Recessive shrunken2 (sh2)-based sweet corn is preferred worldwide as it possesses higher sugar and extended shelf life. However, traditional sh2-based sweet corn is poor in vitamin A and vitamin E. Here, parental lines of two sh2-based sweet corn hybrids, viz. PSSC-2 and ASKH-2, were targeted for introgression of β-carotene hydroxylase 1 (crtRB1) and γ-tocopherol methyltransferase (vte4) genes through marker-assisted backcross breeding. Seeds with sh2sh2sh2 genotype in the endosperm were selected based on the shrunken phenotype in BCF, BCF and BCF generations. Gene-based markers, viz. 3'-TE-InDel and 118-InDel specific for crtRB1 and vte4, respectively, were successfully utilized for foreground selection in BCF, BCF and BCF. Reconstituted hybrids showed high provitamin A (proA: 19.52 ± 0.52 µg/g) with a maximum of 7.8-fold increase over original hybrids (ASKH-2 and PSSC-2: 3.33 ± 0.28 µg/g). High α-tocopherol (20.75 ± 0.44 µg/g) and α/γ-tocopherol ratio (0.55 ± 0.02) with an average enhancement of 2.3- and 1.7-fold, respectively, was recorded among reconstituted hybrids over original versions (α-tocopherol: 9.21 ± 0.33 µg/g, α/γ-tocopherol ratio: 0.31 ± 0.01). The average yield of reconstituted hybrids (11.40 ± 0.22 t/ha) was at par with the original sweetcorn hybrids (11.60 ± 0.20 t/ha). This is the first report of stacking sh2, crtRB1 and vte4 genes to improve nutritional quality in sweet corn. These biofortified sweet corn hybrids hold immense significance to alleviate micronutrient malnutrition.

Chitin, a natural organic compound with content slightly lower than cellulose, is also known for chitosan, a substance derived from chitin through deacetylation. In this experiment, preliminary screening was conducted using the plate discoloration circle method, leading to the selection of a high-yield CDA-producing strain from 28 candidates through rescreening. Morphological characteristics and 16S rDNA sequence analysis revealed 99.93% homology with Enterobacter sichuanensis strain N24, thus naming this strain Enterobacter strain ZCDA27. Initial fermentation of the strain yielded CDA activity of 9.29 U/mL. Single-factor optimization was then performed, followed by a PB test to screen for significant factors affecting enzyme production. The response surface method was used to further optimize the fermentation conditions. The optimal fermentation conditions for the carbon source, nitrogen source, metal ion, fermentation temperature, time, liquid volume, and initial pH were explored. Significant factors affecting enzyme production, including MgSO, initial medium pH, and fructose levels, were identified using the PB test. Finally, the fermentation conditions of ZCDA27 were optimized using the Box-Behnken design combined with RSM, which comprised fructose at 1.020%, magnesium sulfate at 0.016%, and peptone at 1%. The fermentation conditions included a temperature of 37, initial pH of 7.1, rotation speed of 140 × g, fermentation time of 28 h, inoculation amount of 2%, and liquid volume of 40%. Under these conditions, the enzyme activity of ZCDA27 reached 14.52 U/mL, a 1.6-fold increase from the pre-optimization levels. In summary, this study provides an experimental foundation for further development and application of Enterobacter spp. ZCDA27 CDA.

