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Abstract Lotus, an economically significant aquatic crop within the genus Nelumbo (family Nelumbonaceae), includes the two extant species Nelumbo nucifera and Nelumbo lutea. Renowned for its ornamental, culinary, and medicinal value, lotus has seen notable advancements in genomics and molecular biology, particularly in reference genome sequencing and assembly, bioactive compound biosynthetic pathways, and molecular mechanisms underlying key traits. Critical genes linked to horticultural characteristics, edible quality, medicinal properties, and stress resilience have been identified and functionally validated. This review presents a thorough overview of recent molecular developments in lotus research, emphasizing genome sequencing and functional gene analysis. Additionally, it addresses prevailing challenges and future directions, providing valuable insights for foundational research and genetic enhancement of lotus.

Abstract Background Increasing evidence suggests a link between the enzyme cathepsin S (CTSS) and tumour development. However, the potential involvement and molecular functions of CTSS in clear cell renal cell carcinoma (ccRCC) remain unclear. Methods We downloaded original data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated them using R. Kaplan–Meier plots of integrated expression scores were used to analyse survival outcomes. Additionally, we investigated mRNA expression, clinicopathological features, immune infiltrates, and single-cell sequencing analysis of CTSS in ccRCC. In vitro experiments were conducted with qRT-PCR and IHC staining. Results CTSS transcriptomic and proteomic levels were higher in ccRCC than in para-cancerous tissues. Low CTSS expression was correlated with poor prognosis in patients with ccRCC. Our data demonstrated that the expression of CTSS was strongly correlated with immune cell infiltration levels and gene markers of immune cells, chemokines, and receptors. Single-cell sequencing analysis demonstrated that CTSS expression was detectable in monocytes/macrophages. Finally, certain chemicals were confirmed to affect CTSS expression. Conclusion Our findings indicate that CTSS offers promise as a prognostic biomarker and novel immune-related therapeutic target for ccRCC.

Abstract Background MADS-box transcription factors have been shown to be involved in multiple developmental processes, including the regulation of floral organ formation and pollen maturation. However, the role of the MADS-box gene family in floral development of the alpine plant species Coptis teeta Wall, which is widely used in Traditional Chinese Medicine (TCM), is unknown. Results Sixty-six MADS-box genes were identified in the C. teeta genome. These genes were shown to be unevenly distributed throughout the genome of C. teeta. The majority of which (49) were classified as type I MADS-box genes and were further subdivided into four groups (Mα, Mβ, Mγ and Mδ). The remainder were identified as belonging to the type II MADS-box gene category. It was observed that four pairs of segmental and tandem duplication had occurred in the C. teeta MADS-box gene family, and that the ratios of Ka/Ks were less than 1, suggesting that these genes may have experienced purifying selection during evolution. Gene expression profiling analysis revealed that 38 MADS-box genes displayed differential expression patterns between the M and F floral phenotypes. Sixteen of these MADS-box genes were further verified by RT-qPCR. The 3D structure of each subfamily gene was predicted, further indicating that MADS-box genes of the same type possess structural similarities to the known template. Conclusions These data provide new insights into the molecular mechanism of dichogamy and herkogamy formation in C. teeta and establish a solid foundation for future studies of the MADS-box genes family in this medicinal plant species.

Optogenetics has revolutionized the landscape of research on neurological disorders by enabling high spatial specificity and millisecond-level temporal precision in neuroscience studies. In the field of traumatic brain injury (TBI), optogenetic techniques have greatly advanced our understanding of the pathological and physiological processes involved, providing valuable guidance for both monitoring and therapeutic interventions. This article offers a review of the latest research applications of optogenetics in the study of TBI.

BackgroundBreast cancer, particularly triple-negative (TNBC), is a leading malignancy with aggressive traits and high metastasis rates. Clinical trial is an important tool for optimizing therapeutic strategies in the evaluation of the safety and efficacy for TNBC. Our bibliometric study of TNBC clinical trials aims to assess therapeutic strategies, identify trends, and explore advancements in treatment. We focus on mapping knowledge development, including key research entities and topics, and analyzing research trends and emerging methods. This analysis intends to inform future research, especially in personalized and precision medicine for TNBC.MethodsWe selected publications on clinical trials for the treatment of TNBC from 1997 to 2024 in the Web of Science Core Collection (WoSCC). After an initial screening, we downloaded key data including titles, publication years, authors, countries, institutional affiliations, journals, keywords, and abstracts, and saved them in BibTex format. We then conducted a bibliometric analysis using Bibliometrix in R and VOSviewer to illustrate the prospects, highlights, and trends of TNBC treatment options. Furthermore, to emphasize the hot topics in TNBC treatment strategies, we performed a bibliometric analysis of immunotherapy using the same approach.Results1907 publications were included, most of which were from China, Italy, and the United States. The number of annual publications has increased dramatically since 2010. The focus of TNBC clinical trial research has shifted from understanding the biology, such as breast cancer subtyping and genotyping, to novel therapeutic approaches. The major advancement in clinical trials is the switch from late-stage palliative treatment to early preoperative neoadjuvant therapy, as more TNBC cases are discovered at an early stage. Immunotherapy is also highlighted with additional alternatives for advanced or metastasized TNBC, such as targeted inhibitors with unusual mutation rates and antibody drug conjugates (ADC).ConclusionsThis investigation made it apparent how immunotherapy has recently made major advancements in TNBC treatment plans and how ADCs, or targeted therapies, are currently popular for TNBC. By identifying significant papers, comprehending trending topics, and collaborating across multiple disciplines, this study may accelerate research on TNBC therapy options.

Extreme droughts can severely impact terrestrial vegetation productivity. In the summer of 2022, approximately 32.7% of China’s land area experienced extreme drought conditions, marked by reduced rainfall both in terms of amount and intensity, prolonged consecutive dry days, minimal rainy days, and accompanied by heat waves. While previous studies have reported productivity losses in over half of China’s vegetated areas in 2022, how vegetation productivity recover from extreme drought remains to be clarified. In this study, we utilized the Enhanced Vegetation Index (EVI), Gross Primary Productivity (GPP) and meteorological data to evaluate the extent and pace of vegetation productivity change from loss in 2022 to post-drought recovery in 2023. We also assessed the contributions of seven meteorological variables and two drought-related variables to variations in vegetation productivity in regions affected by extreme drought using machine-learning techniques. Our findings revealed that, in 2022, the average EVI and GPP in regions affected by extreme drought were 2.3% and 8.0% lower, respectively, compared to the baseline period from 2018 to 2021. Soil water content (SWC) emerged as the primary factor contributing to the decline in EVI/GPP, followed by the number of rainy days for EVI and vapor pressure deficit for GPP. In 2023, we observed a significant vegetation recovery, with the average EVI increasing by 2.6% and the GPP rising by 14.9% within the study area compared to 2022. SWC played a dominant role in this recovery, and both EVI recovery and GPP recovery displayed a non-linear response to SWC. Additionally, we identified a threshold effect for SWC on recovery; once SWC increased above a certain threshold, EVI and GPP would recover largely and rapidly. Furthermore, rainfall intensity and rainfall amount emerged as the second most important factors influencing the recovery of EVI and GPP, respectively. Our study underscores the significance of soil moisture and rainfall seasonality in influencing plant growth.

