Big Data and Artificial Intelligence in Drug Discovery for Gastric Cancer: Current Applications and Future Perspectives.

Gastric cancer (GC) represents a significant global health burden, ranking as the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Despite recent advancements in GC treatment, the five-year survival rate for advanced-stage GC patients remains low. Consequently, there is an urgent need to identify novel drug targets and develop effective therapies. However, traditional drug discovery approaches are associated with high costs, time-consuming processes, and a high failure rate, posing challenges in meeting this critical need. In recent years, there has been a rapid increase in the utilization of artificial intelligence (AI) algorithms and big data in drug discovery, particularly in cancer research. AI has the potential to improve the drug discovery process by analyzing vast and complex datasets from multiple sources, enabling the prediction of compound efficacy and toxicity, as well as the optimization of drug candidates. This review provides an overview of the latest AI algorithms and big data employed in drug discovery for GC. Additionally, we examine the various applications of AI in this field, with a specific focus on therapeutic discovery. Moreover, we discuss the challenges, limitations, and prospects of emerging AI methods, which hold significant promise for advancing GC research in the future.

Long-term outcomes in patients with Burkitt lymphoma older than 65 years: an analysis of the Texas Cancer Registry.

Burkitt lymphoma (BL) is an extremely aggressive but curable subtype of non-Hodgkin lymphoma. While younger patients have excellent outcomes in response to aggressive chemoimmunotherapy, the rarity of this disease in older patients and limitations caused by age, comorbidities, and performance status may negate survival advantages. This analysis assessed outcomes of older adults with BL through data provided by the Texas Cancer Registry (TCR). Patients ≥65 years with BL were assessed. Patients were dichotomized into 1997-2007 and 2008-2018. Median overall survival (OS) and disease-specific survival (DSS) were assessed using Kaplan-Meier methodology, and covariates including age, race, sex, stage, primary site, and poverty index were analyzed using Pearson Chi-squared analysis. Odds ratio (OR) with 95% confidence intervals (CI) was used to assess factors contributing to patients not offered systemic therapy. P value <0.05 was considered statistically significant. Non-BL mortality events were also categorized. There were 325 adults, 167 in 1997-2007 and 158 in 2008-2018; 106 (63.5%) and 121 (76.6%) received systemic therapy, a trend that increased with time (p = 0.010). Median OS for 1997-2007 and 2008-2018 was 5 months (95% CI 2.469, 7.531) and 9 months (95% CI 0.000, 19.154) (p = 0.013), and DSS was 72 months (95% CI 56.397, 87.603) (p = 0.604) and not reached, respectively. For patients that received systemic therapy, median OS was 8 months (95% CI 1.278, 14.722) and 26 months (95% CI 5.824, 46.176) (p = 0.072), respectively, and DSS was 79 months (95% CI: 56.416, 101.584) and not reached, respectively (p = 0.607). Age ≥75 years (HR 1.39 [95% CI 1.078, 1.791], p = 0.011) and non-Hispanic whites (HR 1.407 [95% CI 1.024, 1.935], p = 0.035) had poorer outcomes, and patients at the 20-100% poverty index (OR 0.387 [95% CI 0.163, 0.921], p = 0.032) and increasing age at diagnosis (OR 0.947 [95% CI 0.913, 0.983], p = 0.004) were less likely to receive systemic therapy. Of 259 (79.7%) deaths, 62 (23.9%) were non-BL deaths, and 6 (9.6%) of these were from a second cancer. This two-decade analysis of older Texas patients with BL indicates a significant improvement in OS over time. Although patients were more likely to receive systemic therapy over time, treatment disparities existed in patients residing in poverty-stricken regions of Texas and in advancing age. These statewide findings reflect an unmet national need to find a systemic therapeutic strategy that can be tolerated by and augment outcomes in the growing elderly population.

Synthesis of ZnO/Au Nanorods for Self Cleaning Applications.

Zinc oxide (ZnO) is a well-known semiconductor with valuable characteristics: wide direct band gap of ˜3.3 eV, large exciton binding energy of 60 meV at room temperature, high efficient photocatalyst, etc. which have been applied in many fields such as optical devices (LEDs, laser), solar cells and sensors. Besides, various low dimensional structures of ZnO in terms of nanoparticles, nanorods, nanoneedles, nanotetrapods find applications in technology and life. This material is also appealing due to the diversity of available processing methods including both chemical and physical approaches such as: hydrothermal, sol-gel, chemical vapor deposition and sputtering. In this report, ZnO nanorods are prepared by hydrothermal method assisted with galvanic-cell effect. The effect of counter electrode materials on the morphology and structure of obtained product was studied. Scanning electron microscopy (SEM) images of the product showed that counter electrodes made of aluminum offers nanorods of higher quality than other materials in terms of uniform size, high density and good preferred orientation. The as-prepared nanorods were then sputtered with gold (Au). ZnO/Au nanostructures show excellent photocatalyst activities which were demonstrated by complete photodegradation of methylene blue (Mb) under UV irradiation and high decomposition rate k of 0.011 min-1.

