Impacts of cascade hydropower development on aquatic environment in middle and lower reaches of Jinsha River, China: a review.

The middle and lower reaches of the Jinsha River, which is the upper reach of the Yangtze River in China, play crucial roles in the water security of people living in the middle and lower reaches of the Yangtze River. The construction of 11 dams in this region has significantly altered the aquatic environment. Although researchers have investigated the effects of cascade hydropower station development in the middle and lower reaches of the Jinsha River based on factors such as flow, sediment, and fish, the overall impact of this station on the aquatic environment remains unclear. Therefore, the purpose of this study is to comprehensively investigate the effects of cascade hydropower station development on the aquatic environment based on three factors: river, aquatic organism, and ecosystem factors. In terms of river factors, the development of cascade hydropower stations increases runoff in the dry season and decreases it in the flood season, leading to sediment deposition and water temperature stratification in cascade reservoirs, and changes in water quality. In terms of aquatic organism factors, cascade hydropower development not only changes the species composition but also reduces biodiversity. Effects of ecosystem factors including the ecological flow, value, and landscape as well as sustainability are summarized, with results indicating positive and negative impacts on river ecosystems. Finally, recommendations for future research on the effects of cascade hydropower development on the aquatic environment of rivers are provided.

Combining SiO2 NPs with biochar: a novel composite for enhanced cadmium removal from wastewater and alleviation of soil cadmium stress.

Cadmium (Cd) pollution in water and soil seriously threatens human health. Biochar and nanomaterials have high potential for solving the cadmium pollution problem due to their abundant pores and high specific surface area. Here, the preparation of the composite material SiO2NPs@BC (SBC) using SiO2 NPs (SN) and silkworm excrement biochar (BC) is described, along with its application in the remediation of cadmium-contaminated water and soil. Characterization experiments (SEM&EDS, BET, FTIR, XRD, and XPS) demonstrated that SiO2NPs@BC has a high specific surface area (46.5767m2/g), a well-developed pore structure (0.608375cm3/g), and abundant surface functional groups (Si-C, Si-O, Si-O-Si), providing active sites for the adsorption of Cd. Batch adsorption experiments in water showed that the adsorption capacity of SBC is higher than that of biochar (BC) and SN, with a maximum Langmuir adsorption capacity of 141.99 mg/g. After five adsorption cycles, the removal rate of SBC was 73.04%, significantly higher than the 64.97% obtained for BC. The application of SBC not only improved the soil physicochemical properties by increasing the soil pH, the cation exchange capacity, and the soil organic matter content but also by reducing the amount of DTPA-Cd (24.6%) and the plant bioconcentration factor (28.28%) in the soil, converting Cd into more stable fractions (Red-Cd, Ox-Cd). Based on the results, SBC can effectively reduce Cd pollution.

Study on the improvement of grouting stone properties in coal mine goafs using combined denitrifying bacteria.

Grouting can effectively reduce residual deformation of coal mine goafs, but fly ash grouting materials suffer from poor flowability and slow early strength development. Microbially -induced calcite precipitation (MICP), with its high environmental compatibility and minimal disturbance to geotechnical bodies, effectively improves the injectability of grouting slurry in goafs. This study combined Castellaniella denitrificans and Sporosarcina pasteurii to induce calcite precipitation, preparing cement-fly ash slurry with varying water-solid ratios, solid ratios and denitrifying bacteria concentrations. The physical properties of the slurry and the mechanical properties of the grouted stone bodies under sealed curing conditions were measured. Results show that the dual-bacteria MICP improves stone body performance by enhancing cohesive, frictional and interlocking forces, so that the strength of the stone bodies cured by MICP increased rapidly within 7 days, and the strength reached the standard 2.03 MPa at 28 days under conditions of low solid ratio and high water-solid ratio, with the best compressive strength at a denitrifying bacteria concentration with an optical density of 0.8 at 600 nm wavelength. At a water-solid ratio of 1 : 1.2 and a solid ratio of 15%, initial and final setting times were 67.2 and 96 h, respectively, which prolonged the initial setting time and final setting time by nearly 70% and 110% compared with that of the slurry without MICP treatment, indicating that MICP enhances slurry fluidity, providing more time for grouting construction in goafs.