Soil salinization is a significant global challenge impacting food security and arable land safety. Biological amelioration for the development and utilization of salt-alkali land has gained attention in recent years but the breeding and selection of salt-alkali-tolerant crop varieties remain a challenge. Cultivated soybeans are moderately salt-tolerant crops; however, a precise threshold for salt-alkali conditions has not been determined and varies by genotype. Therefore, this study evaluated the salt-alkali tolerance of 15 different soybean varieties using correlation, principal component, membership function, and cluster analyses. The average soybean indices decreased with increasing salt-alkali stress concentrations. Under severe salt-alkali stress, the coefficients of variation for grain yield and biomass were significantly higher than those under mild salt-alkali stress. Plant height and node number were significantly positively correlated, whereas bottom pod height was significantly negatively correlated with branch number, effective pod number, and grain number per plant. Node and grain numbers per plant were significantly positively correlated. Branch number, effective pod number, grain number per plant, and hundred-grain weight were significantly and positively correlated. Effective pod number was significantly positively correlated with grain number per plant, biomass, and yield. Grain number per plant exhibited a significant negative correlation with hundred-grain weight. Biomass and yield were significantly positively correlated. The salt-alkali tolerance of 15 soybean varieties ranged from strong weak as follows: Cangdou 1438, 0734, 1426, 1418, 1453, 1327, 1846, 1412, 1817, 1301, 1821, 1819, 1815, 1814, and 1850. Salt-alkali-sensitive and salt-alkali-tolerant varieties were successfully identified.

Abstract Background As a traditional Mongolian medicine, Zhenzhu Tongluo pills has played a good neuroprotective function in clinic. However, the key mechanisms by which it works are poorly studied. Objectives To study the effect and mechanism of Zhenzhu Tongluo pills in treating diabetic peripheral neuropathy injury. Methods Diabetic peripheral neuropathy model was established by injecting STZ into rats. Physiological, behavioral, morphological and functional analyses were used to evaluate that the overall therapeutic effect of rats, ELISA, qRT-PCR, Western blot, immunohistochemical staining, HE staining and TUNEL staining were used to further study the related mechanism. Results Zhenzhu Tongluo pills can significantly improve the physiological changes, behavioral abnormalities, structural and functional damage in diabetic peripheral neuropathy rats, which may be related to the anti-inflammatory and anti-apoptotic effects that realized by regulating PI3K/AKT, MAPK, NF-κB signaling pathways. Conclusions Zhenzhu Tongluo pills has neuroprotective effect, and anti-inflammatory and anti-apoptosis may be the important way of its function.

This is an essay in the field of mineral processing engineering. In China, fluorite mainly exists in the form of concomitant deposits. In the flotation process, other useful minerals are usually preferentially floated, and a large amount of fluorite exists in tailings. In this paper, the restrained fluorite and calcite in the floating tungsten tailings are taken as objects, and ultrasonic wave is added to change the floatability of the two, so as to explore a method to optimize the comprehensive utilization level of fluorite in the floating tungsten tailings. After ultrasonic pretreatment of pulp inhibited by sodium humate for 39 min, the flotation recovery of fluorite reached 84.74%, while the flotation recovery of calcite was only 11.47%, with a difference of 73.27%. Exploring the mechanism of ultrasonic pretreatment, it is found that the absorption intensity of sodium humate on the surface of fluorite is lower than that of calcite in the infrared spectrum detection. Ultrasonic pretreatment can desorb the sodium humate on the surface of fluorite, increase the absorption amount of sodium oleate on the surface, and make the zeta potential move forward; In addition, ultrasonic pretreatment mainly affects the content of sodium humate on the mineral surface, but does not affect the content of sodium oleate on the mineral surface. If only sodium humate exists in the slurry system during ultrasonic pretreatment, the sodium humate desorption speed is faster, which is more conducive to adsorbing the sodium oleate added subsequently.

In this study, sodium polyacrylate (PAAS) and ultrafiltration membranes were used to extract and separate Cu2+ and Ni2+ ions from electroplating wastewater. The effects of pH, the P/M ratio (mass ratio of sodium polyacrylate to metal ions), tartaric acid, and sodium citrate on the complexation of Cu2+ and Ni2+ by sodium polyacrylate were investigated. The retention of Cu2+ and Ni2+ by PAAS in single metal solutions with a P/M ratio = 4 and pH = 5 differed by 45.36%. When the complexation system of PAAS with a single metal contained tartaric acid and sodium citrate, the retention of PAAS for Cu2+ and Ni2+ increased to 80.36% and 58.84%. PAAS retention for Ni2+ decreased, but retention for Cu2+ remained the same. All the results indicated that there was competition between tartaric acid, sodium citrate, and PAAS for the adsorption of Cu2+ and Ni2+. Some of the Ni2+ complexed with PAAS were detached from PAAS complexed by tartaric acid and sodium citrate and permeated through the membrane pores, while the Cu2+ complexed with PAAS was not complexed by tartaric acid and sodium citrate and could not permeate through the membrane pores. Therefore, this study helps to provide a theoretical basis for the separation of Cu2+ and Ni2+ in electroplating wastewater.

Objective: A model that considers the characteristics of dialysis patients may help predict successful fistula maturation. We evaluated factors associated with radiocephalic arteriovenous fistula (RCAVF) maturation at 3 months in dialysis patients with end-stage renal disease (ESRD). Methods: A total of 184 patients who received an initial RCAVF at Beijing Haidian Hospital (Haidian Section of Peking University Third Hospital) were recruited. Fistula maturation was assessed within 3 months. Patient characteristics and preoperative vascular assessment indices were examined. Factors associated with fistula maturation were analyzed using logistic regression and least absolute shrinkage and selection operator (LASSO) binary logistic regression. Boostrapping was used for internal validation. Results: The development data consisted of 184 ESRD patients receiving an initial RCAVF, 140 (76%) of whom achieved fistula maturation. The main predictors of RCAVF maturation in the final model were sex, age-adjusted vein dilation (eVD), radial artery volume (Vartery), and diastolic blood pressure. The difference of vein diameter with and without a tourniquet was significantly larger in the mature RCAVF group (3.0 ± 0.5 vs. 2.2 ± 0.5 mm). The area under receiver operating characteristic (AUROC) curve for prediction of fistula maturation was 0.77, and the Hosmer-Lemeshow statistic indicated agreement between observed and predicted values (P = 0.792). Analysis of internal validation using bootstrapping indicated the C-index was 0.75. Conclusion: The ratio of vein dilation and age were the major predictors of fistula maturation at 3 months in our patients. The resulting online prediction model may help in clinical decision-making for patients receiving a RCAVF.

BackgroundRecent studies show testosterone (T) deficiency worsens cognitive impairment in Alzheimer’s disease (AD) patients. Mitochondrial dysfunction, as an early event of AD, is becoming critical hallmark of AD pathogenesis. However, currently, whether T deficiency exacerbates mitochondrial dysfunction of men with AD remains unclear.ObjectiveThe purpose of this study is to explore the effects of T deficiency on mitochondrial dysfunction of male AD mouse models and its potential mechanisms.MethodsAlzheimer’s disease animal model with T deficiency was performed by castration to 3-month-old male APP/PS1 mice. Hippocampal mitochondrial function of mice was analyzed by spectrophotometry and flow cytometry. The gene expression levels related to mitochondrial biogenesis and mitochondrial dynamics were determined through quantitative real-time PCR (qPCR) and western blot analysis. SH-SY5Y cells treated with flutamide, T and/or H2O2 were processed for analyzing the potential mechanisms of T on mitochondrial dysfunction.ResultsTestosterone deficiency significantly aggravated the cognitive deficits and hippocampal pathologic damage of male APP/PS1 mice. These effects were consistent with exacerbated mitochondrial dysfunction by gonadectomy to male APP/PS1 mice, reflected by further increase in oxidative damage and decrease in mitochondrial membrane potential, complex IV activity and ATP levels. More importantly, T deficiency induced the exacerbation of compromised mitochondrial homeostasis in male APP/PS1 mice by exerting detrimental effects on mitochondrial biogenesis and mitochondrial dynamics at mRNA and protein level, leading to more defective mitochondria accumulated in the hippocampus. In vitro studies using SH-SY5Y cells validated T’s protective effects on the H2O2-induced mitochondrial dysfunction, mitochondrial biogenesis impairment, and mitochondrial dynamics imbalance. Administering androgen receptor (AR) antagonist flutamide weakened the beneficial effects of T pretreatment on H2O2-treated SH-SY5Y cells, demonstrating a critical role of classical AR pathway in maintaining mitochondrial function.ConclusionTestosterone deficiency exacerbates hippocampal mitochondrial dysfunction of male APP/PS1 mice by accumulating more defective mitochondria. Thus, appropriate T levels in the early stage of AD might be beneficial in delaying AD pathology by improving mitochondrial biogenesis and mitochondrial dynamics.