Au nanoparticle-decorated ZnO nanorods as fluorescent non-enzymatic glucose probe.

ZnO nanorods (NRs) synthesized by a hydrothermal method and decorated with Au nanoparticles (NPs) were used for fluorescent non-enzymatic glucose detection. The detection is based on the photoluminescence (PL) quenching of ZnO NRs/Au NPs (at 382 nm under 325 nm excitation) exposed to glucose. The sensor exhibits a high sensitivity of (22 ± 2) % mM-1 (defined as percentage change of the PL peak intensity per mM) and a limit of detection (LOD) as low as 0.01 mM, along with an excellent selectivity and a short response time (less than 5 s). In comparison with a fluorescent non-enzymatic ZnO nanostructure-based glucose sensor, the addition of Au NPs significantly enhances the sensitivity. This is attributed to the surface plasmon resonance, which increases not only the photoluminescence intensity but also the photo-oxidation property of the ZnO NRs. Thus, ZnO NRs/Au NPs can act as an efficient photocatalyst for glucose detection. Most importantly, the probe is applicable to glucose detection in human blood serum. The outstanding performance of the material and its cost-effectiveness allow for potential application in single-use, noninvasive glucose devices.Graphical abstract A sensitive non-enzymatic fluorescent glucose probe-based ZnO nanorod decorated with Au nanoparticles.

Chicken albumen-based whispering gallery mode microlasers.

Microlasers based on biomaterials have attracted enormous interest because of their promising potential for future applications in medical treatments, bio-tracking, and biosensing. In this work, we demonstrate chicken albumen as a novel and excellent low-cost biomaterial for a laser cavity. By using a simple but effective emulsion process, rhodamine B-doped chicken albumen microspheres with various diameters ranging from 20 µm to 100 µm can be fabricated. Under optical pulse excitation, these microspheres emit lasing emission. The lasing mechanism is investigated and ascribed to the whispering gallery mode (WGM). A threshold of 23.2 µJ mm-2 and a high Q-factor of approximately 2400 are obtained from an 82 µm-diameter microsphere. Size-dependent lasing characteristics are also examined, and the result shows good agreement with the WGM theory. Interestingly, these microsphere biolasers can operate in aqueous and biological environments such as water and human blood serum, which makes them a promising candidate for laser-based biosensing and biological applications.

Overcharging of the Zinc Ion in the Structure of the Zinc-Finger Protein Is Needed for DNA Binding Stability.

Zinc-finger structure, in which a Zn2+ ion binds to four cysteines or histidines in a tetrahedral structure, is a very common motif of nucleic acid-binding proteins. The corresponding interaction model is present in 3% of the genes in the human genome. As a result, the zinc finger has been extremely useful in various therapeutic and research capacities and in biotechnology. In a stable configuration of the zinc finger, the cysteine amino acids are deprotonated and become negatively charged. Thus, the Zn2+ ion is overscreened by four cysteine charges (overcharged). Whether this overcharged configuration is also stable when such a negatively charged zinc finger binds to a negatively charged DNA molecule is unknown. We investigated how the deprotonated state of cysteine influences its structure, dynamics, and function in binding to DNA molecules by using an all-atom molecular dynamics simulation up to the microsecond range of an androgen receptor protein dimer. Our results showed that the deprotonated state of cysteine residues is essential for the mechanical stabilization of the functional, folded conformation. This state stabilizes not only the protein structure but also the protein-DNA binding complex. The differences in the structural and energetic properties of the two sequence-identical monomers are also investigated and show the strong influence of DNA on the structure of the zinc-finger protein dimer upon complexation. Our result can potentially lead to a better molecular understanding of one of the most common classes of zinc fingers.

Hodgkin's lymphoma with HLH and complete remission with brentuximab-based therapy.

A 63-year-old man presented to the hospital with generalised weakness, fatigue and a 22 kg weight loss 4 months after being diagnosed with sarcoidosis on a mediastinal lymph node biopsy, with minimal improvement in symptoms on prednisone and methotrexate therapy. On arrival, he was found to have a haemoglobin of 57 g/L and platelet count of 82×109/L. Further work-up revealed six of eight diagnostic criteria for haemophagocytic lymphohistiocytosis (HLH): fever >38.9°C, splenomegaly, cytopaenia, hypertriglyceridaemia, haemophagocytosis and elevated ferritin >31 000 ng/mL. He was also found to have Epstein-Barr viraemia with greater than 17 000 copies. Bone marrow biopsy showed the presence of haemophagocytic histiocytes and evidence of classic Hodgkin's lymphoma. He was started on HLH-94 protocol. Later treatment was switched to lymphoma-directed therapy and he finished six cycles of A+AVD (brentuximab vedotin, doxorubicin, vinblastine and dacarbazine) with end-of-treatment positron emission tomography/CT and bone marrow negative for lymphoma.

