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Abstract Background FGFR genomic aberrations occur in approximately 5–10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer. Methods Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics. Results Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7–63.6); the median progression-free survival was 5.6 months (95% CI, 3.6–12.7) and median overall survival was 40.2 months (95% CI, 12.4–not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5–57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%). Conclusions Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals. Trial registration This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.

BackgroundMalignant atrophic papulosis (MAP) is a rare obliterative vasculopathy whose etiology and pathophysiological mechanisms remain unknown, and the treatment is still empirical. It can involve multiple systems, especially the gastrointestinal tract and central nervous system, and has a poor prognosis.Case presentationA 20-year-old Chinese male appeared to have Widespread atrophic papules and plaques, intermittent abdominal pain, recurrent bowel perforation, and psoas abscess. The clinical diagnosis of MAP was supported by skin biopsy. He was then treated with anticoagulants, antiplatelets, glucocorticoids, and immunosuppressants and started on eculizumab and hirudin after the first surgical interventions. Despite the aggressive immunosuppression, anticoagulant, antiplatelet, humanized monoclonal antibodies, and surgery therapy, he died five months after presentation.ConclusionsMAP is an extremely rare obliterative vasculopathy manifesting as benign cutaneous involvement or potentially malignant systemic involvement. MAP patients who exhibit any abdominal symptoms should undergo laparoscopy and evaluation in time and start on eculizumab and treprostinil as soon as possible, as the combination of them is presently the most effective treatment option for gastrointestinal MAP and hopefully reduce mortality.

Abstract Metal-free porous biochars are popularly utilized as catalysts for peroxydisulfate (PDS) activation. The enhancement effect of PDS activation of porous biochars fabricated by employing both hard template and alkali metal activating agent has not been explored completely. In addition, the role of the inherent carbon defect in PDS activation has not been clearly elucidated. Hence, a series of carbonaceous catalysts were fabricated using a sole template (KCl), a sole activating agent (Na2S2O3) or a combination of template and activating agent (KCl/Na2S2O3, KCl/KHCO3, KCl/NaHCO3, and KCl/Na2C2O4), to systematically investigate the effect of specific surface area (SSA) and intrinsic defect of porous biochar on its PDS activation ability. The biochar synthesized by KCl and Na2S2O3 (SK-C) exhibited the optimum degradation performance. The SK-C was found to possess an interconnected hollow cage with three-dimensional mesh structure showing the largest surface area, pore volume and C-sp 3 edge defect content among all the catalysts, which explained its paramount catalytic ability. The SSA and C-sp 3 content together can determine the catalytic performance in a quantitative relationship. The single electron transfer pathway from SDZ to inner-sphere bound SK-C/PDS* was the protagonist of pollutant oxidation. The degradation intermediates were detected and recognized and their toxicities were evaluated. This study for the first time comprehensively identified the synergistic effect between the SSA and inherent defects on improving the catalytic performance of biochar for PDS activation to removal contaminants. Graphical Abstract

Abstract Background Soil salinization is a major abiotic environmental stress factor threatening crop production throughout the world. Salt stress drastically affects the growth, development, and grain yield of rice (Oryza sativa L.), and the improvement of rice tolerance to salt stress is a desirable approach for meeting increasing food demand. Receptor-like cytoplasmic kinases (RLCKs) play essential roles in plant growth, development and responses to environmental stresses. However, little is known about their functions in salt stress. Previous reports have demonstrated that overexpression of an RLCK gene SALT TOLERANCE KINASE (STK) enhances salt tolerance in rice, and that STK may regulate the expression of GST (Glutathione S-transferase) genes. Results The expression of STK was rapidly induced by ABA. STK was highest expressed in the stem at the heading stage. STK was localized at the plasma membrane. Overexpression of STK in rice increased tolerance to salt stress and oxidative stress by increasing ROS scavenging ability and ABA sensitivity. In contrast, CRISPR/Cas9-mediated knockout of STK increased the sensitivity of rice to salt stress and oxidative stress. Transcriptome sequencing analysis suggested that STK increased the expression of GST genes (LOC_Os03g17480, LOC_Os10g38140 and LOC_Os10g38710) under salt stress. Reverse transcription quantitative PCR (RT-qPCR) suggested that four stress-related genes may be regulated by STK including OsABAR1, Os3BGlu6, OSBZ8 and OsSIK1. Conclusions These findings suggest that STK plays a positive regulatory role in salt stress tolerance by inducing antioxidant defense and associated with the ABA signaling pathway in rice.

