Metal-Binding Protein TaGlo1 Improves Fungal Resistance to Arsenite (AsIII) and Methylarsenite (MAsIII) in Paddy Soil.

Trivalent arsenicals such as arsenite (AsIII) and methylarsenite (MAsIII) are thought to be ubiquitous in flooded paddy soils and have higher toxicity than pentavalent forms. Fungi are widely prevalent in the rice rhizosphere, and the latter is considered a hotspot for As uptake. However, few studies have focused on alleviating As toxicity in paddy soils using fungi. In this study, we investigated the mechanism by which the protein TaGlo1, derived from the As-resistant fungal strain Trichoderma asperellum SM-12F1, mitigates AsIII and MAsIII toxicity in paddy soils. Taglo1 gene expression in Escherichia coli BL21 conferred strong resistance to AsIII and MAsIII, while purified TaGlo1 showed a high affinity for AsIII and MAsIII. Three cysteine residues (Cys13, Cys18, and Cys71) play crucial roles in binding with AsIII, while only two (Cys13 and Cys18) play crucial roles for MAsIII binding. TaGlo1 had a stronger binding strength for MAsIII than AsIII. Importantly, up to 90.2% of the homologous TaGlo1 proteins originate from fungi by GenBank searching. In the rhizospheres of 14 Chinese paddy soils, Taglo1 was widely distributed and its gene abundance increased with porewater As. This study highlights the potential of fungi to mitigate As toxicity and availability in the soil-rice continuum and suggests future microbial strategies for bioremediation.

Targeting novel regulated cell death: Ferroptosis, pyroptosis and necroptosis in anti-PD-1/PD-L1 cancer immunotherapy.

Chemotherapy, radiotherapy, and immunotherapy represent key tumour treatment strategies. Notably, immune checkpoint inhibitors (ICIs), particularly anti-programmed cell death 1 (PD1) and anti-programmed cell death ligand 1 (PD-L1), have shown clinical efficacy in clinical tumour immunotherapy. However, the limited effectiveness of ICIs is evident due to many cancers exhibiting poor responses to this treatment. An emerging avenue involves triggering non-apoptotic regulated cell death (RCD), a significant mechanism driving cancer cell death in diverse cancer treatments. Recent research demonstrates that combining RCD inducers with ICIs significantly enhances their antitumor efficacy across various cancer types. The use of anti-PD-1/PD-L1 immunotherapy activates CD8+ T cells, prompting the initiation of novel RCD forms, such as ferroptosis, pyroptosis, and necroptosis. However, the functions and mechanisms of non-apoptotic RCD in anti-PD1/PD-L1 therapy remain insufficiently explored. This review summarises the emerging roles of ferroptosis, pyroptosis, and necroptosis in anti-PD1/PD-L1 immunotherapy. It emphasises the synergy between nanomaterials and PD-1/PD-L1 inhibitors to induce non-apoptotic RCD in different cancer types. Furthermore, targeting cell death signalling pathways in combination with anti-PD1/PD-L1 therapies holds promise as a prospective immunotherapy strategy for tumour treatment.

Changes in vegetation-water response in the Sahel-Sudan during recent decades.

Study region: The Africa Sahel-Sudan region, defined by annual rainfall between 150 and 1200 mm. Study focus: Understanding the mechanism of vegetation response to water availability could help mitigate the potential adverse effects of climate change on global dryland ecosystems. In the Sahel-Sudan region, spatio-temporal changes and drivers of the vegetation-water response remain unclear. This study employs long-term satellite water and vegetation products as proxies of water availability and vegetation productivity to analyze changes in vegetation-water sensitivity and the cumulative effect duration (CED) representing a measure of the legacy effect of the impact of water constraints on vegetation. A random forest model was subsequently used to analyze potential climatic drivers of the observed vegetation response. New hydrological insights for the region: During 1982-2016 we found a significant decrease (p < 0.05) in the sensitivity of vegetation productivity to water constraints in 26% of the Sahel-Sudan region, while 9% of the area showed a significantly increased sensitivity, mainly in the sub-humid zone. We further showed that CED significantly increased and decreased, respectively in around 9% of the study area in both cases. Our climatic driver attribution analysis suggested the existence of varying underlying mechanisms governing vegetation productivity in response to water deficit across the Sahel-Sudan dryland ecosystems. Our findings emphasize the need for diverse strategies in sustainable ecosystem management to effectively address these varying mechanisms.

