart, as assessed by independent review committee (IRC) using modified Response Evaluation Criteria in Solid Tumours version 1.1. Because of early closure of the BRAFV600 wild-type cohort, the primary endpoint of intracranial objective response rate by IRC assessment was not done in this cohort; intracranial objective response rate by investigator assessment was reported instead. Efficacy and safety were analysed in all patients who received at least one dose of study medication. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT03625141. FINDINGS: Between Dec 13, 2018, and Dec 7, 2020, 65 patients were enrolled in the BRAFV600 mutation-positive cohort; the BRAFV600 wild-type cohort was closed early after enrolment of 15 patients. Median follow-up was 9·7 months (IQR 6·3-15·0) for the BRAFV600 mutation-positive cohort and 6·2 months (3·5-23·0) for the BRAFV600 wild-type cohort. Intracranial objective response rate was 42% (95% CI 29-54) by IRC assessment in the BRAFV600 mutation-positive cohort and 27% (95% CI 8-55) by investigator assessment in the BRAFV600 wild-type cohort. Treatment-related grade 3 or worse adverse events occurred in 41 (68%) of 60 patients who received atezolizumab plus vemurafenib plus cobimetinib in the BRAFV600 mutation-positive cohort, the most common of which were lipase increased (15 [25%] of 60 patients) and blood creatine phosphokinase increased (11 [18%]). Eight (53%) of 15 patients treated with atezolizumab plus cobimetinib in the BRAFV600 wild-type cohort had treatment-related grade 3 or worse adverse events, most commonly anaemia (two [13%]) and dermatitis acneiform (two [13%]). Treatment-related serious adverse events occurred in 14 (23%) of 60 patients who received triplet therapy in the BRAFV600 mutation-positive cohort and two (13%) of 15 in the BRAFV600 wild-type cohort. No treatment-related deaths occurred. INTERPRETATION: Atezolizumab plus vemurafenib and cobimetinib provided intracranial activity in patients with BRAFV600-mutated melanoma with CNS metastases. FUNDING: F Hoffmann-La Roche.

Accurate method for correcting the translation position error of ptychography based on quantum particle swarm optimization.

In ptychography, the translation position error will cause the periodic grid deviation and tremendously decrease the reconstruction quality. It is crucial to attain the precise translation position of the probe with respect to the object. The current correction methods may fall into a local optimal value, and miss the better results. An accurate method based on the quantum particle swarm optimization is proposed to globally correct the translation position error and add the randomness to avoid trapping in local optimum. In our proposed method, particles in a quantum bound state can appear at any point in the solution space with a certain probability density. In order words, the corrected translation position can be spread over the searching space, which can acquire the possibility of jumping out of the local optimum. Experiments are conducted to verify that our proposed method can be used to enhance the correction accuracy of the translation position error as well as avoid local optimum.

Generation of rotationally symmetric power-exponent-phase vortex beams based on digital micromirror devices.

In this paper, what we believe to be a new method for the generation of rotationally symmetric power-exponent-phase vortex beams (RSPEPVBs) based on digital micromirror devices (DMD) was proposed and demonstrated. Based on the theory of binary amplitude holography and Lee method, the two-dimensional amplitude holograms for the generation of RSPEPVBs were obtained. Then, the experimental setup was established for the generation of RSPEPVBs based on DMD and to verify the phase structure of RSPEPVBs by the Mach-Zehnder interferometer. The experimental results showed that the RSPEPVBs can be generated based on DMD with high beam quality and stability, and the ±1st-order diffracted beams were respectively corresponding to the RSPEPVBs with contrary TCs, which was the first time to report the RSPEPVBs with negative TC. Besides, the overall and ±1st-order diffraction efficiencies of RSPEPVBs generated by DMD were 7.18% and 1.73%, respectively. The method can be applied for the generation of RSPEPVBs with different parameters and quickly achieve mode switching by loading different binary amplitude holograms, which provides a new choice for the generation of new structure beams based on DMD.

Experimental and numerical study of multi-pulse picosecond laser ablation on 316†L stainless steel.

