Integrating computational and experimental approaches in discovery and validation of MmpL3 pore domain inhibitors for specific labelling of Mycobacterium tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to pose a significant global health threat. Identifying new druggable targets is crucial for the advancement of drug development. Equally critical is the development of precise methods for monitoring Mtb to effectively combat this disease.

Rational Design of a Novel Class of Human ClpP Agonists through a Ring-Opening Strategy with Enhanced Antileukemia Activity.

The activation of Casein lysing protease P (HsClpP) by a chemical or genetic strategy has been proved to be a new potential therapy in acute myeloid leukemia (AML). However, limited efficacy has been achieved with classic agonist imipridone . Here, a novel class of HsClpP agonists is designed and synthesized using a ring-opening strategy based on the lead compound reported in our previous study.

Discovery and Mechanistic Study of Novel ClpP1P2 Inhibitors.

Caseinolytic protease P (ClpP) responsible for the proteolysis of damaged or misfolded proteins plays a critical role in proteome homeostasis. MtbClpP1P2, a ClpP enzyme complex, is required for survival in , and it is therefore considered as a promising target for the development of antituberculosis drugs. Here, we discovered that cediranib and some of its derivatives are potent MtbClpP1P2 inhibitors and suppress growth.

Development speed of sibling embryo positively reflects live birth rate after fresh day 3 embryo transfer.

The ability of sibling embryos to form blastocysts may reflect the developmental potential of the embryos that were transferred into the uterus. The purpose of the study was to investigate whether the development speed of sibling embryos positively reflects the live birth rate following fresh embryo transfer. We examined 1262 cycles of women who underwent day 3 (D3) cleavage embryo transfer in the Peking Union Medical College Hospital in 2015-2020, who were divided into three groups (D5, D5 + D6, and D6) according to blastocyst formation.

Single-dose administration of a short-acting gonadotropin-releasing hormone agonist does not affect cycle outcome in frozen-thawed embryo transfer cycles.

Objective: This prospective study aimed to assess the effect of short-acting gonadotropin-releasing hormone agonist (GnRHa) administration on pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles.

Methods: Patients who planned to have FET in Peking Union Medical College Hospital (China) were recruited for this study and randomly assigned into two groups. Patients in the experimental group (n = 460) received triptorelin acetate on the day of embryo transfer along with routine luteal support.

Antimicrobial activities of a small molecule compound II-6s against oral streptococci.

: The side effects of present antimicrobials like chlorhexidine (CHX) and the emergence of drug resistance necessitate the development of alternative agents to control dental caries. : This study developed a novel small molecule, namely II-6s, and investigated its antimicrobial activities against common oral streptococci associated with dental caries. : The susceptibility of streptococci to II-6s was evaluated by the microdilution method, time-kill assay and scanning electron microscopy.

Human ClpP protease, a promising therapy target for diseases of mitochondrial dysfunction.

Human caseinolytic protease P (HsClpP), an ATP-dependent unfolding peptidase protein in the mitochondrial matrix, controls protein quality, regulates mitochondrial metabolism, and maintains the integrity and enzyme activity of the mitochondrial respiratory chain (RC). Studies show that abnormalities in HsClpP lead to mitochondrial dysfunction and various human diseases. In this review, we provide a comprehensive overview of the structure and biological function of HsClpP, and the involvement of its dysexpression or mutation in mitochondria for a panel of important human diseases.

Structure-activity relationship study of DEL-22379: ERK dimerization inhibitors with increased safety.

Aberrant activation of ERK signaling pathway usually leads to oncogenesis, and small molecular agents targeting this pathway are impeded by the emergence of drug resistance due to reactivation of ERK signaling. Compound DEL-22379 has been reported to inhibit ERK dimerization which was unaffected by drug-resistant mechanism reactivating the ERK signaling. Here, we discussed a structure-activity relationship study of DEL-22379.

Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers and .

Caseinolytic protease P (ClpP) is considered as a promising target for the treatment of infections. In an unbiased screen of 2632 molecules, a peptidomimetic boronate, MLN9708, was found to be a potent suppressor of ClpP function. A time-saving and cost-efficient strategy integrating position scanning, multistep miniaturized synthesis, and bioactivity testing was deployed for optimization of this hit compound and led to fast exploration of structure-activity relationships.

Efficient discovery of novel antimicrobials through integration of synthesis and testing in crude ribosome extract.

By coupling in situ [2+3] Huisgen cycloaddition with an in vitro transcription/translation luminescence assay in a crude ribosomal extract, a robust and accurate high-throughput platform was successfully developed and applied for efficient identification of novel structural types of ribosomal inhibitors with antimicrobial activity against drug-resistant bacteria.

A Novel Small Molecule, ZY354, Inhibits Dental Caries-Associated Oral Biofilms.

Biofilm control is a critical approach to the better management of dental caries. Antimicrobial small molecules have shown their potential in the disruption of oral biofilm and control of dental caries. The objectives of this study were to examine the antimicrobial activity and cytotoxicity of a newly designed small-molecule compound, ZY354.

Discovery of hybrids of indolin-2-one and nitroimidazole as potent inhibitors against drug-resistant bacteria.