Analysis of clinical evidence on traditional Chinese medicine for the treatment of diabetic nephropathy: a comprehensive review with evidence mapping.

Objective: This study aims to map evidence from Randomized Controlled Trials (RCTs) and systematic reviews/Meta-analyses concerning the treatment of Diabetic Nephropathy (DN) with Traditional Chinese Medicine (TCM), understand the distribution of evidence in this field, and summarize the efficacy and existing problems of TCM in treating DN. The intention is to provide evidence-based data for TCM in preventing and treating DN and to offer a reference for defining future research directions. Methods: Comprehensive searches of major databases were performed, spanning from January 2016 to May 2023, to include clinical RCTs and systematic reviews/Meta-analyses of TCM in treating DN. The analysis encompasses the publishing trend of clinical studies, the staging of research subjects, TCM syndrome differentiation, study scale, intervention plans, and outcome indicators. Methodological quality of systematic reviews was evaluated using the AMSTAR (Assessment of Multiple Systematic Reviews) checklist, and evidence distribution characteristics were analyzed using a combination of text and charts. Results: A total of 1926 RCTs and 110 systematic reviews/Meta-analyses were included. The majority of studies focused on stage III DN, with Qi-Yin deficiency being the predominant syndrome type, and sample sizes most commonly ranging from 60 to 100. The TCM intervention durations were primarily between 12-24 weeks. Therapeutic measures mainly consisted of Chinese herbal decoctions and patented Chinese medicines, with a substantial focus on clinical efficacy rate, TCM symptomatology, and renal function indicators, while attention to quality of life, dosage of Western medicine, and disease progression was inadequate. Systematic reviews mostly scored between 5 and 8 on the AMSTAR scale, and evidence from 94 studies indicated potential positive effects. Conclusion: DN represents a significant health challenge, particularly for the elderly, with TCM showing promise in symptom alleviation and renal protection. Yet, the field is marred by research inconsistencies and methodological shortcomings. Future investigations should prioritize the development of standardized outcome sets tailored to DN, carefully select evaluation indicators that reflect TCM's unique intervention strategies, and aim to improve the robustness of clinical evidence. Emphasizing TCM's foundational theories while incorporating advanced scientific technologies will be essential for innovating research methodologies and uncovering the mechanisms underlying TCM's efficacy in DN management.

Evidence mapping of traditional Chinese medicine in diabetic peripheral neuropathy treatment.

Objective: Diabetic peripheral neuropathy (DPN) stands as a crucial complication of diabetes, significantly affecting patients' quality of life. This study aims to elucidate the evidence distribution from clinical randomized controlled trials (RCTs) on DPN treatment with traditional Chinese medicine (TCM) through evidence mapping. Methods: A comprehensive search was conducted from January 2017 to October 2022 in databases such as Wanfang (China Online Journals), CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), SinoMed (Chinese Biomedical Literature Database), PubMed, Web of Science, and Cochrane Library. Literature related to the treatment of DPN with TCM was selected. From the 1,229 RCTs identified over the past 6 years, relevant data were extracted. The evidence mapping approach was utilized, and trends in publications, study scales, intervention types, and evaluation indicators were analyzed using descriptive text combined with tables and bubble charts. Results: Research on the treatment of DPN with TCM is extensive. The publication trend remains relatively stable with predominantly smaller sample sizes. The main treatments encompass oral Chinese medicine and traditional external treatments. The most common evaluation indicators are neurophysiological, efficiency rate, symptom signs, neuropathy scores, and traditional Chinese symptoms, with less focus on psychological status and the ankle-brachial index (ABI). Conclusion: Shedding light on contemporary research, this study explores the current RCTs evaluating TCM's efficacy in treating DPN. The findings not only highlight the potential role of TCM in addressing diabetic complications but also underscore areas that could benefit from refined research approaches, expanded intervention methods, and broader assessment criteria. Our observations aim to inform and inspire future research directions and clinical practices concerning TCM's role in managing diabetes-associated complications.