Photonanozyme-Kras-ribosome combination treatment of non-small cell lung cancer after COVID-19.

With the outbreak of the coronavirus disease 2019 (COVID-19), reductions in T-cell function and exhaustion have been observed in patients post-infection of COVID-19. T cells are key mediators of anti-infection and antitumor, and their exhaustion increases the risk of compromised immune function and elevated susceptibility to cancer. Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with high incidence and mortality. Although the survival rate after standard treatment such as surgical treatment and chemotherapy has improved, the therapeutic effect is still limited due to drug resistance, side effects, and recurrence. Recent advances in molecular biology and immunology enable the development of highly targeted therapy and immunotherapy for cancer, which has driven cancer therapies into individualized treatments and gradually entered clinicians' views for treating NSCLC. Currently, with the development of photosensitizer materials, phototherapy has been gradually applied to the treatment of NSCLC. This review provides an overview of recent advancements and limitations in different treatment strategies for NSCLC under the background of COVID-19. We discuss the latest advances in phototherapy as a promising treatment method for NSCLC. After critically examining the successes, challenges, and prospects associated with these treatment modalities, their profound prospects were portrayed.

Renal Dysfunction in a Patient With Crohn's Disease During Ustekinumab Treatment: A Case Report and Review of the Literature.

Ustekinumab is a first-line drug for Crohn's disease. However, little is known about its potential adverse effects on renal function. We present the case of a 42-year-old man with Crohn's disease who developed chronic renal dysfunction during ustekinumab treatment, which resolved after discontinuing ustekinumab. The findings underscore the importance of close monitoring of renal function in patients receiving ustekinumab, particularly those with preexisting kidney disease or risk factors for renal dysfunction.

Prevalence and correlates of non-suicidal self-injury among patients with bipolar disorder: A multicenter study across China.

BACKGROUND: Non-suicidal self-injury (NSSI) is increasingly prevalent among patients with bipolar disorder (BD), raising concerns in psychology and mental health. Investigating the incidence and factors associated with NSSI is crucial for developing prevention and intervention strategies. METHODS: NSSI behaviors were identified using the Ottawa Self-injury Inventory. The Clinically Useful Depression Outcome Scale supplemented with questions for the DSM-5 specifier of mixed features (CUDOS-M) and the Mini International Neuropsychiatric Interview (Hypo-)Manic Episode with Mixed Features-DSM-5 Module (MINI-M) were used to evaluate clinical symptoms. Non-parametric tests, chi-square tests, point-biserial correlation and logistic regression analyses were employed for the purposes of data analysis. RESULTS: The enrolled sample comprised 1044 patients with BD from 20 research centers across China. Out of 1044 individuals, 446 exhibited NSSI behaviors, with 101 of them being adolescents, leading to a prevalence of 78.3 % among adolescent patients. The most common methods for females and males were "cutting" (41.2 %) and "hitting" (34.7 %), respectively. By binary logistic regression analysis, young age, female, bipolar type II disorder, with suicidal ideation and mixed states, depressive symptoms and without family history of mental disorder were correlates of NSSI in patients with BD (P < 0.05). LIMITATIONS: As a cross-sectional study, causality between NSSI behaviors and associated factors cannot be established. Reporting and recall biases may occur due to self-rating scales and retrospective reports. CONCLUSION: Our study indicates a concerning prevalence of NSSI, particularly among young patients with BD in China. Future research should focus on understanding NSSI behaviors in this population and developing effective interventions.

Pirarubicin combined with TLR3 or TLR4 agonists enhances anti-tumor efficiency.

