Search Results (2,399)

We aimed to compare the proportion of tuberculosis infection among social contacts of male tuberculosis Index case with and without alcohol use in the Puducherry district. A cross-sectional study using ego-centric approach was conducted between November 2023 and May 2024. A total of 713 social contacts of 106 male pulmonary tuberculosis index cases were enrolled, stratified by alcohol-use (AUDIT ≥ 8): 358 contacts from 45 alcohol-using cases and 355 from 61 non-alcohol-use cases. Social contacts were defined based on the frequency and duration of shared indoor exposure with index cases within the past three months. Tuberculosis infection was screened with Cy-Tb skin test (≥5 mm induration) at the third month of index case treatment. Univariate and multivariable analysis were conducted to identify factors associated with tuberculosis transmission. Among the 358 social contacts of alcohol-use index cases, 33.8% (n = 121; 95% CI, 29.1–38.8%) tested positive for tuberculosis infection, significantly higher than 21.7% (n = 77; 95% CI, 17.7–26.3%) among 355 contacts of non-alcohol-use cases. Regression analysis revealed that contacts of alcohol-using index cases (aOR = 1.6, p < 0.05), were significantly associated with tuberculosis infection. Alcohol-use among tuberculosis patients significantly increases the risk of tuberculosis infection in their social networks. Full article

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a widespread enzymopathy affecting approximately 500 million individuals that represents a significant global health issue. Among the more than 230 identified mutations in the G6PD gene, six class A variants—G6PD Utrecht (Pro409Ser), G6PD Suwalki (Pro409Arg), G6PD Merlo (Pro409Gln), G6PD Kawasaki (Gly410Ala), G6PD Shinagawa (Gly410Asp), and G6PD Riverside (Gly410Cys)—are located in the beta-loop near the NADP+ binding site. These mutations are of particular interest due to their association with severe hematologic phenotypes, including chronic hemolytic anemia, as well as their proposed role in the allosteric regulation of G6PD multimerization. This study presents a comprehensive biochemical and functional characterization of these clinically relevant G6PD variants. The variant enzymes were cloned, expressed, and purified for characterization. Kinetic parameters and thermal stability assays, complemented by molecular dynamics simulations (MDS), were employed to elucidate the structural impacts of the mutations. Our results demonstrate that these mutations significantly impair protein function, characterized by reduced affinity for glucose-6-phosphate (G6P) and NADP⁺, as well as altered thermal stability compared with wild-type G6PD. MDS revealed that point mutations in the βN- and βM-sheets in the NADP⁺s region propagate subtle conformational changes, ultimately affecting the NADP⁺c region and the G6P binding cavity. Furthermore, secondary structure element analyses of the simulation data showed that Pro409 and Gly410 point mutations propagate several changes around residues 195–210 (G6P binding site) and 380–400 (NADP⁺s), explaining their effect on overall catalytic performance. These findings enhance our understanding of the molecular mechanisms underlying G6PD deficiency and its clinical implications, providing a foundation for future therapeutic strategies aimed at mitigating the effects of these variants. Full article

The development of low-background, facile, and robust fluorescent nanoprobes for imaging and monitoring of intracellular mRNA changes remains a great challenge. Taking advantage of the high fluorescence quenching efficiency of core-shell gold@polydopamine (Au@PDA) nanocomposites and Ca²⁺-promoting DNA adsorption stability, a simple and universal bioconjugate strategy was designed to a construct fluorescent nanoprobe for highly efficient tumor-related mRNA imaging. The fluorescence of Cy5-labeled DNA was quenched up to 92.38% by the AuNP and PDA via nanometal surface energy transfer (NSET) and photoinduced electron transfer (PET), respectively. TK1 mRNA, a biomarker of tumor growth, initiates hybridization and results in fluorescence recovery, which built the foundation for identifying the expression level changes in living cells. More importantly, three kinds of tumor-related mRNA (TK1 mRNA, GalNAc-T mRNA, and C-myc mRNA) can be detected simultaneously with different fluorophore-modified recognition sequences, which can avoid false positive signals and improve the reliability of cancer diagnostic, holding great promise for cancer diagnosis, prognosis, and therapy. Full article

