Advancing precision therapy for colorectal cancer: Developing clinical indications for multi-target kinase inhibitor BPR1J481 using patient-derived xenograft models

[[abstract]]The large and rapid increase in the incidence and mortality of colorectal cancer (CRC) demonstrates the urgent need for new drugs with higher efficacy to treat CRC. However, the lack of applicable and reliable preclinical models significantly hinders the progress of drug development. Patient-derived xenograft (PDX) models are currently considered reliable in vivo preclinical models for predicting drug efficacy in cancer patients. This study successfully uses the CRC PDX model to develop clinical indications for the new multi-target kinase inhibitor BPR1J481 and demonstrated the anti-cancer mechanism and competitive advantages of this drug candidate. The results demonstrate that BPR1J481 exhibits significant anticancer efficacy by inducing apoptosis in CRC PDX tumor tissues and corresponding PDX-derived CRC cells. Through kinase competitive binding and kinase activity assays, we discover that BPR1J481 effectively inhibits SRC kinase activity by directly binding to its active site. The reduction in SRC phosphorylation observed in CRC PDX tumor tissues and derived cells upon treatment with BPR1J481 further validates its inhibitory potential. Furthermore, the decrease in viable cells after SRC knockout and the poorer prognosis observed in patients with higher SRC expression, emphasizes the critical significance and clinical relevance of SRC in CRC. Additionally, BPR1J481 exhibits robust anti-angiogenic effects by suppressing VEGF- and PDGF-induced endothelial cell proliferation, migration, and capillary-like tube formation through inhibition of VEGFR2 and PDGFRβ phosphorylation. Remarkably, BPR1J481 appears to demonstrate greater efficacy against CRC compared to regorafenib. These findings highlight the therapeutic potential of BPR1J481 for patients with CRC

Fabrication of multilayer cellulose filters isolated from natural biomass for highly efficient air filtration for replacement of synthetic HEPA filters

[[abstract]]Indoor air pollution can be extensively reduced by using a molecular air filtration system. However, widely utilized synthetic polymer-based filtration medium can lead to waste management difficulty after use. Consequently, this work aimed to synthesize highly efficient air nano-filters derived from renewable and biodegradable resources namely EFB and Pulp. The study successfully presented an air filter from 100 % natural cellulose using a facile physical multilayer filter fabrication method. A combination of chemical and mechanical treatment was applied to prepare nanocellulose. The chemical composition analysis showed that 66–67 % nanocellulose yield was efficiently isolated from both raw materials. The highest particle filtration efficiency (PFE) of 97.30 % (0.3 μm particle size) greater than that of commercial HEPA filters was achieved from multilayer acid-derived microfiber@mechanically treated nanofibers from EFB with low-pressure drop of 11.56 mm H2O. When %PFE and pressure drop were taken into consideration, all single-layer and multilayer-patterned fiber filters in this study provided high quality factor (QF) beyond 0.01 Pa−1 which is the target of the air filter. The findings revealed that the pattern-layer filters through TBA-induced freezing-drying technique could achieve the removal of microbial model and Particulate Matters (PM1.0) represented as 0.1 and 0.3 μm particles, at the very low-pressure drop. Therefore, this study not only enhances the value of natural lignocellulosic wastes but also presents inspiring concepts for creating biodegradable cellulose-based air filters that will pave the way to more eco-friendliness and sustainability for synthetic filter replacement

[[alternative]]Cpg-oligodeoxynucleotide compounds in combination with immune modulators for cancer immunotherapy

[[abstract]]本發明公開一種組合療法，可於免疫抑制性微環境中增強針對腫瘤的免疫檢查點阻斷之功效。更具體言之，這種組合療法涉及透過免疫檢查點抑制劑及CpG-寡脫氧核苷酸來治療癌症

[[alternative]]Benzimidazole compounds and use thereof for treating alzheimer's disease or huntington's disease

[[abstract]]揭露了以下所示式(I)的苯并咪唑化合物，該化合物是有效的人類麩酸胺環化酶抑制劑。還揭露的是一種含有該等化合物中之一化合物及醫藥上可接受載體的醫藥組合物、以及一種藉由對需要治療阿茲海默症或亨丁頓氏症的個體投予有效量的該化合物來治療阿茲海默症或亨丁頓氏症的方法

Inhibitors of positive strand RNA viruses

[[abstract]]Methods of treating a disease caused by a positive strand RNA virus. The methods include administering to a subject in need thereof an effective amount of a compound of Formula I or Formula II

