Search Results (29,378)

Colorectal cancer is one of the most common malignancies worldwide, with liver metastasis being one of its primary metastatic patterns and a significant cause of death. For most patients with unresectable colorectal cancer liver metastasis, a comprehensive treatment strategy that includes chemotherapy and targeted therapy is the primary therapeutic strategy. However, significant breakthroughs in immune therapy for liver metastasis have yet to be achieved. In this article, we summarize the characteristics of the immune microenvironment in colorectal cancer liver metastases and the mechanisms of immune resistance. Additionally, we compile recent clinical trial results on immune combination strategies and biomarker studies and discuss the prospects for applying immune checkpoint inhibitors in the treatment of colorectal cancer liver metastasis. Full article

Growth regulatory factors (GRFs) and growth-regulating interacting factors (GIFs) play significant roles in plant growth, development, and environmental stress responses. Previous studies have reported the functions of GRF and GIF genes in model plants such as Arabidopsis and rice. Nevertheless, the GRF and GIF genes remained unexplored in cassava. Cassava (Manihot esculenta Crantz) is an important tropical economic crop. Its starchy storage roots serve as a major source of food and industrial raw materials, while its protein-rich leaves are widely consumed as leafy vegetables in Africa and other regions, offering high nutritional value and significant horticultural potential. This study identified 28 MeGRFs distributed on 13 chromosomes and 5 MeGIFs on 4 chromosomes through bioinformatic analysis and expression profiling. Promoter analysis uncovered cis-acting elements associated with growth, hormone signaling, and biotic stress responses. Under different tissues and biotic (e.g., cassava bacterial blight, CBB) and abiotic (e.g., drought, low temperature) stress conditions, GRF and GIF genes exhibited differential expression patterns. Real-time quantitative PCR analysis showed a significant expression for 11 MeGRFs and 3 MeGIFs under the Xanthomonas phaseoli pv. manihotis (Xpm) treatment. VIGS functional validation demonstrated that MeGRF28 and MeGIF4 could enhance cassava resistance to bacterial blight, and protein–protein interaction network analysis suggested that they may form a core GRF-GIF complex. This study provides a theoretical basis for understanding the functional evolution of the GRF and GIF gene families in cassava and their roles in horticultural trait development and stress resistance mechanisms. Full article

Effective treatment of ovarian cancer is limited by late-stage detection and chemotherapy resistance. There is a clinical need for the discovery of novel molecular targets to enable the development of innovative theranostic approaches. We investigated the coagulation factor II receptor/protease-activated receptor 1 (F2R/PAR1) as a potential diagnostic/prognostic biomarker and therapeutic target for ovarian cancer treatment. Public RNA sequence and DNA microarray data were used to analyze F2R gene expression in ovarian cancers, with protein expression confirmed in tumor samples by flow cytometry, immunofluorescence, and immunohistochemistry (IHC). Functional assays were conducted to study effects of F2R suppression on tumor progression. Our analysis confirmed elevated F2R mRNA and protein expression in ovarian cancers, notably in patients with metastatic and chemotherapy-resistant disease. Kaplan–Meier survival analysis demonstrated an association between high F2R protein detection and reduced progression-free survival. F2R suppression in ovarian cancer cell lines reduced tumor cell motility, invasion, spheroid formation, and metabolism and enhanced carboplatin sensitivity. F2R is a compelling diagnostic/prognostic and therapeutic target that could be used to treat chemotherapy-resistant and metastatic disease. The evaluation of novel F2R targeting strategies, using antibody-conjugated drugs or F2R ligand-decorated drug carriers, could lead to the development of effective therapeutics for patients with ovarian cancer. Full article