This study addresses the ongoing challenge of optimizing chatbot interactions to significantly enhance customer experience and satisfaction through personalized, empathetic responses. Using advanced NLP tools and strong statistical methodologies, we developed and evaluated a multi-layered analytical framework to accurately identify user intents, assess customer feedback, and generate emotionally intelligent interactions. With over 270,000 customer chatbot interaction records in our dataset, we employed spaCy-based NER and clustering algorithms (HDBSCAN and K-Means) to categorize customer queries precisely. Text classification was performed using random forest, logistic regression, and SVM, achieving near-perfect accuracy. Sentiment analysis was conducted using VADER, Naive Bayes, and TextBlob, complemented by semantic analysis via LDA. Statistical tests, including Chi-square, Kruskal–Wallis, Dunn’s test, ANOVA, and logistic regression, confirmed the significant impact of tailored, empathetic response strategies on customer satisfaction. Correlation analysis indicated that traditional measures like sentiment polarity and text length insufficiently capture customer satisfaction nuances. The results underscore the critical role of context-specific adjustments and emotional responsiveness, paving the way for future research into chatbot personalization and customer-centric system optimization. Full article

Hepatocellular carcinoma (HCC) is a malignancy that is notorious for its dismal prognosis. Dysregulation of the tumor microenvironment (TME) in HCC has emerged as a key hallmark in determining disease progression and the response to immunotherapy. The aim of this study was to identify novel TME regulators that contribute to therapeutic resistance, thus providing mechanistic insights for targeted interventions. The expression of SMIM25 was evaluated in the the Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC) and Guangxi HCC cohorts, and its clinicopathological significance was assessed. RNA sequencing and bioinformatics analyses were performed to elucidate the potential impact of elevated SMIM25 levels. Immunohistochemistry (IHC) and single-cell mass cytometry (CyTOF) were employed to examine the cellular composition of the tumor microenvironment. The biological effects of SMIM25 on cell proliferation and migration were studied in vitro using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide(MTT) and wound healing assays, while its impact on tumor growth was evaluated in vivo in a nude mouse model. Transcriptomic and single-cell proteomic analyses were integrated to explore the mechanism by which SMIM25 affects the progression of HCC. The expression of SMIM25 was significantly up-regulated in both HCC tissues and cell lines (p < 0.05). RNA sequencing analyses revealed a significant positive correlation between SMIM25 expression and immunosuppression, and between SMIM25 expression and extracellular matrix(ECM)-related molecular features. Single-cell mass cytometry revealed two immunosuppressive cell clusters that were enriched in HCC patients with high SMIM25 expression. Moreover, SMIM25 was associated with immune exclusion and ECM remodeling signals in the TME of HCC. SMIM25 overexpression was associated with the expression of the tumor inflammatory marker cyclooxygenase-2(COX-2), and a COX-2 inhibitor could partially reverse the biological phenotype associated with SMIM25 expression in HCC cells (p < 0.05). Further transcriptome analysis in immunotherapy cohorts suggested the SMIM25-COX-2 axis might have predictive value for the response to immunotherapy. Our results suggest that SMIM25 may serve as a biomarker for the prognosis of HCC patients and may also be a predictive biomarker for the response to immunotherapy, enabling more precise and personalized HCC treatment. Full article

Phytoglobins (Pgbs) are plant hemoglobin-like proteins with key roles in nitric oxide (NO) scavenging, oxygen sensing, and hypoxic stress responses. Their typical hexacoordination results in unusually high affinities for gaseous ligands such as NO and carbon monoxide (CO), complicating measurement using conventional methods. Standard assays often require large sample volumes and lack sensitivity for high-affinity, low-abundance proteins like hexacoordinated Pgbs. Here, we present a microscale capillary-based fluorescence assay for the high-precision measurement of protein–gas binding. Fluorophore-labeled proteins are loaded into gas-saturated capillaries and analyzed via dual-wavelength fluorescence to monitor isothermal spectral shifts upon ligand binding. Phosphate-buffered saline with Tween20 (PBS-T20) ensures gas stability and minimizes nonspecific adsorption. Using this approach, we characterized CO and NO binding to the recombinant wildtype (rWT) of Beta vulgaris Pgb 1.2 (BvPgb 1.2) and its C86A mutant. CO titrations revealed biphasic binding, with EC₅₀ ~400 nM and ~700 μM (rWT) and ~500 nM and ~400 μM (C86A). NO binding showed K_D values of ~1600 nM (rWT) and ~400 nM (C86A), implicating Cys86 in ligand affinity. This assay provides a robust, low-volume method for high-affinity protein–gas studies and shows biphasic dynamics in BvPgbs. Full article

