Comparison of neoadjuvant chemotherapy or chemoradiotherapy plus immunotherapy for locally resectable esophageal squamous cell carcinoma.

Background: Neoadjuvant chemotherapy plus immunotherapy (nCT + ICIs) and neoadjuvant chemoradiotherapy plus immunotherapy (nCRT + ICIs) both induced favorable pathological response and tolerant toxicities for locally resectable esophageal squamous cell carcinoma (ESCC). However, few studies compared safety and efficacy between the two treatment strategies. Methods: This retrospective study collected clinical data of locally resectable ESCC patients who underwent nCT + ICIs or nCRT + ICIs followed by esophagectomy from November 2019 to December 2022. The incidence of adverse events, surgical outcomes, short and long-term efficacy, and treatment costs were compared. Results: A total of 206 patients were included, with a ratio of 158:48 between nCT + ICIs group and nCRT + ICIs group. The two groups exhibited well-balanced baseline characteristics. Most adverse events were grade 1-2 in both groups. The nCT + ICIs group had a longer operative time (334.00 ± 170.2 min vs 279.60 ± 88.31 min, P=0.020) than nCRT + ICIs group, but there were no differences in surgical complications. Although nCT + ICIs group had a lower pCR rate (32.3% vs 52.1%, P=0.004), the 2-year overall survival (84.42% vs 81.70%, P=0.860), 2-year disease-free survival (83.21% vs 80.47%, P=0.839), and recurrence patterns were similar to nCRT + ICIs group. In addition, nCT + ICIs group had significantly lower expenses (188796.00 ± 107704.00 RMB vs 231808.00 ± 48067.00 RMB, P=0.045). Conclusion: Overall, nCT + ICIs have comparable safety and efficacy compared to nCRT + ICIs for locally resectable ESCC, but with lower hospitalization costs.

Reconfigurable optoelectronic transistors for multimodal recognition.

Biological nervous system outperforms in both dynamic and static information perception due to their capability to integrate the sensing, memory and processing functions. Reconfigurable neuromorphic transistors, which can be used to emulate different types of biological analogues in a single device, are important for creating compact and efficient neuromorphic computing networks, but their design remains challenging due to the need for opposing physical mechanisms to achieve different functions. Here we report a neuromorphic electrolyte-gated transistor that can be reconfigured to perform physical reservoir and synaptic functions. The device exhibits dynamics with tunable time-scales under optical and electrical stimuli. The nonlinear volatile property is suitable for reservoir computing, which can be used for multimodal pre-processing. The nonvolatility and programmability of the device through ion insertion/extraction achieved via electrolyte gating, which are required to realize synaptic functions, are verified. The device's superior performance in mimicking human perception of dynamic and static multisensory information based on the reconfigurable neuromorphic functions is also demonstrated. The present study provides an exciting paradigm for the realization of multimodal reconfigurable devices and opens an avenue for mimicking biological multisensory fusion.

High-performance terahertz modulators induced by substrate field in Te-based all-2D heterojunctions.

High-performance active terahertz modulators as the indispensable core components are of great importance for the next generation communication technology. However, they currently suffer from the tradeoff between modulation depth and speed. Here, we introduce two-dimensional (2D) tellurium (Te) nanofilms with the unique structure as a new class of optically controlled terahertz modulators and demonstrate their integrated heterojunctions can successfully improve the device performances to the optimal and applicable levels among the existing all-2D broadband modulators. Further photoresponse measurements confirm the significant impact of the stacking order. We first clarify the direction of the substrate-induced electric field through first-principles calculations and uncover the unusual interaction mechanism in the photoexcited carrier dynamics associated with the charge transfer and interlayer exciton recombination. This advances the fundamental and applicative research of Te nanomaterials in high-performance terahertz optoelectronics.

Interface-type tunable oxygen ion dynamics for physical reservoir computing.