Gentiana kurroo Royle, a critically endangered Himalayan herb, is valued in treating leucoderma, syphilis, bronchial asthma, hepatitis, etc. The current investigation performed quantitative and qualitative phytochemical analysis of G. kurroo root extracts prepared in chloroform, methanol, and ethyl acetate. The phenolic and flavonoid contents were the highest in methanol and chloroform extract, respectively. Several pharmacologically important compounds were identified through gas chromatography-mass spectrometry. Antioxidant analysis revealed methanolic extract to be the most efficient scavenger of 2,2-diphenyl-1-picrylhydrazyl (IC = 114 µg mL), hydrogen peroxide (IC = 109.9 µg mL), and superoxide (IC = 74.63 µg mL) radicals. Gentiopicroside was isolated from the methanolic root extract through silica-gel column-chromatography, and the characterization of concentrated fractions was achieved employing various analytical techniques. Pertaining to silver nanoparticle (GkAgNPs) synthesis, different physicochemical parameters were optimized and it was observed that root extract treated with silver-nitrate (0.5 mM) at 60 °C and incubated in dark for at least 120 min after initial color change, yielded GkAgNPs optimally. GkAgNPs were anisotropic and polydisperse and exhibited characteristic surface plasmon resonance (424 nm), crystalline face-centered cubic geometry, size (50-300 nm), and zeta-potential (- 16.3 mV). FT-IR spectra indicated the involvement of phenols and flavonoids in AgNPs synthesis. GkAgNPs were evidenced as strongly cytotoxic (IC = 1.964 µg mL) against HeLa cells and also showed deformed cellular morphology, a significant reduction in viable cell counts and colony-forming efficiency (4.08%). The findings suggest potential applications in drug development for treating serious human diseases. To the best of our knowledge, this study represents the first report on the isolation of gentiopicroside, the bio-fabrication of GkAgNPs using G.kurroo root extract, and their strong bioefficacy against HeLa cells.

Food preservation aims to maintain safe and nutritious food for extended periods by inhibiting microbial growth that causes spoilage and poses health risks. Traditional chemical preservatives like sodium sulfite, sodium nitrite, sodium benzoate, tBHQ and BHA have raised concerns due to potential carcinogenicity, genotoxicity and allergies with long-term consumption. As a natural alternative, bacteriocins have emerged for food preservation. These ribosomally synthesised antimicrobial peptides are produced by various microorganisms, including bacteria, fungi and yeast, typically during their stationary growth phase. Bacteriocins are categorised into four classes based on structure and function, with molecular weights averaging between 30 and 80 kDa. They exhibit antimicrobial activity against a range of bacteria, mediating complex interactions between bacterial species and enhancing competitiveness and survival of producer strains. Both gram-positive and gram-negative bacteria produce bacteriocins. Recent advancements have identified and optimized bacteriocins for applications in food technology, extending shelf life, managing foodborne illnesses and contributing to public health preservation. Their eco-friendly nature and safety profile make bacteriocins promising for future food preservation strategies without detrimental effects on humans or animals. The current review has mainly focused on the preservation of food products using bacteriocin.

Bio-cement is a green and energy-saving building material, which has received wide attention in the field of ecological environment and geotechnical engineering in recent years. The aim of this study is to investigate the improvement effect of plant-based bio-cement (PBBC) in synergistic treatment of sand with organic materials, to highlight the effective use of tap water in PBBC, and to analyze the crack evolution pattern during the damage of specimens by using image processing techniques. The results showed that tap water can be used as a solvent for PBBC instead of deionized water. The characteristic trend of urease solutions prepared at different temperature environments was obvious, and the activity value of urease solution with low concentration is positively correlated with the ambient temperature, although the activity value is not high, it is not easy to inactivate. The incorporation of organic materials increased the peak stress up to 1809.30 kPa compared to the specimens modified only by PBBC. The damage of the specimens under uniaxial compression consisted of four stages: compaction, elastic deformation, pre-peak brittle damage and post-peak macroscopic damage. The corresponding crack evolution is the interpenetration of small-sized cracks into large-sized main cracks. The large-sized main cracks transform into penetration cracks before damage, and the small-sized cracks are distributed around the penetration cracks. The crack evolution parameters obtained by MATLAB processing are positively correlated with the strain.

Nanozymes are a class of nanomaterials that are capable of mimicking the activities of natural enzymes. They are currently receiving considerable attention due to their advantageous properties. The objective of this study is to provide a comprehensive analysis of the advancements and trends in nanozymes for microbial theranostics research over the past decade through a detailed bibliometric approach. For this purpose, an effective search query was formulated, and relevant publications from 2013 to 2023 were collected from the Web of Science Core Collection database. Subsequently, the following softwares were employed for analysis: VOSviewer, the Bibliometrix R package, and GraphPad Prism 8.0.2. The findings revealed a statistically significant positive correlation (r = 0.993; p < 0.0001) between publications and citations, in addition to an important growth rate of scientific output of approximately 28.90%. China, India, and the USA were the most productive countries, whereas progress in low- and middle-income countries remained constrained. The Chinese Academy of Sciences was the most productive institution, and remarkably almost the top 10 productive authors were from China. Regarding keywords analysis, current research hotspots are primarily concentrated on the application of nanozymes in anti-biofilm-related research, antibacterial activity and therapy, the development of biosensors for microbial detection and control, and the advancement of wound disinfection and therapy.