With antibiotics resistance developing rapidly, new antibacterial agents are needed to be discovered. We readily synthesized 11 indolin-2-one compounds and found a hybrid of indolin-2-one and nitroimidazole 3-((1-methyl-5-nitro-1H-imidazol-2-yl)methylene)indolin-2-one to be effective on Staphylococcus aureus strains. Six derivatives of this compound were further designed and synthesized in order to enhance its efficacy.

Effects of fifth day (D5) or sixth day (D6) frozen-thawed blastocysts on neonatal outcomes.

This study aimed to compare the neonatal outcomes of transplanted fifth day (D5) or sixth day (D6) frozen-thawed blastocysts, aiming to provide guidance when choosing blastocyst recovery methods. The clinical data of 1109 patients that were performed for recovered blastocyst transplantation, as well as the data of 515 patients who had already delivered were analyzed retrospectively. The patients were divided into single- or twins-birth groups according to blastocyst formation time (D5 or D6) and the number of fetus(es).

Factors Associated with Effectiveness of Treatment and Reproductive Outcomes in Patients with Thin Endometrium Undergoing Estrogen Treatment.

Background: Thin endometrium is associated with poor reproductive outcomes; estrogen treatment can increase endometrial thickness (EMT). The aim of this retrospective cohort study was to investigate the factors influencing the effectiveness of estrogen treatment and reproductive outcomes after the treatment in patients with thin endometrium.

Methods: Relevant clinical data of 101 patients with thin endometrium who had undergone estrogen treatment were collected.

Pregnancy Outcomes of In Vitro Fertilization with or without Ovarian Hyperstimulation Syndrome: A Retrospective Cohort Study in Chinese Patients.

Background: The effect of ovarian hyperstimulation syndrome (OHSS) on pregnancy outcomes of in vitro fertilization (IVF) patients is still ambiguous. This study aimed to analyze pregnancy outcomes of IVF with or without OHSS in Chinese patients.

Methods: A retrospective cohort study was undertaken to compare pregnancy outcomes between 190 women with OHSS and 197 women without OHSS.

[Evaluation the efficacy and safety of estradiol and drospirenone tablets in the treatment of menopausal symptoms among postmenopausal Chinese healthy women:a randomized, multi-center, double-blind, placebo-controlled clinical study].

Objective: To study the efficacy and safety of estradiol and drospirenone tablets (Angeliq) in treatment of menopausal symptoms among postmenopausal Chinese healthy women.

Methods: Total 244 postmenopausal Chinese healthy women who had moderate to severe hot flushes were randomly assigned into estradiol and drospirenone (observation group, n = 183) or placebo group (n = 61) by the ratio of 3:1 for 16 weeks in this randomized multi-center double-blind placebo-controlled study. During the trial, the follow-up visits were conducted at week 4, 8, 12, 16 of treatment and 2 weeks after treatment respectively.

Gender verification in athletes with disorders of sex development.

Disorders of sex development (DSD) are most controversial issue in gender verification of athletes. To make a more scientific, accurate and humanitarian decision for athletes is the target of gender verification. In this article, we evaluate the used methods of gender verification in athletes, recommend a useful simplified classification of DSD and propose a comprehensive etiological diagnostic system based on this classification for gender verification in athletes.

[Identification of potential neoplastic risk in gonadal development abnormality with Y chromosome of 79 cases].

Objective: To identify the potential neoplastic risk in gonadal development abnormality with Y chromosome.

Methods: Inquiries about the illness history were made. Lymphocyte chromosomal karyotype of peripheral blood was analyzed.

Social and behavior factors related to aged Chinese women with osteoporosis.

Background: Women aged >or=65 years are screened routinely for osteoporosis in the developed world and identifying risk factors for osteoporosis should be highlighted in developing countries such as the People's Republic of China. In the present study, possible factors related to the occurrence of primary osteoporosis in aged Chinese women were explored.

Methods: On appointed attendance at a menopausal outpatient clinic, generally healthy Chinese women aged >or=65 years were requested to complete a self-administered questionnaire.

Changes of total content of serum magnesium in elderly Chinese women with osteoporosis.

Objective: To explore whether the serum levels of magnesium (Mg) and calcium (Ca) differ between osteoporotic and nonosteoporotic elderly Chinese women.

Methods: Using WHO classification criteria based on bone mineral density (BMD), general healthy Chinese women older than 65 yr were classified as osteoporosis (OP), osteopenia, and normal group according to the T-score of the femur neck. Then their physical characteristics, serum levels of magnesium (sMg), calcium (sCa), and other biochemical measurements were analyzed.

[Germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in China Han people].

Objective: To detect BRCA1 and BRCA2 gene germline mutation in the Chinese breast cancer families.

Methods: Samples of peripheral blood were collected to prepare genomic DNA by conventional techniques from 15 inherited breast cancer patients from 14 breast cancer families, 76 sporadic breast cancer patients, and 100 healthy controls based on informed consent. Exons 4, 8, 11 and 18 - 20 of BRCA1, and exons 1 - 14, 17 - 24 and 27 of BRCA2, were analyzed using DNA direct sequencing.

[Monitoring the breast changes of Chinese postmenopausal women under long-term hormone replacement therapy by mammary ultrasonography].

Objective: To investigate the effects of long-term hormone replacement therapy (HRT) on the breasts of postmenopausal women using mammary ultrasonography.

Methods: An open randomized clinical study was designed. The percutaneous estradiol gel was used in a cyclic regimen combined with micronized progesterone (MP) or medroxyprogesterone acetate (MPA).