Hematological toxicity is a severe adverse event (AE) in anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, the pathophysiological mechanism underlying prolonged cytopenia and the relationship between persistent cytopenia, efficacy, and AEs after anti-CD19 CAR T cell therapy are unknown. Therefore, this study explored whether persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs. Thirty-eight patients with R/R DLBCL were enrolled in an anti-CD19 CAR T cell therapy clinical trial. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide before CAR T cell therapy. The degree and duration of cytopenia, clinical response, proportion of CAR T cells, interleukin-6 (IL-6) levels, AEs, and follow-up were observed after therapy. Grades 3–4 persistent cytopenia occurred in 14 patients with R/R DLBCL, who recovered 8–18 weeks after CAR T cell infusion. These patients achieved an objective response rate (ORR) for anti-CD19 CAR T cell therapy. In patients who achieved ORR, the incidence of Grades 3–4 persistent cytopenia was higher in patients with a high tumor load than in those without a high tumor load. The mean peaks of IL-6 and anti-CD19 CAR T cells and the cytokine release syndrome grade in patients with Grades 3–4 persistent cytopenia were higher than those in patients without persistent cytopenia. Anti-CD19 CAR T cells were observed 21 and 28 days after infusion, and patients had Grades 3–4 persistent cytopenia. Progression-free and overall survival were higher in patients with Grades 3–4 persistent cytopenia than in those without cytopenia. Therefore, persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs, allowing clinicians to determine the efficiency of CD-19 CAR T cell therapy and the associated AEs.

AIM: To analyze the differences, agreements, and correlation among total corneal power parameters generated by different instruments after myopic keratorefractive surgery. METHODS: The prospective cross-sectional study included patients who underwent myopic keratorefractive surgery and received measurements of corneal power 3mo after surgery. Automated keratometer was used for the measurement of simulated keratometry (SimK), swept-source optical coherence tomography (SS-OCT) based biometer for total keratometry (TK), anterior segment-OCT for real keratometry (RK), and Scheimpflug keratometer for the true net power (TNP), the total corneal refractive power (TCRP) and equivalent K-readings (EKR). The differences among these parameters were analyzed, and the agreements and correlation between SimK and other total corneal power parameters were investigated. RESULTS: A total of 70 eyes of 70 patients after myopic keratorefractive surgery were included. The evaluated corneal power parameters were as follows: SimK 38.32±1.93 D, TK 37.54±2.12 D, RK 36.64±2.09 D, TNP 36.56±1.97 D, TCRP 36.70±2.01 D, and EKR 37.55±2.00 D. Pairwise comparison showed that there were significant differences (P

Abstract Introduction Although anti‐CD19 chimeric antigen receptor (CAR) T cell therapy was approved as a very effective salvage strategy in relapsed/refractory (R/R) B cell lymphoma, the experience in R/R gastrointestinal (GI) lymphoma is still insufficient. Methods We summarized the efficacy and side effects of anti‐CD19 CAR T‐cell therapy in 12 patients with R/R GI lymphoma. Based on literature, the R/R GI lymphoma patients were divided into subgroups with different characteristics: Bulky/No bulky disease, Gastric/Gastrointestinal involvement, Gastrointestinal/Combined extra‐gastrointestinal lesions, Ulcer/Lumps or nodules type, With/without gastrointestinal bleeding. Results The objective response rate (ORR) was 66.67% in these 12 patients. The ORR was 83.33% in no bulky disease group, 80.00% in gastric involvement group, 100.00% in ulcer type group, and 80.00% in no gastrointestinal bleeding group. The CR rate was 33.33% in these 12 patients. The CR was 50.0% in no bulky disease group, 60.00% in gastric involvement group, and 80.00% in ulcer type group. The PFS and OS rate of the 12 patients at 6 months after infusion were 54.55% and 58.33%, respectively. The overall survival (OS) at 6 months was higher in no bulky disease group. There was no difference of the OS or the progression free survival (PFS) at 6 months between the other groups. The mean peak of CAR‐T cells and Cytokine Release Syndrome (CRS) grade were higher in gastrointestinal lesions group. The mean peak of IFN‐γ and CRS grade were higher in gastrointestinal bleeding group. Four out of six patients in group of gastrointestinal lesions group were patient with high tumor burden. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding. Conclusions The ORR and CR of high tumor load, gastrointestinal involvement, lumps or nodules type and gastrointestinal bleeding group were lower. The CRS grade was higher in gastrointestinal lesions group and in gastrointestinal bleeding group. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding.

Background: C2H2-zinc finger transcription factors comprise one of the largest and most diverse gene superfamilies and are involved in the transcriptional regulation of flowering. Although a large number of C2H2 zinc-finger proteins (C2H2-ZFPs) have been well characterized in a number of model plant species, little is known about their expression and function in Coptis teeta. C. teeta displays two floral phenotypes (herkogamy phenotypes). It has been proposed that the C2H2-zinc finger transcription factor family may play a crucial role in the formation of floral development and herkogamy observed in C. teeta. As such, we performed a genome-wide analysis of the C2H2-ZFP gene family in C. teeta.Results: The complexity and diversity of C. teeta C2H2 zinc finger proteins were established by evaluation of their physicochemical properties, phylogenetic relationships, exon-intron structure, and conserved motifs. Chromosome localization showed that 95 members of the C2H2 zinc-finger genes were unevenly distributed across the nine chromosomes of C. teeta, and that these genes were replicated in tandem and segmentally and had undergone purifying selection. Analysis of cis-acting regulatory elements revealed a possible involvement of C2H2 zinc-finger proteins in the regulation of phytohormones. Transcriptome data was then used to compare the expression levels of these genes during the growth and development of the two floral phenotypes (F-type and M-type). These data demonstrate that in groups A and B, the expression levels of 23 genes were higher in F-type flowers, while 15 genes showed higher expressions in M-type flowers. qRT-PCR analysis further revealed that the relative expression was highly consistent with the transcriptome data.Conclusion: These data provide a solid basis for further in-depth studies of the C2H2 zinc finger transcription factor gene family in this species and provide preliminary information on which to base further research into the role of the C2H2 ZFPs gene family in floral development in C. teeta.

AbstractPurpose To assess the utility of Sonazoid contrast-enhanced ultrasound (CEUS) for guiding percutaneous microwave ablation (MWA) for colorectal liver metastases (CRLMs).Materials and Methods The medical records of patients who had undergone ultrasound (US)-guided percutaneous MWA between July 2020 and June 2022, were reviewed. Propensity score matching (PSM) with a ratio of 1:1 was used to balance the potential bias between the grayscale US-guided and Sonazoid CEUS-guided groups. Local tumor progression (LTP), intrahepatic recurrence (IR), and complication rates were compared between the two groups.Results Of 252 patients enrolled, 247 achieved complete ablation, and the technical effectiveness was 98.0% (247/252). Of these 247 patients, 158 were in the grayscale US-guided group and 89 in the Sonazoid CEUS-guided group. The median follow-up period was 14.6 months. After PSM, there were no significant differences in LTP, IR, or complication rates between the two groups (p = 0.100, p = 0.511, p > 0.99, respectively). Multivariate analysis identified tumor size ≥ 3 cm (hazard ratio [HR], 7.945; 95% CI, 2.591-24.370; p 8 cm (HR, 3.194; 95% CI, 1.439-7.091; p = 0.004) as significant factors associated with LTP. For tumors with poor vision on grayscale US, Sonazoid CEUS-guided ablation achieved a better LTP rate than grayscale US-guided ablation (3.7% vs.14.8%, p = 0.032).Conclusion For tumors with poor vision on grayscale US, Sonazoid CEUS guidance is recommended for better local tumor control.