Large quantities of by-products are generated after processing of rose snapper (Lutjanus guttatus), such as viscera, head, tail, skin, and bones, which are considered a potential source of valuable molecules. Therefore, the aim of the present study was the biochemical characterization of alkaline proteases isolated from the intestines of L. guttatus and the evaluation of their stability against different chemical denaturants (salts, surfactants/reducing agents, organic solvents, and commercial detergent formulations). In addition, the efficiency to hydrolyze proteins from rose snapper wastes (head, tail, skin, and muscle trimmings) by Alcalase® and alkaline protease extract (APE) isolated from Lutjanus guttatus intestine was evaluated. The APE exhibited a maximum activity at pH 12 and 45 °C and high stability at pH and temperature ranges from 9 to 12 and 10 to 40 °C, respectively. Assays with specific protease inhibitors indicated that trypsin and chymotrypsin are the main types of proteases in APE. An 80% of the proteolytic activity was retained in the presence of 25% NaCl and was stable in the presence of the reducing agent DTT; however, it lost around 70% of proteolytic activity in the presence of 2-mercaptoethanol. The enzymatic activity of APE was maintained above 60% in methanol, ethanol, and propanol as well as in liquid commercial detergents. Alkaline proteases from rose snapper exhibited higher hydrolytic efficiency, compared to the microbial enzyme Alcalase when protein from L. guttatus wastes were hydrolyzed. According to these results, the integral exploitation of rose snapper could be reached by proper usage of its by-products, creating a baseline to promote circular economy.

Zinc oxide nanoparticles (ZnO-NPs) can enhance zinc bioavailability in plants, improving crop nutritional quality and addressing global zinc deficiency. This study aimed to investigate the effects of zinc oxide nanoparticles (ZnO-NPs), obtained by a green synthesis method, on the growth, yield parameters, and zinc content of rice plants. In the study, two different application strategies of ZnO-NPs on rice plants were evaluated, i.e., foliar spray and seed priming. To compare the effects of these application strategies, rice plants were treated with ZnO-NPs at two different concentrations, 25 mg/L and 50 mg/L. Effects of ZnO-NPs on plant growth (shoot and root length, fresh and dry mass), chlorophyll and carotenoid content, grain yield and zinc content were investigated. The results showed that both ZnO-NP application methods increased rice growth and yield, especially the combined method (seed priming + foliar spray) provided the highest efficiency. It was observed that seed zinc content was increased up to 10% by seed priming method and foliar spray application increased the zinc content up to 23% while the combination of seed priming and foliar spray increased zinc content up to 122%. In general, applications at 50 mg/L concentration increased more than 25 mg/L. These results indicate that ZnO-NPs can be an effective tool for zinc deficiency management in agricultural practices and can improve the yield and nutritional content of staple foods such as rice.

Specific antibodies, which can be used in various experiments, are critical tools for unraveling genes' function, but many commercial antibodies are not tested for these properties. GPATCH1 is a novel G-patch family protein. Genome-wide association studies (GWAS) revealed it as a gene associated with human osteoporosis, and yeast-based research suggested it may be a splicing factor; however, its molecular mechanism remains a mystery. We report here that currently available commercial GPATCH1 antibodies have poor specificity and are not recommended for immunoprecipitation. We elucidated the apparent molecular weight of GPATCH1 to evaluate the antibodies' specificity. Based on this, a specific polyclonal antibody against GPATCH1 that can be used for Western blotting, immunoprecipitation and immunofluorescence was prepared. With the antibodies, we found that GPATCH1 may be a tissue-specific splicing factor. Our study lays the groundwork for further investigations into the molecular mechanisms by which GPATCH1 affects bone metabolism in the future.

