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ITGB5 is a prognostic factor in colorectal cancer and promotes cancer progression and metastasis through the Wnt signaling pathway

Initiation of transthyretin aggregation at neutral pH by fluid agitation

The transthyretin (TTR) tetramer, assembled as a dimer of dimers, transports thyroxine and retinol binding protein in blood plasma and cerebrospinal fluid. Aggregation of wild type (WT) or pathogenic variant TTR leads to transthyretin amyloidosis, which is associated with neurodegenerative and cardiac disease. The trigger for TTR aggregation under physiological conditions is unknown. The tetramer is extremely stable at neutral pH, but aggregation via tetramer dissociation and monomer misfolding can be induced in vitro by lowering the pH. To elucidate factors that may cause TTR aggregation at neutral pH, we examined the effect of shear forces such as those that arise from fluid flow in the vascular system. Fluid shear forces were generated by rapidly stirring TTR solutions in conical microcentrifuge tubes. Under agitation, TTR formed β-rich aggregates and fibrils at a rate that was dependent upon protein concentration. The lag time before the onset of agitation-induced aggregation increases as the total TTR concentration is increased, consistent with a mechanism in which the tetramer first dissociates to form monomer that either partially unfolds to enter the aggregation pathway or reassociates to form tetramer. NMR spectra recorded at various time points during the lag phase revealed growth of an aggregation-prone intermediate trapped as a dynamically perturbed tetramer. Enhanced conformational fluctuations in the weak dimer–dimer interface suggest loosening of critical intersubunit contacts which likely destabilizes the agitated tetramer and predisposes it toward dissociation. These studies provide insights into the mechanism of aggregation of WT human TTR under near-physiological conditions.

Biochar enhances seed germination and crop early growth for sustainable agriculture in Bangladesh

Biochar (BC) application to low-fertility soils enhances crop yield, soil quality, and sustainable agricultural production. Although many studies have explored the effects of biochar on tropical crops, research specific to Bangladesh is limited. Given the agrarian system in Bangladesh, dense population, and vulnerability to climate change, adopting sustainable agricultural practices is essential. This study evaluates the impact of different biochar dosages on the germination and early growth of five major crops Oryza sativa (rice), Triticum aestivum (wheat), Capsicum annuum (chili), Solanum melongena (eggplant), and Solanum lycopersicum (tomato) using Acacia auriculiformis wood-waste biochar. The research was conducted using a randomized complete block design (RCBD) in a nursery setting. Biochar treatments of 10 t/ha and 15 t/ha were applied, with assessments made of germination (%), germination rate (after 7 days), shoot height (cm), root height (cm), leaf number, and root-shoot dry weight ratio. The results indicated a significant (p < 0.001) increase in germination (%) with higher biochar application rates. The linear mixed-effects model showed a significant effect of biochar treatment on germination (%) (F = 57.33, p < 0.001) and a significant interaction with crop type (F = 15.84, p < 0.001). In C. annuum, the 15 t/ha treatment resulted in a 96% increase in germination compared to the control (43.3 ± 1.08% vs 85.1 ± 2.15%). Similarly, in O. sativa, germination was significantly higher with the 10 t/ha (84.5 ± 1.52%) and 15 t/ha (91.8 ± 1.49%) treatments compared to control (59.3 ± 2.38%). Biochar significantly (p < 0.05) influenced early germination rates (after 7 days) and early growth parameters (e.g., shoot length, leaf count, root-shoot ratio), with the 15 t/ha treatment showing substantial improvements for C. annuum and O. sativa, while no significant effects were observed for S. lycopersicum. These findings underscore the potential of A. auriculiformis in enhancing germination and early growth of economically important crops, highlighting its role in promoting sustainable agriculture in Bangladesh.

Bayesian optimized indoor positioning algorithm based on dual clustering

Abstract Wi-Fi indoor positioning provides a simple, convenient, ubiquitous and cost-effective solution by matching a pre-established Wi-Fi Received Signal Strength Indication (RSSI) fingerprint database with the RSSI values received from mobile terminals. However, due to the influence of the complex indoor environment on the signal, its accuracy can only reach the meter scale, and the huge fingerprint database leads to inefficient positioning. To solve this problem, the Canopy algorithm is used for coarse clustering, and then the K-means algorithm is used for fine clustering to determine the number of clusters and the initial clustering center to form multiple clustering sub-bases, which improves the positioning efficiency by about 95.05%. In the real-time matching stage, the sub-banks with the highest similarity are selected for matching by the correlation coefficient method, and combined with the Weighted K-Nearest Neighbors (WKNN) algorithm, this paper proposes an improved Bayesian probabilistic optimization algorithm, and the final experimental results show that the average positioning accuracy is improved by about 38.64%, the average runtime is shrunk by about 93.51%, and the stability of the system is slightly improved, which effectively improves the positioning accuracy, real-time performance, and stability.