BACKGROUND: Triple-negative breast cancer (TNBC) is prone to relapse due to the lack of effective therapeutic targets. Macrophages are the most abundant immune cells in the tumor microenvironment (TME) of breast cancer. Targeting the cross-talk between macrophages and cancer cells provides a more efficient strategy for anti-tumor therapy. Toll-like receptors (TLRs) are important players involved in macrophage activation, and TLR agonists are known to play roles in cancer therapy. However, the combination strategy of TLR agonists with chemotherapy drugs is still not well characterized. METHODS: RT-PCR and Western blot were used to detect the expression of TLRs. The communication between breast cancer cells and macrophages were determined by co-culture in vitro. Tumor cells proliferation and migration were investigated by MTT assay and scratch wound assay. The effects of drug combinations and toxic side effects were assessed by immunohistochemistry and Hematoxylin & Eosin staining. RESULTS: Expression of TLR3 and TLR4 were lower in breast tumor tissues compared with adjacent normal tissues. Patients with higher TLR3 or TLR4 expression levels had a better prognosis than those with lower expression levels. TLR3/4 expression was significantly inhibited when breast cancer cells MDA-MB-231 and E0771 were conditioned-cultured with macrophages in vitro and was also inhibited by pirarubicin (THP). However, the combination of TLR agonists and THP could reverse this response and inhibit the proliferation and migration of breast cancer cells. Additionally, this combination significantly reduced the tumor volume and weight in the murine model, increased the expression of TLR3/4 in mouse breast tumors. CONCLUSIONS: Our results provide new ideas for the combination strategy of THP with TLR agonists which improves prognosis of breast cancer.

CircRNAs expression profile and potential roles of circRERE-PMN in pre-metastatic lungs.

The successful pulmonary metastasis of malignant cancer cells depends on the survival of circulating tumor cells in a distant and hostile microenvironment. The formation of a pre-metastatic niche (PMN) creates a supportive environment for subsequent metastasis. Circular RNAs (circRNAs) are increasingly acknowledged as crucial elements in the mechanisms of metastasis due to their stable structures and functions, making them promising early metastasis detection markers. However, the specific expression patterns and roles of circRNAs in the lungs before metastasis remain largely unexplored. Our research aims to chart the circRNA expression profile and assess their impact on the lung PMN. We developed a lung PMN model and employed comprehensive RNA sequencing to analyze the differences in circRNA expression between normal and pre-metastatic lungs. We identified 38 significantly different circRNAs, primarily involved in metabolism, apoptosis, and inflammation pathways. We then focused on one specific circRNA, circ:chr4:150406196 - 150406664 (circRERE-PMN), which exhibited a significant change in expression and was prevalent in myeloid-derived suppressor cells (MDSCs), alveolar epithelial cells, and macrophages within the pre-metastatic lung environment. CircRERE-PMN was found to potentially regulate apoptosis and the expression of cytokines and chemokines through its interaction with the downstream target HUR in alveolar epithelial cells. Overall, our study highlights the crucial role of circRNAs in the formation of lung PMNs, supporting their potential as diagnostic or therapeutic targets for lung metastasis.

CEUS LI-RADS in Combination With the Serum Biomarker-Based ASAP Model Improves the Diagnostic Performance of HCC in High-Risk Patients.

OBJECTIVE: To assess the diagnostic efficacy of the CEUS LI-RADS combined with a model constructed on the basis of age, sex, AFP, and PIVKA-II (ASAP) for the diagnosis of HCC in high-risk patients. METHODS: This retrospective study included 366 liver lesions from 366 patients who underwent liver CEUS. All liver lesions were characterized and categorized according to CEUS LI-RADS v2017. Two modified methods were applied: LR-3/4/M nodules accompanied by AFP > 200 ng/mL (Criterion 2) or ASAP model score > 0.5256 and CA 19-9 in the normal range (Criterion 3) were recategorized as LR-5. The reference criteria included histopathological or comprehensive imaging and the clinical follow-up results. The diagnostic performance was evaluated and compared by the sensitivity, specificity, PPV, and NPV. RESULTS: The incidence of HCC in LR-3, LR-4, LR-5, and LR-M was 33.3% (4/12), 86.4% (38/44), 98.5% (191/194) and 82.7% (81/98), respectively. After using Criterion 2 compared to CEUS LI-RADS v2017, the sensitivity of the modified LR-5 for diagnosing HCC increased from 60.8% to 70.7% (p < 0.01) with little effect on its specificity (94.2% vs. 92.3%, p = 1.00) or PPV (98.5% vs. 98.2%, p = 0.86). After using Criterion 3, the sensitivity of the modified LR-5 for the diagnosis of HCC was further improved to 86.9% (p < 0.01), and its specificity and PPV were not significantly changed (92.3% and 98.6%, both p > 0.05). CONCLUSION: CEUS LI-RADS combined with the serum biomarker-based ASAP model improved the sensitivity of LR-5 in diagnosing HCC with little effect on its specificity and PPV.

