Special Issue "Drug Discovery and Application of New Technologies".

Historically, drug discovery and development have proven to be time-consuming and costly, with the process averaging around 15 years and costing approximately USD 2 billion to bring a new small-molecule drug to market [...

USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination.

Background/aims: Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific proteinase 29 (USP29) plays pivotal roles in hepatic ischemia‒reperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression.

Evaluation of tubal patency based on peak injection pressure in four-dimensional hysterosalpingo-contrast sonography among infertile females: a preliminary study.

Background: Although the application of four-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy) has relatively good diagnostic accuracy for assessing the patency of the fallopian tubes, the evaluation process mainly relies on morphological findings of the fallopian tubes and pelvic cavity. The purpose of this study was to explore the relationship of peak injection pressure during 4D-HyCoSy and tubal patency to provide a quantitative indicator for the evaluation of fallopian tube patency.

Methods: This study included infertile patients who underwent 4D-HyCoSy and laparoscopic chromopertubation (LC) between 2020 and 2022, with LC serving as the reference test for assessing tubal patency.

Nongestational ovarian choriocarcinoma with bilateral teratoma: A rare case report and literature review.

Introduction: Trophoblastic neoplasms are often associated with pregnancy, and nongestational trophoblastic neoplasms are extremely rare. Nongestational ovarian choriocarcinoma (NGCO) is a highly aggressive germ cell-derived tumor frequently presenting with early hematogenous metastasis.

Patient Concerns: Herein, we report a case of a 28-year-old unmarried woman with regular menstruation who experienced vaginal bleeding 1 week after her last menstrual cycle.

PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer.

Neoadjuvant chemotherapy (NACT) is a therapeutic option for locally advanced cervical cancer (LACC) patients. This study was aimed to identify potential liquid biopsy biomarkers to monitor the NACT response. Through targeted next-generation sequencing (NGS) analysis of circulating tumor DNA (ctDNA) and tumor tissue DNA (ttDNA) taken from LACC patients undergoing platinum-based NACT, 64 genes with mutations emerge during NACT in the non-responders but none in the responders.

Dynamic and Polarization-Independent Wavefront Control Based on Hybrid Topological Metasurfaces.

Exceptional points (EPs), known as non-Hermitian singularities, have been observed and investigated in parity-time symmetric metasurfaces. However, the chirality and tunability in non-Hermitian metasurfaces still need to be explored. Here, we propose a dynamic topological metasurface with the meta-atom consisting of two orthogonally oriented nanorods, which are placed on the phase change material GeSbTe (GST) and SiO dielectric layer, respectively.

Ectopic expression of SaCTP3 from the hyperaccumulator Sedum alfredii in sorghum increases Cd accumulation for phytoextraction.

The Cd tolerance protein SaCTP3, which responds to Cd stress, was identified in Sedum alfredii; however, how to improve the efficiency of phytoremediation of Cd-contaminated soil using the CTP gene remains unknown. In this study, the phytoremediation potential of SaCTP3 of Sedum alfredii was identified. In the yeast Cd-sensitive strain Δycf1 overexpressing SaCTP3, the accumulation of Cd was higher than that in the Δycf1 strain overexpressing an empty vector.

Hypertension and hyperglycaemia are positively correlated with local invasion of early cervical cancer.

Background: Metabolic disorders are involved in the development of numerous cancers, but their association with the progression of cervical cancer is unclear. This study aims to investigate the association between metabolic disorders and the pathological risk factors and survival in patients with early cervical cancer.

Methods: Patients with FIGO IB1 (2009) primary cervical cancer who underwent radical hysterectomy and systematic pelvic lymph node dissection at our institution from October 2014 to December 2017 were included retrospectively.

Biochemical and Structural Characterization of OvoA: A Mononuclear Nonheme Iron Enzyme from for Ovothiol Biosynthesis.