Comparing color qualia structures through a similarity task in young children versus adults

Examination of the subjective qualitative aspects of an experience, or “qualia” in short, is a fundamental and core aspect of consciousness research. How can we characterize the particular quality of redness, i.e. a red quale? Based on a recent proposal of the structural characterization of qualia, which did not rely on verbal descriptions, we developed a task that obtained pairwise similarity judgments at four graded levels, with easy and intuitive visual interfaces designed to engage young children. We examined color qualia structures in children (3 to 12-y-old in Japan and 6 to 8-y-old in China) and compared these with those of Japanese adults. Approximately half of the assessed 3-y-old children completed the experiment via our touch panel device version of the task and had reliable responses. Despite known developmental and/or cultural effects of color term usage, we found that color qualia structures were quite similar across the age groups and cultures. Our finding supports the view that color qualia structures emerge early. We also observed age-related differences in the evaluations of some color pairs, which implied subtle changes in the structures behind color experience.

The efficacy and safety of acetazolamide in chronic mountain sickness: A systematic review and meta‐analysis of randomized controlled trials

Objective The impact of acetazolamide (ACZ) in chronic mountain sickness (CMS) has not been fully assessed. The purpose of this systematic review is to evaluate the effectiveness and safety of acetazolamide in the treatment of chronic mountain sickness. Research methods This systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome measure was CMS clinical score. Secondary outcomes included CMS total score,hematocrit (HCT), Pondus Hydrogenii‌ (pH), arterial oxygen pressure (PaO2), arterial carbon dioxide pressure (PaCO2), bicarbonate concentration (HCO3), and adverse events. Results Five randomized controlled trials were included, comprising a total of 137 subjects, with 78 in the acetazolamide group and 59 in the control group.The CMS clinical score showed an MD of −0.31 (95% CI, −1.13 to −0.51, P = 0.46),the results indicated no statistical significance.But the CMS total score had an MD of −1.13 [95% CI, −2.03 to −0.23], P = 0.01, showing a significant difference.The HCT results showed an MD of −2.70 (95% CI, −4.58 to −0.82; P = 0.005), indicating a statistically significant reduction. The result of PaO2,PaCO2,pH and HCO3 are statistically significant. In terms of adverse events, increased diuresis and headache were not statistically significant. Paresthesia had a significant difference. Conclusion Based on the available evidence, we conclude that ACZ 250 mg is a safe, reliable, and low-cost treatment option for chronic mountain sickness. By reducing HCT, PaCO2, pH, and HCO3, and increasing PaO2, it improves respiratory and circulatory parameters in CMS patients and effectively treats CMS.

Comparative pregnancy rate after colorectal resection versus other surgical procedures for deep infiltrating rectal endometriosis: a systematic review and meta-analysis

Identification of a ligand-binding site on tubulin mediating the tubulin–RB3 interaction

For decades, microtubules—composed of αβ-tubulin dimers—have been primary targets for cancer chemotherapy. While eight binding sites on the tubulin dimer have been structurally characterized, this study reveals a ninth. We found that the tubulin inhibitor Tumabulin-1 (TM1, a BML284 derivative) binds simultaneously to the well-known colchicine site and a previously unknown site, designated as Tumabulin site. This site resides at the interface of α1-tubulin, β1-tubulin, and RB3 within the tubulin–RB3–tubulintyrosine ligase complex. Remarkably, two TM1 molecules bind cooperatively to this relatively large pocket, interacting with all three proteins. Crucially, this binding is dependent on RB3; it is absent when RB3 is missing or the key residue H71 is mutated (H71Q). We further designed and synthesized Tumabulin-2 (TM2) that selectively binds the Tumabulin site, excluding binding the colchicine site. TM2 acts as a molecular glue, strengthening the interaction between RB3 and the tubulin dimer and consequently enhancing RB3’s tubulin-depolymerizing activity. In conclusion, our findings confirm the existence of a ninth tubulin-binding site and offer a promising foundation for developing Tubulin–RB3 molecular glues as a next generation of anticancer therapeutics.

