An acid-activatable fluorouracil prodrug for colorectal cancer synergistic therapy.

5-Fluorouracil has demonstrated certain efficiency in patients with colorectal cancer. However, significant side effects of use by injection are common. To address this issue defects, a reengineered 5'-deoxy-5-fluorocytidine (DFCR) based drug delivery system (POACa) is developed as a prominent tumor-selective nano-activator. Investigations demonstrate that the constructed nano-activator exhibits good biocompatibility and high therapeutic efficiency in mice with subcutaneous and orthotopic SW-480 colorectal tumors, as its activity is strictly dependent on the tumor-associated acid environment and thymidine phosphorylase. These strategies diminish the off-target toxicity and improve the specificity and sensitivity of human colorectal cancer cells to 5-Fu, obtaining potent efficiency by the combination of H2O2 mediated oxidative stress, calcium overload and 5-Fu-induced chemotherapy (the combination index is 0.11). Overall, the engineered nano-activator exhibits a high therapeutic index in vitro and in vivo. STATEMENT OF SIGNIFICANCE: In this study, we designed and prepared a pH-responsive polymer to synchronously deliver DFCR (5'-deoxy-5-fluorocytidine, a prodrug of 5-Fu), Ca2+ and H2O2. The constructed nano-activator was denoted as POACa. (1) To address the problem of premature leakage of cargo by physical embedding, our research modified the inactive prodrug DFCR through chemical bonding. (2) The activation of the prepared nano-activator was strictly dependent on the tumor-associated acid environment and thymidine phosphorylase, providing the drug delivery system with inherent safety. (3) A distinctly low combination index value (0.11) of CaO2 and DFCR indicated that POACa has a prominent tumor suppression effect by tumor calcium overload sensitized chemotherapy and H2O2 mediated cytotoxicity.

Compensatory thickening of cortical thickness in early stage of schizophrenia.

Brain structural abnormality has been observed in the prodromal and early stages of schizophrenia, but the mechanism behind it is not clear. In this study, to explore the association between cortical abnormalities, metabolite levels, inflammation levels and clinical symptoms of schizophrenia, 51 drug-naive first-episode schizophrenia (FES) patients, 51 ultra-high risk for psychosis (UHR), and 51 healthy controls (HC) were recruited. We estimated gray matter volume (GMV), cortical thickness (CT), concentrations of different metabolites, and inflammatory marks among four groups (UHR converted to psychosis [UHR-C], UHR unconverted to psychosis [UHR-NC], FES, HC). UHR-C group had more CT in the right lateral occipital cortex and the right medial orbito-frontal cortex (rMOF), while a significant reduction in CT of the right fusiform cortex was observed in FES group. UHR-C group had significantly higher concentration of IL-6, while IL-17 could significantly predict CT of the right fusiform and IL-4 and IL-17 were significant predictors of CT in the rMOF. To conclude, it is reasonable to speculate that the increased CT in UHR-C group is related to the inflammatory response, and may participate in some compensatory mechanism, but might become exhaustive with the progress of the disease due to potential neurotoxic effects.

Lysophosphatidic acid promotes ESCC progression by increasing the level of CCL2 secreted by esophageal epithelial cells.

