Association of accommodation and convergence with axial length elongation in children with basic intermittent exotropia: a 12-month observational study.

INTRODUCTION: To investigate the association of parameters related to accommodation and convergence and axial elongation in basic intermittent exotropia (IXT) patients and the potential clinical predictors of axial length (AL) growth. METHODS: A total of 140 basic IXT patients were recruited in this study. The medians of AL growth in different age brackets were chosen to divide the subjects into Group A (slower axial elongation group, n=69) and Group B (faster axial elongation group, n=71). Parameters of dominant and nondominant eyes were compared and analyzed during the 12-month follow-up period. The parameters, including baseline refraction, angle of deviation, Newcastle score (NCS), accommodative amplitude (AMP), accommodative facility (AMF), accommodative response, positive or negative relative accommodation (PRA/NRA), and near point of convergence (NPC), were analyzed via univariate and multivariate regression. RESULTS: Subjects in faster axial elongation group tended to have more myopic spherical equivalents (t=3.956, P<.001), greater accommodative amplitudes of dominant eyes (t=-2.238, P=.027) and less near points of convergence (t=2.347, P=.020) than in slower axial elongation group. For dominant eyes, logistic and linear regression analysis revealed that more negative spherical equivalents (OR=0.603, P<.001; ß=-0.045, P<.001), greater accommodative amplitudes (OR=1.201, P=.027; ß=0.023, P=.010) and less near points of convergence (OR=0.883, P=.021; ß=-0.012, P=.019) were correlated with the faster axial elongation. For nondominant eyes, more myopic spherical equivalent (OR=0.682; P=.001; ß=-0.029, P=.005) was the only parameter correlated with faster axial elongation through regression analysis. CONCLUSION: In children with basic intermittent exotropia, faster axial elongation in the dominant eyes were associated with more myopic spherical equivalents, greater accommodative amplitudes, and lower near points of convergence. These accommodative parameters can serve as potential clinical indicators for monitoring myopia progression in addition to axial length.

Eleven inflammation-related genes risk signature model predicts prognosis of patients with breast cancer.

Background: Changes in gene expression are associated with malignancy. Analysis of gene expression data could be used to reveal cancer subtypes, key molecular drivers, and prognostic characteristics and to predict cancer susceptibility, treatment response, and mortality. It has been reported that inflammation plays an important role in the occurrence and development of tumors. Our aim was to establish a risk signature model of breast cancer with inflammation-related genes (IRGs) to evaluate their survival prognosis. Methods: We downloaded 200 IRGs from the Molecular Signatures Database (MSigDB). The data of breast cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differential gene expression analysis, the least absolute shrinkage and selection operator (LASSO), Cox regression analysis, and overall survival (OS) analysis were used to construct a multiple-IRG risk signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out to annotate functions of the differentially expressed IRGs (DEIRGs) The predictive accuracy of the prognostic model was evaluated by time-dependent receiver operating characteristic (ROC) curves. Subsequently, nomograms were constructed to guide clinical application according to the univariate and multivariate Cox proportional hazards regression analyses. Eventually, we applied gene set variation analysis (GSVA), mutation analysis, immune infiltration analysis, and drug response analysis to compare the differences between high- and low-risk patients. Results: Totally, 65 DEIRGs were obtained after comparing 1,092 breast cancer tissues with 113 paracancerous tissues in TCGA. Among them, 11 IRGs (IL18, IL12B, RASGRP1, HPN, CLEC5A, SCARF1, TACR3, VIP, CCL2, CALCRL, ABCA1) were screened with nonzero coefficient by LASSO regression analysis to construct the prognostic model, which was validated in GSE96058.The 11-gene IRGs risk signature model stratified patients into high- or low-risk groups, with those in the low-risk group having longer survival time and less deaths. Multivariate Cox analysis manifested that risk score, age, and stage were the three independent prognostic factors for breast cancer patients. There were 12 pathways with higher activities and 24 pathways with lower activities in the high-risk group compared with the low-risk group, yet no difference of gene mutation load was observed between the two groups. In immune infiltration analysis, we noted that the proportion of T cells showed a decreased trend according to the increase of risk score and most of the immune cells were enriched in the low-risk group. Inversely, macrophages M2 were more highly distributed in the high-risk group. We identified 67 approved drugs that showed a different effect between the high- and low-risk patients and the top 2 gene-drug pairs were IL12B-sunitinib and SCARF1-ruxolitinib. Conclusions: The 11-IRG risk signature model is a promising tool to predict the survival of breast cancer patients and the expressions of IL12B and SCARF1 may serve as potential targets for therapy of breast cancer.

