Application of collaborative filtering algorithm based on time decay function in music teaching recommendation model.

To address the issues of data sparsity, scalability, and cold start in the traditional teaching resource recommendation process, this paper presents an enhanced collaborative filtering (CF) recommendation algorithm incorporating a time decay (TD) function. By aligning with the human memory forgetting curve, the TD function is employed as a weighting factor, enabling the calculation of similarity and user preferences constrained by the TD, thus amplifying the weight of user interest over a short period and achieving the integration of short-term and long-term interests. The results indicate that the RMSE of the proposed combined recommendation algorithm (TD-CF) is only 8.

Association of serum alkaline phosphatase levels with bone mineral density, osteoporosis prevalence, and mortality in US adults with osteoporosis: evidence from NHANES 2005-2018.

Unlabelled: This study examined the association of serum total alkaline phosphatase (T-ALP) with bone mineral density (BMD) and osteoporosis prevalence in the general population, and investigated its association with mortality in individuals with osteoporosis, using data from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. Elevated serum T-ALP levels were significantly associated with both reduced BMD and an increased risk of osteoporosis in all participants. Moreover, elevated T-ALP levels were linked to higher all-cause mortality among individuals with osteoporosis during this period.

Discovery of a highly potent, N-terminal domain-targeting degrader of AR-FL/AR-V7 for the treatment of prostate cancer.

The clinical development of PROTACs targeting the androgen receptor (AR) for degradation has made significant progress. However, effective treatments for metastatic prostate cancers containing the androgen receptor splice variant 7 (AR-V7), a constitutively active mutant without the ligand-binding domain (LBD), are still lacking. Here, we reported the identification of a highly potent, noncovalent PROTAC targeting the N-terminal domain (NTD) of AR, NP18, which is developed from the covalent AR-NTD antagonist EPI-002, and effectively degrades both AR-FL and AR-V7 in 22Rv1 cells (DC: 18 and 26 nM respectively).

Efficacy and safety of a novel vena cava filter on pulmonary embolism prophylaxis: a prospective, multicenter, randomized, parallel, positive-controlled, noninferiority clinical trial.

Background: There are different types of vena cava filter (VCF) available in clinical practice. However, limited data exist to determine whether one type is superior to another, and no single VCF is universally recommended in clinical guidelines. The objective of this study was to investigate the safety and efficacy of a novel VCF, Octoparms, for the prevention of pulmonary embolism (PE) and to compare it with the Celect filter.

Targeting Protein Kinase, Membrane-Associated Tyrosine/Threonine 1 (PKMYT1) for Precision Cancer Therapy: From Discovery to Clinical Trial.

\Protein kinase membrane-associated tyrosine/threonine 1 (PKMYT1), an overlooked member of the WEE family responsible for regulating cell cycle transition, has recently emerged as a compelling therapeutic target for precision cancer therapy due to its established synthetic lethal relationship with CCNE1 (cyclin E1) amplification. Since the first-in-class selective PKMYT1 inhibitor, RP-6306, entered clinical trials in 2021, the field has experienced renewed interest underscored by the growing number of inhibitor patents and the exploration of additional gene alterations, such as KRAS/p53 mutations, FBXW7 mutation, and PPP2R1A mutation, as novel synthetic lethal partners. This perspective summarizes, for the first time, the PKMYT1 structure, function, and inhibitors in both the literature and patent applications reported to date.

Catalytically active prokaryotic Argonautes employ phospholipase D family proteins to strengthen immunity against different genetic invaders.

Prokaryotic Argonautes (pAgos) provide bacteria and archaea with immunity against plasmids and viruses. Catalytically active pAgos utilize short oligonucleotides as guides to directly cleave foreign nucleic acids, while inactive pAgos lacking catalytic residues employ auxiliary effectors, such as nonspecific nucleases, to trigger abortive infection upon detection of foreign nucleic acids. Here, we report a unique group of catalytically active pAgo proteins that frequently associate with a phospholipase D (PLD) family protein.

Modification of natural compounds through biotransformation process by microorganisms and their pharmacological properties.

The biotransformation of natural compounds by fungal microorganisms is a complex biochemical process. Tandem whole-cell biotransformation offers a promising, alternative, and cost-effective method for modifying of bioactive novel compounds. This approach is particularly beneficial for structurally complex natural products that are difficult to be synthesized through traditional synthetic methods.

STC2 knockdown inhibits cell proliferation and glycolysis in hepatocellular carcinoma through promoting autophagy by PI3K/Akt/mTOR pathway.

Background: The pathogenesis exploration and timely intervention of hepatocellular carcinoma (HCC) are crucial due to its global impact on human health. As a general tumor biomarker, stanniocalcin 2 (STC2), its role in HCC remains unclear. We aimed to analyze the effect and mechanism of STC2 on HCC.

Improved Foucault method with double-shoot shadow grams in optical shop testing.

The lack of rapid, effective, and quantitative testing methods in the initial stages of optical processing has been identified as a significant challenge. In response, an innovative approach has been developed to enhance the Foucault knife-edge test method, integrating digital image processing and spatial geometry algorithms. This has resulted in the creation of a convenient and rapid optical testing method, which has been successfully implemented in practice.