BACKGROUND: Lysophosphatidic acid (LPA) is a small bioactive lipid which acts as a potent regulator in various tumor progressions through six G-protein-coupled receptors (LPA1-LPA6). Our previous study demonstrated that the LPA-producing enzyme, autotaxin (ATX), was upregulated in esophageal squamous cell carcinoma (ESCC) and ATX high expression levels indicated a poor prognosis. Esophageal squamous cell carcinoma is a type of malignant tumor which originates from epithelial cells. Its progression can be affected by the interaction between cancer cells and normal cells. However, the impact of LPA on the interaction between esophageal epithelial cells and cancer cells in the development of ESCC remains uncertain. METHODS: MTS and Edu assays were performed to determine ESCC cell proliferation in culture medium (CM) derived from LPA-stimulated esophageal epithelial cells (Het-1a). A wound healing assay, transwell migration and an invasion assay were performed to assess the metastatic ability of ESCC cells. Cytokine array analysis was conducted to detect the differentially secreted cytokines in CM. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to uncover the pathways and cytokines that are influenced by LPA in ESCC. Immunohistochemical staining was employed to measure the expression of ATX and CCL2 in early-stage ESCC. Quantitative real-time PCR, western blot, enzyme-linked immunosorbent assay and an antibody neutralization assay were employed to measure the mechanism of LPA-mediated communication between epithelial cells and cancer cells. RESULTS: Functional experiments showed that exposing ESCC cancer cells to CM from LPA-treated Het-1a results in promoting proliferation, migration, invasion and epithelial-mesenchymal transition processes. Using cytokine array analysis, we discovered that LPA triggers the release of multiple cytokines from epithelial cells. After screening of the TCGA and GEO databases, CCL2 was identified and found to be correlated with ATX expression in ESCC. Furthermore, CCL2 levels in both mRNA expression and secretion were observed to be upregulated in epithelial cells upon stimulation with LPA. Blocking CCL2 effectively reduced the pro-migration influence of CM derived from LPA-treated Het-1a. Mechanism studies have demonstrated that LPA activated the NF-κB signaling pathway through LPA1/3, ultimately causing an increase in CCL2 expression and secretion in Het-1a. CONCLUSIONS: Our findings, taken together, demonstrate that CM from LPA-treated esophageal epithelial cells plays a significant role in promoting the progression of ESCC, with CCL2 acting as the primary regulator.

Impairment of olfactory identification ability in ultra-high risk for psychosis and drug-naïve first episode psychosis.

OBJECTIVE: Patients with psychotic diseases have been reported to exhibit abnormalities in their olfactory discrimination. These alterations have also been identified in people at high genetic or clinical risk for psychosis, suggesting olfactory discrimination dysfunction may be a potential risk factor for developing psychosis. Thus, the purpose of our study is to explore the difference in olfactory discrimination ability in the prosal stage and early stage of psychosis and to explore the potential risk factor of developed psychosis. METHODS: We compared olfactory identification and cognitive function in 89 ultra-high-risk (UHR) individuals, 103 individuals with Drug-naïve first-episode schizophrenia (FES), 81 genetic high-risk (GHR) individuals, and 97 healthy controls (HC). Additionally, we compared olfactory identification and cognitive function between two groups; UHR individuals who later transitioned to psychosis (UHR-T; n = 33) and those who did not transition (UHR-NT; n = 42)). Furthermore, we analyzed the correlations between olfactory discrimination ability and cognitive function and symptoms and compared the olfactory function between men and women. RESULTS: Patients with first-episode schizophrenia (FES) and those at ultra-high risk (UHR) for psychosis exhibited more significant deficits in olfactory identification than healthy controls (HC), while no differences in olfactory identification dysfunction were observed between the genetic high risk (GHR) and HC groups. Notably, individuals in the UHR group who later developed psyhchosis displayed a steeper marked decline in their baseline olfactory identification ability than that of those in the UHR group who did not develop psychosis. Cognitive dysfunction is widely observed in both the FES and UHR groups, with a distinct correlation identified between olfactory discrimination function and cognitive performance. Finally, overall, women exhibit significantly superior olfactory function than men. CONCLUSION: In conclusion, these findings suggest that impairment of olfactory identification exists in the early stage of psychosis. Olfactory identification dysfunction may therefore be a potential marker of predicting the transition to schizophrenia.

Facile synthesis of Bi3O(OH)(AsO4)2 and simultaneous photocatalytic oxidation and adsorption of Sb(III) from wastewater.