Stable body sizes in soil nematodes across altitudes: The role of intrageneric variation in community assembly.

Animal body size exhibits rapid responses to environmental variations and displays considerable variability across ecological scales, significantly influencing ecological community assembly. However, our understanding of the extent of body size variation and its responses to environmental differences within soil fauna remains limited, impeding a comprehensive grasp of soil fauna's functional ecology. Here, we aim to investigate the magnitude of intrageneric body size variation and its implications for soil nematode community assembly along an altitudinal gradient. We examined soil nematode body size responses along an altitudinal gradient spanning from 3136 to 4128 m in an alpine mountain region of the eastern Tibetan Plateau. We assessed the contributions of intra- and intergeneric variations in body size, both within and among communities, using individual body size values. The implications of these variations for community assembly processes were determined through phenotypic variance ratios employing permutation tests. Our analyses did not reveal statistically significant correlations between altitude and the community-weighted mean body mass, regardless of considering intrageneric trait variation (IGTV). Approximately 15% of the variation in body size among communities and a substantial 72% of the variation in body size within communities can be attributed to IGTV. Altitude did not significantly affect IGTV within or among communities. Furthermore, our results underscored the dominant role of internal filtering within the community in governing nematode community assembly, with external filtering outside the community playing a limited role within our altitudinal range. Our findings emphasize the dominant role of body size variation within communities rather than among communities, attributable to strong internal filtering processes. These findings advance our understanding of body size variation in soil nematodes across ecological scales and highlight the pivotal role of intrageneric variation in shaping the functional ecology of soil fauna.

Synergistic Steric Effect of Precursor And Antisolvent Enables Strongly Confined Perovskite Films with Efficient and Spectral Stable Blue Emission.

Reducing the crystal size of perovskites to the strong quantum confinement regime is an effective way to realize blue luminescence for light-emitting applications. However, challenges remain in directly constraining the crystal growth during film preparation to achieve three-dimensional quantum confinement, and the widely used long-chain ligands may bring difficulties for charge transport and unfavorably affect the device performance. Herein, we report a novel strategy for fabricating strongly confined blue-emitting perovskite nanocrystalline films via synergistic steric effect modulation by precursors and antisolvents. We synthesize cesium pentafluoropropanoate (CsPFPA) as a new type of precursor agent, where the steric effect of the PFPA group can help constrain the growth of perovskite crystals and passivate the defects. Furthermore, different types of antisolvents with varied molecular sizes and steric hindrance are used to regulate the size of perovskite crystals and improve film quality. Consequently, highly emissive blue perovskite films are realized with the emission wavelength effectively tuned in the blue region by varying the concentration of CsPFPA as well as the type of antisolvents. Based on the strongly confined perovskite films, blue light-emitting diodes (LEDs) are constructed, showing good spectral tunability and stability in the electroluminescence. This work demonstrates a novel pathway for developing bright perovskite blue emitters for LEDs, which may potentially advance their future applications in display and lighting.

CircABHD2 Inhibits Malignant Progression of Endometrial Cancer by Regulating NAD+/NAMPT Metabolism Axis.