Effects of polypropylene microplastics on digestion performance, microbial community, and antibiotic resistance during microbial anaerobic digestion.

As an emerging pollutant, microplastics (MPs) have attracted increasing attention worldwide. The effects of polypropylene (PP) MPs on digestion performance, behaviors of dominant microbial communities, antibiotic resistance genes (ARGs) and mobile genetic elements in microbial anaerobic digesters were investigated. The results showed that the addition of PP-MPs to digesters led to an increase in methane production of 10.8% when 300 particles/g TSS of PP-MPs was introduced compared with that in digester not treated with PP-MPs. This increase was attributed to the enrichment of acetogens such as Syntrophobacter (42.0%), Syntrophorhabdus (27.0%), and Syntrophomonas (10.6%), and methanogens including Methanobacterium and Methanosaeta. tetX was highly enriched due to PP-MP exposure, whereas parC exhibited the greatest increase (35.5% - 222.7%). Horizontal gene transfer via ISCR1 and intI1 genes might play an important role in the spread of ARGs. Overall, these findings provide comprehensive insight into the ecological dynamics of PP-MPs during microbial anaerobic digestion.

Optimization of nitrogen and phosphorus fertilization for enhanced forage production and quality of Festuca Krylovianacv. Huanhu artificial grassland in alpine regions.

Artificial grasslands of F. kryloviana in the region surrounding Qinghai Lake have been observed to a decline in productivity following three years of establishment. Traditional fertilization practices, aimed at maintaining ecological balance, have predominantly focused on the application of phosphorus. However, it remains unclear whether phosphorus fertilizers offer a superior advantage over nitrogen fertilizers in sustaining productivity. Consequently, from 2017 to 2019, we conducted an experimental to assess the impact of nitrogen and phosphorus fertilization on forage yield and quality. We designed with four levels of phosphorus and two levels of nitrogen, resulting in eight distinct fertilizer combinations. Our experimental findings indicate that the degradation of artificial grasslands leads to a shift in the allocation pattern of aboveground biomass. There was a respective decrease of 68.2 % and 62.5 % in the biomass proportions of stems and ears, contrasted by a greater than 200 % increase in the biomass proportion of leaves. The application of nitrogen not only elevated the total aboveground biomass but also promoted a preferential allocation of biomass to stems and leaves, consequently enhancing the forage's crude protein content. Nitrogen fertilization significantly increased aboveground biomass, and crude protein content by 63.21 %, and 6 %, respectively. Phosphorus fertilization's impact varied annually but favored the distribution of biomass to stems and ears. The net photosynthetic rate improved by over 53.12 % with fertilizer application, although the differences among treatments were not statistically significant. The balanced application of nitrogen and phosphorus fertilizers significantly bolstered the aboveground biomass, ear biomass, stem biomass, leaf biomass, and crude protein content in varying years by 17.25 %-209.83 %, 34.7 %-438.9 %, 25.5 %-250.2 %, 18.4 %-133.3 %, and 10.21 %-25.62 %, respectively. Our analysis revealed that nitrogen-only fertilization exhibited the most optimal fertilizer use efficiency and economic returns. In conclusion, nitrogen fertilization is crucial for sustaining the productivity and quality of F. kryloviana artificial grasslands. The local practice of 75 kg ha-1 phosphorus fertilizer is detrimental to the maintenance of productivity in F. kryloviana artificial grasslands. This study offers valuable insights into the optimization of fertilization strategies for sustainable forage production within alpine regions.

Study on cell wall deformation in ultrasonic cutting aluminum honeycomb by straight-blade knife.