Antimony (Sb) decontamination in water is necessary owing to the worsening pollution which seriously threatens human life safety. Designing bismuth-based photocatalysts with hydroxyls have attracted growing interest because of the broad bandgap and enhanced separation efficiency of photogenerated electron/hole pairs. Until now, the available photocatalysis information regarding bismuth-based photocatalysts with hydroxyls has remained scarce and the contemporary report has been largely limited to Bi3O(OH)(PO4)2 (BOHP). Herein, Bi3O(OH)(AsO4)2 (BOHAs), a novel ultraviolet photocatalyst, was fabricated via the co-precipitation method for the first time, and developed to simultaneous photocatalytic oxidation and adsorption of Sb(III). The rate constant of Sb(III) removal by the BOHAs was 32.4, 3.0, and 4.3 times higher than those of BiAsO4, BOHP, and TiO2, respectively, indicating that the introduction of hydroxyls could increase the removal of Sb(III). Additionally, the crucial operational parameters affecting the adsorption performance (catalyst dosage, concentration, pH, and common anions) were investigated. The BOHAs maintained 85% antimony decontamination of the initial yield after five successive cycles of photocatalysis. The Sb(III) removal involved photocatalytic oxidation of adsorbed Sb(III) and subsequent adsorption of the yielded Sb(V). With the acquired knowledge, we successfully applied the photocatalyst for antimony removal from industrial wastewater. In addition, BOHAs could also be powerful photocatalysts in the photodegradation of organic pollutants studies of which are ongoing. It reveals an effective strategy for synthesizing bismuth-based photocatalysts with hydroxyls and enhancing pollutants' decontamination.

Clinical outcome of non-curative endoscopic submucosal dissection for early gastric cancer.

Background: Early gastric cancer (EGC) is defined as cancer cells confined to the mucosal or submucosal layer, irrespective of size or presence of lymph node metastasis. The recent EGC endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) guidelines (2021 Japan Gastroenterological Endoscopy Society (JGES) guidelines, 2nd edition) revised the concept from "endoscopic curative/non-curative resection" (NCR) to "endoscopic curability (eCura)". Under this, eCuraA and eCuraB signify curative resections (CRs), while eCuraC (including eCuraC-1 and eCura-C2) indicate NCRs. This study retrospectively analyzes clinical and pathological data from EGC patients who underwent endoscopic resection, assessing the long-term clinical outcomes in a substantial cohort after undergoing NCR. Methods: We retrospectively analyzed clinical and pathological data from 443 EGC patients, encompassing 478 lesions, who received endoscopic treatment. The long-term clinical outcomes of patients who underwent NCR were statistically evaluated. Characteristics of the NCR group were compared with those of the surgical group, employing single- and multi-factor logistic regression analyses to identify risk factors that necessitate further surgical intervention. Prognostically, the Kaplan-Meier method and Log-Rank test determined the impact of risk factors on recurrence-free survival post-surgery in NCR patients. Differences were assessed using a method incorporating statistically significant differences in the multi-factor Cox regression analysis, evaluating the hazard ratio (HR) for disease recurrence following NCR. Results: In this study, 443 EGC cases were pathologically diagnosed, comprising a total of 478 lesions. Of these, 127 cases underwent non-curative endoscopic resection, resulting in a NCR rate of 24.4%. Long-term follow-up was achieved for 117 (92.12%) patients. The metastasis/recurrence rate at 6 months stood at 23.1%. Multivariate Cox regression analysis identified lesion size ≥2.0 and <3 cm [P=0.02, HR =0.12, 95% confidence interval (CI): 0.02-0.67], presence of ulceration (P=0.03, HR =5.48, 95% CI: 1.23-24.33), lymphatic invasion (P=0.05, HR =17.51, 95% CI: 1.07-286.23), positive vertical margins (P=0.09, HR =3.77, 95% CI: 0.81-17.53), and flat macroscopic morphology (P=0.048, HR =4.8, 95% CI: 1.01-22.73) as independent risk factors for recurrence-free survival post non-curative endoscopic resection in EGC patients. Conclusions: The recurrence/metastasis rate in patients who underwent NCR is notably higher compared to the control group. Significant prognostic risk factors include tumor size ≥2.0 and <3 cm, positive vertical margins, lymphatic invasion, and flat type (one of pathological gross classification). Patients in the eCuraC-2 category of NCR should consider further surgical intervention. The necessity for additional surgical intervention in these patients warrants further investigation.