Reservoir computing can more efficiently be used to solve time-dependent tasks than conventional feedforward network owing to various advantages, such as easy training and low hardware overhead. Physical reservoirs that contain intrinsic nonlinear dynamic processes could serve as next-generation dynamic computing systems. High-efficiency reservoir systems require nonlinear and dynamic responses to distinguish time-series input data. Herein, an interface-type dynamic transistor gated by an Hf0.5Zr0.5O2 (HZO) film was introduced to perform reservoir computing. The channel conductance of Mott material La0.67Sr0.33MnO3 (LSMO) can effectively be modulated by taking advantage of the unique coupled property of the polarization process and oxygen migration in hafnium-based ferroelectrics. The large positive value of the oxygen vacancy formation energy and negative value of the oxygen affinity energy resulted in the spontaneous migration of accumulated oxygen ions in the HZO films to the channel, leading to the dynamic relaxation process. The modulation of the channel conductance was found to be closely related to the current state, identified as the origin of the nonlinear response. In the time series recognition and prediction tasks, the proposed reservoir system showed an extremely low decision-making error. This work provides a promising pathway for exploiting dynamic ion systems for high-performance neural network devices.

Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial.

BACKGROUND: Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indicating that a short course of treatment may not be sufficient. Therefore, exploring the effects of intensive treatment is needed for optimal clinical outcomes. METHODS: Locally advanced ESCC patients were administered three cycles of camrelizumab plus nab-paclitaxel and capecitabine, followed by thoracoscopic esophagectomy. The primary endpoint was pathologic response. Secondary endpoints included safety, feasibility, radiologic response, survival outcomes, and immunologic/genomic correlates of efficacy. RESULTS: Forty-seven patients were enrolled in the study. Forty-two patients received surgery, and R0 resection was achieved in all cases. The complete and major pathological response rates were 33.3% and 64.3%, respectively, and the objective response rate was 80.0%. Three cycles of treatment significantly improved T down-staging compared to two cycles (P = 0.03). The most common treatment-related adverse events were grades 1-2, and no surgical delay was reported. With a median follow-up of 24.3 months, the 1-year disease-free survival and overall survival rates were both 97.6%, and the 2-year disease-free survival and overall survival rates were 92.3% and 97.6%, respectively. Three patients experienced disease recurrence or metastasis ranging from 12.5 to 25.8 months after surgery, and one patient died 6 months after surgery due to cardiovascular disease. Neither programmed death-ligand 1 expression nor tumor mutational burden was associated with pathological response. An increased infiltration of CD56dim natural killer cells in the pretreatment tumor was correlated with better pathological response in the primary tumor. CONCLUSIONS: It seems probable that intensive cycles of neoadjuvant camrelizumab plus nab-paclitaxel and capecitabine increased tumor regression and improved survival outcomes. Randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029807, Registered February 14, 2020, https://www.chictr.org.cn/showproj.aspx?proj=49459 .

Photoinduced Phase Transition in Infinite-Layer Nickelates.

The quantum phase transition caused by regulating the electronic correlation in strongly correlated quantum materials has been a research hotspot in condensed matter science. Herein, a photon-induced quantum phase transition from the Kondo-Mott insulating state to the low temperature metallic one accompanying with the magnetoresistance changing from negative to positive in the infinite-layer NdNiO2 films is reported, where the antiferromagnetic coupling among the Ni1+ localized spins and the Kondo effect are effectively suppressed by manipulating the correlation of Ni-3d and Nd-5d electrons under the photoirradiation. Moreover, the critical temperature Tc of the superconducting-like transition exhibits a dome-shaped evolution with the maximum up to ≈42 K, and the electrons dominate the transport process proved by the Hall effect measurements. These findings not only make the photoinduction a promising way to control the quantum phase transition by manipulating the electronic correlation in Mott-like insulators, but also shed some light on the possibility of the superconducting in electron-doped nickelates.

Magnetoelectric coupling in multiferroics probed by optical second harmonic generation.