RETRACTED: Fischer’s ratio and DNA damage in hypoxemia-induced brain injury in rat model: prophylactic role of quercetin and mexamine supplementation

Hypoxemia brain injuries arise when the brain’s oxygen supply is restricted. Brain cells gradually die and become impaired as a result of the restricted oxygen flow a diversity of signaling pathways are involved in the pathophysiology of brain damage. One of the main concerns when examining the rate of protein breakdown is the measurement of the serum amino acid ratio. Valine, leucine, and isoleucine make up branched-chain amino acids, while phenylalanine and tyrosine make up aromatic amino acids. A vital tool for assessing the severity of hypoxemia is Fischer’s ratio. The goal of this article is to determine how quercetin (QUR) and/or mexamine (MEX) prevented synfat (SN)-induced brain damage in a rat models. It also aimed to elucidate the various cross-linked inflammatory pathways, DNA damage, and Fischer’s ratio. Following QUR and MEX therapy, synfat-induced hypoxemia. Hemoglobin (Hb) levels were markedly reduced by synfat-intoxication, and oxidative stress and inflammatory biomarkers, including TNF-??, MDA, interleukin-6 (IL-6), and C -reactive protein (CRP), were elevated. Hemoglobin levels, oxidative stress biomarkers, and the aberrant expression of pro-inflammatory cytokines were all altered by QUR and/or MEX therapy. Similarly, the concentration of γ-aminobutyric acid, serotonine, noradrenaline, and intropin in cerebral tissue is restricted. Similarly, the COMET assay and 8-oxo-7,8-dihydro-2’-deoxyguanosine analysis (8-oxodG) demonstrated that QUR and MEX potentially altered synfat-induced brain DNA damage. The results confirmed the potential impact of this combined strategy as a powerful therapy for brain hypoxemia, concluding that treatment via QUR with MEX was superior therapy in modulating synfat-triggered cerebral injury.

Carbon management in massive electric vehicle temporal and spatial scheduling with automotive electronic forensics

p53 activates circASCC3 to repress R-loops and enhance resistance to chemotherapy

The tumor suppressor p53 can trigger tumor resistance to chemotherapy by facilitating DNA damage repair and maintaining genomic integrity. Here, we report that a p53-induced circular RNA circASCC3 promotes chemotherapeutic resistance by resolving R-loops. Our results reveal that p53 directly activates the transcription of ASCC3 , the host gene of circASCC3. In addition, the RNA-binding protein SFPQ is identified to inhibit the formation of circASCC3 by associating with its flanking regions. Importantly, p53 facilitates the formation of circASCC3 by repressing the expression of SFPQ. CircASCC3 has a marginal effect on the survival and growth of cancer cells under normal growing conditions but surprisingly boosts their survival and growth in response to DNA damage stress. Mechanistic analysis reveals that circASCC3 binds to the DEAD-box RNA helicase DDX5 to inhibit its proteasomal degradation. This results in the prevention of R-loop accumulation due to DNA damage, thereby conferring tumor resistance to chemotherapy. Together, our study uncovers that p53 activates circASCC3 to promote R-loop resolution, which maintains genomic stability and potentially contributes to chemoresistance.

Boosting recovery before surgery: The impact of prehabilitation on upper gastrointestinal cancer patients – A quantitative comparative analysis

Background Emerging research presents divergent perspectives on the efficacy of prehabilitation for patients scheduled for surgery due to upper gastrointestinal (GI) cancers, capturing the attention of both the scientific community and surgical professionals. This quantitative comparative analysis seeks to assess the association of prehabilitation to ameliorate postoperative outcomes in individuals with upper GI cancers, thereby providing a comprehensive evaluation of its potential benefits within a surgical context. Materials and methods Medline, Embase, Cochrane Library and Web of Science were searched up to February 2024. Studies reporting the association between prehabilitation, and postoperative complications, readmissions or other outcomes of interest were included. Fixed or random effect models were used, and forest plots were applied to show the results of the quantitative comparative analysis. Results A total of 198 studies were initially screened based on titles and abstracts, with 129 studies subsequently excluded. Overall, 69 full-text studies were identified, of which 12 studies were finally included for qualitative analysis in the quantitative comparative analysis after determining whether the inclusion and exclusion criteria were met. The pooled results indicated that prehabilitation significantly reduced the overall postoperative complication rates in patients with upper GI cancer undergoing surgical therapy with the pooled OR of 0.59 (95%CI: 0.39–0.88). Moreover, prehabilitation was also shown to be a protective factor of pulmonary complications (OR: 0.54, 95%CI: 0.36–0.80) and ICU readmissions (OR: 0.23, 95%CI: 0.06–0.89). Conclusion The correlation between prehabilitation and a reduction in overall postoperative complications, pulmonary complications, and ICU readmissions among patients with upper GI cancer is substantiated by significant data. This pivotal finding necessitates further empirical investigation to validate these initial results and ascertain the clinical efficacy of prehabilitation protocols, thereby informing future surgical practice strategies.