Smad2/3/4 complex could undergo liquid liquid phase separation and induce apoptosis through TAT in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-ß signaling pathway may be associated with tumor progression. However, the relationship between TGF-ß signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-ß signaling pathway on HCC progression as well as the potential regulatory mechanism involved. METHODS: We conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni-NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo. RESULTS: We found that Smad2/3/4 complex could regulate tyrosine aminotransferase (TAT) expression, and this regulation could relate to LLPS. CHIP qPCR results showed that the key targeted DNA binding site of Smad2/3/4 complex in TAT promoter region is -1032 to -1182. In addition. CCK-8, colony formation, and nude mice tumor transplantation assays showed that Smad2/3/4 complex could repress cell proliferation through TAT. Flow cytometry assay results showed that Smad2/3/4 complex could increase the apoptosis of hepatoma cells. Western blot results showed that Smad2/3/4 complex would active caspase-9 through TAT, which uncovered the mechanism of Smad2/3/4 complex inducing hepatoma cell apoptosis. CONCLUSION: This study proved that Smad2/3/4 complex could undergo LLPS to active TAT transcription, then active caspase-9 to induce hepatoma cell apoptosis in inhibiting HCC progress. The research further elucidate the relationship between TGF-ß signaling pathway and HCC, which contributes to discover the mechanism of HCC development.

Integrated anti-vascular and immune-chemotherapy for colorectal carcinoma using a pH-responsive polymeric delivery system.

Colorectal carcinoma (CRC) has become one of the most prevalent malignant tumors and exploring a potential therapeutic strategy with diminished drug-associated adverse effects to combat CRC is urgent. Herein, we designed a pH-responsive polymer to efficiently encapsulate a stimulator of interferon genes (STING) agonist (5,6- dimethylxanthenone-4-acetic acid, termed ASA404) and a common clinically used chemotherapeutic agent (1-hexylcarbamoyl-5-fluorouracil, termed HCFU). Investigations in vitro demonstrated that polymer encapsulation endowed the system with a pH-dependent disassembly behavior (pHt 6.37), which preferentially selected cancerous cells with a favorable dose reduction (dose reduction index (DRI) of HCFU was 4.09). Moreover, the growth of CRC in tumor-bearing mice was effectively suppressed, with tumor suppression rates up to 94.74%, and a combination index (CI) value of less than one (CI = 0.41 for CT26 cell lines), indicating a significant synergistic therapeutic effect. Histological analysis of the tumor micro-vessel density and enzyme-linked immunosorbent assay (ELISA) tests indicated that the system increased TNF-α and IFN-ß levels in serum. Therefore, this research introduces a pH-responsive polymer-based theranostic platform with great potential for immune-chemotherapeutic and anti-vascular combination therapy of CRC.

Hemodynamics and arrhythmia disorder caused by lithium poisoning: A case report. / 锂中毒导致心律失常、血流动力学障碍1例.

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes. Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder. However, its therapeutic dosage closely approaches toxic levels. Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L, typically giving rise to gastrointestinal and central nervous system reactions. Cardiac toxicity is rare but serious in cases of lithium poisoning. The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers. This resulted in symptoms such as arrhythmia, shock, impaired consciousness, and coarse tremors. Following symptomatic supportive treatment, including blood dialysis, the patient's physical symptoms gradually improved. It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.

Low-cost pyrolysis of biomass-derived nitrogen-doped porous carbon: Chlorella vulgaris replaces melamine as a nitrogen source.

