Iridium(III)-Catalyzed Tandem Annulation of Pyridine-Substituted Anilines and α-Cl Ketones for Obtaining 2-Arylindoles.

A facile and expeditious protocol for the synthesis of 2-arylindole compounds from readily available N-(2-pyridyl)anilines and commercially available α-Cl ketones through iridium-catalyzed C-H activation and cyclization is reported here. As a complementary approach to the conventional strategies for indole synthesis, the transformation exhibits powerful reactivity, tolerates a large number of functional groups, and proceeds with good to excellent yields under mild conditions, providing a straightforward method to obtain structurally diverse and valuable indole scaffolds. Furthermore, the reaction could be easily scaled up to gram scale.

A highly sensitive NIR fluorescence probe for hypoxia imaging in cells and ulcerative colitis.

Ulcerative colitis, a kind of inflammatory bowel disease (IBD), is caused by dysregulated immune response of intestinal bacteria. This chronic disorder can lead to a deficiency of O2 (hypoxia) in the colon microenvironment. Nitroreductase (NTR) is a highly expressed endogenous enzyme under hypoxia, so the detection of NTR can provide diagnostic information about ulcerative colitis. Herein, an ultrasensitive NTR-triggered fluorescence probe (WS-1-NO2) is developed for hypoxia imaging in ulcerative colitis. The probe shows a significant fluorescence enhancement (45-fold) after reacting with NTR, with an extremely low detection limit of 0.096 ng/mL. Furthermore, we apply it for fluorescence imaging of hypoxia in living cells, tumors and dextran sulphate sodium (DSS)-induced ulcerative colitis mouse models. We believe that the probe may be investigated as an effective potential tool for gaining insight into the hypoxia-relevant diseases, such as cancer and ulcerative colitis.

The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

Objective: To investigate the predictive value of Controlling Nutritional Status (CONUT) score and systemic inflammation (SIS) score in the prognosis, short-term efficacy, and immune-related side effects of patient with recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC) receiving immunotherapy as second line therapy combined with or without radiotherapy. Methods: Forty-eight patients with R/M ESCC who received second-line therapy with Camrelizumab were retrospectively studied. They were divided into the high and low score groups according to the CONUT and SIS score. Univariate and multivariate analyses were used to analyze factors that might affect patient prognosis and the effects of different CONUT score and SIS on the short-term efficacy and immune-related toxic and side effects of patients. Results: The 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 42.9% and 22.5%, and 29.0% and 5.8%, respectively. The CONUT score ranged from 0 to 6 (3.31 ± 1.43), whereas the SIS score ranged from 0 to 2 (1.19 ± 0.73). Multivariate analysis showed that treatment related toxicity, number of cycles of Camrelizumab used, short-term effect and SIS score were independent prognostic factors for OS (P=0.044, 0.021, 0.021, 0.030, respectively), whereas SIS and CONUT scores were independent prognostic factors for PFS (P=0.005, 0.047, respectively). Patients with low CONUT/SIS score had a low incidence rate of immune-related adverse reactions (X2 = 9.735, 5.693; P=0.002, 0.017) and better short-term efficacy (X2 = 4.427, 7.438; P=0.035, 0.006). Conclusion: R/M ESCC patients with low CONUT/SIS score have better prognosis, higher objective response rate, lower incidence of immune-related toxic and side effects after receiving immunotherapy as second-line therapy. CONUT scores and SIS scores may be reliable prognostic indicators for patient receiving immunotherapy as second-line therapy for R/M ESCC.

Corrigendum: The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy.

[This corrects the article DOI: 10.3389/fonc.2023.1167625.].

Immune checkpoint inhibitors combined with or without radio(chemo)therapy for locally advanced or recurrent/metastatic esophageal squamous cell carcinoma.

OBJECTIVE: This study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC). METHODS: In this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed. RESULTS: The median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1-45.7 months) and 15.3 months (95% CI 12.8-17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8-75.7 months) and 20.5 months (95% CI 14.1-27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0-21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1-14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs. CONCLUSIONS: ICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.