Background/Objectives: While complete loss-of-function (LoF) SPINK1 variants in the simple heterozygous state cause chronic pancreatitis, biallelic complete LoF variants result in a rare pediatric disorder termed severe infantile isolated exocrine pancreatic insufficiency (SIIEPI). To date, only two individuals with a null SPINK1 genotype have been reported—one homozygous for a whole-gene deletion and the other for an Alu insertion in the 3′ untranslated region. Here, we report the genetic basis of a third SIIEPI case, presenting in early infancy with severe exocrine pancreatic insufficiency and diffuse pancreatic lipomatosis. Methods: Targeted next-generation sequencing (NGS) was used to analyze the entire coding region and exon–intron boundaries of the SPINK1 gene. Copy number variant (CNV) analysis was performed with SeqNext, based on normalized amplicon coverage. Results: The proband harbored compound heterozygous complete LoF SPINK1 variants. One was the known NM_001379610.1:c.180_181del (p.(Cys61PhefsTer2)), inherited from the father. The second, initially detected as an exon 2 deletion and confirmed by quantitative fluorescent multiplex PCR (QFM-PCR), was further characterized by long-range PCR as a complex rearrangement comprising a 1185 bp deletion removing exon 2, a 118 bp templated insertion followed by a non-templated nucleotide, and an 8 bp deletion. The mutational signature is consistent with serial replication slippage or template switching involving translesion synthesis. This maternally inherited variant has not been previously reported. Conclusions: This study expands the mutational spectrum of SPINK1-related SIIEPI and suggests that this distinct pediatric disorder may be under recognized in clinical practice. Full article

To address the brittle matrix failure frequently observed in filament-wound composite layers of onboard pressure vessels operating under cryogenic and high-pressure conditions, we studied a bisphenol-A epoxy resin (DGEBA) system modified with polyetheramine (T5000) and 3,4-Epoxycyclohexylmethyl 3′,4′-epoxycyclohexanecarboxylate (CY179). The curing and rheological behavior of the modified resin were first evaluated, revealing a favorable processing, with viscosity suitable for wet-filament winding. Subsequently, its coefficient of thermal expansion (CTE) and tensile properties were characterized over the 300 K–90 K range, demonstrating a linear increase in elastic modulus and tensile strength with decreasing temperature. Carbon fibre-reinforced polymer composites (CFRP) were then fabricated using this resin system, and both longitudinal and transverse tensile tests, along with microscopic fracture surface analyses, were conducted. The results showed that CFRP-0° specimens exhibited an initial increase followed by a decrease in elastic modulus with decreasing temperature, whereas CFRP-90° specimens demonstrated pronounced cryogenic strengthening, with tensile strength and modulus enhanced by 52.2% and 82.4%, respectively. The findings provide comprehensive properties for the studied resin system and its CFRP under room temperature (RT) to cryogenic conditions, offering a basis for the design and engineering of cryo-compressed hydrogen storage vessels. Full article

The mechanisms through which different types of exogenous carbon enhance the soil organic carbon sequestration rate (C_seq), nitrogen use efficiency (NUE), and corn yield (CY) in rainfed farmland on the Loess Plateau remain inadequately elucidated. This study established a four-year fixed-site experiment in the context of organic materials to increase soil organic carbon storage and enhance corn yield in the dry-farmed areas of the mountainous southern Ningxia region. The research investigates the effects of adding different types of exogenous carbon materials on C_seq, NUE, and CY. The soil type at the experimental base is loessial soil (Huangmian soil), with a soil pH of 8.28 and a baseline organic carbon content of 8.20 g kg⁻¹. The main crop cultivated in this area is corn. The experimental treatments were as follows: (i) N, no fertilization; (ii) CK, 100% nitrogen, phosphorus, and potassium fertilizers; (iii) C, 50%CK + corn straw (pulverized); (iv) M, 50%CK + fermented cow manure; (v) C/M, 50%CK + fermented cow manure + corn straw (1:1). The results show that compared with the CK treatment, the C_seq of C, M, and C/M treatments increased by 488.89%, 355.56%, and 527.78%, respectively. Compared with the CK treatment, the NUE of C, M, and C/M treatments increased by 15.04%, 7.70%, and 12.20%, respectively. Compared with the CK treatment, the CY under the C, M, and C/M treatments were increased by 7.91%, 19.10%, and 11.59%, respectively. The linear regression results show that the C_seq had a significant positive effect on CY (R² = 0.37) and NUE, R² = 0.39) (p < 0.0001). The TOPSIS (technique for order preference by similarity to ideal solution) evaluation results indicate that the C/M treatment was the optimal measure for achieving increased corn yield while enhancing Cseq and NUE. Therefore, incorporating a 1:1 mixture of corn straw and cattle manure in rainfed farmland in the mountainous area of southern Ningxia may be the best strategy to improve C_seq and NUE. Full article