Our previous research has demonstrated the role of optimal temperatures and reactive oxygen species (ROS) in maintaining symptomless nonhost resistance (NHR) of barley to powdery mildews. However, the exact functions of temperature and ROS in NHR of plants, including barley, to viral infections are not known. Although barley is a nonhost for Tobacco mosaic virus (TMV), this virus can replicate in barley leaves at temperatures of ca. 30 °C. Here we elucidated the influence of short-term heat stress pre-treatments (30 °C, 3 h; heat shock at 49 °C, 20 s) on the symptomless NHR of barley to TMV and the role of the ROS superoxide (O₂^.−) in maintaining NHR. Heat stress and antioxidant (superoxide dismutase and catalase, SOD + CAT) treatments resulted in 50–100% higher TMV levels, while combined heat shock and SOD + CAT application caused further increases in TMV and appearance of cell and tissue death resembling a hypersensitive response (HR). An early (from 2 h after inoculation) burst of O₂^.− was essentially absent in TMV-infected barley exposed to short-term heat stress pre-treatments. Expression of barley genes regulating ROS (O₂^.−) metabolism (HvRBOHF2, HvSOD1) and cell death (HvBI-1) displayed an inverse correlation with TMV levels even at later time points (1–4 days after inoculation), implying a role in symptomless NHR, while increased levels of the antioxidant glutathione marked heat stress-induced suppression of NHR. We demonstrated that short-term heat stress and antioxidant treatments result in compromised NHR of barley to TMV, pointing to the role of optimal temperatures and ROS (O₂^.−) in symptomless NHR to virus infections. Full article

Because of their potential to enhance pathways for diagnosis and treatment, a great deal of research has been conducted to identify brain biomarkers of mental illnesses such as depression and anxiety. Similarly, the investigation of the biomarkers of those protective factors that help individuals resist, or recover from, these mental illnesses is also directly relevant to clinical practice. One such protective factor is Psychological Resilience (PR) but relatively little is known about its neurobiological underpinnings. A literature search was conducted of electroencephalographic data and PR, revealing seven studies that reported brain electrical activity categorised into bands of specified frequencies. Several studies reported significant associations between PR and alpha band activity, and somewhat less on beta band activity, principally via their roles in emotion regulation and problem solving. However, despite having a major role in many aspects of cognition and brain function, and being implicated in depression, only two studies examined gamma band activity specifically, and their results were equivocal. Several possible reasons for these apparently null results of the association between gamma band activity and PR are discussed, leading to a brief description of gamma, and suggestions for future research into its association with PR. Full article

This study investigates the effects of ultrasonic surface rolling process (USRP) parameters—static load, indentation depth—on the surface integrity, mechanical properties, and high-temperature oxidation properties of laser-clad NiCrAl coatings. Comprehensive experimental results demonstrate that USRP treatment effectively eliminates surface cracks and significantly enhances surface integrity. The process simultaneously improves mechanical properties, with microhardness increasing by 24.6% due to grain refinement-induced strengthening and elevated dislocation density. Under constant preload, increasing the ultrasonic rolling indentation depth effectively transforms residual tensile stress into beneficial compressive stress (from +69.8 MPa to −1315.3 MPa), with higher preload further enhancing this effect. Moreover, USRP-treated coatings achieve complete oxidation resistance at elevated temperatures by forming a denser and more continuous oxide layer while effectively suppressing internal oxidation, resulting in markedly improved high-temperature oxidation performance. Quantitative analysis confirms that the enhancement in surface mechanical properties is primarily attributed to microstructural refinement and dislocation strengthening mechanisms. Full article

Background/Objectives: This study aimed to evaluate the effect of sacral epidural laser discectomy (SELD) on clinical parameters in patients with chronic low back and/or leg pain (CLBLP) resistant to conservative treatment. Methods: A total of 75 patients with CLBLP who received SELD treatment were retrospectively included in this study. Patients were assessed for pain (numeric rating scale—NRS) and disability (Oswestry Disability Index—ODI). NRS and ODI scores were recorded before the operation and 1, 6, and 12 months after the operation. Results: Of the 75 patients, with a mean age of 52 ± 11 years (range: 30–78 years), 45 (60.0%) were female and 35 (40.0%) were male. The baseline pain intensity (7.43 ± 0.774) and pain intensities obtained at three time points following the surgeries (1 month [3.93 ± 1.571], 6 months [4.36 ± 1.591], 12 months [5.00 ± 1.716]) showed statistically significant differences (p < 0.001). The baseline pain-related disability (2.92 ± 0.539) and the data obtained at three subsequent time points (1 month [1.76 ± 0.883], 6 months [1.85 ± 0.896], and 12 months [2.01 ± 0.923]) showed a statistically significant difference in pain-related disability (p < 0.001). The most common complications were headache (five patients) and incisional pain (five patients). Conclusions: As a result of this study, we found that SELD reduces pain and disability in patients with conservative-treatment-resistant CLBLP. Although serious complications may rarely occur, the procedure is generally associated with an acceptable and low complication rate. Full article