Protein-based microsphere biolasers fabricated by dehydration.

Biolasers made of biological materials have attracted considerable research attention due to their biocompatibility and biodegradability, and have the potential for biosensing and biointegration. However, the current fabrication methods of biolasers suffer from several limitations, such as complicated processing, time-consuming and environmentally unfriendly nature. In this study, a novel approach with green processes for fabricating solid-state microsphere biolasers has been demonstrated. By dehydration via a modified Microglassification™ technology, dye-doped bovine serum albumin (BSA) droplets could be quickly (less than 10 minutes) and easily changed into solid microspheres with diameters ranging from 10 µm to 150 µm. The size of the microspheres could be effectively controlled by changing either the concentration of the BSA solution or the diameter of the initial droplets. The fabricated microspheres could act as efficient microlasers under an optical pulse excitation. A lasing threshold of 7.8 µJ mm-2 and a quality (Q) factor of about 1700 to 3100 were obtained. The size dependence of lasing characteristics was investigated, and the results showed a good agreement with whispering gallery mode (WGM) theory. Our findings contribute an effective technique for the fabrication of high-Q factor microlasers that may be potential for applications in biological and chemical sensors.

Non-enzymatic fluorescent glucose sensor using vertically aligned ZnO nanotubes grown by a one-step, seedless hydrothermal method.

A sensitive non-enzymatic fluorescent glucose sensor, consisting of vertically aligned ZnO nanotubes (NTs) grown on low-cost printed circuit board substrates, is described. The ZnO NTs were synthesized by a one-step hydrothermal method without using a seed layer. The sensor function is based on the photoluminescence (PL) quenching of ZnO NTs treated with different concentrations of glucose. The UV emission (emission maximum at 384 nm under 325 nm excitation) decreases linearly with increasing glucose concentration. The sensor exhibits a sensitivity of 3.5%·mM-1 (defined as percentage change of the PL peak intensity per mM) and a lower limit of detection (LOD) of 70 µM. This is better than previously reported work based on the use of ZnO nanostructures. The detection range is 0.1-15 mM which makes the sensor suitable for practical uses in glucose sensing. The sensor was successfully applied to the analysis of human blood serum samples. It is not interfered by common concentrations of ascorbic acid, uric acid, bovine serum albumin, maltose, fructose, and sucrose. Graphical abstract Schematic of the one-step, seedless hydrothermal method utilized for synthesizing vertically aligned ZnO nanotubes on printed circuit board substrates (PCBs). The ZnO nanotubes were used to monitor glucose concentrations in a non-enzymatic fluorescent sensor.

Genetics of Hypercoagulable and Hypocoagulable States.

Hemostasis is the normal process of blood coagulation in vivo to stop pathologic bleeding. Virchow triad includes venous stasis, hypercoagulability, and vascular injury. Natural anticoagulants include protein C, protein S, and antithrombin. Factor V Leiden is the most common inherited thrombophilia, followed by prothrombin gene mutation. All inherited thrombophilias are passed down in an autosomal dominant fashion. Patients harboring the antiphospholipid antibodies have an increased risk for thrombosis. von Willebrand disease is the most common inherited bleeding disorder; the pattern of inheritance is autosomal. Hemophilia A and B are the only hereditary bleeding disorders inherited in a sex-linked recessive pattern.

Tetracycline effects on Candida albicans virulence factors.

OBJECT: To determine if tetracycline, previously reported to increase the probability of developing symptomatic vaginal yeast infections, has a direct effect on Candida albicans growth or induction of virulent phenotypes. METHOD: In vitro, clinical isolates of yeast were cultivated with sublethal concentrations of tetracycline and yeast cell counts, hyphal formation, drug efflux pump activity, biofilm production, and hemolysin production were determined by previously reported methods. RESULTS: Tetracycline concentrations above 150 microg/mL inhibited Candida albicans, but at submicrogram/mL, a modest growth increase during the early hours of the growth curve was observed. Tetracycline did not inhibit hyphal formation at sublethal concentrations. Hypha formation appeared augmented by exposure to tetracycline in the presence of chemically defined medium and especially in the presence of human serum. Efflux pump CDR1 was upregulated and a nonsignificant trend toward increased biofilm formation was noted. CONCLUSION: Tetracycline appears to have a small growth enhancing effect and may influence virulence through augmentation of hypha formation, and a modest effect on drug efflux and biofilm formation, although tetracycline did not affect hemolysin. It is not clear if the magnitude of the effect is sufficient to attribute vaginitis following tetracycline treatment to direct action of tetracycline on yeast.