Circular RNAs (circRNAs) perform important functions in the regulation of diverse physiological and pathological processes. CircABHD2 exhibits down-regulation in both endometrial cancer (EC) cells and tissues, but the biological roles and mechanisms of action in EC are still unclear. This study aims to provide a theoretical basis for the role of circABHD2 in EC and potential targets for individualized precision therapy. Dysregulated circRNAs were identified using RNA sequencing (RNA-Seq) from EC tissues and validated using RT-qPCR. CCK-8, colony formation assay, wound healing assay, transwell assay, cell cycle, and apoptosis assay were used to evaluate the effects of circABHD2 on EC cells. Metabolomics assay and western blot analyses were used to investigate the potential mechanisms of circABHD2. From sequencing of RNA (RNA-Seq) analysis of EC tissues, we obtained 19 dysregulated circRNAs, including 8 upregulated ones and 11 downregulated ones. Using RT-qPCR on 32 EC tissues and 19 normal endometrial tissues, we confirmed that circABHD2 was downregulated in EC tissues. The expression levels of circABHD2 were closely relevant to the International Federation of Gynecology and Obstetrics (FIGO) stage and differentiation degree of EC. Functional experiments demonstrated that overexpression of circABHD2 decreased proliferation, migration, invasion, and promoted cell apoptosis. Un-targeted metabolomic assay revealed 31 differential metabolites in EC cells overexpressing circABHD2. KEGG analysis of differential metabolites indicated that NAD+ is the core metabolite regulated by circABHD2. NAMPT is one key enzyme involved in the synthetic pathway responsible for NAD+. Subsequent experiments confirmed that by inhibiting NAMPT protein expression in EC cells, cirABHD2 can inhibit NAD+ level, suggesting that circABHD2 may inhibit EC by regulating the metabolic axis of NAD+/NAMPT. CircABHD2, a downregulated circRNA in EC cells and tissues, inhibits the malignant progression of EC via the NAD+/NAMPT metabolic axis. This discovery presents a promising diagnostic biomarker and potential therapeutic target for EC.

Bilateral Embedded Anchoring via Tailored Polymer Brush for Large-Area Air-processed Blue Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) that can be air-processed promises the development of displaying optoelectronic device, while is challenged by technical difficulty on both the active layer and hole transport layer (HTL) caused by the unavoidable humidity interference. Here, we propose and validate that, planting the polymer brush with tailored functional groups in inorganic HTL, provides unique bilateral embedded anchoring that is capable of simultaneously addressing the n phases crystallization rates in the active layer as well as the deteriorated particulate surface defects in HTL. Exemplified by zwitterionic polyethyleneimine-sulfonate (PEIS) in present study, its implanting in NiOx HTL offers abundant nuclei sites of amino and sulfonate groups that balance the growth rate of different n phases in quasi-2D perovskite films. Moreover, the PEIS effectively nailed the interfacial contact between perovskite and NiOx, and reduced the particulate surface defects in HTL, leading to the enhanced PLQY and stability of large-area blue perovskite film in ambient air. By virtue of these merits, present work achieves the first demonstration of the air-processed blue PeLEDs in large emitting area of 1.0 cm2 with peak external quantum efficiency (EQE) of 2.09 %, which is comparable to the similar pure-bromide blue PeLEDs fabricated in glovebox.

Downregulation of the (pro)renin receptor alleviates ferroptosis-associated cardiac pathological changes via the NCOA 4-mediated ferritinophagy pathway in diabetic cardiomyopathy.

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxidation, is involved in various cardiovascular diseases. (Pro)renin receptor (PRR) in performs as ligands in the autophagic process, and its function in diabetic cardiomyopathy (DCM) is not fully understood. We investigated whether PRR promotes ferroptosis through the nuclear receptor coactivator 4 (NCOA 4)-mediated ferritinophagy pathway and thus contributes to DCM. We first established a mouse model of DCM with downregulated and upregulated PRR expression and used a ferroptosis inhibitor. Myocardial inflammation and fibrosis levels were then measured, cardiac function and ferroptosis-related indices were assessed. In vitro, neonatal rat ventricular primary cardiomyocytes were cultured with high glucose and transfected with recombinant adenoviruses knocking down or overexpressing the PRR, along with a ferroptosis inhibitor and small interfering RNA for the ferritinophagy receptor, NCOA4. Ferroptosis levels were measured in vitro. The results showed that the knockdown of PRR not only alleviated cardiomyocyte ferroptosis in vivo but also mitigated the HG-induced ferroptosis in vitro. Moreover, administration of Fer-1 can inhibit HG-induced ferroptosis. NCOA4 knockdown blocked the effect of PRR on ferroptosis and improved cell survival. Our result indicated that inhibition of PRR and NCOA4 expression provides a new therapeutic strategy for the treatment of DCM. The effect of PRR on the pathological process of DCM in mice may be in promoting cardiomyocyte ferroptosis through the NCOA 4-mediated ferritinophagy pathway.

Hydrogel activation of Mincle receptors for tumor cell processing: A novel approach in cancer immunotherapy.