Although traditional genetically modified (GM) cotton has reduced lepidopteran pests, secondary pests such as Adelphocoris suturalis Jakovlev (Hemiptera: Miridae) have become increasingly problematic. RNA interference (RNAi)-based insect-resistant plants offer a promising alternative, but their potential ecological risks, particularly within the plant–pest–natural enemy framework, require comprehensive evaluation. As a key natural enemy in cotton agroecosystems, Harmonia axyridis Pallas (Coleoptera: Coccinellidae) plays a vital role in regulating pest populations and thus serves as an important non-target insect for environmental risk assessment. In this study, dsAsFAR transgenic cotton and the non-target insect H. axyridis were used to evaluate potential ecological risks. Based on the sequences of the HaFAR, AsFAR, and GFP genes, dsAsFAR, dsHaFAR, and dsGFP were synthesized in vitro and incorporated into artificial diets fed to H. axyridis, along with a ddH₂O control group. No significant differences were observed among the treatments across various developmental stages. Furthermore, H. axyridis was fed aphids that had been reared on either transgenic or non-transgenic cotton plants cultivated in a greenhouse. The findings indicated no significant differences in the growth, development, predatory ability, or fecundity of H. axyridis. These results suggest that transgenic dsAsFAR cotton targeting A. suturalis poses no detectable adverse effects on H. axyridis, supporting the environmental safety of RNAi crops within a plant–pest–natural enemy ecological interaction framework. Moreover, the dsAsFAR expressed in transgenic cotton was not effectively transferred through the food chain to affect homologous gene expression in H. axyridis. Full article

Background: Meniere’s disease (MD) is a chronic inner ear disorder affecting approximately 0.2% of the population, with 30% of patients remaining refractory to conventional treatments. The pathophysiology involves endolymphatic hydrops, suggesting that agents affecting fluid homeostasis might provide therapeutic benefit. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, originally developed for diabetes, offer unique mechanisms including natriuresis and osmotic diuresis that may address the underlying fluid imbalance in MD. Methods: We conducted a retrospective observational study at the Korea University Anam Hospital, analyzing the medical records of patients with definite MD (Bárány Society criteria) who received off-label empagliflozin 10 mg daily between January 2023 and December 2023. Six patients (3 men, 3 women; mean age 55.8 years) with treatment-resistant MD were identified who had failed conventional therapy for at least 3 months. Primary outcomes included changes in pure tone threshold average (PTA), low-frequency threshold average (LFA), vertigo episode frequency, and vertigo severity using visual analog scale (VAS) scores, assessed at baseline and after 3 months of treatment. Results: All patients demonstrated clinically significant improvements in both auditory and vestibular symptoms. Mean PTA improved from 31.4 dB to 20.8 dB (improvement of 10.6 dB, p < 0.05). Low-frequency hearing showed more substantial recovery, with LFA improving from 37.2 dB to 15.6 dB (improvement of 21.6 dB, p < 0.01). Vertigo frequency decreased dramatically from 1.6 episodes per month to 0.1 episodes per month, with four patients experiencing a complete resolution of vertigo episodes. VAS scores for vertigo severity decreased from 5.2 to 0.5. Treatment was well-tolerated, with only minor adverse effects reported in two patients: transient polyuria in one patient and 5 kg weight loss in another, both consistent with the known pharmacological profile of SGLT-2 inhibitors. Conclusions: This preliminary study suggests a potential clinical benefit of repurposing SGLT-2 inhibitors for treatment-resistant MD. However, the retrospective design and inherent limitations prevent definitive conclusions about causality. The significant improvements observed in both hearing thresholds and vestibular symptoms warrant further investigation through randomized controlled trials with objective outcome measures to establish the true efficacy of this therapeutic approach. Full article