Engineered minimal type I CRISPR-Cas system for transcriptional activation and base editing in human cells.

Type I CRISPR-Cas systems are widespread and have exhibited high versatility and efficiency in genome editing and gene regulation in prokaryotes. However, due to the multi-subunit composition and large size, their application in eukaryotes has not been thoroughly investigated. Here, we demonstrate that the type I-F2 Cascade, the most compact among type I systems, with a total gene size smaller than that of SpCas9, can be developed for transcriptional activation in human cells.

Inhibition of porcine origin Klebsiella pneumoniae capsular polysaccharide and immune escape by BY3 compounded traditional Chinese medicine residue fermentation broth.

Klebsiella pneumoniae (K. pneumoniae) is a gram-negative conditionally pathogenic bacterium that causes disease primarily in immunocompromised individuals. Recently, highly virulent K.

A facile strategy for the construction of a phage display cyclic peptide library for the selection of functional macrocycles.

Cyclic peptides represent invaluable scaffolds in biological affinity, providing diverse collections for discovering functional molecules targeting challenging biological entities and protein-protein interactions. The field increasingly focuses on developing cyclization strategies and chemically modified combinatorial libraries in conjunction with M13 phage display, to identify macrocyclic peptide inhibitors for traditionally challenging targets. Here, we introduce a cyclization strategy utilizing -phthalaldehyde (OPA) for the discovery of active macrocycles characterized by asymmetric scaffolds with side-chain cyclization.

Formation of NifA-P complex represses ammonium-sensitive nitrogen fixation in diazotrophic proteobacteria lacking NifL.

Biological nitrogen fixation catalyzed by nitrogenase contributes greatly to the global nitrogen cycle. Nitrogenase expression is subject to regulation in response to nitrogen availability. However, the mechanism through which the transcriptional activator NifA regulates nitrogenase expression by interacting with P nitrogen regulatory proteins remains unclear in diazotrophic proteobacteria lacking NifL.

Complete genome sequence of a haloalkaliphilic heterotrophic bacterium IM328.

The genome of a halophilic bacterium IM328 was completely sequenced in order to offer convenience for the research such as the synthesis of compatible solutes. The genome contains a circular chromosome which was sequenced by PacBio system.

Rational engineering of Halomonas salifodinae to enhance hydroxyectoine production under lower-salt conditions.

Hydroxyectoine is an important compatible solute that holds potential for development into a high-value chemical with broad applications. However, the traditional high-salt fermentation for hydroxyectoine production presents challenges in treating the high-salt wastewater. Here, we report the rational engineering of Halomonas salifodinae to improve the bioproduction of hydroxyectoine under lower-salt conditions.

Targeting focal adhesion kinase (FAK) for cancer therapy: FAK inhibitors, FAK-based dual-target inhibitors and PROTAC degraders.

Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, plays an essential role in regulating cell proliferation, migration and invasion through both kinase-dependent enzymatic function and kinase-independent scaffolding function. The overexpression and activation of FAK is commonly observed in various cancers and some drug-resistant settings. Therefore, targeted disruption of FAK has been identified as an attractive strategy for cancer treatment.

Respiration and growth of R-1 with nitrous oxide as an electron acceptor.

Unlabelled: In the nitrogen biogeochemical cycle, the reduction of nitrous oxide (NO) to N by NO reductase, which is encoded by gene, is the only biological pathway for NO consumption. In this study, we successfully isolated a strain of denitrifying R-1 from sewage treatment plant sludge. This strain has strong NO reduction capability, and the average NO reduction rate was 5.

Dual-target inhibitors based on ERα: Novel therapeutic approaches for endocrine resistant breast cancer.

Estrogen receptor alpha (ERα), a nuclear transcription factor, is a well-validated therapeutic target for more than 70% of all breast cancers (BCs). Antagonizing ERα either by selective estrogen receptor modulators (SERMs) or selective estrogen receptor degraders (SERDs) forms the foundation of endocrine therapy and has achieved great success in the treatment of ERα positive (ERα+) BCs. Unfortunately, despite initial effectiveness, endocrine resistance eventually emerges in up to 30% of ERα+ BC patients and remains a significant medical challenge.

Structure-Activity Relationship (SAR) Studies of Novel Monovalent AR/AR-V7 Dual Degraders with Potent Efficacy against Advanced Prostate Cancer.

Androgen receptor (AR) has been extensively established as a potential therapeutic target for nearly all stages of prostate cancer (PCa). However, acquired resistance to AR-targeted drugs inevitably develops and severely limits their clinical efficacy. Particularly, there currently exists no efficient treatment for patients expressing the constitutively active AR splice variants, such as AR-V7.

Unveiling the repressive mechanism of a PPS-like regulator (PspR) in polyhydroxyalkanoates biosynthesis network.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a type of polyhydroxyalkanoates (PHA) that exhibits numerous outstanding properties and is naturally synthesized and elaborately regulated in various microorganisms. However, the regulatory mechanism involving the specific regulator PhaR in Haloferax mediterranei, a major PHBV production model among Haloarchaea, is not well understood. In our previous study, we showed that deletion of the phosphoenolpyruvate (PEP) synthetase-like (pps-like) gene activates the cryptic phaC genes in H.