An obstacle in current tumor immunotherapies lies in the challenge of achieving sustained and tumor-targeting T cell immunity, impeded by the limited antigen processing and cross-presentation of tumor antigens. Here, we propose a hydrogel-based multicellular immune factory within the body that autonomously converts tumor cells into an antitumor vaccine. Within the body, the scaffold, formed by a calcium-containing chitosan hydrogel complex (ChitoCa) entraps tumor cells and attracts immune cells to establish a durable and multicellular microenvironment. Within this context, tumor cells are completely eliminated by antigen-presenting cells (APCs) and processed for cross-antigen presentation. The regulatory mechanism relies on the Mincle receptor, a cell-phagocytosis-inducing C-type lectin receptor specifically activated on ChitoCa-recruited APCs, which serves as a recognition synapse, facilitating a tenfold increase in tumor cell engulfment and subsequent elimination. The ChitoCa-induced tumor cell processing further promotes the cross-presentation of tumor antigens to prime protective CD8+ T cell responses. Therefore, the ChitoCa treatment establishes an immune niche within the tumor microenvironment, resulting in effective tumor regression either used alone or in combination with other immunotherapies. This hydrogel-induced immune factory establishes a functional organ-like multicellular colony for tumor-specific immunotherapy, paving the way for innovative strategies in cancer treatment.

Matrine exhibits antiviral activities against PEDV by directly targeting Spike protein of the virus and inducing apoptosis via the MAPK signaling pathway.

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious virus that causes Porcine Epidemic Diarrhea (PED). This enteric disease results in high mortality rates in piglets, leading to significant financial losses in the pig industry. However, vaccines cannot provide sufficient protection against epidemic strains. Spike (S) protein exposed on the surface of virion mediates PEDV entry into cells. Our findings imply that matrine (MT), a naturally occurring alkaloid, inhibits PEDV infection targeting S protein of virions and biological process of cells. The GLY434 residue in the autodocking site of the S protein and MT conserved based on sequence comparison. This study provides a comprehensive analysis of viral attachment, entry, and virucidal effects to investigate how that MT inhibits virus replication. MT inhibits PEDV attachment and entry by targeting S protein. MT was added to cells before, during, or after infection, it exhibits anti-PEDV activities and viricidal effects. Network pharmacology focuses on addressing causal mechanisms rather than just treating symptoms. We identified the key genes and screened the cell apoptosis involved in the inhibition of MT on PEDV infection in network pharmacology. MT significantly promotes cell apoptosis in PEDV-infected cells to inhibit PEDV infection by activating the MAPK signaling pathway. Collectively, we provide the biological foundations for the development of single components of traditional Chinese medicine to inhibit PEDV infection and spread.

Circulating micrornas as potential diagnostic biomarkers for cervical intraepithelial neoplasia and cervical cancer: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. METHODS: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. RESULTS: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73-0.81), the specificity was 0.81 (95% CI 0.73-0.86), the PLR was 3.99 (95% CI 2.81-5.65), the NLR was 0.28 (95% CI 0.23-0.35), the DOR was 14.18 (95% CI 8.47-23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81-0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68-0.86), the specificity was 0.85 (95% CI 0.78-0.90), and the AUC was 0.89 (95% CI 0.86-0.91). CONCLUSION: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis.

Endogenous IAA affected fluoranthene accumulation by regulating H+-ATPase and SOD activity in ryegrass.

This study explores the role of endogenous indole-3-acetic acid (IAA) in modulating plant responses to pollution stress and its effect on pollutant accumulation, with a focus on fluoranthene (Flu) in ryegrass. To elucidate the mechanism, we employed an IAA promoter (α-aminobutyric acid [α-AB]) and an IAA inhibitor (naphthylphthalamic acid [NPA]) to regulate IAA levels and analyze Flu uptake characteristics. The experimental setup included a Flu treatment group (ryegrass with Flu addition) and a control group (ryegrass without Flu). Our findings demonstrate that Flu treatment enhanced IAA content and plant growth in ryegrass compared to the control. The Flu+AB treatment further enhanced these effects, while the Flu+NPA treatment exhibited a contrasting trend. Moreover, Flu+AB treatment led to increased Flu accumulation, in contrast to the inhibitory effect observed with Flu+NPA treatment. Flu treatment also enhanced the activities of key antioxidant enzymes (SOD, POD, CAT) and increased soluble sugar and protein levels, indicative of enzymatic and nonenzymatic defense responses, respectively. The Flu+AB treatment amplified these responses, whereas the Flu+NPA treatment attenuated them. Significantly, Flu treatment raised H+-ATPase activity compared to the control, an effect further elevated by Flu+AB treatment and diminished by Flu+NPA treatment. A random forest analysis suggested that Flu accumulation dependency varied under different treatments: it relied more on H+-ATPase activity under Flu+AB treatment and more on SOD activity under Flu+NPA treatment. Additionally, Flu+AB treatment boosted the transpiration rate in ryegrass, thereby increasing the Flu translocation factor, a trend reversed by Flu+NPA treatment. This research highlights crucial factors influencing Flu accumulation in ryegrass, offering potential new avenues for controlling the gathering of contaminants within plant systems.