Necroptosis-related lncRNA-based novel signature to predict the prognosis and immune landscape in soft tissue sarcomas.

BACKGROUND: Necroptosis-related long noncoding RNAs (lncRNAs) play crucial roles in cancer initiation and progression. Nevertheless, the role and mechanism of necroptosis-related lncRNAs in soft tissue sarcomas (STS) is so far unknown and needs to be explored further. METHODS: Clinical and genomic data were obtained from the UCSC Xena database. All STS patients' subclusters were performed by unsupervised consensus clustering method based on the prognosis-specific lncRNAs, and then assessed their survival advantage and immune infiltrates. In addition, we explored the pathways and biological processes in subclusters through gene set enrichment analysis. At last, we established the necroptosis-related lncRNA-based risk signature (NRLncSig) using the least absolute shrinkage and selection operator (LASSO) method, and explored the prediction performance and immune microenvironment of this signature in STS. RESULTS: A total of 911 normal soft tissue samples and 259 STS patients were included in current study. 39 prognosis-specific necroptosis-related lncRNAs were selected. Cluster 2 had a worse survival than the cluster 1 and characterized by different immune landscape in STS. A worse outcome in the high-risk group was observed by survival analysis and indicated an immunosuppressive microenvironment. The ROC curve analyses illustrated that the NRLncSig performing competitively in prediction of prognosis for STS patients. In addition, the nomogram presents excellent performance in predicting prognosis, which may be more beneficial towards STS patients' treatment. CONCLUSIONS: Our result indicated that the NRLncSig could be a good independent predictor of prognosis, and significantly connected with immune microenvironment, thereby providing new insights into the roles of necroptosis-related lncRNAs in STS.

Abnormal heart rate responses to exercise in non-severe COPD: relationship with pulmonary vascular volume and ventilatory efficiency.

BACKGROUND: Despite being a prognostic predictor, cardiac autonomic dysfunction (AD) has not been well investigated in chronic obstructive pulmonary disease (COPD). We aimed to characterise computed tomography (CT), spirometry, and cardiopulmonary exercise test (CPET) features of COPD patients with cardiac AD and the association of AD with CT-derived vascular and CPET-derived ventilatory efficiency metrics. METHODS: This observational cohort study included stable, non-severe COPD patients. They underwent clinical evaluation, spirometry, CPET, and CT. Cardiac AD was determined based on abnormal heart rate responses to exercise, including chronotropic incompetence (CI) or delayed heart rate recovery (HRR) during CPET. RESULTS: We included 49 patients with FEV1 of 1.2-5.0 L (51.1-129.7%), 24 (49%) had CI, and 15 (31%) had delayed HRR. According to multivariate analyses, CI was independently related to reduced vascular volume (VV; VV ≤ median; OR [95% CI], 7.26 [1.56-33.91]) and low ventilatory efficiency (nadir VE/VCO2 ≥ median; OR [95% CI], 10.67 [2.23-51.05]). Similar results were observed for delayed HRR (VV ≤ median; OR [95% CI], 11.46 [2.03-64.89], nadir VE/VCO2 ≥ median; OR [95% CI], 6.36 [1.18-34.42]). CONCLUSIONS: Cardiac AD is associated with impaired pulmonary vascular volume and ventilatory efficiency. This suggests that lung blood perfusion abnormalities may occur in these patients. Further confirmation is required in a large population-based cohort.