Population genomic analysis identifies the complex structural variation at the fibromelanosis (FM) locus in chicken

Abstract Phenotypic diversity and its genetic basis are central questions in biology, with domesticated animals offering valuable insights due to their rapid evolution the last 10,000 years. In chickens, fibromelanosis (FM) is a striking pigmentation phenotype characterized by hyperpigmentation. A previous study identified a complex structural variant involving both two large duplications (127.4 and 170.5 kb in size) and inversions associated with upregulated expression of the Endothelin 3 (EDN3) gene. However, the detailed organization of the structural arrangements have remained unclear. In this study, we conducted a comprehensive genomic survey of 517 FM chickens representing 44 different populations. Our results elucidate the complex arrangement of the duplications and inversions at the FM locus based on the large-scale genomic survey, population level genotyping, and linkage disequilibrium analysis, providing conclusive support for one specific configuration of the two large duplications, resolving a controversy that has been unresolved for more than a decade. Our results show that the birth of this complex structural variant must have involved an interchromosomal rearrangement creating fixed heterozygosity due to sequence differences between the two copies of the 127.4 kb duplication. This study shows how population genomics can be used to understand complex structural variations that underlie phenotypic variation.

NBS1 facilitates preribosomal RNA biogenesis

Mutations in the NBS1 gene result in Nijmegen breakage syndrome (NBS), and the gene encodes NBS1 that forms a complex with MRE11 and RAD50 and participates in DNA damage repair. However, the molecular mechanism by which NBS1 mutations cause clinical phenotypes of NBS, such as craniofacial dysmorphism, is still unclear. Here, we show that NBS1 localizes at the ribosomal DNA (rDNA) loci in nucleoli and interacts with ribosomal RNA (rRNA) transcription machinery including RNA polymerase I (Pol I) and TCOF1. Loss of NBS1 impairs Pol I-dependent transcription of pre-rRNA and induces nucleolar stress. In particular, lacking Nbs1 in mouse neural crest cells not only leads to the reduction of ribosome biogenesis but also craniofacial abnormalities during prenatal development. Moreover, the C-terminus of NBS1 is associated with pre-rRNA and a number of pre-rRNA processing factors, which may also facilitate pre-rRNA maturation. Taken together, our study reveals the functions of NBS1 in rRNA biogenesis.

Enhancement of standardized precipitation evapotranspiration index predictions by machine learning based on regression and soft computing for Iran’s arid and hyper–arid region

Drought is a climate risk that affects access to safe water, crop development, ecological stability, and food production. Therefore, developing drought prediction methods can lead to better management of surface and groundwater resources. Similarly, machine learning can be used to find improved relationships between nonlinear variables in complex systems. Initially, the standardized precipitation evapotranspiration index (SPEI) was calculated, and then using large–scale signals such as large–scale climate signals (the North Atlantic Oscillation, the Arctic Oscillation, the Pacific Decadal Oscillation, and the Southern Oscillation Index), along with climatic variables including temperature, precipitation, and potential evapotranspiration, predictions were made for the period of 1966–2014. Several new machine learning models including Least Square Support Vector Regression (LSSVR), Group Method of Data Handling (GMDH), and Multivariate Adaptive Regression Splines (MARS) were used for prediction. The results showed that in estimating SPEI in moderately arid climates, the GMDH model with criteria (RMSE = 0.26, MAE = 0.17, NSE = 0.95 in validation) under scenario S1 (included all variables plus the SPEI of the previous month) performed better, while in arid and cold climates, the LSSVR model (RMSE = 0.22, MAE = 0.18, NSE = 0.95 in validation) under S1, and in arid and hot climate, the LSSVR model (RMSE = 0.29, MAE = 0.19, NSE = 0.93 in validation) under scenario S2 (included meteorological variables plus the SPEI of the previous month) had higher prediction accuracy. Although the MARS model was less accurate in validation, it showed higher accuracy during calibration compared to the other two models in all climates. The results showed that using large–scale signals for predicting SPEI was beneficial. It can be concluded that machine learning models are useful tools for predicting the SPEI drought index in different climates within similar ranges.

