Impact of the interval between neoadjuvant immunotherapy and surgery on prognosis in esophageal squamous cell carcinoma (ESCC): a real-world study.

BACKGROUND: The time interval between neoadjuvant immunotherapy and surgery is 6 weeks for esophageal squamous cell carcinoma (ESCC), but whether delayed surgery affects prognosis remains unclear. METHODS: Clinical data of locally advanced ESCC who underwent neoadjuvant immunotherapy followed by esophagectomy from November 2019 to December 2022 were collected. The surgery outcomes and prognosis were compared between short-interval (time to surgery ≤ 6 weeks) and long-interval groups (time to surgery > 6 weeks). RESULTS: 152 patients were enrolled totally, with a ratio of 91:61 between short-interval and long-interval groups. The rate of pathological complete response in the short-interval and long-interval groups were 34.1% and 24.6% (P = 0.257). Delayed surgery did not have a significantly impact on the number of lymph node dissections (P = 0.133), operative duration (P = 0.689), blood loss (P = 0.837), hospitalization duration (P = 0.293), chest drainage duration (P = 0.886) and postoperative complications (P > 0.050). The 3-year Overall survival (OS) rates were 85.10% in the short-interval group, and 82.07% in the long-interval group (P = 0.435). The 3-year disease-free survival (DFS) rates were 83.41% and 70.86% in the two groups (P = 0.037). Subgroup analysis revealed that patients with a favorable response to immunotherapy (tumor regression grade 0) exhibited inferior 3-year OS (long-interval vs. short-interval: 51.85% vs. 91.08%, P = 0.035) and DFS (long-interval vs. short-interval: 47.40% vs. 91.08%, P = 0.014) in the long-interval group. CONCLUSIONS: Delayed surgery after neoadjuvant immunotherapy does not further improve pathological response; instead, it resulted in a poorer DFS. Especially for patients with a favorable response to immunotherapy, delayed surgery increases the risk of mortality and recurrence.

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.

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 .

Reproductive toxicity of melamine against male mice and the related mechanism.

Melamine is a nitrogen-containing heterocyclic organic compound with a triazine skeleton, which has been widely applied in industrial and chemical fields. Previous toxicity studies of melamine mainly focused on renal toxicity and hepatic pathological changes, but its toxicity against the reproductive system has seldom been assessed. We investigated the effects of melamine on the reproductive system of male mice. Forty healthy male Kunming mice were randomly divided into a normal saline negative control group, a low-dose melamine group, a medium-dose melamine group and a high-dose melamine group (n = 10). The mice were administered for five consecutive days and killed on the 35th day after first administration. In melamine administration groups, seminiferous tubules had disordered, loose arrangement, and spermatogenic cells at all levels obviously decreased. The sperm count and motility decreased significantly, and the sperm deformity rate increased significantly. Melamine induced apoptosis of testicular spermatogenic cells. To further explore the mechanism, we detected metabolism-related enzymes sorbitol dehydrogenase (SDH) and lactate dehydrogenase (LDH) as well as oxidative stress indices superoxide dismutase (SOD) and malondialdehyde (MDA). The activities of SDH, LDH and SOD in melamine treatment groups decreased significantly, and the MDA level increased obviously. The expressions of apoptosis-related proteins Bcl-2, Bax and caspase-3 were detected by immunohistochemistry. The expression of Bcl-2 significantly increased, but those of Bax and caspase-3 significantly reduced (p < 0.05). In conclusion, melamine damaged the reproductive system of mice via the oxidative stress pathway and by inducing cell apoptosis.

Oblique-incidence reflectivity difference application for morphology detection.

Analogous with scanning electron microscopy, we use an oblique-incidence reflectivity difference (OIRD) approach for morphology detection. By scanning the active carbon clusters in a one-dimensional way and the reservoir rocks in a two-dimensional way, the morphology of the samples' surface can be revealed in OIRD signal images. High OIRD signals of active carbon samples refer to the centralized distribution areas of carbon, and the fluctuations are caused by the uneven distribution of carbon pellets. OIRD intensity is proportional to the thickness of materials. In terms of rocks, the trough areas with smaller values refer to the low-lying fields. The areas with relatively large OIRD intensities correspond to the protuberance areas of rocks. Consequently, OIRD is a sensitive yet rapid measure of surface detection in material and petrogeology science.

Controllable growth of ultrathin BiFeO3 from finger-like nanostripes to atomically flat films.