Abstract To fundamentally explore the correlation between crop nutritional quality and mineral elements, specific tests and accurate analysis were carried out on all organs and root soil of watermelon (Citrullus lanatus). The results showed that the distribution patterns of nitrogen and phosphorus at watermelon maturity were similar, and the average nitrogen and phosphorus contents were in the orders of leaf and seed > stem, peel, root > pulp > root soil, and peel > seed > root, stem, leaf > root soil > pulp, respectively. From the perspective of element geochemistry, biophile and lithophile elements had the strongest correlation with nitrogen and phosphorus, and watermelon did not antagonize soil nitrogen and phosphorus uptake. The prediction model of nitrogen translocation factor in watermelon organs to total acid was established by partial least squares with R 2 = 0.81. Significantly, when the isometric log-ratio of nitrogen to phosphorus in watermelon leaves was 1.97 to 2.19, the watermelon pulp showed better quality with total acid > 0.5%, total sugar > 5% and soluble solids > 10%. Therefore, the characterization of nitrogen and phosphorus in watermelon leaves can serve as a non-destructive analysis to predict watermelon fruit quality.

Carbon dots have many new and interesting phenomena, and the concentration dependent luminescence wavelength is an intriguing one. Herein, nitrogen-sulfur co-doped carbon dots (NSCDs) diluted to different concentrations, the high concentration of G-NSCDs (0.2 mg mL−1) with green fluorescence and the low-concentration of B-NSCDs (0.01 mg mL−1) with blue fluorescence were obtained. Further, it was found that the detection behaviors are different for different concentrations. The “turn-off” fluorescent sensor of G-NSCDs can specifically recognize rifampicin in a linear range of 0.2–20 μM with a detection limit of 56.6 nM employing the mutual effect of photo-induced electron transfer and dynamic quenching. Meanwhile, a “turn-off” B-NSCDs fluorescence sensor was constructed to effectively identify morin based on the internal filtration effect and static quenching, achieving a suitable linearity of 0.2–30 μM and a detection limit of 51.2 nM. Due to the strong chelation of morin and Al3+, a “turn-on” fluorescent probe for sequential detection Al3+ was fabricated based on B-NSCDs-morin system, obtaining a good linearity of 0.1–2.0 μM with a satisfactory detection limit of 45.8 nM. These interesting behaviors indicate that NSCDs are expected to become novel sensing materials for the monitoring of rifampicin, morin and Al3+ in organisms, which is beneficial for our health.

To improve the main shortcomings of insufficient nutrients, high salinity and low productivity in saline-alkali soils, this study collected saline-alkali soil samples from Da'an City of Baicheng and sediment samples from the adjacent Qianguo irrigation district, measured their pH values and major element contents, designed and verified the improvement scheme of saline-alkali soil based on geochemical engineering principles. Results indicated that the pH value and various element contents of saline-alkali soil could be adjusted by adding sediment to make it close to reference soil. Both theoretical calculation and experimental determination (soil pH, mineral composition, functional group composition and crop growth) revealed that the optimal mixing ratio of saline-alkali soil and sediment was 2:1. The saline-alkali soil amelioration with sediment of adjacent irrigation areas was effectively, low-cost and environment-friendly. The geochemical engineering principle was applicable to the amelioration of saline-alkali soil, but the mixing ratio of saline-alkali soil and sediment in different areas should vary with the local conditions. Meanwhile, theoretical calculation could basically replace the experimental determination to simplify the actual engineering application process. This saline-alkaline soil amelioration method makes full use of the surrounding natural waste and has the advantage of adapting measures to local conditions.