Author Correction: Endurance exercise attenuates Gαq-RNAi induced hereditary obesity and skeletal muscle dysfunction via improving skeletal muscle Srl/MRCC-I pathway in Drosophila

Cryo-ET reveals the in situ architecture of the polar tube invasion apparatus from microsporidian parasites

Microsporidia are divergent fungal pathogens that employ a unique harpoon-like apparatus called the polar tube (PT) to invade host cells. The long PT is fired out of the microsporidian spore over the course of just a few hundred milliseconds. Once fired, the PT is thought to pierce the plasma membrane of a target cell and act as a conduit for the transfer of the parasite into the host cell, which initiates infection. The PT architecture and its association with neighboring organelles within the parasite cell remain poorly understood. Here, we use cryoelectron tomography to investigate the structural cell biology of the PT in dormant spores from the human-infecting microsporidian species, Encephalitozoon intestinalis . Segmentation and subtomogram averaging of the PT reveal at least four layers: two protein-based layers surrounded by a membrane layer and filled with a dense core. Regularly spaced protein filaments form the structural skeleton of the PT. Combining cryoelectron tomography with cellular modeling, we propose a model for the three-dimensional organization of the polaroplast, an organelle that surrounds the PT and is continuous with the outermost, membranous layer of the PT. Our results reveal the ultrastructure of the microsporidian invasion apparatus in situ, laying the foundation for understanding infection mechanisms.

Effects of occupational therapy synchronized with dual transcranial direct current stimulation on upper limb function and electroencephalography power in subacute stroke patients: A randomized, double-blind, controlled study

Background Occupational therapy (OT) and transcranial direct current stimulation (tDCS) are both important methods for promoting the recovery after stroke. There are limited researches that simultaneously apply both methods and investigate their effects on upper limb function. Objective To investigate the effects of OT synchronized with dual tDCS on upper limb motor function and Electroencephalogram (EEG) power in subacute stroke patients. Methods Forty-five subacute stroke patients were randomly assigned to control group (n = 23) and experimental group (n = 22), receiving sham and real dual tDCS concurrent with OT respectively, five times a week, for a duration of two weeks. Upper limb motor function and cortical EEG power were evaluated by Fugl-Meyer Assessment Upper Extremity (FMA-UE), Modified Barthel Index (MBI) and Action Research Arm Test (ARAT), Delta/Alpha Ratio (DAR) and pairwise derived Brain Symmetry Index (pdBSI) at baseline and two weeks. Results Finally, a total of 39 patients completed the study and were included in the analysis. The results revealed that participants in the experimental group showed a significant better evolution for FMA-UE (p < 0.001), MBI (p = 0.034), DAR in the primary motor cortex (M1) area (p = 0.022) and pdBSI (p = 0.025) compared to the control group. Conclusions In subacute stroke patients, the central-peripheral combined stimulation approach, which involves dual tDCS (central stimulation) and synchronous OT (peripheral sensory-motor stimulation) enhanced the effects of OT alone, leading to greater improvements in upper limb function and normalization of brain activity. Trial registration This trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2400082749).

Salivary apoptotic microvesicles as biomarkers for prognostic non-healing oral ulcers and oral cancer: a cross-sectional study

Unintegrated HIV-1 DNA recruits cGAS via its histone-binding domain to escape innate immunity

To ensure optimal replication and spread, viruses have evolved countermeasures to evade type 1 IFN-mediated antiviral activity. During the early viral replication cycle steps until uncoating, the HIV-1 core protects viral pathogen associated molecular patterns (viral RNA and reverse transcription products) from recognition by innate immune sensors, including cGAS. However, after capsid uncoating, unintegrated viral DNA (uvDNA) becomes accessible. Here, we show that HIV-1 uses chromatin-mediated cGAS inactivation as a mechanism to protect its uvDNA from innate immune activation.