Porous carbon generated from biomass has a rich pore structure, is inexpensive, and has a lot of promise for use as a carbon material for energy storage devices. In this work, nitrogen-doped porous carbon was prepared by co-pyrolysis using bagasse as the precursor and chlorella as the nitrogen source. ZnCl2 acts as both an activator and a nitrogen fixer during activation to generate pores and reduce nitrogen loss. The thermal weight loss experiments showed that the pyrolysis temperatures of bagasse and chlorella overlap, which created the possibility for the synthesis of nitrogen-rich biochar. The optimum sample (ZBC@C-5) possessed a surface area of 1508 m2g-1 with abundant nitrogen-containing functional groups. ZBC@C-5 in the three-electrode system exhibited 244.1F/g at 0.5A/g, which was extremely close to ZBC@M made with melamine as the nitrogen source. This provides new opportunities for the use of low-cost nitrogen sources. Furthermore, the devices exhibit better voltage retention (39%) and capacitance retention (96.3%). The goal of this research is to find a low cost, and effective method for creating nitrogen-doped porous carbon materials with better electrochemical performance for highly valuable applications using bagasse and chlorella.

CncC-Keap1-P450s pathway is involved in the detoxification of emamectin benzoate in the spongy moth Lymantria dispar.

The detoxification of insecticides in insects is dependent on the expression and activity of multiple detoxification enzymes. As an important modulator of detoxification enzymes, the CncC-Keap1 pathway was involved in the detoxification of various pesticides. However, whether the CncC-Keap1 pathway is involved in the detoxification of emamectin benzoate (EMB) is unclear. In this study, we cloned the LdCncC and LdKeap1 from spongy moths (Lymantria dispar). Our results showed that EMB exposure induced oxidative stress, and activated the CncC-Keap1 pathway at mRNA and protein levels. Removing ROS by N-acetylcysteine remarkably decreased H2O2 levels and restored the expression of LdCncC and LdKeap1. The silencing LdCncC, not LdKeap1, by dsRNA significantly decreased the cytochrome P450 activities, and increased the sensitivity of larvae to EMB. Besides, the expression of CYP6B7v1, CYP321A7 and CYP4S4v1 were significantly decreased after silencing LdCncC. Notably, the knockdown of CYP6B7v1, CYP321A7 or CYP4S4v1 significantly increased the mortality induced by EMB exposure. Therefore, we proposed that activation of CncC-Keap1 pathway induced by ROS increased the detoxification of EMB in spongy moths by regulating the expression of CYP6B7v1, CYP321A7 and CYP4S4v1. Our study strengthened the understanding of the detoxification of EMB from the perspective of CncC-Keap1-P450s pathway.

Unraveling the multi-pollutant removal using M-MoWTi (M = Fe, Mn, Cr) catalyst: experiment and mechanistic study of competition for active sites.

Multi-pollutant removal (MPR) of NO and VOCs simultaneously is efficient of flue gas treatment in coal-fired power plants. But reducing the competition for active sites between NH3, NO, C6H6, and C7H8 remains challenging. Herein, Cr, Mn, and Fe were respectively doped to MoWTi catalyst via wet impregnation. The Fe3+ + Mo5+ ↔ Fe2+ + Mo6+ redox cycle led to an increased proportion of low valence ions (Mo5+ and W5+) and facilitated the creation of active oxygen vacancies with several active sites. It also possessed plentiful mild to strong acid sites with ideal ratio. These factors enhanced catalytic activity of Fe-MoWTi. Remarkable MPR efficiencies of NO, C6H6, and C7H8 were achieved under industrial SCR condition, characterized by low oxygen but high SO2 levels at 340 °C, with removal rates reaching 89.85%, 97.57%, and 86.30% respectively. Theory calculations further revealed that Fe-MoWTi favor NH3 and O2 adsorptions. NO elimination was found to follow both Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) processes, supported by in situ DRIFTS analysis. The reactions involving NO/NO2/nitrite/nitrate occurred with NH3(ads)/ NH4+(ads)/NH2 (ads). C6H6 and C7H8 underwent gradual oxidation, formatting alcohols, aldehydes, acids, and maleic acids, before eventually being mineralized to gaseous CO2 and H2O. Findings hold significant potential for application, providing guidance for the development of catalysts with improved resistance against SO2 poisoning and enhanced MPR capabilities.