Exploring the Median Effective Dose of Ciprofol for Anesthesia Induction in Elderly Patients: Impact of Frailty on ED50.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

Causal association between genetically predicted circulating immune cell counts and frailty: a two-sample Mendelian randomization study.

Background: Despite the recognized link between immune responses and frailty, the association between immune cell counts and frailty based on previous observational studies remains disputed, with uncertain causal nexus. This study aimed to elucidate causal association between genetically predicted circulating immune cell counts and frailty. Methods: We conducted the two-sample Mendelian randomization (MR) study with independent genetic variants associated with six immune cell subtype counts from genome-wide association studies in 563,946 European individuals. Frailty summary data, assessed via frailty index (FI), was obtained from study comprising 175,226 subjects. Univariate MR, reverse MR and multivariate MR were conducted to comprehensive investigate the association between immune cell counts and FI, with two-step MR analysis for mediation analysis. Results: Univariate MR evidence indicated that among six leukocyte subtype counts, only elevated eosinophil count was significantly correlated with higher FI (ß = 0.059, 95% confidence interval [CI], 0.042-0.078, P=5.63E-11), with no reverse causal relationship identified in reverse MR. In multivariate MR, the causal effect of eosinophil count retained statistical significance (ß = 0.063, 95% CI, 0.021-0.104, P = 0.003). Ultimately, the two-step MR analysis demonstrated two mediators in this causal pathway: asthma (ß= 0.019, 95% CI, 0.013-0.025, P = 35.84E-10, mediated proportion, 31.732%) and rheumatoid arthritis (ß= 0.004, 95% CI, 0.001-0.006, P=1.75E-03, mediated proportion, 6.411%). Conclusions: Within immune cell subtypes, MR evidence indicated only genetically predicted circulating eosinophil count had irreversible and independent causal effect on frailty, with asthma and rheumatoid arthritis possibly serving as partial mediators. The finding stressed the need for further exploring physiological functions of eosinophils in order to develop effective strategies against frailty.

Nutritional status and nutritional intervention of older inpatients in China.

BACKGROUND: Malnutrition is a critical issue among older inpatients, yet limited large-scale research related to this issue has been conducted in China. This study aimed to examine the nutritional status and support of older inpatients in China, assess the associations between disease categories and malnutrition on admission, and explore effective nutritional intervention. METHODS: A total of 24,139 older participants from the China Nutrition Fundamental Data 2020 Project were included. Malnutrition was measured by the Global Leadership Initiative on Malnutrition criteria. Adjusted odds ratios (aORs) were calculated using logistic analysis. RESULTS: The overall frequency of malnutrition on admission was 18.9%. Participants with infections were more likely to have malnutrition (aOR = 1.929, 95% CI 1.486-2.504). Risks that were also noted for malnutrition included neoplasms (aOR = 1.822, 95% CI 1.697-1.957), hemic and lymphatic diseases (aOR = 1.671, 95% CI 1.361-2.051), nervous system diseases (aOR = 1.222, 95% CI 1.126-1.326), respiratory diseases (aOR = 1.613, 95% CI 1.490-1.746), and digestive system diseases (aOR = 1.462, 95% CI 1.357-1.577). Further, 32.26% inpatients with malnutrition during hospitalization didn't receive nutritional support. Oral nutrition supplements, enteral tube feeding, and parenteral nutrition were associated with stable or improved nutritional status. CONCLUSIONS: Older inpatients were at a high risk for malnutrition but did not receive adequate nutritional intervention. More resources and attention need to be devoted to the nutritional status of older inpatients and targeted nutritional support.