Activatable near-infrared fluorescent probe triggered by nitroreductase for in vivo ulcerative colitis hypoxia imaging.

Ulcerative colitis is a prevalent inflammatory disease caused by the intestinal bacterial infection. And it is related to the hypoxic degrees in the colon microenvironment. Hypoxia, a condition of imbalance in O2 supply and consumption, is accompanied by the overexpressed level of nitroreductase (NTR). Therefore, the NTR detection has been widely applied for the diagnosis of hypoxia-related diseases. In this study, we developed a novel near-infrared fluorescent probe (IW-1) for NTR. Upon reaction with NTR, IW-1 exhibited a significant fluorescence off-on response at 740 nm with a low detection limit of 0.043 µg/mL. Confocal fluorescence imaging verified its ability to detect the overexpression of NTR in cancer cells. More significantly, IW-1 was applied for in vivo hypoxia imaging in tumors and dextran sulphate sodium (DSS)-induced ulcerative colitis mouse model. We expect that the probe may present a new tool for better understanding the biological functions of NTR as well as revealing essential information about hypoxia-related pathological processes, including cancer and ulcerative colitis.

Synthesis of oxazolidinones through ring-opening and annulation of vinylene carbonate with 2-pyrrolyl/indolylanilines under Rh(III) catalysis.

Herein, we have developed a rhodium-catalyzed C-H functionalization and subsequent intramolecular ring-opening/cyclization of vinylene carbonate with 2-pyrrolyl/indolylanilines, which leads to oxazolidinones in moderate to good yields. In this transformation, vinylene carbonate only eliminates one oxygen atom rather than -CO3 or CO2. Furthermore, some control experiments are conducted to elucidate the reaction mechanism.

[Characters of ecosystem vulnerability in southwestern China based on vegetation productivity]. / 基于植被生产力的西南地区生态系统脆弱性特征.

Southwestern China is one of the most important areas for global biodiversity conservation. Under the background of global climate change, the vulnerability of this area has showed an increasing trend. According to the IPCC concept of vulnerability, we calculated the spatial distribution of ecosystem's vulnerability in southwestern China based on gross primary productivity (GPP) and then analyzed the spatial variation of different levels of vulnerability. Besides, we analyzed the relationship between environmental factors and ecosystem vulnerability, including precipitation, temperature, altitude, slope and vegetation type. The results showed that ecosystem vulnerability in the southwestern China gradually increased from southeast to northwest, with most area within the region being slight and mild vulnerable area (together occupied 69% of the total). The vulnerability level decreased with the increasing of mean annual precipitation and temperature but increased with increasing elevation and slope. Karst area in southwest and borders between farming and ranging regions in northwest Mountain ecotone of the study area had higher vulnerability, being more easily affected by climate change or other disturbances. The vulnerabilities of needle-leaved forest, grassland, and shrubland were relatively higher than other vegetation types, with the potential to be more easily affected by climate change.

[Net carbon exchange and its driving factors of Haloxylon ammodendron plantation in the oasis-desert ecotone of Minqin, China]. / 民勤绿洲-è’æ¼ è¿‡æ¸¡å¸¦æ¢­æ¢­äººå·¥æž—å‡€ç¢³äº¤æ¢åŠå ¶å½±å“å› å­.

Carbon fluxes in a Haloxylon ammodendron plantation in the oasis-desert ecotone of Minqin was measured using an eddy covariance system. To provide scientific data for carbon source/sink assessment, we quantitatively analyzed the characteristics of CO2 flux and its driving factors in the growing season from May to October, 2018. The results showed that the trend of daily net carbon exchange in the growing season followed a symmetrical "U" shape curve. As to seasonality, bimodal curve was obvious. The plantation ecosystem was a carbon sink every month. The total carbon sequestrated was 34.38 g C·m-2, with the peak of 12.31 g C·m-2 in September and the lowest value of 0.89 g C·m-2 in July. The net carbon exchange in this ecosystem increased during the daytime with the increasing photosynthetically active radiation, consistent with the Michaelis-Menten rectangular hyperbola change. When the vapor pressure deficit was greater than 2.5 kPa, the increasing trend tended to flat. Ecosystem respiration increased exponentially with temperature, with temperature sensitivity being 1.7. Net carbon exchange in either day or night was significantly correlated with soil temperature through the whole growing season.