Lignin, a vital plant component, is key in providing structural integrity and is the second most abundant biopolymer in nature. The growing interest in sustainable and efficient biocatalysis has driven the exploration of lignin nanoparticles (LNPs) as a promising platform for enzyme immobilization. Given lignin's abundance and structural role in plants, converting it into nanoparticles offers a potential eco-friendly alternative to traditional supports. This comprehensive review explores recent advancements in using LNPs for enzyme immobilization, focusing on loading techniques, immobilization efficiency, enzyme activity levels, and various factors that affect the performance of enzymes immobilized on LNPs. The review also addresses the primary challenges associated with enzyme immobilization on LNPs and discusses future innovations in this field. Adopting eco-friendly immobilization platforms based on LNPs is expected to have broad applications in industries like food, pharmaceuticals, animal feed, and detergents. However, there is still potential to customize LNPs further and develop novel immobilization techniques to leverage their benefits fully. By understanding the properties and advantages of these nanostructured lignin supports, researchers can design and create innovative nanocatalysts for various industrial applications.

Foot-and-mouth disease (FMD) is known for its highly contagious properties among cloven-hoofed animals resulting in significant morbidity rates. Incursions of this disease have caused significant losses in affected countries in Southeast Asia and Africa, even within EU countries which resulted in significant financial losses. This study is aimed at addressing existing limitations by creating a diagnostic method using aptamer-based assay. Three DNA aptamers were engineered to target the VP2 region of the FMD viral capsid protein. Since VP2 demonstrates a highly conserved amino acid sequence across serotypes, the specifically designed aptamers can detect different serotypes of the virus. Aptamers were evaluated against VP2 capsid protein, which was synthesized based on sequences from serotypes A, O, and Asia 1 of the FMD virus. After the recombinant VP2 capsid protein was developed, expressed, and refined, it was applied using enzyme-linked aptamer sorbent assay (ELASA) to determine aptamers' binding capability. A similar test was further conducted with purified FMD virus from serotype A and serotype O. The ELASA results displayed a notable sensitivity in identifying the FMDV. Under optimized conditions, the aptamers have LOD as low as 0.11 ng/mL with LOQ as low as 0.34 ng/mL. The binding strength analyzed using the equilibrium dissociation constant (Kd) showed strong binding affinity at 3.092 ± 0.05 nM. Based on these findings, the method shows significant potential with high sensitivity and specificity for FMD virus detection assay.

An efficient and green method was developed using deep eutectic solvent assistance to enhance the biotransformation method of producing resveratrol from Polygonum cuspidatum Siebold & Zucc, using cellulose-based immobilised Aspergillus niger in the process. Various deep eutectic solvents (DES) were screened to obtain a superior biocatalytic effect. The increase in DES concentration aggravated the degree of cell membrane damage. Natural deep eutectic solvents (NADES) exhibited a more favourable catalytic effect than DES due to their excellent biocompatibility. This enhancement is associated with the hydrogen bonding donor components present in NADES, with catalytic ability ranking as alcohol-based > sugar-based > organic acid. CHCL/EG exhibited the maximum catalytic effect at 1.0 wt%. Under optimal conditions (pH 6.5; temperature, 29.5 °C; ratio of liquid to solid 20:1 (mL/g), and time 47 h), the resveratrol yield reached 32.79 mg/g, which was 13.06-fold to that of the untreated sample (2.51 mg/g). The residual activity of the cellulose-based microreactor was 81.46% after ten trials. The proposed method was successfully employed, demonstrating higher biocatalysis efficiencies and superior environmental protection compared to conventional solvents for resveratrol biocatalysis.