Surgical treatment of multiple magnet ingestion by children: A single-center experience from China.

BACKGROUND: The incidence of magnet ingestion in children has escalated concurrent with the rise in popularity of magnetic playthings, bearing the capacity to induce substantial morbidity. AIM: The objective of this study was to encapsulate our accumulated expertise in handling pediatric cases featuring multiple magnetic foreign bodies within the gastrointestinal tract sometimes necessitating surgical intervention, as well as to formulate a clinical management algorithm. METHODS: This was a retrospective review of patients with multiple magnetic foreign bodies in the digestive tract, admitted to Shenzhen Children's Hospital, between January 2018 and December 2022. RESULTS: A total of 100 cases were included in this study, including 66 males and 34 females. The main clinical manifestation ns were abdominal pain and vomiting. All patients had abdominal x-ray, all of which indicated foreign bodies in the digestive tract. 33 patients had to undergo a surgical intervention. Among these cases, the gastrointestinal complications occurred in 31 patients, including gastric rupture (n = 9), intestinal obstruction (n = 11) and intestinal perforation (n = 30). Postoperative intestinal obstruction occurred in 6 children. There was no statistical significant difference in age and gender between the Surgical group and Non-surgical group, but the Surgical group had a higher number of magnets ([7.5(2-44) vs 4(2-20)], p = 0.009), a longer interval between time of misingestion to clinical visit ([48(7.2-480) vs 5(2-336)]hours, p < 0.001), and a longer length of hospital stay ([10(6-19) vs 2(1-8)]days, p < 0.001). CONCLUSIONS: Multiple magnet ingestion in children can lead to serious complications and carry severe risks. Timely diagnosis and effective treatment are crucial for managing such patients.

Association between physical activity and the prevalence of kidney stones in American adults: results from a multi-year national survey.

OBJECTIVE: To investigate the association between physical activity and the prevalence of kidney stones. METHODS: A cross-section study was conducted using data from National Health and Nutrition Examination Survey 2007-2018. Physical activity was evaluated based on the Global Physical Activity Questionnaire. Multivariable logistic regression was performed to elucidate the association between physical activity (patterns, intensity, duration and frequency of moderate and vigorous physical activity) and the prevalence of kidney stones after adjusting for potential confounders. Stratified and interaction analyses were conducted to detect potential effect modifiers. In addition, physical activity was assessed using metabolic equivalent and physical volume, and followed the regression above. Water intake was obtained from the day 2 dietary recall and was included in the sensitivity analysis. RESULTS: A total of 34,390 participants were included in the analysis. The multivariable logistic regression revealed that individuals who engaged in moderate physical activity for 30-60 minutes per day had a significant inverse association with the prevalence of kidney stones in the fully-adjusted model (OR=0.804, 95%CI 0.700 to 0.923), while no more significant finding was observed for other physical activity parameters. Interaction and stratified analyses indicated no covariate modifying the association. The results above were robust in the sensitivity analysis. CONCLUSION: The duration of moderate physical activity (30-60 mins/day) is inversely associated with the prevalence of kidney stones, while no more significant association was observed between other physical activity parameters (including patterns, intensity, duration and frequency of vigorous physical activity, frequency of moderate physical activity) and kidney stones. DATA AVAILABILITY: Data available in a publicly accessible repository that does not issue DOIs. Publicly available datasets were analyzed in this study. These data can be found here: https://www.cdc.gov/nchs/nhanes/index.htm.

[Effect of Low-Dose Recombinant Interleukin-2 Therapy on Immunocyte Subsets in Children with Solid Tumor].

