4'-Demethylpodophyllotoxin functions as a mechanism-driven therapy by targeting the PI3K-AKT pathway in Colorectal cancer.

The treatment of colorectal cancer (CRC) poses significant challenges in terms of drug resistance and poor prognosis, necessitating the exploration of effective therapeutic strategies. In this study, high-throughput drug screening was utilized to identify Chinese herbal medicines with notable therapeutic effects on CRC. Among the compounds identified, 4'-demethylpodophyllotoxin (DOP), a derivative of podophyllotoxin, emerged as a potent anti-cancer compound.

USP3 plays a critical role in the induction of innate immune tolerance.

Microbial products, such as lipopolysaccharide (LPS), can elicit efficient innate immune responses against invading pathogens. However, priming with LPS can induce a form of innate immune memory, termed innate immune "tolerance", which blunts subsequent NF-κB signaling. Although epigenetic and transcriptional reprogramming has been shown to play a role in innate immune memory, the involvement of post-translational regulation remains unclear.

Targeting RPA promotes autophagic flux and the antitumor response to radiation in nasopharyngeal carcinoma.

Background: Autophagy is involved in nasopharyngeal carcinoma (NPC) radioresistance. Replication protein A 1 (RPA1) and RPA3, substrates of the RPA complex, are potential therapeutic targets for reversing NPC radioresistance. Nevertheless, the role of RPA in autophagy is not adequately understood.

LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer.

Background: Ladinin-1 (LAD1), an anchoring filament protein, has been associated with several cancer types, including cancers of the colon, lungs, and breast. However, it is still unclear how and why LAD1 causes gastric cancer (GC).

Methods: Multiple in vitro and in vivo, functional gains and loss experiments were carried out in the current study to confirm the function of LAD1.

USP2 promotes tumor immune evasion via deubiquitination and stabilization of PD-L1.

The abnormal upregulation of programmed death ligand-1 (PD-L1) on tumor cells impedes T-cell mediated cytotoxicity through PD-1 engagement, and further exploring the mechanisms regulation of PD-L1 in cancers may enhance the clinical efficacy of PD-L1 blockade. Here, using single-guide RNAs (sgRNAs) screening system, we identify ubiquitin-specific processing protease 2 (USP2) as a novel regulator of PD-L1 stabilization for tumor immune evasion. USP2 directly interacts with and increases PD-L1 abundance in colorectal and prostate cancer cells.

Knockdown LIMP2 inhibits colorectal cancer cells migration, invasion, and metastasis.

Colorectal cancer (CRC) is a common malignancy worldwide nowadays and liver metastasis is the primary cause of death in patients with CRC. Although lysosomal integral membrane protein 2 (LIMP2) has been reported to play important roles in gastric cancer and prostate cancer, its role in CRC remains unclear. The aim of this study was to investigate the function of LIMP2 in CRC invasion and migration, along with the potential underlying molecular mechanisms.

RBFOX2/GOLIM4 Splicing Axis Activates Vesicular Transport Pathway to Promote Nasopharyngeal Carcinogenesis.

20-30% of patients with nasopharyngeal carcinoma (NPC) develop distant metastasis or recurrence leading to poor survival, of which the underlying key molecular events have yet to be addressed. Here alternative splicing events in 85 NPC samples are profiled using transcriptome analysis and it is revealed that the long isoform of GOLIM4 (-L) with exon-7 is highly expressed in NPC and associated with poor prognosis. Lines of evidence demonstrate the pro-tumorigenic function of GOLIM4-L in NPC cells.

Identification of Multi-Class Drugs Based on Near Infrared Spectroscopy and Bidirectional Generative Adversarial Networks.

Drug detection and identification technology are of great significance in drug supervision and management. To determine the exact source of drugs, it is often necessary to directly identify multiple varieties of drugs produced by multiple manufacturers. Near-infrared spectroscopy (NIR) combined with chemometrics is generally used in these cases.

Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome-Wide Association Study in Multiple Cohorts.

Germline polymorphisms are linked with differential survival outcomes in cancers but are not well studied in nasopharyngeal carcinoma (NPC). Here, a two-phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China.

Effect of abscisic acid (ABA) and chitosan/nano-silica/sodium alginate composite film on the color development and quality of postharvest Chinese winter jujube (Zizyphus jujuba Mill. cv. Dongzao).

The color change of the jujube fruit after harvest is used as a quality indicator. The effects of abscisic acid (ABA) and a chitosan/nano-silica/sodium alginate composite film on the color development and qualitative properties of harvested jujube in cold storage were investigated. The results indicate that a composite film could prolong the shelf life of post-harvested winter jujube for approximately 1 month, while the ABA treatment induced ripening and reduced the quality.

LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation.

The RIG-I-like receptors (RLRs) are critical for protection against RNA virus infection, and their activities must be stringently controlled to maintain immune homeostasis. Here, we report that leucine-rich repeat containing protein 25 (LRRC25) is a key negative regulator of RLR-mediated type I interferon (IFN) signaling. Upon RNA virus infection, LRRC25 specifically binds to ISG15-associated RIG-I to promote interaction between RIG-I and the autophagic cargo receptor p62 and to mediate RIG-I degradation via selective autophagy.

LRRC25 Functions as an Inhibitor of NF-κB Signaling Pathway by Promoting p65/RelA for Autophagic Degradation.

Nuclear factor κB (NF-κB) is a family of critical transcription factors that play a critical role in innate immune responses and inflammation, yet the molecular mechanisms responsible for its tight regulation is not fully understood. In this study, we identified LRRC25, a member of leucine-rich repeat (LRR)-containing protein family, as a negative regulator in the NF-κB signaling pathway. Ectopic expression of LRRC25 impaired NF-κB activation, whereas knockout of LRRC25 potentiated NF-κB activation and enhanced the production of inflammatory cytokines.

[Drug Discrimination Method Based on Near Infrared Reflectance Spectrum and Balance Cascading Sparse Representation Based Classification].

The combination of near infrared spectrum and pattern recognition methods has a wide application prospect in rapid and nondestructive supervision and management of drugs. The traditional identification methods regard the smallest error rate as the goal while the imbalance of classes is ignored. This makes the positive class is overwhelming covered by the negative class and reduces its effect for the classifier, so that the classification results tend to recognize the negative class correctly, which severely affects the identification accuracy.

[Study on the Selection of Parameters for Evaluating Drug NIR Universal Quantitative Models].

In order to find out the optimum combination of the evaluation parameters for the selection of the best drug near infrared (NIR) universal quantitative model during model optimization, 13 common evaluation parameters of NIR quantitative models were collected and arranged from commercial chemometrics software or References based on the requirements of validation of quantitative analytical procedures of ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use). Then all these parameters of 92 drug NIR universal quantitative models were calculated and analyzed. By studying the correlation of these parameters, the optimum combination of evaluation parameters for drug NIR universal quantitative models was determined.

[Construction of the quantitative structure retention relationship of cefdinir related substances].

The molecular descriptors of impurities with known structure in cefdinir were calculated, selected and associated with the chromatographic retention behavior to establish a model. This quantitative structure retention relationships (QSRR) model for the related substances of cefdinir was established under specific chromatographic condition and verified by other impurities. 12 molecular descriptors were used to establish the QSRR model, F_AFRBWF, Blbn_J, SsCH3, SssCH2, SsNH2, SssNH, SssS, SHdCH2, EEM_AFc, EEM_AFpl, EEM_XFpl and Pi_MaxQ.

[Update of near-infrared models for testing ceftazidime, water and arginine in ceftazidime for injection].