Purpose: To analyze crystalline lens decentration and tilt in eyes with different axial lengths (ALs) using a swept-source anterior segment optical coherence tomography (SS-AS-OCT). Methods: Patients with normal right eyes who visited our hospital between December 2020 and January 2021 were included in this cross-sectional study. Data on crystalline lens decentration and tilt, AL, aqueous depth (AD), central corneal thickness (CCT), lens thickness (LT), lens vault (LV), anterior chamber width (ACW), and angle κ were collected. Results: A total of 252 patients were included and divided into normal (n = 82), medium–long (n = 89), and long (n = 81) AL groups. The average age of these patients was 43.63 ± 17.02 years. The crystalline lens decentration (0.16 ± 0.08, 0.16 ± 0.09, and 0.20 ± 0.09 mm, P = 0.009) and tilt (4.58° ± 1.42°, 4.06° ± 1.32°, and 2.84° ± 1.19°, P < 0.001) were significantly different among the normal, medium, and long AL groups. Crystalline lens decentration was correlated with AL (r = 0.466, P = 0.004), AD (r = 0.358, P = 0.006), ACW (r = −0.004, P = 0.020), LT (r = −0.141, P = 0.013), and LV (r = −0.371, P = 0.003). Crystalline lens tilt was correlated with age (r = 0.312, P < 0.001), AL (r = −0.592, P < 0.001), AD (r = −0.436, P < 0.001), ACW (r = −0.018, P = 0.004), LT (r = 0.216, P = 0.001), and LV (r = 0.311, P = 0.003). Conclusion: Crystalline lens decentration was positively correlated with AL, and tilt was negatively correlated with AL.

Purpose: To examine the role of the strain ratio in elastosonography for the differential diagnosis of common intraocular tumors such as choroidal melanoma, choroidal hemangioma, choroidal metastatic carcinoma, and retinoblastoma. Methods: This study included patients suffering from intraocular space-occupying lesions and who visited Beijing Tongren Eye Center of Beijing Tongren Hospital affiliated to Capital Medical University from June 2016 to March 2020. All patients underwent a physical examination, fundus examination with mydriasis, color Doppler ultrasonography, elastosonography, magnetic resonance imaging (MRI), and fundus angiography within 1 week. All patients were grouped as choroidal melanoma, choroidal metastatic carcinoma, retinoblastoma, choroidal hemangioma, and optic disk melanocytoma. A receiver operating characteristic (ROC) curve analysis was performed to assess the strain ratio for diagnosing malignant intraocular tumors. Results: A total of 155 patients (161 eyes) were recruited. The strain ratios measured were 39.59 ± 15.92 for choroidal melanoma, 36.85 ± 13.64 for choroidal metastatic carcinoma, 38.93 ± 17.27 for retinoblastoma, 13.42 ± 10.93 for choroidal hemangioma, and 3.84 ± 1.32 for optic disk melanocytoma. The strain ratios of the three malignant lesions were significantly higher than those of the two benign lesions (all P < 0.001). The area under the ROC curve was 0.95 ± 0.028. The optimal cutoff point was 22.67, with 85.7% sensitivity and 96.4% specificity. Conclusion: There were significant differences in elasticity between the malignant and benign intraocular tumors. The strain ratio using elastosonography could serve as an important auxiliary examination to distinguish between benign and malignant intraocular tumors.

Abstract Background Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are involved in regulating tumor cell ferroptosis. However, prognostic signatures based on ferroptosis-related lncRNAs (FRLs) and their relationship to the immune microenvironment have not been comprehensively explored in clear cell renal cell carcinoma (ccRCC). Methods In the present study, the expression profiles of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database; 459 patient specimens and 69 adjacent normal tissues were randomly separated into training or validation cohorts at a 7:3 ratio. We identified 7 FRLs that constitute a prognostic signature according to the differential analysis, correlation analysis, univariate regression, and least absolute shrinkage and selection operator (LASSO) Cox analysis. To identify the independence of risk score as a prognostic factor, univariate and multivariate regression analyses were also performed. Furthermore, CIBERSORT was conducted to analyze the immune infiltration of patients in the high-risk and low-risk groups. Subsequently, the differential expression of immune checkpoint and m6A genes was analyzed in the two risk groups. Results A 7-FRLs prognostic signature of ccRCC was developed to distinguish patients into high-risk and low-risk groups with significant survival differences. This signature has great prognostic performance, with the area under the curve (AUC) for 1, 3, and 5 years of 0.713, 0.700, 0.726 in the training set and 0.727, 0.667, and 0.736 in the testing set, respectively. Moreover, this signature was significantly associated with immune infiltration. Correlation analysis showed that risk score was positively correlated with regulatory T cells (Tregs), activated CD4 memory T cells, CD8 T cells and follicular helper T cells, whereas it was inversely correlated with monocytes and M2 macrophages. In addition, the expression of fourteen immune checkpoint genes and nine m6A-related genes varied significantly between the two risk groups. Conclusion We established a novel FRLs-based prognostic signature for patients with ccRCC, containing seven lncRNAs with precise predictive performance. The FRLs prognostic signature may play a significant role in antitumor immunity and provide a promising idea for individualized targeted therapy for patients with ccRCC.

Purpose The present study identified predictors of intrahepatic progression-free survival (ihPFS) after ultrasound (US)-guided percutaneous microwave ablation (MWA) for colorectal liver metastases (CRLMs) and developed a nomogram to predict ihPFS. Methods From January 2013 to December 2018, a total of 314 patients (224 men and 90 women; mean age, 57.1 ± 11.8 years; range, 23–86 years) with 645 CRLMs (mean diameter, 16.6 ± 6.5 mm; range, 6.0–45.0 mm) treated with US-guided percutaneous MWA were included and analyzed. The average number of CRLMs per patient treated was 2 (range, 1–8). A nomogram to predict ihPFS was developed based on a multivariable Cox model. Validation of the nomogram was performed using the concordance index (C-index), calibration curves, and decision curve analyses. Results The 1-, 2-, and 3-year cumulative ihPFS rates were 59.0%, 38.9%, and 30.8%, respectively. Maximal CRLM size, number of CRLMs, ablative margin, primary tumor lymph node status, and chemotherapy were five independent prognostic factors for ihPFS. The C-index of the nomogram was 0.702 (CI: 0.681–0.723). A risk classification system that perfectly classified the patients into three risk groups was constructed. The median ihPFS of patients in the low-, intermediate-, and high-risk groups was 36.3 months (95% CI: 21.4–51.1), 13.4 months (95% CI: 12.1–14.6), and 3.8 months (95% CI: 2.3–5.3), respectively. Conclusion The nomogram and risk classification system will facilitate the personalized assessment of ihPFS for patients receiving US-guided percutaneous MWA for CRLMs.