OBJECTIVE: To evaluate the effect of low-dose recombinant interleukin-2 (rIL-2) therapy on immunocyte subsets and its side effects in children with solid tumor. METHODS: A total of 22 children (11 males and 11 females) with solid tumor in our department from December 2012 to November 2017 were selected, with a median age of 9 (3-16) years old when starting IL-2 therapy. ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy, and 17 cases achieved complete remission (CR) and 5 cases achieved partial remission (PR). A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year: 4×105 IU/(m2·d), s.c. for every other day, 3 times per week. The immunocyte subsets were detected every 3 months until the end of treatment, meanwhile, disease condition and therapy-related side effects were followed up. RESULTS: After low-dose rIL-2 therapy in 22 children, the absolute values of CD3+ T cells, CD3-CD56+ natural killer cells, CD3+CD4+ helper T cells (Th) and CD3+CD8+ cytotoxic T cells were up-regulated remarkably, as well as Th/suppressor T cells (all P < 0.05). While, there were no significant differences in absolute value and proportion of CD4+CD25+CD127- Treg cells during therapy. Among the 17 children who achieved CR before rIL-2 therapy, 14 cases continued to maintain CR after therapy, while 3 cases relapsed, and with 2 died after treatment abandonment. The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment. In the early stage of low-dose rIL-2 therapy, 1 child developed skin rashes at the injection sites, and 2 children ran a slight to mild transient fever. Their symptoms disappeared without any organ damage after symptomatic treatment. CONCLUSION: Low-dose rIL-2 therapy has good drug tolerance, and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

A sensitive and versatile electrochemical sensor based on hybridization chain reaction and CRISPR/Cas12a system for antibiotic detection.

A sensitive electrochemical platform was constructed with NH2-Cu-MOF as electrochemical probe to detect antibiotics using CRISPR/Cas12a system triggered by hybridization chain reaction (HCR). The sensing system consists of two HCR systems. HCR1 occurred on the electrode surface independent of the target, generating long dsDNA to connect signal probes and producing a strong electrochemical signal. HCR2 was triggered by target, and the resulting dsDNA products activated the CRISPR/Cas12a, thereby resulting in effective and rapid cleavage of the trigger of HCR1, hindering the occurrence of HCR1, and reducing the number of NH2-Cu-MOF on the electrode surface. Eventually, significant signal change depended on the target was obtained. On this basis and with the help of the programmability of DNA, kanamycin and ampicillin were sensitively detected with detection limits of 60 fM and 10 fM (S/N = 3), respectively. Furthermore, the sensing platform showed good detection performance in milk and livestock wastewater samples, demonstrating its great application prospects in the detection of antibiotics in food and environmental water samples.

UPLC-Q-TOF/MS analysis of chemical components of single decoction and combined decoction of Qige decoction reveals the differences between various preparation processes.

The aim of this work was to explore the differences between various pharmaceutical processes in combined solutions of a single decoction (QGHBY) and a combined decoction (QGHJY) of Qi-Ge decoction from the perspective of chemical composition changes, so as to further guide the clinical application of drugs. A combined solution of a single decoction and a combined decoction of Astragali Radix, Puerariae Lobatae Radix and Citri Reticulatae Chachiensis Pericarpium was prepared with the same technological parameters. The chemical components of the two were detected and identified based on UPLC-Q-TOF/MS, and the different components were determined by principal component analysis. Eighty-eight compounds were identified in the pharmaceutical solution of Qi-Ge decoction. Principal component analysis revealed 11 different components of QGHBY and QGHJY with the conditions of Variable Importance in Projection (VIP) ≥ 1, fold change ≥ 2 and p < 0.05, among which hesperidin, hesperitin, isosinensetin, sinensetin and 5-demethylnobiletin were the components of Citri Reticulatae Chachiensis Pericarpium. The levels of these 11 different components in QGHJY were higher than those of QGHBY. The combined decoction is beneficial for the dissolution of flavonoids and other chemical components, and there is a significant difference in the content of chemical components between modern herbal concentrate granules and traditional decoctions.

Portable purge and trap-microplasma optical emission spectrometric device for field detection of iodine in water.