[Effects of environmental factors on evapotranspiration characteristics of Haloxylon ammodendron plantation in the Minqin oasis-desert ectone, Northwest China.] / çŽ¯å¢ƒå› å­å¯¹æ°‘å‹¤ç»¿æ´²è’æ¼ è¿‡æ¸¡å¸¦æ¢­æ¢­äººå·¥æž—è’¸æ•£çš„å½±å“.

This study continuously measured the evapotranspiration (ET) of degraded Haloxylon ammodendron shrub plantation of Minqin oasis-desert ectone using an eddy covariance system for ET, and TDR for soil moisture profile, analyzing ET in relation to the weather conditions and describing the responses of ET to the microclimate variables in different weather from July 2014 to June 2015. Results showed that the hourly ET dynamics had an apparent seasonal trend in the growing season. This trend gradually increased in the beginning of season from the low level of non-growing season, reached its maximum peak value (0.07 mm·h-1) in the most physiologically active period, and decreased to the minimum peak value (0.01 mm·h-1) in December. The diurnal change in ET of the plantation depended on the weather conditions. The ET fluctuated less with a small magnitude in a cloud day, but fluctuated obviously with a greater magnitude after rain if weather was clear. After a strong rainfall (>9 mm·d-1), ET increased sharply to a high level of 28 folds prior to rain, at which it took four clear days to gradually decease to the pre-rain ET level. The yearly ET over H. ammodendron plantation was 108 mm, equivalent to 98% of annual precipitation. Soil moisture was the water source for ET. Therefore, soil moisture was the dominant factor for theET over the plantation. Net radiation, photosynthesis active radiation, air temperature, and vapor pressure deficit were the microclimate variables to drive the transpiration of vegetation and evaporation over the soil surface, being the major factors forET over the plantation. The regression equation of ET to the dominant factor and major factors had a coefficient of multiple determination (R2) over 0.80.

[Variation of apple tree canopy-air temperature difference and its relations to environment factors].

By using portable infrared thermometer, the canopy temperature (Tc) of apple tree in its main growth season was measured in 2002-2005. Combined with the synchronous micro-meteorological data on the canopy, such as net radiation (Rn), wind speed (V), air temperature (Ta) and relative humidity (RH), as well as the soil water content (SW) at 0-80 cm depth, the variation of apple tree canopy-air temperature differential (DeltaT) and its relationships to environmental factor were analyzed. The results showed that from bud stage to fruit-developing stage, there were several peaks in the diurnal curve of DeltaT, with the maximum at 12:00-13:00 in fine days, and the absolute value of DeltaT in fine days was higher than that in overcast days. Based on data of 2003 and 2004, the DeltaT at 14:00 was significantly correlated with the RH, V, Rn, SW in fine days, and the regression equation was DeltaT = 7.159 - 0.002Rn - 0.061V - 0.7RH - 46.0SW (P < 0.01, r = 0.825). The partial coefficient for Rn, RH, V and SW was 0.125, -0.078, -0.036, -0.874, respectively, and the stepwise regression equation was DeltaT = 5.317 - 43.1SW (P < 0.01), suggesting that SW was the most important environmental factor affecting DeltaT. After validated with the measured data in 2002 and 2005, it was found that the measured DeltaT was highly accorded with the simulated one (r = 0.9083, P < 0.01, n = 40), and thus, it was of possibility to use the data of DeltaT at 14:00 in fine days to predict the soil water content in apple orchard.