Abstract Background Capacitively coupled electrode (CC electrode), as a non-contact and unobtrusive technology for measuring physiological signals, has been widely applied in sleep monitoring scenarios. The most common implementation is capacitive electrocardiogram (cECG) that could provide useful clinical information for assessing cardiac function and detecting cardiovascular diseases. In the current study, we sought to explore another potential application of cECG in sleep monitoring, i.e., sleep postures recognition. Methods Two sets of experiments, the short-term experiment, and the overnight experiment, were conducted. The cECG signals were measured by a smart mattress based on flexible CC electrodes and sleep postures were recorded simultaneously. Then, a classifier model based on a deep recurrent neural network (RNN) was proposed to distinguish sleep postures (supine, left lateral and right lateral). To verify the reliability of the proposed model, leave-one-subject-out cross-validation was introduced. Results In the short-term experiment, the overall accuracy of 96.2% was achieved based on 30-s segment, while the overall accuracy was 88.8% using one heart beat segment. For the unconstrained overnight experiment, the accuracy of 91.0% was achieved based on 30-s segment, while the accuracy was 81.4% using one heart beat segment. Conclusions The results suggest that cECG could render valuable information about sleep postures detection and potentially be helpful for sleep disorder diagnosis.

Despite being a common therapy for hepatocellular carcinoma (HCC), insufficient thermal ablation can leave behind tumor residues that can cause recurrence. This is believed to augment M2 inflammatory macrophages that usually play a pro-tumorigenic role. To address this problem, we designed d-mannose-chelated iron oxide nanoparticles (man-IONPs) to polarize M2-like macrophages into the antitumor M1 phenotype. In vitro and in vivo experiments demonstrated that man-IONPs specifically targeted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation (MWA). The nanoparticles simultaneously induced polarization of pro-tumorigenic M2 macrophages into antitumor M1 phenotypes, enabling the transformation of the immunosuppressive microenvironment into an immunoactivating one. Post-MWA macrophage polarization exerted robust inhibitory effects on HCC progression in a well-established orthotopic liver cancer mouse model. Thus, combining thermal ablation with man-IONPs can salvage residual tumors after insufficient MWA. These results have strong potential for clinical translation.

Summary: Simultaneous photocatalytic biorefinery and CO2 reduction to co-produce fuels and high value-added chemicals have recently attracted significant attention; however, comprehensive studies are still lacking. Herein, we report the preparation of highly crystalline oxygen-doped carbon nitride nanotubes (O-CNNTs-x) using an ammonium fluoride-assisted hydrothermal/calcination strategy. The hollow structure, high crystallinity, and O incorporation endowed the O-CNNTs-x with photocatalytic activity by considerably improving optical absorption and modulating the charge carrier motion. The lactic acid yield and CO evolution rate over O-CNNTs-2.0 reached 82.08% and 67.95 μmol g−1 h−1, which are 1.57- and 7.37-fold times higher than those of CN, respectively. Moreover, ·OH plays a key role in the oxidation half-reaction. This study offers a facile approach for fabricating highly crystalline element-doped CN with a customizable morphology and electronic properties and demonstrates the viability of co-photocatalytic CO2 reduction and biomass selective oxidation.

Purpose: Microwave ablation (MWA) is difficult to perform in colorectal liver metastases (CRLMs) adjacent to the cardiophrenic angle. Therefore, a modified approach involving antenna array placement parallel to the diaphragm was initially attempted. Its safety and efficacy were compared with those involving non-parallel placement. Methods: Sixty-three patients with CRLMs adjacent to the cardiophrenic angle (lesions within 10 ​mm of the diaphragm) who underwent MWA were included in the study. All patients were further classified into parallel and non-parallel groups according to the method of antenna placement. The distance between the lesion and diaphragmatic surface before MWA, complications, and local tumor progression (LTP) at the last imaging follow-up were recorded. LTPs in the two groups were compared using the log-rank test. Prognostic factors for LTP were assessed using the Cox proportional hazards regression model. Results: Thirty and 33 lesions were ablated using parallel and non-parallel antenna placement, respectively. During the mean follow-up duration of 19.7 ​± ​8.2 months, the LTP rate in the parallel and non-parallel placement groups were 3.3% (1/30) and 24.2% (8/33), respectively. The log-rank test showed that parallel antenna placement was associated with delayed LTP (p ​= ​0.018). Multivariate Cox regression analysis showed that parallel antenna placement was an independent predictor of delayed LTP after adjusting for possible risk factors, including age, sex, tumor size, and KRAS mutation (hazard ratio, 0.1; 95% confidence interval, 0.00, 0.80; p ​= ​0.034). Conclusion: The placement of the antenna parallel to the diaphragm is an alternative and effective method for MWA of CRLMs near the cardiophrenic angle and can contribute to the reduction of the LTP rate.

The permeability of reservoirs is a key factor affecting the exploitation and utilization of geothermal resources. This test used a core flow meter and other advanced experimental devices to investigate the evolution of the permeability characteristics of loose sandstone samples (with a diameter of 25 mm and a length of 50 mm) in the Zijiao Town area under various temperatures, confining pressures, injection rates, and cyclic loading and unloading conditions. The results show that (1) as the temperature increases, the overall trend of rock permeability decreases, which is mainly related to the thermal expansion of rock particles. In addition, the higher the temperature, the greater the gravel outflow. (2) The critical pressure for pore closure in the unconsolidated sandstone in the region is approximately 15 MPa. (3) The permeability change of loose sandstone under low injection rate conditions is relatively small and can be neglected. However, there is reason to believe that under high-flow injection conditions, the permeability of this type of rock mass will undergo significant changes. (4) Under the condition of loading and unloading, the permeability ratio curve of the unloading stage at three temperatures is almost a straight line. The higher the temperature, the smaller the slope, and the permeability at 20 °C with the highest recovery degree is only about 50% of the initial one.

Clove essential oil (CEO) was immobilized in mesoporous silica nanoparticles (MSN) (0, 1, 2, and 3 wt%) and incorporated into poly(lactic acid) (PLA) matrix via a casting method. The functional properties including mechanical property, thermal property, antimicrobial property, and CEO release behavior of the PLA nanocomposite film were investigated. The compatibility of CEO-loading MSN with PLA was verified by scanning electron microscopy analysis. The tensile strength, tensile module, and glass transition temperature of the MSN/CEO/PLA composite film was improved with the increase in MSN content. The release study indicated that the MSN/CEO/PLA composite films exhibited sustained release profile of CEO. The MSN/CEO/PLA films demonstrated efficient antimicrobial activity. The results indicated that CEO immobilized MSN incorporated PLA nanocomposite film showed promising features for active food packaging material.

Objective To prospectively evaluate the efficacy of microwave ablation (MWA) for benign breast lesions (BBLs) ≥2 cm and explore the possible factors associated with the volume reduction rate (VRR) of ablated lesions. Materials and methods From November 2013 to December 2017, a total of 80 patients with 104 biopsy-proved BBLs larger than 2 cm in size underwent MWA. After the procedure, patients were followed up via physical and imaging examination consisting of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI). Possible factors associated with 12-month VRR were assessed, including basic patient characteristics, index lesions and parameters of ablation technique. Results The mean tumor size was 2.6 ± 0.6 cm (ranging 2.0–6.3 cm). Of the 104 lesions, 70 were fibroadenomas, 27 adenosis and 7 fibrocystic changes. Post-procedure CEUS or contrast-enhanced MRI showed that all lesions were completely ablated. No immediate or delayed complications were observed. All patients were followed up for more than 12 months (median follow-up 12.5 months). After MWA, the ablated lesion volume decreased significantly by 12 months (p

Bacteria can use type VI secretion systems (T6SSs) to inject toxic effector proteins into adjacent cells, in a contact-dependent manner. Here, the authors provide evidence of contact-independent killing by a T6SS effector that is secreted into the extracellular milieu and then taken up by other bacterial cells.