An endoplasmic reticulum stress-related signature featuring ASNS for predicting prognosis and immune landscape in prostate cancer.

Prostate cancer (PRAD) is one of the common malignant tumors of the urinary system. In order to predict the treatment results for PRAD patients, this study proposes to develop a risk profile based on endoplasmic reticulum stress (ERS). Based on the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort and the Gene Expression Omnibus database (GSE70769), we verified the predictive signature. Using a random survival forest analysis, prognostically significant ERS-related genes were found. An ERS-related risk score (ERscore) was created using multivariable Cox analysis. In addition, the biological functions, genetic mutations and immune landscape related to ERscore are also studied to reveal the underlying mechanisms related to ERS in PRAD. We further explored the ERscore-related mechanisms by profiling a single-cell RNA sequencing (scRNA-seq) dataset (GSE137829) and explored the oncogenic role of ASNS in PRAD through in vitro experiments. The risk signature composed of eight ERS-related genes constructed in this study is an independent prognostic factor and validated in the MSKCC and GSE70769 data sets. The scRNA-seq data additionally revealed that several carcinogenic pathways were noticeably overactivated in the group with high ERS scores. As one of the prognostic genes, ASNS will significantly inhibit the proliferation, migration and invasion abilities of PRAD cells after its expression is interfered with. In conclusion, this study developed a novel risk-specific ERS-based clinical treatment strategy for patients with PRAD.

Biochar loaded with ferrihydrite and Bacillus pseudomycoides enhances remediation of co-existed Cd(II) and As(III) in solution.

Bioremediation is one of the effective ways for heavy metal remediation. Iron-modified biochar (F@BC) loaded with Bacillus pseudomycoides (BF@BC) was synthesized to remove the coexistence of cadmium (Cd) and arsenic (As) in solutions. The results showed that B. pseudomycoides significantly increased the removal rate of Cd(II) by enhancing the specific surface area and Si-containing functional groups of biochar (BC). The surface of F@BC was enriched with Fe-containing functional groups, significantly improving As(III) adsorption. The combination of ferrihydrite and strains on BF@BC enhanced the removal of Cd(II) and As(III). It also promoted the oxidation of As(III) by producing an abundance of hydroxyl radicals (·OH). The maximum saturated adsorption capacity of BF@BC for Cd(II) and As(III) increased by 52.47% and 2.99 folds compared with BC, respectively. This study suggests that biochar loaded with Fe and bacteria could be sustainable for the remediation of the coexistence of Cd(II) and As(III) in solutions.

A Versatile Nanovaccine Enhancement Strategy Based on Suction-Inspired Physical Therapy.

Vaccine technology is effective in preventing and treating diseases, including cancers and viruses. The efficiency of vaccines can be improved by increasing the dosage and frequency of injections, but it would bring an extra burden to people. Therefore, it is necessary to develop vaccine-boosting techniques with negligible side effects. Herein, we reported a cupping-inspired noninvasive suction therapy that could enhance the efficacy of cancer/SARS-CoV-2 nanovaccines. Negative pressure caused mechanical immunogenic cell death and released endogenous adjuvants. This created a subcutaneous niche that would recruit and activate antigen-presenting cells. Based on this universal central mechanism, suction therapy was successfully applied in a variety of nanovaccine models, which include prophylactic/therapeutic tumor nanovaccine, photothermal therapy induced in situ tumor nanovaccine, and SARS-CoV-2 nanovaccine. As a well-established physical therapy method, suction therapy may usher in an era of noninvasive and high-safety auxiliary strategies when combined with vaccines.

Magnetic resonance imaging of extraocular rectus muscles abnormalities in acute acquired concomitant esotropia.