Ovothiol A and ergothioneine are thiol-histidine derivatives with sulfur substitutions at the δ-carbon or ε-carbon of the l-histidine imidazole ring, respectively. Both ovothiol A and ergothioneine have protective effects on many aging-related diseases, and the sulfur substitution plays a key role in determining their chemical and biological properties, while factors governing sulfur incorporation regioselectivities in ovothiol and ergothioneine biosynthesis in the corresponding enzymes (OvoA, Egt1, or EgtB) are not yet known. In this study, we have successfully obtained the first OvoA crystal structure, which provides critical information to explain their C-S bond formation regioselectivity.

An S=1 Iron(IV) Intermediate Revealed in a Non-Heme Iron Enzyme-Catalyzed Oxidative C-S Bond Formation.

Ergothioneine (ESH) and ovothiol A (OSHA) are two natural thiol-histidine derivatives. ESH has been implicated as a longevity vitamin and OSHA inhibits the proliferation of hepatocarcinoma. The key biosynthetic step of ESH and OSHA in the aerobic pathways is the O -dependent C-S bond formation catalyzed by non-heme iron enzymes (e.

Effect of resistance training on lipid profile in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

Objective: Physical exercise decreases cardiovascular risk and can alter the lipid profile in postmenopausal women. Although it is believed that resistance training can potentially decrease serum lipid levels in postmenopausal females, the evidence remains inconclusive. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to clarify the impact of resistance training on the lipid profile in postmenopausal women.

Lysosomal-associated protein transmembrane 5 ameliorates non-alcoholic steatohepatitis by promoting the degradation of CDC42 in mice.

Non-alcoholic steatohepatitis (NASH) has received great attention due to its high incidence. Here, we show that lysosomal-associated protein transmembrane 5 (LAPTM5) is associated with NASH progression through extensive bioinformatical analysis. The protein level of LAPTM5 bears a negative correlation with NAS score.

Quinolines and isoquinolines as HIV-1 inhibitors: Chemical structures, action targets, and biological activities.

Human immunodeficiency virus type 1 (HIV-1), a lentivirus that causes acquired immunodeficiency syndrome (AIDS), poses a serious threat to global public health. Since the advent of the first drug zidovudine, a number of anti-HIV agents acting on different targets have been approved to combat HIV/AIDS. Among the abundant heterocyclic families, quinoline and isoquinoline moieties are recognized as promising scaffolds for HIV inhibition.

Red-to-blue colorimetric probe based on biomass carbon dots for smartphone-integrated optosensing of Cu(II) and L-cysteine.

We constructed a smartphone-integrated optosensor with inexpensive, reversible, environmental friendly, and rapid adsorption to detect Cu(II) and L-cysteine (L-Cys). The key part of this study was to prepare a red-to-blue colorimetric probe from herbaceous andrographis paniculata using one-pot polymerization at room temperature. When Cu(II) existed, the red fluorescence on the surface of the core-shell probe was quenched, while the blue fluorescence of the core did not respond, because the colorimetric probe interacted with the Cu(II) on the surface of red CDs.

Energy-efficient Preparation of Amino and Sulfhydryl Functionalized Biomass Carbon Dots via a Reverse Microemulsion for Specific Recognition of Fe and L-cysteine.

Amino- and sulfhydryl- functionalized biomass carbon dots (BCDs) were prepared by one-pot reverse microemulsion for specific recognition of ferric ions (Fe) and L-cysteine (L-Cys). Green grapefruit peel was used as the carbon source while aminosilane and mercaptosilane were used as N- and S-supplier. Following the adsorption of Fe on the surfaces of BCDs-NH and BCDs-SH, the fluorescence responses was quenched step by step, while adding L-Cys to the BCDs-NH/Fe system restored the fluorescence.

Social and Moral Practices of the Organizations and Employee-Based Brand Equity: Female Digital Labor Perspective.

This study investigates the role of socially responsible management as a significant determining factor for employees' morale engagement (EME), employee vitality (EV), and employee-based brand equity (EBBE). Human resource management policies and strategies are important for addressing the interests of the employees and boosting the overall effectiveness of the organization. To examine this, this study analyzes the role of socially responsible management and organizational morality on EME with the mediation of EV.

Breviscapine alleviates NASH by inhibiting TGF-β-activated kinase 1-dependent signaling.