Crowdsourcing provides an effective way to construct a location recognition image database. Comparing with traditional location image database construction, crowdsourced image database has massive advantages, e.g., much richer information for location, with various angles, timestamps, distances and weather information, providing useful potential for high recognition precision. However, when capturing the crowdsourced images, it is inevitable to have various disturbances on these location images, for example, moving vehicles and pedestrians, hindering the realization of potential. To address this challenge, we first propose a Rich Common Crucial Feature (RCCF) detection framework to exclude unimportant visual SURF features from crucial features. To achieve a good balance between the efficiency and accuracy, we further propose an RCCF based Visual Hash Bits (VHB) scheme to encode RCCF features into hash bits to vote for most matching images. Furthermore, deep feature extraction is also utilized with visual search architecture MobileNet. Extensive experiments are conducted on a crowdsourced dataset with 9,064 location images, demonstrating that our scheme outperforms other state-of-the-art schemes.

A controlled-release antibacterial active food packaging film was prepared from polylactic acid (PLA), poly (ε-caprolactone) (PCL), carbon nanotubes (CNTs), and cinnamaldehyde (CIN) by solvent evaporation method. The properties and antibacterial activities of CIN loaded PLA/CNTs/CIN film was characterized. Furthermore, the release behavior of CIN from PLA-based antibacterial film was quantified. The introduction of CNT and CIN would not significantly affect the barrier properties of PLA-based film, but would significantly enhance the UV resistance of the film. The co-action of CNTs and CIN led to the decrease of the glass transition temperature of the film and enhanced the elongation at break of the film. The PLA/CNTs/CIN film could continuously release CIN for 21 days in ambient storage, and antibacterial effect of the film on Staphylococcus aureus and Escherichia coli could be maintained for 21 days, during which the antibacterial effect gradually reduced and maintained for 7 days longer than the film without CNTs. According to the research results, The PLA/CNTs/CIN composites have great application potential in antibacterial active food packaging film.

Abstract. Background. TOSO, also named Fas inhibitory molecule 3 (FAIM3), has recently been identified as an immunoglobulin M (IgM) Fc receptor (FcμR). Previous studies have shown that TOSO is specifically over-expressed in chronic lymphocytic leukemia (CLL). However, the functions of TOSO in CLL remain unknown. The B-cell receptor (BCR) signaling pathway has been reported to be constitutively activated in CLL. Here, we aimed to investigate the functions of TOSO in the BCR signaling pathway and the pathogenesis of CLL. Methods. We over-expressed TOSO in B-cell lymphoma cell lines (Granta-519 and Z138) by lentiviral transduction and knocked down TOSO by siRNA in primary CLL cells. The over-expression and knockdown of TOSO were confirmed at the RNA level by polymerase chain reaction and protein level by Western blotting. Co-immunoprecipitation with TOSO antibody followed by liquid chromatography coupled with tandem mass spectrometry (IP/LCMS) was used to identify TOSO interacting proteins. Western blotting was performed to detect the activation status of BCR signaling pathways as well as B-cell lymphoma 2 (BCL-2). Flow cytometry was used to examine the apoptosis of TOSO-over-expressing B lymphoma cell lines and TOSO-down-regulated CLL cells via the staining of Annexin V and 7-AAD. One-way analyses of variance were used for intergroup comparisons, while independent samples t tests were used for two-sample comparisons. Results. From IP/LCMS, we identified spleen tyrosine kinase (SYK) as a crucial candidate of TOSO-interacting protein and confirmed it by co-immunoprecipitation. After stimulation with anti-IgM, TOSO over-expression increased the phosphorylation of SYK, and subsequently activated the BCR signaling pathway, which could be reversed by a SYK inhibitor. TOSO knockdown in primary CLL cells resulted in reduced SYK phosphorylation as well as attenuated BCR signaling pathway. The apoptosis rates of the Granta-519 and Z138 cells expressing TOSO were (8.46 ± 2.90)% and (4.20 ± 1.21)%, respectively, significantly lower than the rates of the control groups, which were (25.20 ± 4.60)% and (19.72 ± 1.10)%, respectively (P

Drug‐induced liver injury (DILI) can lead to acute liver failure, a lethal condition which may require liver transplantation. Hepatotoxicity associated with nonsteroidal anti‐inflammatory drugs (NSAIDs) accounts for ~ 10% of all DILI. In the current study, we determined whether indomethacin, one of the most commonly used NSAIDS, induced apoptosis in hepatocytes and investigated the underlying mechanism. Meanwhile, we investigated the protective effect of S‐allyl‐L‐cysteine (SAC), an active garlic derivative, on indomethacin‐induced hepatocyte apoptosis, and its implication on endoplasmic reticulum (ER) stress. We found that indomethacin triggered ER stress, as indicated by the elevated expression of phosphorylated eukaryotic translation initiation factor 2α (eIF2α), C/EBP homologous protein (CHOP) and spliced XBP1 in a rat liver BRL‐3A cell line. Following indomethacin treatment, caspase 3 activation and hepatocyte apoptosis were also observed. Inhibition of ER stress by chemical chaperone 4‐phenyl butyric acid alleviated cell apoptosis caused by indomethacin, indicating that ER stress is involved in indomethacin‐induced hepatocyte apoptosis. Moreover, SAC abated indomethacin‐induced eIF2α phosphorylation, inhibited CHOP upregulation and its nuclear translocation, abrogated the activation of caspase 3 and finally, protected hepatocytes from apoptosis. In conclusion, SAC protects indomethacin‐induced hepatocyte apoptosis through mitigating ER stress and may be suitable for development into a potential new therapeutic agent for the treatment of DILI.

Objective: To explore the association between cholecystectomy and the prognostic outcomes of patients with hepatocellular carcinoma (HCC) who underwent microwave ablation (MWA). Methods: Patients with HCC (n = 921) who underwent MWA were included and divided into cholecystectomy (n = 114) and non-cholecystectomy groups (n = 807). After propensity score matching (PSM) at a 1:2 ratio, overall survival (OS) and disease-free survival (DFS) rates were analyzed to compare prognostic outcomes between the cholecystectomy (n = 114) and non-cholecystectomy groups (n = 228). Univariate and multivariate Cox analyses were performed to assess potential risk factors for OS and DFS. Major complications were also compared between the groups. Results: After matching, no significant differences between groups were observed in baseline characteristics. The 1-, 3-, and 5-year OS rates were 96.5%, 82.1%, and 67.1% in the cholecystectomy group, and 97.4%, 85.2%, and 74.4% in the non-cholecystectomy group (P = 0.396); the 1-, 3-, and 5-year DFS rates were 58.4%, 34.5%, and 26.6% in the cholecystectomy group, and 73.6%, 44.7%, and 32.2% in the non-cholecystectomy group (P = 0.026), respectively. The intrahepatic distant recurrence rate in the cholecystectomy group was significantly higher than that in the non-cholecystectomy group (P = 0.026), and the local tumor recurrence and extrahepatic recurrence rates did not significantly differ between the groups (P = 0.609 and P = 0.879). Multivariate analysis revealed that cholecystectomy (HR = 1.364, 95% CI 1.023–1.819, P = 0.035), number of tumors (2 vs. 1: HR = 2.744, 95% CI 1.925–3.912, P < 0.001; 3 vs. 1: HR = 3.411, 95% CI 2.021–5.759, P < 0.001), and γ-GT levels (HR = 1.003, 95% CI 1.000–1.006, P < 0.024) were independent risk factors for DFS. The best γ-GT level cut-off value for predicting median DFS was 39.6 U/L (area under the curve = 0.600, P < 0.05). A positive correlation was observed between cholecystectomy and γ-GT level (r = 0.108, 95% CI −0.001–0.214, P = 0.047). Subgroup analysis showed that the DFS rates were significantly higher in the non-cholecystectomy group than the cholecystectomy group when γ-GT ≥39.6 U/L (P = 0.044). The 5-, 10-, 15-, 20-, and 25-year recurrence rates from the time of cholecystectomy were 2.63%, 21.93%, 42.11%, 58.77%, and 65.79%, respectively. A significant positive correlation was observed between cholecystectomy and the time from cholecystectomy to recurrence (r = 0.205, 95% CI 0.016–0.379, P = 0.029). There were no significant differences in complications between groups (P = 0.685). Conclusions: Patients with HCC who underwent cholecystectomy were more likely to develop intrahepatic distant recurrence after MWA, an outcome probably associated with increased γ-GT levels. Moreover, the recurrence rates increased with time.