Aluminum honeycomb sandwich structure has been widely used in the aeronautic and astronautic fields. As the core part, aluminum honeycomb needs to be machined but defects are easily generated. Ultrasonic cutting is an advanced machining technology for honeycomb materials due to improved machining quality. However, ultrasonic cutting aluminum honeycomb by straight-blade knife is usually accompanied by cell wall deformation, which results in poor machining quality. To facilitate the industrial use of ultrasonic cutting aluminum honeycomb with a straight-blade knife, a finite element (FE) model was developed, and experimental studies had been performed. The effects of the blade-inclined angle and lead angle of the straight-blade knife were studied by analyzing the cutting force, the stress and deformation in the cutting zone. Results showed that the cell wall deformation was significantly suppressed when cutting with a corresponding blade-inclined angle and a lead angle. Meanwhile, effects of ultrasonic cutting parameters on the cell wall deformation were also studied, indicating that a well-machined cell wall could be obtained when cutting with large ultrasonic amplitude.

Molecular mechanisms regulating glucose metabolism in quinoa (Chenopodium quinoa Willd.) seeds under drought stress.

BACKGROUND: Abiotic stress seriously affects the growth and yield of crops. It is necessary to search and utilize novel abiotic stress resistant genes for 2.0 breeding programme in quinoa. In this study, the impact of drought stress on glucose metabolism were investigated through transcriptomic and metabolomic analyses in quinoa seeds. Candidate drought tolerance genes on glucose metabolism pathway were verified by qRT-PCR combined with yeast expression system. RESULTS: From 70 quinoa germplasms, drought tolerant material M059 and drought sensitive material M024 were selected by comprehensive evaluation of drought resistance. 7042 differentially expressed genes (DEGs) were indentified through transcriptomic analyses. Gene Ontology (GO) analysis revealed that these DEGs were closely related to carbohydrate metabolic process, phosphorus-containing groups, and intracellular membrane-bounded organelles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis detected that DEGs were related to pathways involving carbohydrate metabolisms, glycolysis and gluconeogenesis. Twelve key differentially accumulated metabolites (DAMs), (D-galactose, UDP-glucose, succinate, inositol, D-galactose, D-fructose-6-phosphate, D-glucose-6-phosphate, D-glucose-1-phosphate, dihydroxyacetone phosphate, ribulose-5-phosphate, citric acid and L-malate), and ten key candidate DEGs (CqAGAL2, CqINV, CqFrK7, CqCELB, Cqbg1x, CqFBP, CqALDO, CqPGM, CqIDH3, and CqSDH) involved in drought response were identified. CqSDH, CqAGAL2, and Cqß-GAL13 were candidate genes that have been validated in both transcriptomics and yeast expression screen system. CONCLUSION: These findings provide a foundation for elucidating the molecular regulatory mechanisms governing glucose metabolism in quinoa seeds under drought stress, providing insights for future research exploring responses to drought stress in quinoa.

The Discovery, Molecular Cloning, and Characterization of Dextransucrase LmDexA and Its Active Truncated Mutant from Leuconostoc mesenteroides NN710.

Dextransucrases play a crucial role in the production of dextran from economical sucrose; therefore, there is a pressing demand to explore novel dextransucrases with better performance. This study characterized a dextransucrase enzyme, LmDexA, which was identified from the Leuconostoc mesenteroides NN710. This bacterium was isolated from the soil of growing dragon fruit in Guangxi province, China. We successfully constructed six different N-terminal truncated variants through sequential analysis. Additionally, a truncated variant, ΔN190LmDexA, was constructed by removing the 190 amino acids fragment from the N-terminal. This truncated variant was then successfully expressed heterologously in Escherichia coli and purified. The purified ΔN190LmDexA demonstrated optimal hydrolysis activity at a pH of 5.6 and a temperature of 30 °C. Its maximum specific activity was measured to be 126.13 U/mg, with a Km of 13.7 mM. Results demonstrated a significant improvement in the heterologous expression level and total enzyme activity of ΔN190LmDexA. ΔN190LmDexA exhibited both hydrolytic and transsaccharolytic enzymatic activities. When sucrose was used as the substrate, it primarily produced high-molecular-weight dextran (>400 kDa). However, upon the addition of maltose as a receptor, it resulted in the production of a significant amount of oligosaccharides. Our results can provide valuable information for enhancing the characteristics of recombinant dextransucrase and potentially converting sucrose into high-value-added dextran and oligosaccharides.

Near-Full-Spectrum Emission Realized in a Single Lead Halide Perovskite across the Visible-Light Region.