With an aging population, the number of joint replacement surgeries is on the rise. One of the most common implant materials is cobalt–chromium–molybdenum (CoCrMo) alloy. Hence, the surface properties of this alloy have attracted increasing attention. In this study, nanosecond and femtosecond laser processing, followed by annealing, was employed to modify the CoCrMo surface. The effects of the treatment conditions on the surface morphology, structure, composition, hardness, roughness, contact angle, wear properties, and corrosion current were studied. Femtosecond laser processing with an energy density of 1273 mJ/cm², followed by heat treatment at 160 °C for 2 h, produced laser-induced periodic surface structures (LIPSS) without altering the chemical composition of the alloy and rendered the surface superhydrophobic. In contrast, nanosecond laser treatment at higher laser energy densities promoted the formation of an oxide layer, which improved the hardness and corrosion resistance of the substrate. Overall, the CoCrMo samples processed using the femtosecond laser system exhibited superior corrosion and wear resistance, with a protection efficiency of approximately 92%. Full article

Feline infectious peritonitis (FIP) is a progressive and often fatal disease caused by a virulent biotype of feline coronavirus (FCoV). Although antiviral treatments are now available, relapse and resistance remain ongoing concerns. This study investigates the therapeutic potential of P. indusiatus, a medicinal mushroom, for its antiviral and anti-inflammatory activities against FIP. The main protease (FIPV M^pro) of feline infectious peritonitis virus (FIPV) was recombinantly expressed and purified to facilitate enzyme inhibition screening. P. indusiatus exhibited the strongest FIPV M^pro inhibitory activity among the 17 mushroom extracts tested (69.2%), showing a notable level of inhibition relative to standard antiviral agents such as lopinavir and ritonavir. To assess its anti-inflammatory potential, PBMCs derived from healthy cats and FIP-associated effusions (FIP fluid) were cultured and stimulated with LPS to induce inflammation. In healthy PBMCs, P. indusiatus significantly reduced nitrite levels, with effects similar to dexamethasone. However, PBMCs from FIP fluid, already in an activated state, showed no additional response. Notably, this study is the first to successfully isolate and culture PBMCs from FIP fluid, providing a new platform for future immunological research. These findings suggest that P. indusiatus possesses both antiviral and anti-inflammatory properties, positioning it as a potential dual-action therapeutic candidate for FIP. Further investigation into cytokine signaling pathways is warranted to clarify its mechanisms of action and advance future therapeutic development. Full article

Background: Vascular malformations are relatively common in children. Current therapeutic strategies include observation, medical therapy, sclerotherapy or embolization, laser therapy, cryoablation, and surgery, depending on the type and anatomical location of the malformation. Surgery is commonly limited to small and/or circumscribed lesions, to debulking in case of large volumes, or in drug-resistant cases. Sclerotherapy is a minimally invasive treatment generally used to treat dysplastic vasculature and to significantly improve patients’ symptoms. Herein, we describe our preliminary experience with bleomycin electrosclerotherapy (BEST) in the treatment of peripheral low-flow venous and lymphatic malformations in the pediatric population. Methods: We prospectively collected and analyzed data from patients who underwent BEST for peripheral low-flow vascular malformations (venous and lymphatic) and were treated at our institution from May 2022 onward. Results: Twelve patients (4 boys and 8 girls) with peripheral low-flow vascular malformations who underwent BEST were enrolled in this preliminary study. The median patient age at the first procedure was 81 months (IQR = 46–128). The most frequent anomaly was peripheral low-flow venous malformation. No relevant postoperative complications were encountered in any of the patients. All patients underwent a clinical evaluation of the malformation 1 month after the procedure. A clinical and ultrasonographic evaluation of the malformation was performed 2 months after the procedure to determine whether to repeat BEST. In cases of clinical resolution, a second ultrasonographic evaluation was performed 6 months after the procedure. Conclusions: BEST appears to be a promising and safe option for treating peripheral low-flow vascular malformations in children. Further studies with a greater number of patients and longer follow-up periods are needed to confirm our preliminary experience. Full article