Mantle cell lymphoma (MCL) is a phenotypically and genetically heterogeneous malignancy in which the genetic alterations determining clinical indications are not fully understood. Here, we performed a comprehensive whole-exome sequencing analysis of 152 primary samples derived from 134 MCL patients, including longitudinal samples from 16 patients and matched RNA-Seq data from 48 samples. We classified MCL into 4 robust clusters (C1–C4). C1 featured mutated immunoglobulin heavy variable (IGHV), CCND1 mutation, amp(11q13), and active B cell receptor (BCR) signaling. C2 was enriched with del(11q)/ATM mutations and upregulation of NF-κB and DNA repair pathways. C3 was characterized by mutations in SP140, NOTCH1, and NSD2, with downregulation of BCR signaling and MYC targets. C4 harbored del(17p)/TP53 mutations, del(13q), and del(9p), and active MYC pathway and hyperproliferation signatures. Patients in these 4 clusters had distinct outcomes (5-year overall survival [OS] rates for C1–C4 were 100%, 56.7%, 48.7%, and 14.2%, respectively). We also inferred the temporal order of genetic events and studied clonal evolution of 16 patients before treatment and at progression/relapse. Eleven of these samples showed drastic clonal evolution that was associated with inferior survival, while the other samples showed modest or no evolution. Our study thus identifies genetic subsets that clinically define this malignancy and delineates clonal evolution patterns and their impact on clinical outcomes.

Hot dry rocks, as clean and abundant sources of new energy, are crucial in the restructuring of energy. Predicting the temperature field of hot dry rocks is of great significance for trapping the target areas of hot dry rocks. How to use limited logging data to predict the temperature field within a work area is a difficulty faced in hot dry rock exploration. We propose a method to predict the hot dry rock temperature field (using seismic inversion results). The relationship between porosity and transverse wave velocity was established with petrophysical modeling. The difference in porosity calculated from the density and transverse wave velocity was incorporated in the seismic inversion results to find the thermal expansion and predict the temperature field. We applied the method to predict the temperature of hot dry rocks in the Gonghe Basin. The results showed that the temperature in the northeast work area was higher than in the southwest area at the same depth, and a depth of 150 °C of the hot dry rock reservoir was shallower. The thermal storage cover was analyzed from the geological stratigraphic data of the Gonghe Basin. The thermal storage cover in the northeastern part was thicker than in the southwestern part and had better thermal insulation, which is consistent with the prediction of the temperature field.

Boron (B) excess gives rise to a serious agricultural problem. In this study, we identified a B toxicity responsive transcription factor AtWRKY47 in Arabidopsis thaliana. The T-DNA insertion mutants Atwrky47 showed enhanced tolerance to B toxicity with better growth parameters under high B conditions compared to wild-type Col-0 plants. Quantitative analysis of AtWRKY47 mRNA abundance indicated that it was down-regulated under B toxicity conditions. Fluorescently labeled AtWRKY47 protein was localized in nucleus. In contrast to the phenotype of Atwrky47 mutants, overexpression of AtWRKY47 in Col-0 background resulted in lower biomass, less chlorophyll content, and increased sensitivity to B toxicity. More importantly, the B concentration in shoots was higher in the overexpression lines and lower in the Atwrky47 mutants than in Col-0 plants, respectively. These results demonstrate that AtWRKY47 gene plays a key role in regulating plant tolerance to B toxicity.

In recent years, many new treatments for relapsed/refractory (R/R) multiple myeloma (MM) have improved patient prognosis, but the prognosis of patients with extramedullary MM is still particularly poor. Therefore, more efficacious therapies and novel strategies are urgently needed for these patients. The aim of this study was to observe and compare the efficacy and safety of humanized anti-B cell maturation antigen (anti-BCMA) chimeric antigen receptor (CAR) T cell therapy in R/R MM patients with and without extramedullary disease. Seven R/R MM patients with extramedullary disease and 13 without extramedullary disease received humanized anti-BCMA CAR T cell therapy. The overall response rate was not different between patients with and without extramedullary disease. There was no difference in the progression-free survival (PFS) or overall survival (OS) rates between the two groups at 180 days, but the PFS and OS rates in patients with extramedullary disease were lower at 360 days than those in patients without extramedullary disease. Although some patients with extramedullary disease experienced further disease progression, their M protein level did not increase. We did not see this change trend of M protein in patients without extramedullary disease. However, this was not observed in patients without extramedullary disease. Among patients who responded to CAR T cell therapy, the grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS) were much higher among patients with extramedullary disease. In summary, R/R MM patients with extramedullary disease could benefit from humanized anti-BCMA CAR T cell therapy in the short term, although the CRS and ICANS grades were much higher in patients with extramedullary disease. Therefore, anti-BCMA CAR T cell therapy allows for a remission time for R/R MM patients with extramedullary disease, which could be maintained by bridging hematopoietic stem cell transplantation, radiotherapy, and other therapies.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifiers ChiCTR1800017051 and ChiCTR2000033925.

Anti-CD19 chimeric antigen receptor T (CAR-T) therapy has achieved remarkable effects in refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL). However, when high tumor bulk occurs, patients tend to early progression after CAR-T therapy. Here, we investigated whether pretreatment with intensive debulking chemotherapy could improve the outcome of CAR-T in such patients. Fifty-seven patients with R/R DLBCL were enrolled, and 42 patients received anti-CD19-CAR-T therapy, among which, 25 patients (the combined group) with high tumor bulk received debulking chemotherapy and anti-CD19-CAR-T therapy sequentially. Another 17 patients (the control group) without high tumor bulk received anti-CD19-CAR-T therapy only. According to the response to debulking chemotherapy, patients of the combined group were divided into chemo-sensitive and chemo-refractory groups. Within 2 months, the objective response rate (ORR) was higher in the chemo-sensitive group than in the chemo-refractory group (P = 0.031). Grades 1–3 cytokine release syndrome (CRS) was reported, and no difference was shown in CRS grade distribution between the chemo-sensitive and chemo-refractory groups (P = 0.514). The chemo-sensitive group demonstrated longer overall survival (OS) than the chemo-refractory group (P = 0.042). Of the chemo-sensitive group, the 1-year disease free survival (DFS) and OS rates were 52.6 and 57.9%, respectively. Besides, no significant differences were found in ORR, DFS, and OS between the chemo-sensitive and control groups (ORR: P = 0.593; DFS: P = 0.762; OS: P = 0.531). In summary, effective debulking chemotherapy improved the short-term ORR and long-term OS of CAR-T therapy in R/R DLBCL with high tumor bulk, with outcomes comparable to those of R/R DLBCL without high tumor bulk. The clinical trial of our study was registered at http://www.chictr.org.cn/index.aspx as ChiCTR-ONN-16009862 and ChiCTR1800019622.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifier (ChiCTR-ONN-16009862 and ChiCTR1800019622).