Unlabelled: To find a more reasonable index to decide whether the universal quantitative NIR model needs to be updated and to develop a general method to update universal quantitative NIR models, the quantitative models for testing ceftazidime, water and arginine contents in ceftazidime for injection were taken as example. The study was performed by analyzing the similarity between new sample spectra and the training set spectra of the original models. At first, new samples of ceftazidime for injection were divided into five groups by cluster analysis.

Identification of a new isomer from a reversible isomerization of ceftriaxone in aqueous solution.

A reversible isomerization of ceftriaxone in aqueous solution was observed, and the structure of the isomer was determined by mass spectrometry and various 1D and 2D NMR techniques. The mechanism of isomerization was also discussed. Finally, molecular docking simulations were performed and the antimicrobial activities of the isomers were measured.

Isolation, identification and characterization of related substances in furbenicillin.

Furbenicillin is a broad-spectrum semisynthetic penicillin with strong antibacterial activity against Gram-negative bacteria. In this study, three impurities in furbenicillin, including an unknown epimer, were determined. On the basis of a complete analysis of the spectrum (MS, (1)H,(13)C, 2D NMR and CD) and the results of chemical methods, the unknown epimer impurity was identified as 10-epi-furbenicillin (impurity 1).

[Research progress in using near infrared for monitoring drug quality in domestic circulation].

Drugs are special goods that are directly related to public health, so their quality should be monitored in any link of their whole lifecycle. With nondestructive, rapid and environmentally friendly characteristics, near infrared technique is highly suitable for monitoring drug quality in the open market as well as the distribution channels. The present paper reviewed the current situation (analytical objects, methods and instruments) about the application of near infrared spectroscopy in monitoring the quality of the final drug products, Chinese crude drug or decoction pieces in domestic circulation since 1997, expounded the unsolved problems and future prospects.

Rapid identification of illegal synthetic adulterants in herbal anti-diabetic medicines using near infrared spectroscopy.

We created a rapid detection procedure for identifying herbal medicines illegally adulterated with synthetic drugs using near infrared spectroscopy. This procedure includes a reverse correlation coefficient method (RCCM) and comparison of characteristic peaks. Moreover, we made improvements to the RCCM based on new strategies for threshold settings.

A training set selection strategy for a universal near-infrared quantitative model.

The purpose of this article is to propose an empirical solution to the problem of how many clusters of complex samples should be selected to construct the training set for a universal near infrared quantitative model based on the Naes method. The sample spectra were hierarchically classified into clusters by Ward's algorithm and Euclidean distance. If the sample spectra were classified into two clusters, the 1/50 of the largest Heterogeneity value in the cluster with larger variation was set as the threshold to determine the total number of clusters.

[Feasibility of the extended application of near infrared universal quantitative models].

Construction of a successful near infrared analysis model is a complex task. It spends a lot of manpower and material resources, and is restricted by sample collection and model optimization. So it is important to study on the extended application of the existing near infrared (NIR) models.

Construction of identification system for non-invasive analysis of macrolides tablets using near infrared diffuse reflectance spectroscopy.

A NIR identification system consisting of two proposed models (Model I and Model II) has been developed for the analysis of 10 different products of macrolides tablets from different manufacturers. A total of 253 batches of the 10 products from 93 manufacturers in China were used for the system construction. First, a universal classification model (termed Model I) was constructed for 10 products using all the samples with the objective to distinguish the macrolides homologues which have the similar molecular structures.

Berberine analogues as a novel class of the low-density-lipoprotein receptor up-regulators: synthesis, structure-activity relationships, and cholesterol-lowering efficacy.

Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed, semisynthesized, and evaluated for their up-regulatory activity on the low-density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i) the methylenedioxy group at the 2- and 3-position is an essential element to keep the activity, (ii) the 7-position quaternary ammonium and planar structure of the compound are activity-required, and (iii) addition of electron-donating groups at the 7- or 13-position reduced the activity. Of the compound 1 analogues, compound 2 exhibited an increased activity on LDLR expression compared to 1.