Iodine ion is one of the most indispensable anions in living organisms, particularly being an important substance for the synthesis of thyroid hormones. Curcumin is a yellow-orange polyphenol compound derived from the rhizome of Curcuma longa L., which has been commonly used as a spice and natural coloring agent, food additives, cosmetics as well as Chinese medicine. However, excess curcumin may cause DNA inactivation, lead to a decrease in intracellular ATP levels, and trigger the tissue necrosis. Therefore, quantitative detection of iodine and curcumin is of great significance in the fields of food and life sciences. Herein, we develop nitrogen-doped fluorescent carbon dots (NCDs) as a multi-mechanism detection for iodide and curcumin in actual complex biological and food samples, which was prepared by a one-step solid-phase synthesis using tartaric acid and urea as precursors without adding any other reagents. An assembled NCDs-Hg2+ fluorescence-enhanced sensor for the quantitative detection of I− was established based on a fluorescence “turn-off-on” mechanism in a linear range of 0.3–15 μM with a detection limit of 69.4 nM and successfully quantified trace amounts of I− in water samples and urine sample. Meanwhile, the as-synthesized NCDs also can be used as a fluorescent quenched sensor for curcumin detection based on the synergistic internal filtration effect (IFE) and static quenching, achieving a good linear range of 0.1–20 μM with a satisfactory detection limit of 29.8 nM. These results indicate that carbon dots are potential sensing materials for iodine and curcumin detection for the good of our health.

Abstract At present, the direct gold determination in geological samples by inductively coupled plasma mass spectrometry (ICP-MS) is still an arduous challenge due to both spectral and background interferences. It is very important and necessary to study the pretreatment processes; therefore, the polyurethane foam treatment and sample digestion methods are explored and compared here. The experimental results showed that the gold adsorption rate of treated foam was significantly improved as the impurities in the foam were cleaned up, and the potential difference of the liquid membrane was increased. Meanwhile, the combination of the foam enrichment and thiourea desorption achieved the selective adsorption and desorption of gold ions, eliminated the interference of coexisting ions, and perfected the detection limits. Compared with the traditional electric heating plate digestion method, microwave digestion, a closed digestion method, had the advantages of less sample and reagent dosage, short time consumption, high degree of automation, thorough digestion, good security, and environmental friendliness and met the requirements of green chemistry development. The proposed microwave digestion-foam enrichment-thiourea desorption-ICP-MS determination method was applied to the gold test in soil samples of the actual gold mining area. It has the great potential as a routine laboratory procedure.

A linking procedure establishes a "bridge" between the scores from different patient-reported outcome (PRO) instruments that measure similar constructs. After developing a linking relationship however, it is critical to evaluate whether this relationship can be generalized to different groups. Our study aims to validate a published crosswalk for score conversion between the Brief Symptom Inventory Depression subscale and the Patient-Reported Outcomes Measurement Information System Depression 8a using an independent sample. Data were from a sample of young men who have sex with men (MSM), which differs in terms of participant age, race, and ethnicity from the sample used to develop the existing crosswalk. The validity of the newly derived crosswalk was evaluated in terms of the correlation, mean difference and standard deviation between the observed and the linked scores. The two crosswalks were further compared to evaluate if the difference was within an acceptable range. More than half of the item parameters obtained from the two samples were found to overlap in their confidence intervals. Differences between each pair of scores in the two crosswalks was within three T-score points, well within the range of each crosswalk score's standard error. This study concludes that an existing crosswalk is replicable on a sample that differs from that used for crosswalk development, but future research should continue to examine the generalizability of the linked parameters and evaluate the reproducibility of this crosswalk to other populations.

Sudan dyes are strictly prohibited from being added to edible products as carcinogens and tetracycline hydrochloride (TC) remaining in animal-derived food may cause harm to the human body. Therefore, it is necessary to establish a high-sensitivity, simple and convenient method for the detection of Sudan dyes and TC in foods for safety purposes. In this work, multifunctional blue fluorescent carbon dots (B-CDs) were prepared by a one-step hydrothermal synthesis using glucose as the carbon source. The results show that the fluorescence intensity of B-CDs was significantly affected by the acidity of the solution and can be quenched by Sudan I, IV and TC through selective studies. Interestingly, the fluorescence quenching intensities of B-CDs have a good linear relationship with the concentration of Sudan I and IV at pH = 3–7. The wide range of pH is beneficial to broaden the application of B-CDs in a practical samples analysis. The method has been successfully applied to real food samples of tomato paste, palm oil and honey, and the detection limits are 26.3 nM, 54.2 nM and 31.1 nM for Sudan I, Sudan IV and TC, respectively. This method integrates Sudan dyes and TC into the same multifunctional B-CDs, which shows that the sensor has a great potential in food safety detection.