Spirulina platensis low-molecular-weight peptides (SP) have been reported to exhibit antioxidant and hepatoprotective properties. However, the limited bioavailability and solubility of SPs limit their potential applications. In this study, to examine the potential anti-obesity effects and underlying mechanisms of SPs, high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) model rats were treated with SPs and SP-loaded nanoliposomes. Furthermore, hepatic biochemical parameters, inflammatory markers, histopathological changes, and genes involved in AMPK signaling were analyzed. SP-loaded nanoliposomes demonstrated a spherical shape with slower and sustained SP release. SP and SP-loaded nanoliposomes mitigated hepatic damage by lowering serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and increasing hepatic antioxidant enzymes, which are manifested in improving histopathological findings. In addition, notably, SP-loaded nanoliposomes downregulated lipogenic fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) in the liver. Meanwhile, an upregulation of phosphorylated AMP-activated protein kinase (P-AMPK), lipid acid oxidation-related genes carnitine palmitoyltransferase-1 (CPT-1), and peroxisome proliferator-activated receptor alpha (PPAR-α) was found in the rat liver. This data implies that SP and SP-loaded nanoliposomes exhibit protective potential in rats against the HFD-induced NAFLD, which is mediated through the activation of the AMPK signaling pathway.

Antimicrobial resistance is one of the principal global health problems, and it is imperative to develop new drugs to reduce the spread of antimicrobial-resistant microorganisms. The flower extract of Butea monosperma and the root extract of Glycyrrhiza glabra are used to green synthesize zinc oxide nanoparticles (ZnO-NPs) using zinc acetate dihydrate. We characterized the biosynthesized ZnO-NPs using various techniques. The UV-visible spectra of ZnO-NPs using flower extract of B. monosperma and root extract of G. glabra were observed at 276 and 261 nm, respectively. Fourier transform infrared spectroscopy (FT-IR) analysis depicted different functional groups. The size of the biosynthesized ZnO-NPs was calculated at 19.72 nm. Moreover, scanning electron microscopy (SEM) analysis showed that ZnO-NPs synthesized from flower extracts of B. monosperma were agglomerated in rod-shaped clusters. The nanoparticles synthesized from G. glabra were dispersed and semi-spherical in shape. The most pronounced increases in antioxidant activity against 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid [ABTS] were detected at the high concentrations of ZnO-NPs (800 µg/ml) biosynthesized from B. monosperma (48.8%) and G. glabra (38.8%). Antibiotics revealed smaller inhibition zones, while the higher concentrations of ZnO-NPs (800 µg/ml) biosynthesized from B. monosperma and G. glabra displayed strong antibacterial activity against Bacillus subtilis, Escherichia coli, and Klebsiella pneumoniae. The results indicated that the ZnO-NPs synthesized using B. monosperma and G. glabra extracts demonstrated significant antibacterial and antioxidant properties. This green synthesis approach highlights plant-mediated ZnO-NPs potential as effective agents for biomedical applications and offers an eco-friendly alternative to conventional chemical synthesis methods.

Haloalkane dehalogenase DhaA is a member of the α/β-hydrolase superfamily and can degrade the halogenated compounds. However, the enzyme could not tolerate harsh and extreme environmental conditions, such as high temperature, extreme pH, and hypersaline, which limits its practical applications. Pullulan is a hydrophilic polysaccharide and acts as an additive to improve the enzyme stability. Polyethyleneimine (PEI) is a protein stabilizer and a polymer with a high density of ionizable amino groups. In the present study, DhaA was covalently conjugated with acetylated pullulan and adsorbed with PEI by electrostatic interactions to form nanoparticles (PEI-pullulan-DhaA). As compared with DhaA, PEI-pullulan-DhaA essentially maintained the enzymatic activity of DhaA, along with slight change in the kinetic parameters and enzyme conformation. The conjugated pullulan tends to form a large hydrated layer around DhaA. PEI, a cationic polymer, generated an amphiphilic microenvironment around DhaA. Pullulan conjugation and PEI adsorption could significantly improve the stability of DhaA against high temperature and low pH by structural stabilization of DhaA. PEI-pullulan-DhaA could also tolerate the hypersaline, organic solvents, and long-term storage. Thus, PEI-pullulan-DhaA has a strong environmental stability and is promising for industrial and environmental applications.