Magnetoelectric coupling, as a fundamental physical nature and with the potential to add functionality to devices while also reducing energy consumption, has been challenging to be probed in freestanding membranes or two-dimensional materials due to their instability and fragility. In this paper, we report a magnetoelectric coupling probed by optical second harmonic generation with external magnetic field, and show the manipulation of the ferroelectric and antiferromagnetic orders by the magnetic and thermal fields in BiFeO3 films epitaxially grown on the substrates and in the freestanding ones. Here we define an optical magnetoelectric-coupling constant, denoting the ability of controlling light-induced nonlinear polarization by the magnetic field, and found the magnetoelectric-coupling was suppressed by strain releasing but remain robust against thermal fluctuation for freestanding BiFeO3.

Reversible fatigue-rejuvenation procedure and its mechanism in Hf0.5Zr0.5O2epitaxial films.

HfO2-based ferroelectrics, such as Hf0.5Zr0.5O2, arouse great attention in recent years because of their CMOS compatibility and robust nano-scale ferroelectricity. However, fatigue is one of the toughest problems for ferroelectric applications. The fatigue mechanism of HfO2-based ferroelectrics is different from conventional ferroelectric materials, and research on the fatigue mechanism in HfO2-based epitaxial films have been rarely reported. In this work, we fabricate 10 nm Hf0.5Zr0.5O2epitaxial films and investigate the fatigue mechanism. The experimental data show that the remanent ferroelectric polarization value decreased by 50% after 108cycles. It is worth noting that the fatigued Hf0.5Zr0.5O2epitaxial films can be recovered through applying electric stimulus. Combined with the temperature-dependent endurance analysis, we propose that fatigue of our Hf0.5Zr0.5O2films comes from both phase transition between ferroelectric Pca21and antiferroelectric Pbca as well as defects generation and dipole pinned. This result offers a fundamental understanding of HfO2-based film system, and could provide an important guideline for subsequent studies and future applications.

Are more courses of immunochemotherapy beneficial for the short-term outcome of locally advanced esophageal squamous cell carcinoma?

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy and neoadjuvant immunochemotherapy have shown promising results in esophageal carcinoma. However, it is still unclear whether more courses of immunochemotherapy are therapeutically better. We aimed to investigate the safety and efficacy of three courses of neoadjuvant treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC received three courses of camrelizumab plus nab-paclitaxel and capecitabine before undergoing surgery. Additionally, patients received safety, computed tomography (CT), and endoscopy (with endoscopic ultrasonography and mucosal biopsy) assessments before and in the second and third courses of treatment. We used the CT and endoscopic assessment results from the second and third courses for comparison. RESULTS: From May 2020 to December 2021, 47 patients were enrolled at Sun Yat-sen University Cancer Center. In our study, 43 patients completed three courses of preoperative chemotherapy combined with anti-Programmed cell death-1 (PD-1) therapy and radical surgical resection. The toxicity of the third course of immunochemotherapy was mild and well tolerated without increased treatment-related adverse events (TRAEs) and mortality compared with that of the second course of treatment. In terms of efficacy, an additional course of treatment after the second course of treatment was effective, with increased CT and endoscopy T (clinical T stage) downstaging rates by 16.3% and 25.9%, N (clincial N stage) downstaging rates by 7.0% and 11.1%, and objective response rates (ORRs) by 13.6% and 22.0%, respectively. CONCLUSIONS: Regardless of downstaging or ORR, three courses of immunochemotherapy appear to be superior to two courses of treatment without increasing TRAEs.

Manipulating the electronic structure and physical properties in monolayer Mo2I3Br3via strain and doping.