An experimental and numerical study on 10 ps laser ablation of 316 L stainless steel up to 400 hundred pulse exposure has been carried out. In this simulation, the material removal threshold temperature has been carefully discussed depending on the different ablation driving mechanisms. The influence of the instantaneous material removal has also been considered which will affect the calculation of the next pulse's absorption. For single-pulse ablation, the simulated ablation threshold Fsim = 0.26 J/cm2 is close to the fitted experimental result F0th = (0.29 ± 0.01) J/cm2. For multi-pulse ablation, the simulated ablation rate Rsim = 11.4 nm/pulse is close to the fitted experimental result Rexp = (12.4 ± 0.1) nm/pulse under 0.9 J/cm2 fluence, while the simulated ablation rate Rsim = 19.8 nm/pulse is slightly larger than the fitted experimental result Rexp = (16.1 ± 0.7) nm/pulse at 2.7 J/cm2, providing good agreement between theory and experiment for both single and multi-pulse ablation. This study could be used to predict the multi-pulse laser processing performance, especially with the help of a machine learning method to find the best parameters automatically.

Enhancement of the phase sensitivity with two-mode squeezed coherent state based on a Mach-Zehnder interferometer.

We theoretically study the phase estimation based on a Mach-Zehnder interferometer (MZI) with a two-mode squeezed coherent state. By maximizing the quantum Fisher information, we find that the quantum Cramér-Rao bounds (QCRB) can reach sub-Heisenberg limit under the phase-matched condition. The optimal phase sensitivity can reach the sub-shot noise limit (SNL) and approach the QCRB by employing the intensity difference detection. Meanwhile, compared with the MZI fed with a coherent plus a single-mode squeezed vacuum state, this scheme can have better performance by adjusting the squeezing parameter and the mean photon number. With the same parameter, our scheme shows more sensitive phase measurement than the SU(1,1) interferometer with a coherent plus a vacuum state. We also show that the phase sensitivity of our proposal can still reach the SNL when the loss of the photon is 36%. This scheme can provide potential applications in optical sensors.

Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study.

BACKGROUND: Targeted therapy and immunotherapy have shown intracranial activity in melanoma with CNS metastases, but there remains an unmet need, particularly for patients with symptomatic CNS metastases. We aimed to evaluate atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastases. METHODS: TRICOTEL was a multicentre, open-label, single-arm, phase 2 study done in two cohorts: a BRAFV600 wild-type cohort and a BRAFV600 mutation-positive cohort, recruited at 21 hospitals and oncology centres in Brazil, France, Germany, Hungary, Italy, Spain, and Switzerland. Eligible patients were aged 18 years or older with previously untreated metastatic melanoma, CNS metastases of 5 mm or larger in at least one dimension, and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients in the BRAFV600 wild-type cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21). Patients in the BRAFV600 mutation-positive cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab was withheld in cycle 1. Treatment was continued until progression, toxicity, or death. The primary outcome was intracranial objective response rate confirmed by assessments at least 4 weeks apart, as assessed by independent review committee (IRC) using modified Response Evaluation Criteria in Solid Tumours version 1.1. Because of early closure of the BRAFV600 wild-type cohort, the primary endpoint of intracranial objective response rate by IRC assessment was not done in this cohort; intracranial objective response rate by investigator assessment was reported instead. Efficacy and safety were analysed in all patients who received at least one dose of study medication. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT03625141. FINDINGS: Between Dec 13, 2018, and Dec 7, 2020, 65 patients were enrolled in the BRAFV600 mutation-positive cohort; the BRAFV600 wild-type cohort was closed early after enrolment of 15 patients. Median follow-up was 9·7 months (IQR 6·3-15·0) for the BRAFV600 mutation-positive cohort and 6·2 months (3·5-23·0) for the BRAFV600 wild-type cohort. Intracranial objective response rate was 42% (95% CI 29-54) by IRC assessment in the BRAFV600 mutation-positive cohort and 27% (95% CI 8-55) by investigator assessment in the BRAFV600 wild-type cohort. Treatment-related grade 3 or worse adverse events occurred in 41 (68%) of 60 patients who received atezolizumab plus vemurafenib plus cobimetinib in the BRAFV600 mutation-positive cohort, the most common of which were lipase increased (15 [25%] of 60 patients) and blood creatine phosphokinase increased (ten [17%]). Eight (53%) of 15 patients treated with atezolizumab plus cobimetinib in the BRAFV600 wild-type cohort had treatment-related grade 3 or worse adverse events, most commonly anaemia (two [13%]) and dermatitis acneiform (two [13%]). Treatment-related serious adverse events occurred in 14 (23%) of 60 patients in the BRAFV600 mutation-positive cohort and two (13%) of 15 in the BRAFV600 wild-type cohort. One death in the BRAFV600 mutation-positive cohort (limbic encephalitis) was considered to be related to atezolizumab treatment. INTERPRETATION: Adding atezolizumab to vemurafenib plus cobimetinib provided promising intracranial activity in patients with BRAFV600-mutated melanoma with CNS metastases. FUNDING: F Hoffmann-La Roche.