To explore the existing characteristics of nitrogen and phosphorus in the main rivers of Changchun City, the overlying water and sediment were sampled and tested. The results showed that the spatial distribution of nitrogen and phosphorus contents in overlying water and sediment was diverse. In overlying water, nitrogen and phosphorus contents in the north and west of Changchun were high, while their contents in the south were low. In the sediment, their contents were high in the south and west and low in the north. The pollution of nitrogen and phosphorus was serious in most rivers. Xinkai River, Chuan Lake, and West Lake had the acutest pollution of ammonia, total nitrogen, and total phosphorus, and their contamination degree in Yongchun River was the lowest. In terms of time, with the government actively carrying out river management, the pollution control of ammonia and phosphorus has achieved remarkable results. The pollution of nitrogen and phosphorus was closely related to the quality of the water environment, and the phosphorus content in overlying water and sediment had the strongest correlation with other water quality parameters. Moreover, the change in chemical oxygen demand could be predicted by the partial least squares method on the basis of its high correlation with nitrogen and phosphorus in overlying water. This study provides a scientific reference for the investigation and treatment of nitrogen and phosphorus pollution in surface water of typical old industrial cities in China.

Human Werner syndrome (WS) is an autosomal recessive progeria disease. A mouse model of WS manifests the disease through telomere dysfunction-induced aging phenotypes, which might result from cell cycle control and cellular senescence. Both p21Waf1/Cip1 (p21, encoded by the Cdkn1a gene) and p16Ink4a (p16, encoded by the Ink4a gene) are cell cycle inhibitors and are involved in regulating two key pathways of cellular senescence. To test the effect of p21 and p16 deficiencies in WS, we crossed WS mice (DKO) with p21–/– or p16–/– mice to construct triple knockout (p21-TKO or p16-TKO) mice. By studying the survival curve, bone density, regenerative tissue (testis), and stem cell capacity (intestine), we surprisingly found that p21-TKO mice displayed accelerated premature aging compared with DKO mice, while p16-TKO mice showed attenuation of the aging phenotypes. The incidence of apoptosis and cellular senescence were upregulated in p21-TKO mice tissue and downregulated in p16-TKO mice. Surprisingly, cellular proliferation in p21-TKO mice tissue was also upregulated, and the p21-TKO mice did not show telomere shortening compared with age-matched DKO mice, although p16-TKO mice displayed obvious enhancement of telomere lengthening. Consistent with these phenotypes, the SIRT1-PGC1 pathway was upregulated in p16-TKO but downregulated in p21-TKO compared with DKO mouse embryo fibroblasts (MEFs). However, the DNA damage response pathway was highly activated in p21-TKO, but rescued in p16-TKO, compared with DKO MEFs. These data suggest that p21 protected the stem cell reservoir by regulating cellular proliferation and turnover at a proper rate and that p21 loss in WS activated fairly severe DNA damage responses (DDR), which might cause an abnormal increase in tissue homeostasis. On the other hand, p16 promoted cellular senescence by inhibiting cellular proliferation, and p16 deficiency released this barrier signal without causing severe DDR.

The coming Big Data Era requires progress in storage and computing technologies. As an emerging memory technology, Resistive RAM (RRAM) has shown its potential in the next generation high-density storage and neuromorphic computing applications, which extremely demand low switching voltage and power consumption. In this work, a 10 nm-thick amorphous GeS2 thin film was utilized as the functional layer of RRAM in a combination with Ag and Pt electrodes. The structure and memory performance of the GeS2-based RRAM device was characterized — it presents high on/off ratio, fast switching time, ultralow switching voltage (0.15 V) and power consumption (1.0 pJ and 0.56 pJ for PROGRAM and ERASE operations, respectively). We attribute these competitive memory characteristics to Ag doping phenomena and subsequent formation of Ag nano-islands in the functional layer that occurs due to diffusion of Ag from electrode into the GeS2 thin film. These properties enable applications of GeS2 for low energy RRAM device.