Identifying new two-dimensional intrinsic ferromagnets with high transition temperatures is a key step of improving device performance. Here we used first-principles calculations to demonstrate that the monolayer Janus Mo2I3Br3 is an intrinsic ferromagnetic bipolar semiconductor with a large out-of-plane spin orientation. The calculated phonon dispersion and ab initio molecular dynamic simulations indicate the stability dynamically and thermally. Furthermore, we investigated the effect of electrostatic doping or in-plane biaxial strain on the electronic structures and magnetic and optical properties of monolayer Mo2I3Br3. We find that the magnetic anisotropy energy and Curie temperature are enhanced more than 4 and 2 times with the hole doping compared with those in the pristine monolayer Mo2I3Br3, respectively. The calculated electronic structures show that the stable half-metallic states are formed by electron or hole doping due to the strong spin polarization of the electronic states around the Fermi level. Furthermore, the spin orientation in the metallic channel of the doped monolayer Mo2I3Br3 can be flipped with the increase of electron doping concentration. In addition, the magnetic anisotropy energy and Curie temperature can also be effectively manipulated by in-plane biaxial strain. The spin polarization of the conduction band minimum can be reversed by the tensile strain of 3% for the monolayer Mo2I3Br3, transforming it into an indirect band gap semiconductor. Finally, the calculated large and tunable optical absorption coefficient indicates that monolayer Mo2I3Br3 is a promising candidate for potential optoelectronic applications. Our results may open up more opportunities for few-layer van der Waals crystals in magnetic storage, spintronics, and optoelectronic devices.

Photo-induced non-volatile VO2 phase transition for neuromorphic ultraviolet sensors.

In the quest for emerging in-sensor computing, materials that respond to optical stimuli in conjunction with non-volatile phase transition are highly desired for realizing bioinspired neuromorphic vision components. Here, we report a non-volatile multi-level control of VO2 films by oxygen stoichiometry engineering under ultraviolet irradiation. Based on the reversible regulation of VO2 films using ultraviolet irradiation and electrolyte gating, we demonstrate a proof-of-principle neuromorphic ultraviolet sensor with integrated sensing, memory, and processing functions at room temperature, and also prove its silicon compatible potential through the wafer-scale integration of a neuromorphic sensor array. The device displays linear weight update with optical writing because its metallic phase proportion increases almost linearly with the light dosage. Moreover, the artificial neural network consisting of this neuromorphic sensor can extract ultraviolet information from the surrounding environment, and significantly improve the recognition accuracy from 24% to 93%. This work provides a path to design neuromorphic sensors and will facilitate the potential applications in artificial vision systems.

Large-Scale Hf0.5 Zr0.5 O2 Membranes with Robust Ferroelectricity.

Hafnia-based compounds have considerable potential for use in nanoelectronics due to their compatibility with complementary metal-oxide-semiconductor devices and robust ferroelectricity at nanoscale sizes. However, the unexpected ferroelectricity in this class of compounds often remains elusive due to the polymorphic nature of hafnia, as well as the lack of suitable methods for the characterization of the mixed/complex phases in hafnia thin films. Herein, the preparation of centimeter-scale, crack-free, freestanding Hf0.5 Zr0.5 O2 (HZO) nanomembranes that are well suited for investigating the local crystallographic phases, orientations, and grain boundaries at both the microscopic and mesoscopic scales is reported. Atomic-level imaging of the plan-view crystallographic patterns shows that more than 80% of the grains are the ferroelectric orthorhombic phase, and that the mean equivalent diameter of these grains is about 12.1 nm, with values ranging from 4 to 50 nm. Moreover, the ferroelectric orthorhombic phase is stable in substrate-free HZO membranes, indicating that strain from the substrate is not responsible for maintaining the polar phase. It is also demonstrated that HZO capacitors prepared on flexible substrates are highly uniform, stable, and robust. These freestanding membranes provide a viable platform for the exploration of HZO polymorphic films with complex structures and pave the way to flexible nanoelectronics.

Ferroelectric Proximity Effect and Topological Hall Effect in SrRuO3/BiFeO3 Multilayers.