Influences of salinity and temperature on propagation of radially polarized rotationally-symmetric power-exponent-phase vortex beams in oceanic turbulence.

In this paper, the propagation properties of radially polarized rotationally-symmetric power-exponent-phase vortex beams (RP-RSPEPVBs) in oceanic turbulence were theoretically and experimentally studied. Based on the extended Huygens-Fresnel diffraction integral and vector beams theories, the theoretical propagation model of RP-RSPEPVBs in the oceanic turbulence was established. Then, the numerical simulations were carried out to study the influences of the propagation distance z, the rate of dissipation of turbulence kinetic energy per unit mass of fluid ε, the temperature-salinity contribution ratio ω, and the dissipation rate of the mean-squared temperature χT on the optical intensity, spectral degree of polarization (DOP) and spectral degree of coherence (DOC) of RP-RSPEPVBs. Further, an experiment setup was demonstrated to confirm the influences of salinity and temperature on propagation of RP-RSPEPVBs in oceanic turbulence. The results showed that increasing salinity, propagation distance, and turbulence intensity, will result in beam diffusion and intensity reduction of the RP-RSPEPVBs, as well as depolarization and decoherence. Contrarily, high temperature mitigated the intensity loss of the RP-RSPEPVBs and the spectral DOP and spectral DOC increased when the turbulence tends to be dominated by temperature. As a vector beam, the RP-RSPEPVB shows well anti-turbulence interference characteristics, which provides a new choice for optical underwater communication and imaging.

Optical trapping of multiple particles based on a rotationally-symmetric power-exponent-phase vortex beam.

In this paper, the optical trapping of multiple particles based on a rotationally-symmetric power-exponent-phase vortex beam (RSPEPVB) was introduced and demonstrated. Based on the theories of tight focusing and optical force, the optical force model of RSPEPVB was established to analyze the optical trapping force of tightly focused RSPEPVB. Then, an experimental setup of optical tweezer, by utilizing the RSPEPVB, was built to demonstrate that the optical tweezer of RSPEPVBs can achieve the optical trapping of multiple particles, and the number of captured particles is equal to the topological charge l of RSPEPVB, which shows that the RSPEPVBs can achieve multi-particles trapping with controllable number. Moreover, compared to vortex beam, the captured particles by RSPEPVB will not rotate around the circular light intensity distribution. The results will provide a new option for optical trapping of multiple particles in biomedicine, laser cooling and so on.

Controlled generation of mode-switchable nanosecond pulsed vector vortex beams from a Q-switched fiber laser.

We reported and demonstrated a ring Q-switched Ytterbium-doped fiber laser that can generate mode-switchable nanosecond pulsed vector vortex beams between two different orders. In the spatial optical path of the fiber laser, several cascaded Q-plates, divided into two Q-plate groups, are applied for intracavity mode conversion between LP01 mode and vector vortex beams. In one Q-plate group, two quarter-wave plates are inserted to achieve the addition and subtraction of the order of Q-plates. By tuning the polarization state in the cavity, mode-switchable vector vortex beams (VVBs), including cylindrical vector beams (CVBs), elliptically polarized cylindrical vector beams (EPCVBs), and vortex beams, of two different orders can be generated on demand. The experimental results show that by using the group of 1st and 3rd orders Q-plates, the 2nd and 4th orders mode-switchable VVBs (vortex beams with topological charges of ±2, ±4, CVBs and EPCVBs of 2nd- and 4th-order) can be obtained from the fiber laser. The slope efficiency, pulse width, and repetition rate are 33.4%, 360 ns, and 241kHz respectively. To the best of our knowledge, this is the first time to realize the direct generation of mode-switchable VVBs on the arbitrary position of the higher-order Poincaré sphere between two different orders from a fiber laser. This work lays the foundation for the flexible generation of arbitrary modes of VVBs with multiple different orders in the laser cavity.

Dual-metal-driven Selective Pathway of Nitrogen Reduction in Orderly Atomic-hybridized Re2MnS6 Ultrathin Nanosheets.