The engineering of tunable photoluminescence (PL) in single materials with a full-spectrum emission represents a highly coveted objective but poses a formidable challenge. In this context, the realization of near-full-spectrum PL emission, spanning the visible light range from 424 to 620 nm, in a single-component two-dimensional (2D) hybrid lead halide perovskite, (ETA)2PbBr4 (ETA+ = (HO)(CH2)2NH3+), is reported, achieved through high-pressure treatment. A pressure-induced phase transition occurs upon compression, transforming the crystal structure from an orthorhombic phase under ambient conditions to a monoclinic structure at high pressure. This phase transition driven by the adaptive and dynamic configuration changes of organic amine cations enables an effective and continuous narrowing of the bandgap in this halide crystal. The hydrogen bonding interactions between inorganic layers and organic amine cations (N-H…Br and O-H…Br hydrogen bonds) efficiently modulate the organic amine cations penetration and the octahedral distortion. Consequently, this phenomenon induces a phase transition and results in red-shifted PL emissions, leading to the near-full-spectrum emission. This work opens a possibility for achieving wide PL emissions with coverage across the visible light spectrum by employing high pressure in single halide perovskites.

Multiple-perspective design of hollow-structured cerium-vanadium-based nanopillar arrays for enhanced overall water electrolysis.

It is critical and challenging to develop highly active and low cost bifunctional electrocatalysts for the hydrogen/oxygen evolution reaction (HER/OER) in water electrolysis. Herein, we propose cerium-vanadium-based hollow nanopillar arrays supported on nickel foam (CeV-HNA/NF) as bifunctional HER/OER electrocatalysts, which are prepared by etching the V metal-organic framework with Ce salt and then pyrolyzing. Etching results in multidimensional optimizations of electrocatalysts, covering substantial oxygen vacancies, optimized electronic configurations, and an open-type structure of hollow nanopillar arrays, which contribute to accelerating the charge transfer rate, regulating the adsorption energy of H/O-containing reaction intermediates, and fully exposing the active sites. The reconstruction of the electrocatalyst is also accelerated by Ce doping, which results in highly active hydroxy vanadium oxide interfaces. Therefore, extremely low overpotentials of 170 and 240 mV under a current density of 100 mA cm-2 are achieved for the HER and OER under alkaline conditions, respectively, with long-term stability for 300 h. An electrolysis cell with CeV-HNA/NF as both the cathode and anode delivers a small voltage of 1.53 V to achieve water electrolysis under 10 mA cm-2, accompanied by superior durability for 150 h. This design provides an innovative way to develop advanced bifunctional electrocatalysts for overall water electrolysis.

Efficacy and safety of MIL62, a novel glycoengineered type â ¡ anti-CD20 monoclonal antibody, combined with lenalidomide in patients with relapsed/refractory follicular lymphoma or marginal zone lymphoma: a multicentre, single-arm, phase 1b/2 trial.

Background: MIL62, a novel glycoengineered type Ⅱ anti-CD20 monoclonal antibody, with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively. Methods: This multicentre, single-arm, phase 1b/2 trial aimed to explore the efficacy, pharmacokinetics, and safety of MIL62 combined with lenalidomide in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Eligible patients included those who had histopathologically confirmed CD20 positive FL (grade 1-3a) or MZL and failed to be treated with rituximab. Patients received intravenously infused MIL62 1000 mg (cycle 1: day 1, 15; cycles 2-8: day 1, cycles 10 and 12: day 1) combined with oral lenalidomide (once a day, days 2-22, the initial dose was 10 mg, and the maximum dose was 20 mg) for 12 cycles, 28 days as a cycle. The primary endpoint was objective response rate (ORR) assessed by investigator per Lugano 2014 criteria every 3 cycles. This study was registered in ClinicalTrials.gov (NCT04110301). Findings: Between November 22, 2019 and December 22, 2020, 54 patients were enrolled from 11 hospitals in China and received study treatment. Fifty patients were included in the efficacy analysis set, and 43 patients (86%, 95% CI: 73, 94) achieved objective response, meeting the pre-specified primary endpoint. Disease control rate was 96% (48/50, 95% CI: 86, 100), proportion of patients with duration of response (DoR) > 6 months was 77% (33/43). The median follow-up for survival was 12.3 months (IQR 12.0-12.6). The 1-year progression-free survival rate was 72% (95% CI: 57, 83), 9-month DoR rate was 74% (95% CI: 58, 85), and 1-year overall survival rate was 98% (95% CI: 85, 100). Most common TRAEs were neutropenia (93%, 50/54), leukopenia (85% 46/54), thrombocytopenia (61% 33/54), lymphopenia (32% 17/54), and alanine aminotransferase increased (20% 11/54). Interpretation: MIL62 combined with lenalidomide showed promising efficacy in patients with R/R FL and MZL. A multicentre, randomized, open-label, phase Ⅲ trial of MIL62 combined with lenalidomide versus lenalidomide in anti-CD20 monoclonal antibody refractory FL patients is ongoing (NCT04834024). Funding: Beijing Mabworks Biotech Co. Ltd, Beijing China and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Risk prediction model of uterine corpus endometrial carcinoma based on immune-related genes.