Recurrence is of utmost importance for hepatocellular carcinoma (HCC) after ultrasound-guided microwave ablation (UGMWA) therapy. The fibrosis 4 (FIB-4) index is a valuable predictor of HCC recurrence after surgical resection. However, whether FIB-4 can predict the recurrence of HCC patients receiving UGMWA remains unclear. The FIB-4 index was detected in healthy controls, hepatitis patients, and HCC patients. The predictive value of FIB-4 in HCC occurrence and recurrence following UGMWA therapy was evaluated using receiver operating characteristic analysis. The associated factors of FIB-4 in HCC patients were compared between patients with high and low levels of FIB-4. A Kaplan-Meier plot was used to assess the impact of FIB-4 on overall survival (OS) and recurrence-free survival (RFS). FIB-4 levels were increased in HCC patients and could predict the occurrence of HCC. Meanwhile, it was associated with five factors, including recurrence. Furthermore, FIB-4 levels decreased in HCC patients after UGMWA therapy but increased in recurrent HCC patients following UGMWA therapy. Importantly, FIB-4 could predict recurrence after UGMWA. The HCC patients had shorter OS and RFS. FIB-4 was associated with HCC recurrence after UGMWA therapy. Specifically, it had a predictive value for HCC occurrence and recurrence following UGMWA therapy.

Edible and medicinal mushrooms are valuable sources of polysaccharides, known for their dual roles as immunostimulants and immunosuppressants. This study aimed to enhance polysaccharide content by fusing two mushroom species, P. florida and C. militaris, while exploring their antioxidant and antibacterial potential. These mushrooms have diverse health benefits, including lowering high cholesterol, providing anti-inflammatory effects, supporting diabetes management, aiding in cancer treatment, and enhancing the efficacy of COVID-19 vaccines. Successful hyphal fusion was achieved, and optimal culture conditions were determined using response surface methodology. The hybrids exhibited superior growth compared to the parental strains. Hyphal fusion improved several attributes, resulting in diverse hybrids with increased biomass and metabolite production. FTIR analysis confirmed the presence of exopolysaccharides, with concentrations measured at 28.4 g/L (P1), 31.50 g/L (CD), and 36.74 g/L (F3). GC-MS analysis identified various bioactive metabolites, including a higher concentration of dimethyl palmitamine in the hybrid, a novel compound, butanenitrile, 2-(methoxymethoxy), which was not found in the parental strains. These compounds are likely responsible for the enhanced antimicrobial and antioxidant activities.

Breast cancer remains a challenging health issue, demanding innovative treatment approaches that maximize efficacy while minimizing damage to healthy cells. Targeted therapy offers a promising strategy tailored to the unique characteristics of breast cancer tumors. Gold nanoparticles have been studied in the context of their therapeutic potential towards cancer treatment showing great success. Recently, aptamers were also investigated for their targeting efficiency towards specific receptors allowing their use in targeting delivery systems. In this study, computational analysis was used to confirm the strong binding between AS1411 aptamer and the nucleolin receptor extensively present on the surface of breast cancer cells, highlighting the aptamer's potential for specific targeting. Furthermore, we investigated and compared the use of AS1411 aptamer-conjugated chemically synthesized (GNPs) and flaxseed-green-synthesized (Fs-GNPs) gold nanoparticles as targeting therapeutic systems for breast cancer cells. Our results showed successful conjugation of the AS1411 aptamer with both, the GNPs and Fs-GNPs. Characterization of the nanoparticles and their conjugates validates their size, charge, and morphology, affirming the success of the conjugation process. Cytotoxicity assessments using the MTT assay demonstrated the effectiveness of the conjugates against breast cancer cells, with the AS1411-Fs-GNPs conjugate exhibiting higher inhibitory efficacy, featuring an IC value of 11.13 µg/ml. In contrast, they showed minimal effect on normal cells, emphasizing the selectivity and potential safety of these therapies. To our knowledge, this is the first report of conjugating AS1411 aptamer to green-synthesized gold nanoparticles and its use as a targeting therapeutic system.