The future of sustainable fertilizers and carbon-free energy carrier demands innovative breakthroughs in the exploitation of efficient electrocatalysts for synthesizing ammonia (NH3) from nitrogen (N2) in mild conditions. Understanding and regulating the reaction intermediates that form on the catalyst surface through careful catalyst design could bypass certain limitations associated with ambiguous adsorbate evolution mechanism. Herein, we propose ternary intermetallic Re2MnS6 ultrathin nanosheets that include orderly hybridized Mn-Re dual-metal sites through strong Hubbard e-e interaction, demonstrating a promising selectivity toward reaction process from N2 to NH3. The ordered inclusion of Mn sites leads to a structural phase transition and appearance of nonbonding semimetal states, in which the rate-limiting activation energy barrier is significantly decreased through a conversion in reaction pathway. As a result, the performance of N2 reduction in Re2MnS6 is increased about 6.6 times compared to the single-metal ReS2.

Accelerated convergence extended ptychographical iterative engine using multiple axial intensity constraints.

The extended ptychographical iterative engine (ePIE) is widely applied in the field of ptychographic imaging due to its great flexibility and computational efficiency. A technique of ePIE with multiple axial intensity constraints, which is called MAIC-PIE, is proposed to drastically improve the convergence speed and reduce the calculation time. This technique requires that the diffracted light from the sample is propagated to the multiple individual axial planes, which can be achieved by using the beam splitter and multiple CCDs. In this technique, an additional intensity constraint is involved in the iterative process that makes for building the reasonable guesses of the probe and object in the first few iterations and accelerating the convergence. Simulations and experiments have verified that MAIC-PIE behaves good performance with fast convergence. The great performance and limited computational complexity make it a very attractive and promising technique for ptychographic imaging.

Vectorial eigenvector method for simulating the polarization dependent resonator.

Derived from the eigenvector method (EM), a vectorial eigenvector method (VEM) for the mode calculation of polarization dependent resonator is presented. New transfer matrices of laser resonant cavities with polarization-selective devices are built by using Jones matrix representation. The eigenvectors computed by solving the matrix eigenequation manifest the mode characteristics of resonators, including cylindrical vector (CV) modes. Comparing with EM, the VEM inherits EM's superiorities and extends scalar models to vector models. Then, an example utilizing VEM to simulate axicon mirror resonator was given, which proved the VEM feasible and efficacious. Finally, upon a fast axial flow (FAT) CO2 laser with an axicon mirror as rear mirror, we experimentally corroborated the validity of the VEM and a working-stable 1.5 kW radially polarized beam was obtained.

1.5 kW radially polarized beam irradiated from a FAF CO2 laser based on an intracavity triple-axicon retroreflector and quarter wave phase retarders.

In this paper, a three folds spatial resonator composed of a triple-axicon retroreflector and four pieces of quarter wave phase retarder is demonstrated to directly output radially polarized beams in a fast axial flow (FAF) CO2 laser system. The triple-axicon retroreflector serves as the azimuthally polarized beams' selective element, and the quarter wave phase retarders convert the azimuthally polarized beams to radially polarized beams. Finally, a stable 1.5 kW radially polarized beam is generated in this laser system.

Unveiling different antibiotic degradation mechanisms on dual reaction center catalysts with nitrogen vacancies via peroxymonosulfate activation.

Metal-nitrogen-site catalysts are widely recognized as effective heterogeneous catalysts in peroxymonosulfate (PMS)-based advanced oxidation processes. However, the selective oxidation mechanism for organic pollutants is still contradictory. In this work, manganese-nitrogen active centers and tunable nitrogen vacancies were synchronously constructed on graphitic carbon nitride (LMCN) through l-cysteine-assisted thermal polymerization to reveal different antibiotic degradation mechanisms. Benefiting from the synergism of manganese-nitrogen bond and nitrogen vacancies, the LMCN catalyst exhibited excellent catalytic activity for the degradation of tetracycline (TC) and sulfamethoxazole (SMX) antibiotics with first-order kinetic rate constants of 0.136 min-1 and 0.047 min-1, which were higher than those of other catalysts. Electron transfer dominated TC degradation at low redox potentials, while electron transfer and high-valent manganese (Mn (V)) were responsible for SMX degradation at high redox potentials. Further experimental studies unveiled that the pivotal role of nitrogen vacancies is to promote electron transfer pathway and Mn(V) generation, while nitrogen-coordinated manganese as the primary catalytic active site determines Mn(V) generation. In addition, the antibiotic degradation pathways were proposed and the toxicity of byproducts was analyzed. This work provides an inspiring idea for the controlled generation of reactive oxygen species by targeted activation of PMS.

Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab.

Introduction: In the Phase 3 IMbrave150 trial (NCT03434379), atezolizumab + bevacizumab demonstrated a clinically meaningful survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (HCC), including those with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. We used IMbrave150 data to investigate the safety and risk of viral reactivation or flare in infected patients treated with atezolizumab + bevacizumab or sorafenib. Methods: Patients with unresectable HCC not previously treated with systemic therapy were randomized 2:1 to atezolizumab + bevacizumab or sorafenib. In this exploratory analysis, safety was continually evaluated, including for hepatic adverse events. Patients were monitored for HBV and HCV reactivation and flare at screening, the beginning of Cycles 5 and 9, and at treatment discontinuation. Results: Of 501 enrolled patients, 485 were included in the safety population; 329 (68%) received atezolizumab + bevacizumab, and 156 (32%) received sorafenib. Overall, 150 (31%) and 58 (12%) patients had HBV and HCV infections, respectively. The safety profiles of atezolizumab + bevacizumab and sorafenib were consistent across patients, regardless of viral infection. Overall, hepatic serious adverse events occurred in 11% of patients receiving atezolizumab + bevacizumab and 8% receiving sorafenib. HBV or HCV reactivation occurred in 2% or 16% of atezolizumab + bevacizumab-treated patients, respectively, versus 7% or 14% with sorafenib. There were no instances of hepatitis flare with atezolizumab + bevacizumab. Conclusions: Atezolizumab + bevacizumab had a similar hepatic safety profile in patients with and without HBV or HCV infection. Viral reactivation rates were similar between arms. Overall, these data support the use of atezolizumab + bevacizumab in patients with HCC and HBV or HCV infection without any special precaution.

In situ anchoring strategy to enhance dual nonradical degradation of sulfamethoxazole with high loading manganese doped carbon nitride.

A low-cost catalyst with high metal loading and unique catalytic activities is highly desired for peroxymonosulfate (PMS) activation in environmental remediation. Herein, in situ anchoring strategy using 1,10-phenanthroline is reported to construct manganese doped carbon nitride (PMCN) with 8.2 wt% manganese loading and dramatically enhanced PMS adsorption and sulfamethoxazole (SMX) removal efficiency. Our study revealed that the PMCN/PMS system readily reacted with contaminants with electron-rich groups, where complete degradation of sulfamethoxazole (SMX) was achieved within 60 min. Combining quenching experiments, EPR tests, and electrochemical analysis, we proposed a dual nonradical pathway dominated by high-valent manganese oxygen species (Mn(V) = O) and electron transfer. Systematic investigation elucidated that the introduction of 1,10-phenanthroline constructed denser catalyst active sites, and identified the manganese center and pyridine nitrogen as the active sites for PMS activation. Furthermore, PMCN exhibited excellent pH anti-interference ability and good reusability, achieving more than 90% SMX degradation efficiency after four cycles. This study provides new insights into the regulation of Mn-N active sites and promotes the mechanistic understanding of the synergistic effect of manganese and pyridine nitrogen in PMS activation.

Efficient degradation of aqueous organic contaminants in manganese(II)/peroxymonosulfate system assisted by pyridine organic ligands.

Although manganese(II) is known to have no role in peroxymonosulfate (PMS) activation, through a series of sulfamethoxazole (SMX) oxidation experiments, we found that the addition of pyridine organic ligands can improve the catalytic activity and accelerate SMX oxidation. For the organic ligands to be effective: the stability constant of the Mn(III) complex should be higher than that of the Mn(II) complex. A positive correlation was observed between the SMX oxidation rate and Mn(II) concentration, and the maximum PMS utilization efficiency was achieved. Many shreds of evidence verified that neither •SO4- nor •OH was associated with SMX oxidation. The enhanced effect of phenanthroline on the Mn(II)/PMS system was attributed to the highly oxidative intermediate manganese species (Mn(V)), originating from the two-electron transfer reaction of complexed Mn(III) and PMS. Notably, the main oxidizing species did not change (η-(PMSO2) âˆ¼ 100%) regardless of the initial PMSO concentration or pH value. Additionally, the analysis of SMX degradation products revealed that the oxygen transfer oxidation pathway was dominant in the Mn(II)/phenanthroline/PMS system, while the N radical coupling pathway also contributed significantly to SMX oxidation. This work offers new insights into the formation of high-valent manganese species and provides a potential strategy for applying low-concentration Mn(II) to wastewater treatment.