Effect of microwave pretreatment on pyrolysis of chili straw: thermodynamics, activation energy, and solid reaction mechanism.

In this work, chili straw (CS) was pretreated by microwave at 250 W, 406 W, 567 W, and 700 W. The pyrolysis characteristics, kinetics, thermodynamic parameters, and solid reaction mechanism were investigated. The maximum weight loss rate increases from - 24.72%/°C at P0 to - 28.01%/°C at P700 after microwave pretreatment, and the residual mass decreases from 31.81 at P0 to 26.71% at P700. In addition, microwave pretreatment leads to a decrease in activation energy, ∆H, and ∆G at the end of the pyrolysis (α > 0.7). The solid reaction mechanism of CS pyrolysis is revealed by the Z-master plots method, with un-pretreated CS conforming to P2, D4, F3/2, and F3, respectively. Microwave pretreatment changes the solid reaction mechanism mainly in the third stage, when α = 0.8, the mechanism function changes from f(α) = (1 - α)3 at P0 to f(α) = (1 - α) at P700, and the number of reaction order is reduced, which is profitable for CS pyrolysis.

Facile synthesis of δ-MnO2 biotemplated by waste tobacco stem-silks for enhanced removal of Sb(III).

The elimination of antimony pollution has attracted increasing concerns because of its high toxicity to human health and the natural environment. In this work, biomimetic δ-MnO2 was synthesized by using waste tobacco stem-silks as biotemplate (Bio-δ-MnO2) and used in the capture of Sb(III)from aqueous solution. The tobacco stem-silks not only provided unique wrinkled morphologies but also contained carbon element self-doped into the resulting samples. The maximum Sb(III) adsorption capacity reached 763.4 mg∙g -1, which is 2.06 times higher than δ-MnO2 without template (370.0 mg∙g -1), 4.53 times than tobacco stem-silks carbon (168.5 mg∙g -1), and 10.39 times than commercial MnO2 (73.5 mg∙g -1), respectively. The isotherm and kinetic studies indicated that the adsorption behavior was consistent with the Langmuir isotherm model and the pseudo-second-order kinetic equation. As far as we are aware, the adsorption capacity of Bio-δ-MnO2 is much higher than that of most Sb(III) adsorbents. FT-IR, XPS, SEM, XRD, and Zeta potential analyses showed that the main mechanism for the adsorption of Sb(III) by Bio-δ-MnO2 includes electrostatic attraction, surface complexation, and redox. Overall, this study provides a new sustainable way to convert agricultural wastes to more valuable products such as biomimetic adsorbent for Sb(III) removal in addition to conventional activated carbon and biochar.

Transcriptome analysis and identification of the low potassium stress-responsive gene SiSnRK2.6 in foxtail millet (Setaria italica L.).

KEY MESSAGE: The transcriptome is beneficial for dissecting the mechanism of millet in response to low potassium stress and SiSnRK2.6 was identified as a potential target for improving low potassium stress tolerance. Foxtail millet (Setaria italica L.), which originated in China, has high nutrient utilization character. Nevertheless, the molecular mechanism of its tolerance to low potassium stress is largely unclear. In this research, the low potassium tolerant variety "Yugu28" was screened out by low potassium stress treatment, and the transcriptome of "Yugu28" under low potassium stress was comprehensively analyzed. A total of 4254 differentially expressed genes (DEGs) were identified, including 1618 up-regulated and 2636 down-regulated genes, respectively. In addition, there were 302 transcription factor (TF) genes in the DEGs and MYB TFs accounted for the highest proportion, which was 14.9%. After functional analysis of all DEGs, a total of 7 genes involved in potassium transport and potassium ion channels and 50 genes corresponding to hormones were screened. The expression levels of randomly selected 17 DEGs were verified by qRT-PCR and the results coincided well with the RNA-seq analysis, indicating the reliability of our transcriptome data. Moreover, one of the ABA signaling pathway genes, SiSnRK2.6, was identified and selected for further functional verification. Compared with the wild type, transgenic rice with ecotopic expression of SiSnRK2.6 showed remarkably increased root length and root number, indicating that overexpression of SiSnRK2.6 can enhance the resistance of transgenic plants to low potassium stress.