Interfaces between complex oxides provide a unique opportunity to discover novel interfacial physics and functionalities. Here, we fabricate the multilayers of itinerant ferromagnet SrRuO3 (SRO) and multiferroic BiFeO3 (BFO) with atomically sharp interfaces. Atomically resolved transmission electron microscopy reveals that a large ionic displacement in BFO can penetrate into SRO layers near the BFO/SRO interfaces to a depth of 2-3 unit cells, indicating the ferroelectric proximity effect. A topological Hall effect is indicated by hump-like anomalies in the Hall measurements of the multilayer with a moderate thickness of the SRO layer. With magnetic measurements, it can be further confirmed that each SRO layer in the multilayers can be divided into interfacial and middle regions, which possess different magnetic ground states. Our work highlights the key role of functional heterointerfaces in exotic properties and provides an important guideline to design spintronic devices based on magnetic skyrmions.

Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Immunotherapy is effective in treating unresectable esophageal squamous cell carcinoma (ESCC), but little is known about its role in the preoperative setting. The aim of this study was to evaluate the safety, feasibility and efficacy of neoadjuvant treatment with camrelizumab plus chemotherapy in locally advanced ESCC. METHODS: Patients diagnosed with locally advanced ESCC were retrospectively included if they had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy between November, 2019 and June, 2020 at Sun Yat-sen University Cancer Center. Primary endpoints were safety and feasibility. In addition, pathological response and the relationship between tumor immune microenvironment (TIME)/tumor mutational burden (TMB) and treatment response were also investigated. RESULTS: Twelve patients were included and they all received three courses of preoperative treatment with camrelizumab plus nab-paclitaxel/S1. No grade 3 or higher toxicities occurred. No surgical delay or perioperative death was reported. Nine patients (75%) responded to the treatment, four with a complete pathological response (pCR) and five with a major pathological response (MPR). Neither programmed death-ligand 1 (PD-L1) expression nor TMB was correlated with treatment response. TIME analysis revealed that a higher abundance of CD56dim natural killer cells was associated with better pathological response in the primary tumor, while lower density of M2-tumor-associated macrophages was associated with better pathological response in the lymph nodes (LNs). CONCLUSIONS: Neoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective in locally advanced ESCC and is worth further investigation.

Emergent Magnetic Phenomenon with Unconventional Structure in Epitaxial Manganate Thin Films.

A variety of emergent phenomena are enabled by interface engineering in the complex oxides heterostructures. While extensive attention is attracted to LaMnO3 (LMO) thin films for observing the control of functionalities at its interface with substrate, the nature of the magnetic phases in the thin film is, however, controversial. Here, it is reported that the ferromagnetism in two and five unit cells thick LMO films epitaxially deposited on (001)-SrTiO3 substrates, a ferromagnetic/ferromagnetic coupling in eight and ten unit cells ones, and a striking ferromagnetic/antiferromagnetic pinning effect with apparent positive exchange bias in 15 and 20 unit cells ones are observed. This novel phenomenon in both 15 and 20 unit cells films indicates a coexistence of three magnetic orderings in a single LMO film. The high-resolution scanning transmission electron microscopy suggests a P21/n to Pbnm symmetry transition from interface to surface, with the spatial stratification of MnO6 octahedral morphology, corresponding to different magnetic orderings. These results can shed some new lights on manipulating the functionality of oxides by interface engineering.

Reproducible Ultrathin Ferroelectric Domain Switching for High-Performance Neuromorphic Computing.

Neuromorphic computing consisting of artificial synapses and neural network algorithms provides a promising approach for overcoming the inherent limitations of current computing architecture. Developments in electronic devices that can accurately mimic the synaptic plasticity of biological synapses, have promoted the research boom of neuromorphic computing. It is reported that robust ferroelectric tunnel junctions can be employed to design high-performance electronic synapses. These devices show an excellent memristor function with many reproducible states (≈200) through gradual ferroelectric domain switching. Both short- and long-term plasticity can be emulated by finely tuning the applied pulse parameters in the electronic synapse. The analog conductance switching exhibits high linearity and symmetry with small switching variations. A simulated artificial neural network with supervised learning built from these synaptic devices exhibited high classification accuracy (96.4%) for the Mixed National Institute of Standards and Technology (MNIST) handwritten recognition data set.

Energy-Efficient Artificial Synapses Based on Oxide Tunnel Junctions.