Portable X-ray fluorescence spectrometry (pXRF) is an analytical technique that can be used for rapid and non-destructive analysis in the field. However, the testing accuracy and precision for trace elements are significantly affected by the matrix effect, which comes mainly from major elements that constitute most of the matrix of a sample. To solve this problem, many methods based on linear regression models have been proposed, but when extreme values or outliers occur, the application of these methods will be greatly affected. In this study, 16 certified reference materials were collected for pXRF analysis, and the major elements most closely related to the elements to be measured were employed as correction indicators to calibrate the analysis results through the application of multiple linear regression analysis. Some statistical parameters were calculated to evaluate the correction results. Compared with the calibration data obtained from simple linear regression analysis without taking major elements into account, those corrected by the new method were of higher quality, especially for elements of Co, Zn, Mo, Ta, Tl, Pb, Cd and Sn. The results show that the new method can effectively suppress the influence of the matrix effect.

SnSe single crystals have been demonstrated to possess excellent thermoelectric properties. In this work, we demonstrate a grain size control method in growing nanocrystalline SnSe thin films through a glancing angle pulsed-laser deposition approach. Structural characterization reveals that the SnSe film deposited at a normal angle has a preferred orientation along a axis, while by contrast, the SnSe film deposited at an 80° glancing angle develops a nanopillar structure with the growth direction towards the incident atomic flux. The glancing angle deposition greatly reduces the grain size of the thin film due to a shadowing effect to the adatoms, resulting in significantly increased power factor for more than 100%. The maximum Seebeck coefficient and power factor are 498.5μV/K and 18.5μWcm−1K−2, respectively. The enhancement of thermoelectric property can be attributed to the potential barrier scattering at grain boundaries owing to the reduced grain size and increased grain boundaries in the film. Given this enhanced power factor, and considering the fact that the nanopillar structure should have much lower thermal conductivity than a plain film, the zT value of such made SnSe film could be significantly larger than the corresponding single crystal film, making it a good candidate for thin film-based thermoelectric device.

Sample pretreatment is important for chemical phase analysis of elements. In this study, the geological samples of the Laozuoshan gold mine are chosen to pretreat by ultrasonic centrifugation and cyclotron oscillation, and the content of gold in eight chemical phases (water-soluble, ion exchange and clay adsorption, organic matter bound, iron-manganese oxide bound, naked or seminaked, carbonate bound, sulfide bound, and insoluble silicate states) is determined by atomic absorption spectrometry. The results show that the gold content of water-soluble, ion exchange and clay adsorption, iron-manganese oxide, and naked or seminaked states in the rock and ore samples is low, and some samples have high gold content of insoluble silicate states in the two methods. However, the gold content of organic matter bound, carbonate bound, and sulfide bound states obtained by ultrasonic centrifugation and cyclotron oscillation methods is significantly different. According to the X-ray fluorescence spectrometry data and the actual geological condition, the result given by the cyclotron oscillation method is more reasonable. The gold content of sulfide bound state in sediment samples is the highest and consistent with the mineral information, which could be applied to preliminarily predict the rock and ore conditions in the corresponding mining areas. In contrast with ultrasonic centrifugation, the cyclotron oscillation method has the advantages of simplicity, high efficiency, practicality, and environmental protection, and it can be better used for the determination of gold chemical phase state in geological samples by atomic absorption spectrometry.

14-α-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2) is an analogue of andrographolide (Andro, 1) coupled to α-lipoic acid (LA, 4). AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF)-κB activation in RIN-m cells. In the present study, glutathione (GSH, 3) was used as a simple chemical model molecule of NF-κB with cysteine 62. The characteristics of the reaction between AL-1 or Andro and GSH were investigated to trace some possible elucidation for the inhibitive mechanism and stronger inhibition of AL-1 to NF-κB activation. The results showed that the main reaction products of AL-1 and Andro were identical, sulfhydryl adduct and amino adduct. AL-1 reacted much faster than Andro with GSH. The product yield of AL-1 was much higher than that of Andro. It was speculated that AL-1 might inhibit NF-κB by the same mechanism as Andro. And the faster reaction rate and higher yield may account for the stronger NF-κB inhibition of AL-1 when compared with Andro.