Iodine is essential for human growth and can enter the body through food, water, and air. Analyzing its presence in the environment is crucial for ensuring healthy human development. However, current large-scale instruments have limitations in the field analysis of iodine. Herein, a miniaturized purge and trap point discharge microplasma optical emission spectrometric (P&T-µPD-OES) device was developed for the field analysis of iodine in water. Volatile iodine molecules were produced from total inorganic iodine (TII) through a basic redox reaction under acidic conditions, then the purge and trap module effectively separated and preconcentrated iodine molecules. The iodine molecules were subsequently atomized and excited by the integrated point discharge microplasma and an iodine atomic emission line at 206.24 nm was monitored by the spectrometer. Under optimal conditions, this proposed method had a detection limit of 16.2 µg L-1 for iodine and a precision better than 4.8%. Besides, the accuracy of the portable device was validated by successful analysis of surface and groundwater samples and a comparison of the mass spectrometry method. This proposed portable, low-power device is expected to support rapid access to iodine levels and distribution in water.

Label-free electrochemical sensing platform for sensitive detection of ampicillin by combining nucleic acid isothermal enzyme-free amplification circuits with CRISPR/Cas12a.

The residue of ampicillin (AMP) in food and ecological environment poses a potential harm to human health. Therefore, a reliable system for detecting AMP is in great demand. Herein, a label-free and sensitive electrochemical sensor utilizing NH2-Co-MOF as an electrocatalytic active material for methylene blue (MB) was developed for rapid and facile AMP detection by combining hybridization chain reaction (HCR), catalytic hairpin assembly (CHA) with CRISPR/Cas12a. The surface of glassy carbon electrode modified with NH2-Co-MOF was able to undergo HCR independent of the AMP, forming long dsDNA complexes to load MB, resulting in strong original electrochemical signal. The presence of AMP could trigger upstream CHA circuit to activate the CRISPR/Cas12a system, thereby achieving rapid non-specific cleavage of the trigger ssDNA of HCR on the electrode surface, hindering the occurrence of HCR and reducing the load of MB. Significant signal change triggered by the target was ultimately obtained, thus achieving sensitive detection of the AMP with a detection limit as low as 1.60 pM (S/N = 3). The proposed sensor exhibited good stability, selectivity, and stability, and achieved reliable detection of AMP in milk and livestock wastewater samples, demonstrating its promising application prospects in food safety and environmental monitoring.

Multiple signal amplification strategy induced by biomarkers of lung cancer: A self-powered biosensing platform adapted for smartphones.

Lung cancer is a major malignant cancer with low survival rates, and early diagnosis is crucial for effective treatment. Herein, a biosensing platform that is self-powered derived from a capacitor-coupled EBFC has been developed for ultra-sensitive real-time identification of microRNA-21 (miRNA-21) with the assistance of a mobile phone. The flexible substrate of the platform is prepared on a carbon paper modified with graphdiyne and gold nanoparticles. The biosensor employs DNAzyme-mediated dual strand displacement amplification, which enhances the signal output intensity of the EBFC and improves selectivity. The coupling of the capacitor with the EBFC significantly amplifies the sensing signal, causing a 10.6-fold surge in current respond and further improving the sensitivity of the sensing platform. The established detection approach demonstrates a linear relationship varied from 0.0001 to 10,000 pM, with a sensitivity down to 32.3 aM as the minimum detectable limit, which has been effectively utilized for detecting miRNA-21 in practical samples. This sensing system provides strong support for the construction of portable detection devices, and the strategy of the platform construction provides an effective method for ultra-sensitive and accurate detection of miRNA, holding great potential in clinical diagnosis, prognosis evaluation, and drug screening for cancer.

Interleukin-2/anti-interleukin-2 complex attenuates inflammation in a mouse COPD model by expanding CD4+ CD25+ Foxp3+ regulatory T cells.