Background: Leber’s hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and an inherited optic neuropathy. Recently, two different LHON inheritance types have been discovered: mitochondrially inherited LHON (mtLHON) and autosomal recessive LHON (arLHON). Our case report is the first diagnosed case of arLHON in a patient of Lithuanian descent and confirms the DnaJ Heat Shock Protein Family (Hsp40) Member C30 (DNAJC30) c.152A>G p.(Tyr51Cys) founder variant. Case Presentation: A 34-year-old Lithuanian man complained of headache and sudden, painless loss of central vision in his right eye. On examination, the visual acuity of the right and left eyes was 0.1 and 1.0, respectively. Visual-field examination revealed a central scotoma in the right eye, and visual evoked potentials (VEPs) showed prolonged latency in both eyes. Optical coherence tomography showed thickening of the retinal nerve fiber layer in the upper quadrant of the optic disk in the left eye. Magnetic resonance imaging of the head showed evidence of optic nerve inflammation in the right eye. Blood tests were within normal range and showed no signs of inflammation. Retrobulbar neuritis of the right eye was suspected, and the patient was treated with steroids, which did not improve visual acuity. He later developed visual loss in the left eye as well. A genetic origin of the optic neuropathy was suspected, and a complete mitochondrial DNA analysis was performed, but it did not reveal any pathologic mutations. Over time, the visual acuity of both eyes slowly deteriorated, and the retinal nerve fiber layer (RNFL) thinning of the optic disks progressed. A multidisciplinary team of specialists concluded that vasculitis or infectious disease was unlikely to be the cause of the vision loss, and a genetic cause for the disease was still suspected, although a first-stage genetic test did not yield the diagnosis. Thirty-three months after disease onset, whole-exome sequencing revealed a pathogenic variant in the DNAJC30 gene, leading to the diagnosis of arLHON. Treatment with Idebenone was started 35 months after the onset of the disease, resulting in no significant worsening of the patient’s condition. Conclusion: This case highlights the importance of considering arLHON as a possible diagnosis for patients with optic neuropathy, because the phenotype of arLHON appears to be identical to that of mtLHON and cannot be distinguished by clinicians. Full article

Humans are being exposed to a variety of potentially toxic metal compounds through the diet and/or the intravenous administration of metal-containing medicinal drugs. The organomercurial thimerosal (THI) is a bactericidal that is present in vaccines, but its potential degradation by biomolecules in vivo is incompletely understood. To probe its interaction with low-molecular-weight thiols that are highly abundant within cells, we have employed an LC-based analytical approach in conjunction with a mercury-specific detector. The injection of THI into a C₁₈-HPLC column equilibrated with mobile phases that contained increasing concentrations of up to 15 mM of glutathione (GSH) and 30% acetonitrile revealed the elution of a GS-EtHg adduct in conjunction with THI, as evidenced by electrospray ionization mass spectrometry. These results were confirmed by ¹⁹⁹Hg-NMR spectroscopy. While these results imply a rapid degradation of THI by GSH at physiological pH, it is important to point out that our results were obtained in aqueous solutions containing 30% (v:v) acetonitrile. Further studies need to confirm if the GS-EtHg adduct is also formed in biological fluids. Our results nevertheless demonstrate that GSH and L-cysteine (Cys) are potential targets of THI at physiological pH, which is relevant to better understand its side effects, including previously reported effects on Ca²⁺ channels. Full article

Green mold formed by Penicillium digitatum is a major disease that limits the yield and overall value of postharvest citrus fruits. The antifungal activity of sodium cuminate (SC) against P. digitatum and the corresponding mechanism were explored in this research. The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of SC against P. digitatum were 0.4 and 0.8 g L⁻¹, respectively. SC (8× MFC) reduced the incidence of disease in Ponkan fruits without compromising their quality. The results of CFW staining and extracellular alkaline phosphatase assays revealed that 1/2MIC SC for 30 min had no impact on the cell wall integrity of P. digitatum. In contrast, 1/2MIC SC apparently destroyed cell membrane integrity, as shown by the increase in the content of reactive oxygen species (ROS), malondialdehyde, and H₂O₂. The addition of exogenous cysteine (Cys) or diphenyleneiodonium chloride (DPI) significantly mitigated the cytotoxic effects of SC. At the same time, mitochondrial membrane potential was significantly decreased by 1/2MIC SC, and the addition of exogenous Cys or DPI restored it to normal levels. In summary, the antifungal capacity of SC might be attributable to membrane damage in P. digitatum caused by oxidative stress. Full article