Background: Trajectory planning is the premise of the control of orthopedic robots, which is directly related to the safety of the human body. However, to date, the trajectory of orthopedic robots has been restricted to lines and spline curves. This limits the flexibility of the robot and leads to unsatisfactory performance. In this paper, a trajectory planning method based on improved RRT* and B-spline curve is proposed in order to improve the control accuracy and flexibility. Method: Firstly, combined with the shortcomings of current trajectory planning methods and bone docking task analysis, the characteristics of the trajectory for orthopedic robot are illustrated, and the problem is described. Secondly, a sampling strategy and an extension strategy are proposed to solve the optimal problem of the RRT* algorithm. Meanwhile, B-spline curve is selected for path smoothing. Thirdly, based on our orthopedic robot, kinematics analysis is introduced briefly, and hypotonic polynomial is used to fit the joint variables. Finally, a comparative study of the improved RRT*, RRT*, and other algorithms are completed, and the feasibility of the robot’s trajectory is verified by algorithm simulation and platform simulation. Results: Compared with RRT*, shorter path and high node utilization are shown in the improved RRT*, which cut down about 1mm in the average path length and increased about half in the average node utilization. In the meantime, the fitting results are accepted, and the results of algorithm simulation and platform simulation showed good consistency and feasibility. Conclusions: This study revealed that the improved RRT* was superior to RRT*, and the proposed method could be used for the trajectory planning of parallel orthopedic robots, which has some significance for bone fracture and deformity correction.

We studied the acute graft-versus-host disease (GVHD) after humanized anti-CD19-CAR T therapy in relapsed B-acute lymphoblastic leukemia (ALL) patients after allogeneic hematopoietic stem cell transplant (allo-HSCT). Fifteen B-ALL patients were enrolled in our study. Thirteen patients (86.67%) achieved a complete response (CR) or CR with incomplete count recovery. The donor chimerism of the 13 patients reached 99.86 ± 0.21%. The development of aGVHD was observed in 10 patients (66.67%). Six patients developed grade I-II of aGVHD, while the other four patients developed grade III-IV of aGVHD. The notable adverse events were grade 1–2 cytokine release syndrome (CRS) in 10 patients and grade 3–4 CRS in five patients. Two patients died of infection, while another patient died of sudden cardiac arrest. The anti-CD19-CAR T cells were not eliminated in peripheral blood when the patients developed aGVHD. However, we did not observe their expansion peaks again in the process of aGVHD. During the aGVHD, the peaks of IL-6 and TNF-a were correlated with aGVHD levels. By May 31, 2020, the rates of leukemia-free survival (LFS) and overall survival (OS) at 180 days were 53.846 and 61.638%, respectively. All the patients who survived to date experienced aGVHD after humanized anti-CD19-CAR T cell therapy.Trial registration: The patients were enrolled in clinical trials of ChiCTR-ONN-16009862 and ChiCTR1800019622.

The booms of big data and graphic processing unit technologies have allowed us to explore more appropriate data structures and algorithms with smaller time complexity. However, the application of machine learning as a potential alternative for the traditional data structures, especially using deep learning, is a relatively new and largely uncharted territory. In this paper, we propose a novel recurrent neural network-based learned inverted index, called Pavo, to efficiently and flexibly organize inverted data. The basic hash function in the traditional inverted index is replaced by a hierarchical neural network, which makes Pavo be able to well adapt for various data distributions while showing lower collision rate as well as higher space utilization rate. A particular feature of our approach is that a novel unsupervised learning strategy to construct the hash function is proposed. To the best of our knowledge, there are no similar results, in which the unsupervised learning strategy is employed to design hash functions, in the existing literature. Extensive experimental results show that the unsupervised model owns some advantages than the supervised one. Our approaches not only demonstrate the feasibility of deep learning-based data structures for index purpose but also provide benefits for developers to make more accurate decisions on both the design and the configuration of data organization, operation, and parameters tuning of neural network so as to improve the performance of information searching.

HpaR, a MarR family transcriptional regulator, was first identified in Escherichia coli W for its regulation of the hpa-meta operon. Little else is known regarding its functionality. Here, we report that in Yersinia pseudotuberculosis, HpaR negatively regulates the hpa-meta operon similar to in E. coli W. To investigate additional functions of HpaR, RNA sequencing was performed for both the wild-type and the ΔhpaR mutant, which revealed that the type VI secretion system (T6SS) was positively regulated by HpaR. T6SS4 is important for bacteria resisting environmental stress, especially oxidative stress. We demonstrate that HpaR facilitates bacteria resist oxidative stress by upregulating the expression of T6SS4 in Y. pseudotuberculosis. HpaR is also involved in biofilm formation, antibiotic resistance, adhesion to eukaryotic cells, and virulence in mice. These results greatly expand our knowledge of the functionality of HpaR and reveal a new pathway that regulates T6SS4.

Abstract Androgen plays a pivotal role in the progression of renal fibrosis. However, whether exogenous androgen treatment to aged male rats can improve the age-related renal fibrosis was not explored. In our study, the changes of morphological structure, renal fibrosis, ultrastructure and renal function, the expressions of extracellular matrix (ECM), matrix metalloproteinases (MMPs) and its tissue inhibitors of metalloproteinases (TIMPs), the expressions of tumor growth factor β1 (TGF-β1)/Smad signaling and oxidative stress parameters as well as nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling were tested in kidney of aged male Wistar rats after subcutaneous testosterone propionate (TP, 2 mg/kg/d, 84-day) injection. Aged rats showed significantly renal histopathological changes, increased renal fibrosis, increased thickening of the glomerular basement membrane and the Bowman’s capsule basement membrane, declined renal functional, increased ECM, lower expressions of MMP-2 and MMP-9 and higher expressions of TIMP-1 and TIMP-2 in renal tissues and higher expressions of TGF-β1/Smad signaling, as well as lower expressions of Nrf2-ARE signaling compared to young rats. TP treatment significantly improved age-related above indexes. These results suggested that TP supplement may alleviate age-related renal fibrosis via suppression of TGF-β1/Smad signaling and activation of Nrf2-ARE signaling in aged rats.

Abstract Background Cancer cachexia is a cancer-induced metabolic disorder and a major cause of cancer-induced death. The constituents of cancer cachexia include an increase in energy expenditure, hepatic gluconeogenesis, fat lipolysis, and skeletal-muscle proteolysis and a decrease in body weight. The aetiology of cancer cachexia is unclear and may involve cancer-cell metabolism and secretion. In this study, we investigated whether the high glycolysis in cancer cells (the Warburg effect) triggers cachexia in athymic mice carrying pancreatic cancer cells. Methods First, we examined five human pancreatic cancer cell lines for glycolysis and cachectic-cytokine secretion. Consequently, MiaPaCa2 and AsPC1 cells were selected for the present study, because the glycolysis in MiaPaCa2 cells was typically high and that in AsPC1 cells was exceptionally low. In addition, both MiaPaCa2 and AsPC1 cells were competent in the secretion of examined cytokines. Next, we transplanted MiaPaCa2 and AsPC1 cells subcutaneously in different athymic mice for 8 weeks, using intact athymic mice for control. In another experiment, we treated normal mice with the supernatants of MiaPaCa2 or AsPC1 cells for 7 days, using vehicle-treated mice for control. In both models, we measured food intake and body weight, assayed plasma glucose, triglycerides, and TNF-α and used Western blot to determine the proteins that regulated hepatic gluconeogenesis, fat lipolysis, and skeletal-muscle proteolysis in the corresponding tissues. We also studied the effect of MiaPaCa2-cell supernatants on the proteolysis of C2C12 skeletal-muscle cells in vitro. Results The athymic mice carrying high-glycolytic MiaPaCa2 cells had anorexia and also showed evidence for cachexia, including increased hepatic gluconeogenesis, fat lipolysis and skeletal-muscle proteolysis and decreased body weight. The athymic mice carrying low-glycolytic AsPC1 cells had anorexia but did not show the above-mentioned evidence for cachexia. When normal mice were treated with the supernatants of MiaPaCa2 or AsPC1 cells, their energy homeostasis was largely normal. Thus, the cachexia in the athymic mice carrying MiaPaCa2 cells may not result from humeral factors released by the cancer cells. In vitro, MiaPaCa2-cell supernatants did not induce proteolysis in C2C12 cells. Conclusion The Warburg effect in pancreatic cancer cells is an independent aetiological factor for pancreatic cancer-induced cachexia.