BACKGROUND: Given the significant role of immune-related genes in uterine corpus endometrial carcinoma (UCEC) and the long-term outcomes of patients, our objective was to develop a prognostic risk prediction model using immune-related genes to improve the accuracy of UCEC prognosis prediction. METHODS: The Limma, ESTIMATE, and CIBERSORT methods were used for cluster analysis, immune score calculation, and estimation of immune cell proportions. Univariate and multivariate analyses were utilized to develop a prognostic risk model for UCEC. Risk model scores and nomograms were used to evaluate the models. String constructs a protein-protein interaction (PPI) network of genes. The qRT-PCR, immunofluorescence, and immunohistochemistry (IHC) all confirmed the genes. RESULTS: Cluster analysis divided the immune-related genes into four subtypes. 33 immune-related genes were used to independently predict the prognosis of UCEC and construct the prognosis model and risk score. The analysis of the survival nomogram indicated that the model has excellent predictive ability and strong reliability for predicting the survival of patients with UCEC. The protein-protein interaction network analysis of key genes indicates that four genes play a pivotal role in interactions: GZMK, IL7, GIMAP, and UBD. The quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and immunohistochemistry (IHC) all confirmed the expression of the aforementioned genes and their correlation with immune cell levels. This further revealed that GZMK, IL7, GIMAP, and UBD could potentially serve as biomarkers associated with immune levels in endometrial cancer. CONCLUSION: The study identified genes related to immune response in UCEC, including GZMK, IL7, GIMAP, and UBD, which may serve as new biomarkers and therapeutic targets for evaluating immune levels in the future.

A novel high-risk model identified by epithelial-mesenchymal transition predicts prognosis and radioresistance in rectal cancer.

Many studies have shown that tumor cells that survive radiotherapy are more likely to metastasize, but the underlying mechanism remains unclear. Here we aimed to identify epithelial-mesenchymal transition (EMT)-related key genes, which associated with prognosis and radiosensitivity in rectal cancer. First, we obtained differentially expressed genes by analyzing the RNA expression profiles of rectal cancer retrieved from The Cancer Genome Atlas database, EMT-related genes, and radiotherapy-related databases, respectively. Then, Lasso and Cox regression analyses were used to establish an EMT-related prognosis model (EMTPM) based on the identified independent protective factor Fibulin5 (FBLN5) and independent risk gene EHMT2. The high-EMTPM group exhibited significantly poorer prognosis. Then, we evaluated the signature in an external clinical validation cohort. Through in vivo experiments, we further demonstrated that EMTPM effectively distinguishes radioresistant from radiosensitive patients with rectal cancer. Moreover, individuals in the high-EMTPM group showed increased expression of immune checkpoints compared to their counterparts. Finally, pan-cancer analysis of the EMTPM model also indicated its potential for predicting the prognosis of lung squamous cell carcinoma and breast cancer patients undergoing radiotherapy. In summary, we established a novel predictive model for rectal cancer prognosis and radioresistance based on FBLN5 and EHMT2 expressions, and suggested that immune microenvironment may be involved in the process of radioresistance. This predictive model could be used to select management strategies for rectal cancer.