Cholangiocarcinoma is a hepatobiliary system tumor with a high mortality rate. Although durvalumab and trastuzumab deruxtecan (T-DXd) have shown efficacy in treating cancers such as non-small cell lung cancer, their effects and regulatory mechanisms in cholangiocarcinoma remain unclear. In this study, we aimed to investigate the role and mechanism of durvalumab and T-DXd in inducing apoptosis in cholangiocarcinoma cells. Cholangiocarcinoma cells were treated with varying concentrations of durvalumab and T-DXd, either individually or in combination, to evaluate their effects. Apoptosis was quantified using flow cytometry. Quantitative real-time PCR (qPCR) and Western blotting were used to measure the mRNA expression and protein levels of genes associated with apoptosis and cell cycle regulation. The underlying mechanism was further explored through pathway enrichment analysis of differentially expressed genes (DEGs) and corroborated by qPCR and Western blotting. Xenotransplantation models using immune-deficient NOD-SCID/IL2Rγnull (NSG) mice were established to assess the in vivo effects of durvalumab and T-DXd. Our results showed that both durvalumab and T-DXd inhibited cholangiocarcinoma cell proliferation in a dose-dependent manner. Both agents promoted apoptosis and arrested the cell cycle of cholangiocarcinoma cells, with the combination treatment having the most significant effect. Furthermore, treatment with durvalumab, T-DXd, and the combination downregulated the protein levels of early growth response 1 (EGR1) by inactivating the p38 mitogen-activated protein kinase (MAPK) pathway. In vivo experiments indicated that durvalumab and T-DXd prolonged the survival of NSG mice bearing cholangiocarcinoma xenografts. In conclusion, our findings demonstrated that durvalumab and T-DXd synergistically promoted apoptosis in cholangiocarcinoma cells by inhibiting EGR1 expression through inactivation of the p38 MAPK pathway. This study confirmed the potential of durvalumab and T-DXd for the treatment of cholangiocarcinoma.

The significance of exopolysaccharides (EPS) in various applications has garnered increasing attention. In this study, two bacteria, Liquorilactobacillus hordei SK6 and Liquorilactobacillus mali SK26, isolated from traditional water kefir grains, produced 8.89 g/L and 7.2 g/L of homopolymeric glucan, respectively. NMR analysis revealed that both glucans were dextrans composed of (1 → 6)-linked α-D-glucose units, with (1 → 3)-linked α-D-glucose units serving as branching points, accounting for 5.3 ± 0.2% in dextran SK6 and 2.7 ± 0.15% in SK26. FTIR and XRD analyses further confirmed the amorphous nature of the dextrans, although dextran SK6 exhibited micro-arranged structures. Thermal characterization using TGA and DSC showed degradation temperatures of 298.5 °C for dextran SK6 and 282.1 °C for dextran SK26. Clear differences in morphological properties were observed using AFM and SEM. These findings provide valuable insights into dextran-producing strains and their potential applications in various industries.

Diabetic retinopathy (DR) is one of the most common microvascular complications in diabetes. Accumulating evidence demonstrated that long non-coding RNAs (lncRNAs) played critical regulatory roles in DR. However, the role of lncRNA HOX Transcript Antisense Intergenic RNA (HOTAIR) in the high glucose (HG)-induced human retinal pigment epithelial (RPE) cell injury remains unclear. Herein, we found the expression of HOTAIR was increased in the retina of DR rats and HG-induced ARPE-19 cells. Knockdown of HOTAIR improved viability, inhibited apoptosis, increased Bcl-2 protein levels, and decreased Bax and cleaved caspase 3 protein levels in HG-treated ARPE-19 cells. Moreover, enzyme-linked immunosorbent assay showed that HOTAIR silencing reduced interleukin 6 and tumor necrosis factor-α release of ARPE-19 cells under HG conditions. Mechanistically, luciferase reporter assay and RNA immunoprecipitation assay validated that HOTAIR could directly sponge miR-326 to upregulate transcription factor 4 (TCF4) expression. Furthermore, rescue experiments confirmed that HOTAIR promoted apoptosis and inflammation of HG-treated ARPE-19 cells by the miR-326/TCF4 axis. In summary, HOTAIR enhanced HG-induced retinal pigment epithelial cell injury by promoting apoptosis and inflammation, shedding light on the importance of HOTAIR as a novel potential target for DR treatment.