Copper/Nickel/Cobalt modified molybdenum-tungsten-titanium dioxide-based catalysts for multi-pollution control of nitrogen oxide, benzene, and toluene: Enhanced redox capacity and mechanism study.

Previous studies have indicated the potential of monometallic-modified TiO2 catalysts in controlling nitrogen oxide (NOx) and volatile organic compounds (VOCs) in coal-fired flue gas. Unfortunately, increasing selective catalytic reduction (SCR) activity under complicated coal-fired flue gas status is tricky. In this study, modified Co-MoWTiO2 catalysts with multiple active sites were synthesized using the wet impregnation method, which exhibited excellent multi-pollution control ability of NO, benzene and toluene under low oxygen and high SO2 concentrations. The modification of Mo and Co achieved high dispersion and electron transfer. The interaction between W5+/W6+ and Co2+/Co3+ promoted gas-phase O2 adsorption on the catalyst surface, forming of reactive oxygen species (Oα). Density functional theory (DFT) calculations informed that the doping of Co effectively enhanced the NH3 and O2 adsorption capacity of the catalyst, and Co possessed the maximum adsorption energy for NH3 and O2. Possible pathways of multi-pollution control of NO, C6H6, and C7H8 were speculated. NH3/NH4+ on the Lewis/Bronsted acid site is reacted with intermediates of NO (e.g., NO2, nitrite, nitrate) via the Langmuir-Hinshelwood and Eley-Rideal mechanism. The introduction of NO and NH3 did not disrupt the oxidation pathways of benzene and toluene. Following the Mars-van Krevelen mechanism, C6H6 and C7H8 were progressively mineralized by Oα into CO2 and H2O.

Impact of waste separation on the biological nitrogen removal in a MSW incineration leachate treatment plant: Performance and microbial community shift.

After waste separation program was launched in China in 2019, incineration leachate treatment plants are facing a challenge of effective removal of nitrogen from leachate due to lack of sufficient carbon source. In this study, the performance of a biological incineration leachate treatment process (anaerobic digestion (AD) - two-stage anoxic/aerobic (A/O) process) was evaluated after adopting the waste separation program, and the changes in the microbial community and function was analyzed using 16S rRNA amplicon sequencing technology. Results showed that after the waste separation, the influent chemical oxygen demand (COD) concentration reduced by 90% (from 19,300 to 1780 mg L-1) with the COD/N ratio decreased from 12.3 to 1.4, which led to a decreased nitrogen removal efficiency (NRE) of <65% and a high effluent NO3- accumulation (445.8-986.5 mg N·L-1). By bypassing approximately 60% of the influent to the two-stage A/O process and adding external carbon source (glucose), the mean NRE increased to 86.3 ± 7.4%. Spearman's analysis revealed that refractory compounds in the bypassed leachate were closely related to the variations in bacterial community composition and nitrogen removal function in the two-stage A/O, leading to a weakened correlation of microbial network. KEGG functional pathway predictions based on Tax4Fun also confirmed that the bypassed leachate induced xenobiotic compounds to the two-stage A/O process, the relative abundance of nitrogen metabolism was reduced by 32%, and more external carbon source was required to ensure the satisfactory nitrogen removal of >80%. The findings provide a good guide for regulation of incineration leachate treatment processes after the waste separation.

Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis.

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (ß = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (ß = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.

Glutamatergic basis of antipsychotic response in first-episode psychosis: a dual voxel study of the anterior cingulate cortex.