Trace proteinuria is a high-risk marker for developing ESRD and for shortening the lifespan: Findings from an 18-year follow-up cohort with half a million Asian participants

[[abstract]]Background: Trace proteinuria, obtained by urine dipstick, has not received its due attention in clinic visits. It was particularly overlooked in the younger people, even though it had three times more trace proteinuria than the elderly. This study aims to investigate its role in kidney diseases such as End Stage Renal Disease and its association with mortality outcomes and life-shortening effects in a large Asian cohort. Methods: A cohort of 646,987 adults, who have undergone health screening programs successively since 1994, were followed for a median of 18 years. Through encrypted identification numbers, 49,216 deaths and 4,101 ESRD cases were identified. Dipstick, in contrast to the old color-comparison method, is a semi-automated computer- assisted urinalysis system. Results reported as trace, 1+, 2+, and more. The association between proteinuria, ESRD, and mortality risks was evaluated using Cox proportional hazards models. Results: Trace proteinuria existed around 5% among healthy adults, contributed to nearly half of all CKD (9.5%), with younger adults (age <60 years) having a threefold higher prevalence than the elderly (age 60 years). Trace proteinuria significantly increased the risk of ESRD independent of eGFR, with up to 4-5 folds in normal eGFR subjects. The HR was 3.54, 95% CI: 2.67, 4.69 when eGFR 90 ; HR: 3.86, 95% CI: 3.08, 4.84 when eGFR 60-89; HR: 12.26, 95% CI: 9.24, 16.28 when eGFR 45-59; HR: 44.60, 95% CI: 31.39, 60.55 when eGFR 30-44 ml/min/1.73m^2) when compared with negative proteinuria. Participants with trace proteinuria also had a significantly higher risk of all-cause mortality (HR: 1.48, 95% CI: 1.42, 1.54), and associated with a reduction in life expectancy of up to 4-5 years. Dipstick tests demonstrated relatively high sensitivity (84%) and specificity (96%) in detecting microalbuminuria. Conclusions: Trace proteinuria, overlooked in the clinics, was associated with a 4-5 fold increase in developing ESRD later in life and a shortened lifespan of five years, with nearly 50% increase in all-cause mortality. Trace proteinuria can be screened easily in the clinic or among the public with a dipstick, an inexpensive test with instant results. More than 80% with microalbuminuria in an apparently healthy population could be identified

[[alternative]]Author Correction: Crosstalk between FTH1 and PYCR1 dysregulates proline metabolism and mediates cell growth in KRAS-mutant pancreatic cancer cells

[[abstract]]After online publication of this article, the authors noticed an error in the results section and supplementary information. The correct statement of this article should have read as below. Modification of language around FTH1 and PYCR1 interaction in the paragraph of Result, under the title of “FTH1-PYCR1 crosstalk mediates pancreatic cancer progression” on pages 2071-2073. We would like to clarify of experimental findings supporting the feedback mechanism between FTH1 and PYCR1

基於核酸疫苗的方法

[[abstract]]本發明涉及一種可用於提供電轉移源的新型裝置，特別是一種提供方波電脈衝的電裝置，藉由電探針可促進將核酸輸送到細胞內

Aminothiazole compounds as protein kinase inhibitors

[[abstract]]Aminothiazole compounds of Formula (I) shown below and pharmaceutical compositions containing one of such compounds. Also disclosed are methods of inhibiting a tyrosine kinase and treating cancer associated with a tyrosine kinase with one of the aminothiazole compounds

Antibodies and method for determining deletions in HBV pre-S2 region

[[abstract]]A HBS-specific antibody, a LHBS-specific antibody, a WT LHBS-specific antibody, an immunoassay kit comprising the antibodies, and a method of detecting pre-S2 deletion mutant LHBS using the immunoassay kit are disclosed herein. The method comprises incubating a biological sample with a first antibody to captured HBS proteins; detecting the LHBS and WT LHBS bound to the immobilized first antibody, respectively; and calculating the amount of the pre-S2 deletion mutant LHBS protein by subtracting the amount of the WT LHBS protein from that of the LHBS protein. Advantageously, by the method described herein, the amount of the pre-S2 deletion mutant LHBS, a potential high-risk marker for HCC incidence in chronic HBV carriers and recurrence in HCC patients after hepatectomy surgery, in a biological sample may be easily calculated without mutual influence between the WT and pre-S mutant LHBS while reducing the labor-intensive process for cloning each gene product before analysis