BACKGROUND AND PURPOSE: Chronic, nonspecific inflammation of the alveoli and airways is an important pathological feature of chronic obstructive pulmonary disease (COPD), while sustained inflammatory reactions can cause alveolar damage. Regulatory T cells (Tregs) inhibit inflammation, whereas the interleukin-2/anti-interleukin-2 complex (IL-2C) increases the number of Tregs; however, whether the IL-2C has a therapeutic role in COPD remains unknown. Therefore, this study investigated whether IL-2C alleviates lung inflammation in COPD by increasing the number of Tregs. EXPERIMENTAL APPROACH: A mouse COPD model was created by exposing mice to lipopolysaccharides (LPS) and cigarette smoke (CS), and the effects of IL-2C treatment on COPD were evaluated. The number of Tregs in the spleen and lung, pulmonary pathological changes, and inflammatory damage were examined through flow cytometry, histopathology, and immunofluorescence, respectively. KEY RESULTS: IL-2C increased the number of Treg cells in the spleen and lungs after exposure to CS and LPS, reduced the number of T helper 17 (Th17) cells in lung tissue, and improved the Th17/Treg balance. IL-2C decreased the number of inflammatory cells and reduced the levels of pro-inflammatory cytokines IL-6, TNF-α, IL-1ß, CCL5, KC, and MCP-1 in bronchoalveolar lavage fluid and serum. IL-2C significantly reduced the pathological scores for lung inflammation, as well as decreased airway mucus secretion and infiltration of neutrophils and macrophages in the lungs. The depletion of Tregs using anti-CD25 antibodies eliminated the beneficial effects of IL-2C. CONCLUSIONS AND IMPLICATIONS: IL-2C is a potential therapeutic agent for alleviating excessive inflammation in the lungs of patients with COPD.

Hypoxia leads to gill endoplasmic reticulum stress and disruption of mitochondrial homeostasis in grass carp (Ctenopharyngodon idella): Mitigation effect of thiamine.

Hypoxia in water environment is one of the important problems faced by intensive aquaculture. Under hypoxia stress, the effects of dietary thiamine were investigated on grass carp gill tissue damage and their mechanisms. Six thiamine diets with different thiamine levels (0.22, 0.43, 0.73, 1.03, 1.33 and 1.63 mg/kg) were fed grass carp (Ctenopharyngodon idella) for 63 days. Then, 96-hour hypoxia stress test was conducted. This study described that thiamine enhanced the growth performance of adult grass carp and ameliorated nutritional status of thiamine (pyruvic acid, glucose, lactic acid and transketolase). Additionally, thiamine alleviated the deterioration of blood parameters [glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), glucose, cortisol, lactic dehydrogenase (LDH), erythrocyte fragility, and red blood cell count (RBC count)] caused by hypoxia stress, and reduced reactive oxygen species (ROS) content and oxidative damage to the gills. In addition, thiamine alleviated endoplasmic reticulum stress in the gills, which may be related to its inhibition of RNA-dependent protein kinase-like ER kinase (PERK)/eukaryotic translation initiation factor-2α (eIF2α)/activating transcription factor4 (ATF4), inositol-requiring enzyme 1 (IRE1)/X-Box binding protein 1 (XBP1) and activating transcription factor 6 (ATF6) pathways. Furthermore, thiamine maintaining mitochondrial dynamics balance was probably related to promoting mitochondrial fusion and inhibiting mitochondrial fission, and inhibiting mitophagy may involve PTEN induced putative kinase 1 (PINK1)/Parkin-dependent pathway and hypoxia-inducible factor (HIF)-Bcl-2 adenovirus E1B 19 kDa interacting protein 3 (BNIP3) pathway. In summary, thiamine alleviated hypoxia stress in fish gills, which may be related to reducing endoplasmic reticulum stress, regulating mitochondrial dynamics balance and reducing mitophagy. The thiamine requirement for optimum growth [percent weight gain (PWG)] of adult grass carp was estimated to be 0.81 mg/kg diet. Based on the index of anti-hypoxia stress (ROS content in gill), the thiamine requirement for adult grass carp was estimated to be 1.32 mg/kg diet.