The development of artificial synapses has enabled the establishment of brain-inspired computing systems, which provides a promising approach for overcoming the inherent limitations of current computer systems. The two-terminal memristors that faithfully mimic the function of biological synapses have intensive prospects in the neural network field. Here, we propose a high-performance artificial synapse based on oxide tunnel junctions with oxygen vacancy migration. Both short-term and long-term plasticities are mimicked in one device. The oxygen vacancy migration through oxide ultrathin films is utilized to manipulate long-term plasticity. Essential synaptic functions, such as paired pulse facilitation, post-tetanic potentiation, as well as spike-timing-dependent plasticity, are successfully implemented in one device by finely modifying the shape of the pre- and postsynaptic spikes. Ultralow femtojoule energy consumption comparable to that of the human brain indicates its potential application in efficient neuromorphic computing. Oxide tunnel junctions proposed in this work provide an alternative approach for realizing energy-efficient brain-like chips.

Anionic Polymerization of Methylene Malonate for High-Performance Coatings.

Here, we demonstrate the anionic polymerization and the high reactivity of the novel monomer diethyl methylene malonate (DEMM). At room temperature and under atmospheric conditions, water and anionic functional groups (i.e., carboxyl, boronic, and phenol) quickly initiate DEMM. The polymerization of DEMM in water and the final molecular weight of the polymer were both demonstrated to be pH-dependent. Systematically, investigations were conducted to study the conversion rate of DEMM with various functional groups, and the polymerization was verified to occur with anionic groups using a carboxylate-initiated DEMM system. For coating applications, we also investigated a multifunctional derivative monomer called (DEMM)6 that is an oligomeric polyester of DEMM esterified with butanediol that contains on average six repeat units of reactive DEMM (commercially known as Forza B3000 XP). The incorporation of 15 wt % (DEMM)6 into latex containing methacrylate acid as a functional monomer yielded cross-linked coatings with a gel content of 76.25 wt % that had a 289% improvement in rub-resistance performance compared to controls (without (DEMM)6). This study provides a facile methodology to synthesize cross-linked latex coatings at room temperature.

Giant Electroresistance in Ferroionic Tunnel Junctions.

Oxide-based resistive switching devices, including ferroelectric tunnel junctions and resistance random access memory, are promising candidates for the next-generation non-volatile memory technology. In this work, we propose a ferroionic tunnel junction to realize a giant electroresistance. It functions as a ferroelectric tunnel junction at low resistance state and as a Schottky junction at high resistance state, due to interface engineering through the field-induced migration of oxygen vacancies. An extremely large electroresistance with ON/OFF ratios of 5.1×107 at room temperature and 2.1×109 at 10 K is achieved, using an ultrathin BaTiO3-δ layer as the ferroelectric barrier and a semiconducting Nb-doped SrTiO3 substrate as the bottom electrode. The results point toward an appealing way for the design of high-performance resistive switching devices based on ultrathin oxide heterostructures by ionic controlled interface engineering.

A Ferrite Synaptic Transistor with Topotactic Transformation.

Hardware implementation of artificial synaptic devices that emulate the functions of biological synapses is inspired by the biological neuromorphic system and has drawn considerable interest. Here, a three-terminal ferrite synaptic device based on a topotactic phase transition between crystalline phases is presented. The electrolyte-gating-controlled topotactic phase transformation between brownmillerite SrFeO2.5 and perovskite SrFeO3- δ is confirmed from the examination of the crystal and electronic structure. A synaptic transistor with electrolyte-gated ferrite films by harnessing gate-controllable multilevel conduction states, which originate from many distinct oxygen-deficient perovskite structures of SrFeOx induced by topotactic phase transformation, is successfully constructed. This three-terminal artificial synapse can mimic important synaptic functions, such as synaptic plasticity and spike-timing-dependent plasticity. Simulations of a neural network consisting of ferrite synaptic transistors indicate that the system offers high classification accuracy. These results provide insight into the potential application of advanced topotactic phase transformation materials for designing artificial synapses with high performance.