Solid-state fermentation (SSF) enhances the nutritional profile of legumes. This study evaluated Rhizopus oligosporus-mediated SSF for selenium (Se) biofortification in soybean tempeh (a traditional Southeast Asian food), assessing the effects of selenate and selenite (0–60 mg kg⁻¹) on R. oligosporus growth, substrate consumption, mycelium morphology, and Se speciation in tempeh. Selenium supplementation at 18–24 mg kg⁻¹ reduced soybean protein content by 9.4~13.8% relative to the protein content of the Se-free fermented tempeh (control group, 19.85%) and significantly promoted proteolysis. Higher concentrations (48–60 mg kg⁻¹) restored protein levels to control values (19%), indicating concentration-dependent regulation of protein stability. Selenate at 42 mg kg⁻¹ significantly increased the levels of flavor amino acids (e.g., glutamate, aspartate), essential amino acids, and total amino acids in tempeh. In contrast, selenite showed no significant improvement in amino acid content and even reduced non-essential amino acids (e.g., alanine, glycine) at high concentrations (42 mg kg⁻¹). Selenium biofortification converted selenate to selenomethionine (SeMet) and Se(VI), but transformed selenite into methylselenocysteine (MeSeCys), selenocystine (SeCys₂), and SeMet. Fermented Se-tempeh demonstrated potent α-glucosidase inhibition (IC₅₀ values ranging from 1.66 ± 0.05 to 2.89 ± 0.03 mg mL⁻¹), suggesting Se-enriched soybean tempeh could be considered a promising blood-sugar-friendly food. Thus, developing soybean-based functional foods via co-inoculation of R. oligosporus with inorganic Se is a promising way to enhance tempeh bioactivity. Full article

Chronic kidney disease (CKD) is a global public health issue linked to toxic elements like cadmium (Cd) and mercury (Hg), which harm the kidneys even at low exposure levels. Copper (Cu) and zinc (Zn) imbalances could exacerbate inflammation, oxidative stress, and kidney damage because the Cu/Zn ratio could be a critical marker of renal dysfunction. The study evaluated 914 adolescents aged 11–18 through urine samples to assess the presence of kidney damage biomarkers (OPN, KIM-1, CLU, NGAL, and Cys-C) by using Luminex Magpix and trace metals (Cd, Hg, Cu, Zn) by using ICP-mass. Overweight (18.71%) and obesity (12.58%) rates were noted. Cd and Cu showed positive correlations with kidney damage biomarkers, while Zn exhibited protective effects. Regression models indicated that Cd exposure increased kidney damage markers, emphasizing the importance of Cu/Zn ratio. Environmental exposure to Cd affects kidney health even at low levels, as the Cu/Zn ratio correlates with kidney damage markers in low-Cd exposure, suggesting that the Cu/Zn ratio could participate in the nephrotoxicity process, highlighting trace element imbalance as a potential predictor of kidney function decline. Full article

The rapid growth of scientific literature necessitates effective information extraction. However, existing methods face significant challenges, particularly when applied to multi-domain documents and low-resource languages. For Kazakh and Russian, there is a notable lack of annotated corpora and dedicated tools for scientific information extraction. To address this gap, we introduce SciMDIX (Scientific Multi-Domain Information extraction), a novel multi-domain dataset of scientific documents in Russian and Kazakh, annotated with entities and relations. Our study includes a comprehensive evaluation of entity recognition performance, comparing state-of-the-art models, such as BERT, LLaMA, GLiNER, and spaCy across four diverse domains (IT, Linguistics, Medicine, and Psychology) in both languages. The findings highlight the promise of spaCy and GLiNER for practical deployment in under-resourced language settings. Furthermore, we propose a new zero-shot relation extraction model that leverages a multimodal representation by integrating sentence context, entity mentions, and textual definitions of relation classes. Our model can predict semantic relations between entities in new documents, even for a language encountered during training. This capability is especially valuable for low-resource language scenarios. Full article