A subgroup of patients with schizophrenia is believed to have aberrant excess of glutamate in the frontal cortex; this subgroup is thought to show poor response to first-line antipsychotic treatments that focus on dopamine blockade. If we can identify this subgroup early in the course of illness, we can reduce the repeated use of first-line antipsychotics and potentially stratify first-episode patients to intervene early with second-line treatments such as clozapine. The use of proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate and Glx (glutamate plus glutamine) may provide a means for such a stratification. We must first establish if there is robust evidence linking elevations in anterior cingulate cortex (ACC) glutamate metabolites to poor response, and determine if the use of antipsychotics worsens the glutamatergic excess in eventual nonresponders. In this study, we estimated glutamate levels at baseline in 42 drug-naive patients with schizophrenia. We then treated them all with risperidone at a standard dose range of 2-6 mg/day and followed them up for 3 months to categorize their response status. We expected to see baseline "hyperglutamatergia" in nonresponders, and expected this to worsen over time at the follow-up. In line with our predictions, nonresponders had higher glutamate than responders, but patients as a group did not differ in glutamate and Glx from the healthy control (HC) group before treatment-onset (F1,79 = 3.20, p = 0.046, partial η2 = 0.075). Glutamatergic metabolites did not change significantly over time in both nonresponders and responders over the 3 months of antipsychotic exposure (F1,31 = 1.26, p = 0.270, partial η2 = 0.039). We conclude that the use of antipsychotics without prior knowledge of later response delays symptom relief in a subgroup of first-episode patients, but does not worsen the glutamatergic excess seen at the baseline. Given the current practice of nonstratified use of antipsychotics, longer-time follow-up MRS studies are required to see if improvement in symptoms accompanies a dynamic shift in glutamate profile.

Comprehensive Scrna-Seq Analysis and Identification of CD8_+T Cell related Gene Markers for Predicting Prognosis and Drug Resistance of Hepatocellular Carcinoma.

BACKGROUND: Tumor heterogeneity of immune infiltration of cells plays a decisive role in hepatocellular carcinoma (HCC) therapy response and prognosis. This study investigated the effect of different subtypes of CD8+T cells on the HCC tumor microenvironment about its prognosis. METHODS: Single-cell RNA sequencing, transcriptome, and single-nucleotide variant data from LUAD patients were obtained based on the GEO, TCGA, and HCCD18 databases. CD8+ T cells-associated subtypes were identified by consensus clustering analysis, and genes with the highest correlation with prognostic CD8+ T cell subtypes were identified using WGCNA. The ssGSEA and ESTIMATE algorithms were used to calculate pathway enrichment scores and immune cell infiltration levels between different subtypes. Finally, the TIDE algorithm, CYT score, and tumor responsiveness score were utilized to predict patient response to immunotherapy. RESULTS: We defined 3 CD8+T cell clusters (CD8_0, CD8_1, CD8_2) based on the scRNA- seq dataset (GSE149614). Among, CD8_2 was prognosis-related risk factor with HCC. We screened 30 prognosis genes from CD8_2, and identified 3 molecular subtypes (clust1, clust2, clust3). Clust1 had better survival outcomes, higher gene mutation, and enhanced immune infiltration. Furthermore, we identified a 12 genes signature (including CYP7A1, SPP1, MSC, CXCL8, CXCL1, GCNT3, TMEM45A, SPP2, ME1, TSPAN13, S100A9, and NQO1) with excellent prediction performance for HCC prognosis. In addition, High-score patients with higher immune infiltration benefited less from immunotherapy. The sensitivity of low-score patients to multiple drugs including Parthenolide and Shikonin was significantly higher than that of high-score patients. Moreover, high-score patients had increased oxidative stress pathways scores, and the RiskScore was closely associated with oxidative stress pathways scores. And the nomogram had good clinical utility. CONCLUSION: To predict the survival outcome and immunotherapy response for HCC, we developed a 12-gene signature based on the heterogeneity of the CD8+ T cells.