Helicobacter pylori (Hp), a Class I carcinogen infecting over 50% of the global population, is increasingly resistant to conventional antibiotics. This study presents an AI-engineered probiotic strategy targeting urease, a key Hp virulence factor. A humanized single-domain antibody (UreBAb), previously identified and selected in our laboratory, was synthesized commercially and modeled using AlphaFold2, with structural validation conducted via SAVES 6.0. Molecular docking (PyMOL/ClusPro2) and binding energy analysis (InterProSurf) identified critical urease-active residues: K40, P41, K43, E82, F84, T86, K104, I107, K108, and R109. Machine learning-guided optimization using mCSA-AB, I-Mutant, and FoldX prioritized four mutational hotspots (K43, E82, I107, R109), leading to the generation of nine antibody variants. Among them, the I107W mutant exhibited the highest activity, achieving 65.6% urease inhibition—a 24.95% improvement over the wild-type antibody (p < 0.001). Engineered Escherichia coli Nissle 1917 (EcN) expressing the I107W antibody significantly reduced gastric HP colonization by 4.42 log10 CFU in the treatment group and 3.30 log10 CFU in the prevention group (p < 0.001 and p < 0.05, respectively), while also suppressing pro-inflammatory cytokine levels. Histopathological (H&E) analysis confirmed that the I107W antibody group showed significantly enhanced mucosal repair compared to wild-type probiotic-treated mice. Notably, 16S rRNA sequencing revealed that intestinal microbiota diversity and the abundance of core microbial species remained stable across different ethnic backgrounds. By integrating AI-guided antibody engineering with targeted probiotic delivery, this platform provides a transformative and microbiota-friendly strategy to combat antibiotic-resistant Hp infections. Full article

This study systematically investigates the effects of aging treatment (AT) on the microstructure and properties of Cr/DLC coatings deposited via cathodic arc ion plating onto the surface of ECAP-7075 aluminum alloy. Utilizing a comprehensive approach combining performance tests (nanoindentation, nanoscratch testing, dynamic polarization analysis) with characterization tests (scanning electron microscopy, energy dispersive spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy), the synergistic effects of equal channel angular pressing (ECAP) and aging treatment(AT) were elucidated. The results demonstrate that the combined ECAP and AT significantly enhance the coating’s performance. Specifically, AT promotes the precipitation of η’ phase within the 7075 aluminum alloy substrate, increases the size of Cr₇C₃ crystallites in the Cr-based interlayer, improves the crystallinity of the Cr₇C₃ phase on the (060) or (242) crystal planes, and elevates the sp³-C/sp²-C ratio in the diamond-like carbon(DLC) top layer, leading to partial healing of defects and a denser overall coating structure. These microstructural transformations, induced by AT, result in substantial improvements in the mechanical properties (hardness reaching 5.2 GPa, bond strength achieving 15.1 N) and corrosion resistance (corrosion potential increasing to -0.698 V) of the Cr/DLC-coated ECAP-7075 aluminum alloy. This enhanced combination of properties makes these coatings particularly well-suited for high-performance aerospace components requiring both wear resistance and corrosion protection in demanding environments. Full article

Objectives: This study aimed to identify differences in risk factors for carbapenem-resistant Enterobacteriaceae (CRE) infections across different anatomical sites and to explore risk factors associated with mortality in CRE-infected patients. Methods: Patients who underwent CRE screening and were subsequently diagnosed with CRE infections were included and categorized by infection site: respiratory tract (RTI), urinary tract (UTI), and bloodstream (BSI). Forty ICU patients without CRE infection were randomly selected as controls. Statistical comparisons were performed using the Mann–Whitney U or Chi-square test, as appropriate. Potential risk factors were evaluated via univariate and multivariate analyses, and a predictive model was constructed, with its performance assessed using ROC curve analysis. Results: CRE colonization was identified as a common independent risk factor across all three groups (RTI, UTI, and BSI). Infection-site-specific analyses revealed independent risk factors: RTI was associated with mechanical ventilation, UTI with trauma, and BSI with gastrointestinal injury. Predictive models for RTI, UTI, and BSI demonstrated good discrimination, with ROC AUCs of 0.94, 0.94, and 0.95, respectively. In the analysis of Survived versus Deceased patients, the BSI group had the highest mortality, though the difference was not statistically significant. Deceased patients exhibited significantly higher PCT levels than Survived patients (p = 0.005). Prior use of carbapenems and antifungal agents, as well as Ln(PCT), were independently associated with mortality in CRE-infected patients. Conclusions: Risk factors for CRE infections vary across anatomical sites, with CRE colonization, mechanical ventilation, trauma, and gastrointestinal injury playing key roles. Overuse of antibiotics and elevated inflammatory responses are associated with increased mortality. These findings provide evidence for early identification of high-risk patients and optimization of individualized treatment strategies. Full article