Background And Aims: NAFLD is a key component of metabolic syndrome, ranging from nonalcoholic fatty liver to NASH, and is now becoming the leading cause of cirrhosis and HCC worldwide. However, due to the complex and unclear pathophysiological mechanism, there are no specific approved agents for treating NASH. Breviscapine, a natural flavonoid prescription drug isolated from the traditional Chinese herb Erigeron breviscapus, exhibits a wide range of pharmacological properties, including effects on metabolism.

Melanoma differentiation-Associated gene 5 protects against NASH in mice.

Background And Aims: NASH is a complicated disease characterized by hepatocyte steatosis, inflammation infiltration, and liver fibrosis. Accumulating evidence suggests that the innate immunity plays a key role in NASH progression. Here, we aimed to reveal the role of melanoma differentiation-associated gene 5 (MDA5, also known as Ifih1), a conventional innate immune regulator following viral infection, in the progression of NASH and investigate its underlying mechanism.

SIMPLE Is an Endosomal Regulator That Protects Against NAFLD by Targeting the Lysosomal Degradation of EGFR.

Background And Aims: NAFLD has become a tremendous burden for public health; however, there is no drug for NAFLD therapy at present. Impaired endo-lysosome-mediated protein degradation is observed in a variety of metabolic disorders, such as atherosclerosis, type 2 diabetes mellitus, and NAFLD. Small integral membrane protein of lysosome/late endosome (SIMPLE) is a regulator of endosome-to-lysosome trafficking and cell signaling, but the role that SIMPLE plays in NAFLD progression remains unknown.

Gastrodin Improves Nonalcoholic Fatty Liver Disease Through Activation of the Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway.

Background And Aims: NASH is currently one of the most common causes of liver transplantation and hepatocellular carcinoma. Thus far, there is still no effective pharmacological therapy for this disease. Recently, Gastrodin has demonstrated hepatoprotective effects in a variety of liver diseases.

The E3 Ubiquitin Ligase Ring Finger Protein 5 Ameliorates NASH Through Ubiquitin-Mediated Degradation of 3-Hydroxy-3-Methylglutaryl CoA Reductase Degradation Protein 1.

Background And Aims: NAFLD is the most prevalent chronic liver disease worldwide, but no effective pharmacological therapeutics are available for clinical use. NASH is the more severe stage of NAFLD. During this progress, dysregulation of endoplasmic reticulum (ER)-related pathways and proteins is one of the predominant hallmarks.

TfOH-Catalyzed [4 + 1] Annulation of -Quinone Methides with α-Aryl Diazoacetates: Straightforward Access to Highly Functionalized 2,3-Dihydrobenzofurans.

We have developed a methodology for the greatly efficient construction of significant 2,3-dihydrobenzofuran scaffolds bearing a quaternary carbon center at the C2 position by means of [4 + 1] annulation reactions between -quinone methides and α-aryl diazoacetates as C1 synthons through organocatalysis by readily accessible TfOH catalyst under mild and transition metal-free conditions. This metal-free protocol furnishes an operationally simple and swift process for the free assembly of diverse highly functionalized 2,3-dihydrobenzofurans and also features broad substrate scope, excellent functional group compatibility, and environmental friendliness. Mechanistic investigation suggested that the reaction undergoes a rapid cascade protonation/intermolecular Michael addition/intramolecular substitution process.

[Problems and countermeasures in clinical studies on acupuncture and moxibustion in course of developing ].

To explore the problems and countermeasures existing in acupuncture and moxibustion clinical studies, in the perspective of the key steps of . The problems include: confusion of disease names and disunity of diagnostic criteria, inadequate refined clinical problems that need to be addressed, lack of targeted analysis of efficacy evaluation index, lack of adequate research on common acupuncture, difficulty to balance innovation and universality, lack of emphasis on the importance of timing for acupuncture, lack of attention to healthy lifestyles and self-care. We suggests that the disease name and diagnostic criteria should refer to the authoritative standards; the clinical study design should based on the realistic clinical problems; the efficacy evaluation index should based on the clinical needs and be analyzed targetedly; further research on common acupuncture or therapy should be carried out.