Local Treatment of Children Suffering From Parameningeal Rhabdomyosarcoma: A Retrospective Single-Center Study From China.

BACKGROUND: Treatment for parameningeal rhabdomyosarcoma (PM-RMS) has been a challenge since local control is difficult. The goal of this study was to analyse the impact of different local treatment approaches on childhood PM-RMS patients and help dispel the doubt that whether secondary radical surgery (SRS) should be encouraged in the management of PM-RMS. METHODS: A total of 17 children with PM-RMS who received unified systemic chemotherapy and individualized local therapy such as radiotherapy (RT) and/or SRS were included in this retrospective study. The overall survival (OS) and event free survival (EFS) were compared between groups adopting different local strategies. RESULTS: The 3-year OS and EFS of our PM-RMS patients was 75.5% and 56.5% respectively. The OS and EFS of patients who received SRS were both significantly lower than that of the non-SRS group (3-year OS: 50.0% vs 90.0%, P = .031; 3-year EFS: 33.3% vs 60.6%, P = .020). The OS and EFS of the patients who received RT was higher than that of the patients of the non-RT group (3-year OS: 85.6% vs 0%, P = .001; 3-year EFS: 64.0% vs 0%, P = .011). CONCLUSION: This study illustrates that SRS was associated with poor prognosis of PM-RMS and should not be routinely performed. Optimized RT strategies along with more intensive chemotherapy may be alternative options to improve the survival of patients with PM-RMS. Multi-center, large sample and prospective studies are needed to further validate these findings.

Cycloplatinated (II) Complex Based on Isoquinoline Alkaloid Elicits Ferritinophagy-Dependent Ferroptosis in Triple-Negative Breast Cancer Cells.

The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance and side effects. Agents that simultaneously induce ferroptosis and autophagic death have received extensive attention as potential modalities for cancer therapy. However, only a limited set of drugs or treatment modalities can synergistically induce ferroptosis and autophagic tumor cell death. In this work, we designed and synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C∧N ligand. On screening the in vitro activity of these agents, we found that Pt-3 exhibited greater selectivity of cytotoxicity, decreased resistance factors, and improved anticancer activity compared to cisplatin. Furthermore, Pt-3, which we demonstrate can initiate potent ferritinophagy-dependent ferroptosis, exhibits less toxic and better therapeutic activity than cisplatin in vivo. Our results identify Pt-3 as a promising candidate or paradigm for further drug development in cancer treatment.

Arsenic field test kits based on solid-phase fluorescence filter effect induced by silver nanoparticle formation.

Millions of people worldwide are affected by naturally occurring arsenic in groundwater. The development of a low-cost, highly sensitive, portable assay for rapid field detection of arsenic in water is important to identify areas for safe wells and to help prioritize testing. Herein, a novel paper-based fluorescence assay was developed for the on-site analysis of arsenic, which was constructed by the solid-phase fluorescence filter effect (SPFFE) of AsH3-induced the generation of silver nanoparticles (AgNPs) toward carbon dots. The proposed SPFFE-based assay achieves a low arsenic detection limit of 0.36 µg/L due to the efficient reduction of Ag+ by AsH3 and the high molar extinction coefficient of AgNPs. In conjunction with a smartphone and an integrated sample processing and sensing platform, field-sensitive detection of arsenic could be achieved. The accuracy of the portable assay was validated by successfully analyzing surface and groundwater samples, with no significant difference from the results obtained through mass spectrometry. Compared to other methods for arsenic analysis, this developed system offers excellent sensitivity, portability, and low cost. It holds promising potential for on-site analysis of arsenic in groundwater to identify safe well locations and quickly obtain output from the global map of groundwater arsenic.