BiFeO3 (BFO) ultrathin films with nominal thicknesses from 2 to 12 nm were grown with a SrRuO3 (SRO) buffer layer on TiO2-terminated (001) SrTiO3 (STO) substrates using pulsed laser deposition. The surface morphologies and domain configurations of the thin films were investigated using atomic force microscopy and piezoelectric force microscopy. Periodical one-dimensional finger-like nanostripes of BFO on the SRO covered STO substrates were observed. With increasing thickness, the BFO ultrathin films develop from the finger-like nanostripes to an atomically flat surface. The formation of the finger-like nanostructures of BFO is related to the atomic step or terrace structure of the substrate. The BFO nanostripes and the atomically flat thin films both show good ferroelectricity. The as-grown domain orientations of the BFO ultrathin films are ascribed to the chemical terminations at the surface of the SRO layer. These results indicate that the surface morphologies and the domain configurations of BFO ultrathin films can be artificially designed by using substrates with optimized terrace structures and chemical termination, and these films are potentially useful in multifunctional nanoelectronic devices.

High-performance visible blind ultraviolet photodetector based on KTaO3 single crystal.

We report a visible-blind ultraviolet photoconductive detector with interdigitated electrodes based on KTaO3 (KTO) single crystals. Both the steady spectral responses and the transient photovoltaic measurements clearly exhibit a cutoff wavelength at 344 nm (∼3.6 eV), in accordance with the bandgap of KTO. The KTO photodetectors show a low dark current ∼1.5 pA at 20 V, and a high UV-to-visible rejection ratio with 3 orders of magnitude at room temperature. The quantum efficiency is 37.49% under 20 V bias, and the detectivity D* of 3.85×1012 cm·Hz0.5/W, which is comparable to that of silicon photodetectors in the UV region. The rise time of photoelectric response is ∼260 ps, indicating an ultrafast photoelectric response characteristic. The present work offers appealing prospects for the application of KTO materials in high-performance visible blind ultraviolet photodetectors.

Tuning the nonlinear optical absorption of reduced graphene oxide by chemical reduction.

Reduced graphene oxides with varying degrees of reduction have been produced by hydrazine reduction of graphene oxide. The linear and nonlinear optical properties of both graphene oxide as well as the reduced graphene oxides have been measured by single beam Z-scan measurement in the picosecond region. The results reveal both saturable absorption and two-photon absorption, strongly dependent on the intensity of the pump pulse: saturable absorption occurs at lower pump pulse intensity (~1.5 GW/cm2 saturation intensity) whereas two-photon absorption dominates at higher intensities (≥5.7 GW/cm2). Intriguingly, we find that the two-photon absorption coefficient (from 1.5 cm/GW to 4.5cm/GW) and the saturation intensity (from 1 GW/cm2 to 2 GW/cm2) vary with chemical reduction, which is ascribed to the varying concentrations of sp2 domains and sp2 clusters in the reduced graphene oxides. Our results not only provide an insight into the evolution of the nonlinear optical coefficient in reduced graphene oxide, but also suggest that chemical engineering techniques may usefully be applied to tune the nonlinear optical properties of various nano-materials, including atomically thick graphene sheets.

Two hydroxypyruvate reductases encoded by OsHPR1 and OsHPR2 are involved in photorespiratory metabolism in rice.

Mutations in the photorespiration pathway display a lethal phenotype in atmospheric air, which can be fully recovered by elevated CO2 . An exception is that mutants of peroxisomal hydroxypyruvate reductase (HPR1) do not have this phenotype, indicating the presence of cytosolic bypass in the photorespiration pathway. In this study, we constructed overexpression of the OsHPR1 gene and RNA interference plants of OsHPR1 and OsHPR2 genes in rice (Oryza sativa L. cv. Zhonghua 11). Results from reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and enzyme assays showed that HPR1 activity changed significantly in corresponding transgenic lines without any effect on HPR2 activity, which is the same for HPR2. However, metabolite analysis and the serine glyoxylate aminotransferase (SGAT) activity assay showed that the metabolite flux of photorespiration was disturbed in RNAi lines of both HPR genes. Furthermore, HPR1 and HPR2 proteins were located to the peroxisome and cytosol, respectively, by transient expression experiment. Double mutant hpr1 × hpr2 was generated by crossing individual mutant of hpr1 and hpr2. The phenotypes of all transgenic lines were determined in ambient air and CO2 -elevated air. The phenotype typical of photorespiration mutants was observed only where activity of both HPR1 and HPR2 were downregulated in the same line. These findings demonstrate that two hydroxypyruvate reductases encoded by OsHPR1 and OsHPR2 are involved in photorespiratory metabolism in rice.

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.