AIM: To investigate the difference of medial rectus (MR) and lateral rectus (LR) between acute acquired concomitant esotropia (AACE) and the healthy controls (HCs) detected by magnetic resonance imaging (MRI). METHODS: A case-control study. Eighteen subjects with AACE and eighteen HCs were enrolled. MRI scanning data were conducted in target-controlled central gaze with a 3-Tesla magnetic resonance scanner. Extraocular muscles (EOMs) were scanned in contiguous image planes 2-mm thick spanning the EOM origins to the globe equator. To form posterior partial volumes (PPVs), the LR and MR cross-sections in the image planes 8, 10, 12, and 14 mm posterior to the globe were summed and multiplied by the 2-mm slice thickness. The data were classified according to the right eye, left eye, dominant eye, and non-dominant eye, and the differences in mean cross-sectional area, maximum cross-sectional area, and PPVs of the MR and LR muscle in the AACE group and HCs group were compared under the above classifications respectively. RESULTS: There were no significant differences between the two groups of demographic characteristics. The mean cross-sectional area of the LR muscle was significantly greater in the AACE group than that in the HCs group in the non-dominant eyes (P=0.028). The maximum cross-sectional area of the LR muscle both in the dominant and non-dominant eye of the AACE group was significantly greater than the HCs group (P=0.009, P=0.016). For the dominant eye, the PPVs of the LR muscle were significantly greater in the AACE than that in the HCs group (P=0.013), but not in the MR muscle (P=0.698). CONCLUSION: The size and volume of muscles dominant eyes of AACE subjects change significantly to overcome binocular diplopia. The LR muscle become larger to compensate for the enhanced convergence in the AACE.

Deciphering the biotic and abiotic drivers of coalescence asymmetry between soil and manure microbiomes.

Manure application improves soil fertility, yet its implications on the success of invasion of manure-borne microorganisms in the soil are poorly understood. Here, we assessed the importance of abiotic and biotic factors in modulating the extent to which manure-borne fungal and bacterial communities can invade resident soil microbial communities. For this purpose, we applied varying frequencies of two different amounts of manure to nine soils differing in physico-chemical properties, as well as in land-use history, over 180 days and monitored changes in bacterial and fungal communities. Variance partitioning revealed differential contributions of abiotic and biotic factors to invasion success, which together accounted for up to 82 % of the variance explained. We showed that the effects of interactions between biotic and abiotic factors increased with coalescence frequency and manure amount for the bacterial and fungal communities, respectively. Both abiotic and biotic factors were important for modulating coalescence asymmetry for the bacterial community, whereas abiotic factors had a greater effect on the fungal community. These results provide new insights into the drivers of coalescence events between manure and resident soil microbial communities. Moreover, our findings highlight the roles of the mixing ratio and frequency of coalescence events in modulating the survival of manure-borne microorganisms.

Single-cell RNA-seq reveals MIF-(CD74 + CXCR4) dependent inhibition of macrophages in metastatic papillary thyroid carcinoma.

BACKGROUND: The mechanism promoting papillary thyroid carcinoma (PTC) metastasis remains unclear. We aimed to investigate the potential metastatic mechanisms at a single-cell resolution. METHODS: We performed single-cell RNA-seq (scRNA-seq) profiling of thyroid tumour (TT), adjacent normal thyroid (NT) and lymph node metastasized tumour (LN) from a young female with PTC. Validation of our results was conducted in 31 tumours with metastasis and 30 without metastasis. RESULTS: ScRNA-seq analysis generated data on 38,215 genes and 0.14 billion transcripts from 28,839 cells, classified into 18 clusters, each annotated to represent 10 cell types. PTC cells were found to originate from epithelial cells. Epithelial cells and macrophages emerged as the strongest signal emitters and receivers, respectively. After reclustering epithelial cells and macrophages, our analysis, incorporating gene set variation analysis (GSVA), SCENIC analysis, and pseudotime trajectory analysis, indicated that subcluster 0 of epithelial cells (EP_0) showed a more malignant phenotype, and subclusters 3 and 4 of macrophages (M_3 and M_4) demonstrated heightened activity. Further analysis suggested that EP_0 may suppress the activity of M_3 and M_4 via MIF - (CD74 + CXCR4) in the MIF pathway. After analysing the expression of the 4 genes in the MIF pathway in both the TCGA cohort and our cohort (n = 61), CD74 was identified as significantly overexpressed in PTC tumours particularly those with lymph node metastasis. CONCLUSION: Our study revealed that PTC may facilitate lymph node metastasis by inhibiting macrophages via MIF signalling. It is suggested that malignant PTC cells may suppress the immune activity of macrophages by consistently releasing signals to them via MIF-(CD74 + CXCR4).