Bisubstrate inhibitors of 6-hydroxymethyl-7,8-dihydroptein pyrophosphokinase: Toward cell permeability.

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate biosynthesis pathway. It catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). HPPK is essential for microorganisms but is absent in mammals.

Inhibition of HIV-1 release by ADAM metalloproteinase inhibitors.

HIV-1 gp120 glycan binding to C-type lectin adhesion receptor L-selectin/CD62L on CD4 T cells facilitates viral attachment and entry. Paradoxically, the adhesion receptor impedes HIV-1 budding from infected T cells and the viral release requires the shedding of CD62L. To systematically investigate CD62L-shedding mediated viral release and its potential inhibition, we screened compounds specific for serine-, cysteine-, aspartyl-, and Zn-dependent proteases for CD62L shedding inhibition and found that a subclass of Zn-metalloproteinase inhibitors, including BB-94, TAPI, prinomastat, GM6001, and GI25423X, suppressed CD62L shedding.

Antibiotic resistance profile of to 14 antibiotics: a multicenter study in Fujian, China.

Background And Aim: Efficacy of . ) eradication is related to the local antimicrobial resistance epidemiology. We aimed to investigate the antibiotic resistance of in Fujian, China.

Factors Influencing the Sharing of Personal Health Data Based on the Integrated Theory of Privacy Calculus and Theory of Planned Behaviors Framework: Results of a Cross-Sectional Study of Chinese Patients in the Yangtze River Delta.

Background: The health care system in China is fragmented, and the distribution of high-quality resources remains uneven and irrational. Information sharing is essential to the development of an integrated health care system and maximizing its benefits. Nevertheless, data sharing raises concerns regarding the privacy and confidentiality of personal health information, which affect the willingness of patients to share information.

Crystal structure of Escherichia coli thiamine pyrophosphate-sensing riboswitch in the apo state.

The thiamine pyrophosphate (TPP)-sensing riboswitch is one of the earliest discovered and most widespread riboswitches. Numerous structural studies have been reported for this riboswitch bound with various ligands. However, the ligand-free (apo) structure remains unknown.

Structure of dihydroneopterin aldolase suggests a fragment-based strategy for isozyme-specific inhibitor design.

Dihydroneopterin aldolase (DHNA) is essential for folate biosynthesis in microorganisms. Without a counterpart in mammals, DHNA is an attractive target for antimicrobial agents. infection occurs in human stomach of over 50% of the world population, but first-line therapies for the infection are facing rapidly increasing resistance.

Prognosis of Congenital Anomalies in Conceptions Following Fertilization: A Multicenter Retrospective Cohort Study in China.

Background: Conceptions following fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have an increased risk of congenital anomalies. Few studies have explored the prognosis of fetuses with congenital anomalies. This study aimed to investigate the prevalence and prognosis of congenital anomalies in IVF/ICSI pregnancies, and to analyze the influencing factors contributing to poor prognosis.

Structural basis for Dicer-like function of an engineered RNase III variant and insights into the reaction trajectory of two-Mg-ion catalysis.

The RNase III family of dsRNA-specific endonucleases is exemplified by prokaryotic RNase III and eukaryotic Rnt1p, Drosha, and Dicer. Structures of RNase III (AaRNase III) and Rnt1p (ScRnt1p) show that both enzymes recognize substrates in a sequence-specific manner and propel RNA hydrolysis by two-Mg-ion catalysis. Previously, we created an RNase III variant (EcEEQ) by eliminating the sequence specificity via protein engineering and called it bacterial Dicer for the fact that it produces heterogeneous small interfering RNA cocktails.

Effect of PM exposure on Vitamin D status among pregnant women: A distributed lag analysis.

Background: Serum vitamin D levels are associated with exposure to air pollution, however, the lagged effect of exposure to air pollution remains unknown in pregnant women.

Methods: Pregnant women who delivered at a maternity center in Shanghai, China, from 2015 to 2019 were included in the present study. The concentration of particulate matter 2.

Associations of PM exposure with blood glucose impairment in early pregnancy and gestational diabetes mellitus.

Exposure to fine particulate matter (PM) during pregnancy has been linked to the risk of gestational diabetes mellitus (GDM), while conclusions are inconsistent. In this study we aimed to estimate the effects of prenatal PM exposure with blood glucose in early pregnancy and the GDM risk. Participants were recruited from the SH-IPMCH-BTH cohort (n = 41,929), a study of air pollution and birth outcome.

Minimum inhibitory concentrations of commonly used antibiotics against Helicobacter Pylori: A multicenter study in South China.

Aim: To determine the minimum inhibitory concentrations (MICs) of commonly used antibiotics against Helicobacter Pylori (H. pylori) in South China and compare their resistance rates by using EUCAST breakpoints and other breakpoints.

Methods: Patients who had not previously received H.

Influence of ambient temperature and diurnal temperature variation on the premature rupture of membranes in East China: A distributed lag nonlinear time series analysis.

Background: Extreme ambient temperature has an adverse effect on pregnancy outcomes, but the conclusions have been inconsistent. The influence of ambient temperature and diurnal temperature variation on the premature rupture of membranes (PROM) needs further study.

Methods And Findings: The daily data of PROMs, daily meteorological and air pollutant were obtained.

Dual-Target Inhibitors of the Folate Pathway Inhibit Intrinsically Trimethoprim-Resistant DfrB Dihydrofolate Reductases.

Trimethoprim (TMP) is widely used to treat infections in humans and in livestock, accelerating the incidence of TMP resistance. The emergent and largely untracked type II dihydrofolate reductases (DfrBs) are intrinsically TMP-resistant plasmid-borne Dfrs that are structurally and evolutionarily unrelated to chromosomal Dfrs. We report kinetic characterization of the known DfrB family members.

Overproduction of a Dominant Mutant of the Conserved Era GTPase Inhibits Cell Division in Escherichia coli.

Cell growth and division are coordinated, ensuring homeostasis under any given growth condition, with division occurring as cell mass doubles. The signals and controlling circuit(s) between growth and division are not well understood; however, it is known in that the essential GTPase Era, which is growth rate regulated, coordinates the two functions and may be a checkpoint regulator of both. We have isolated a mutant of Era that separates its effect on growth and division.

Structure and activity of PPX/GppA homologs from Escherichia coli and Helicobacter pylori.

Rapid adaptation to environmental changes is crucial for bacterial survival. Almost all bacteria possess a conserved stringent response system to prompt transcriptional and metabolic responses toward stress. The adaptive process relies on alarmones, guanosine pentaphosphate (pppGpp), and tetraphosphate (ppGpp), to regulate global gene expression.

The mechanism of RNA duplex recognition and unwinding by DEAD-box helicase DDX3X.

DEAD-box helicases (DDXs) regulate RNA processing and metabolism by unwinding short double-stranded (ds) RNAs. Sharing a helicase core composed of two RecA-like domains (D1D2), DDXs function in an ATP-dependent, non-processive manner. As an attractive target for cancer and AIDS treatment, DDX3X and its orthologs are extensively studied, yielding a wealth of biochemical and biophysical data, including structures of apo-D1D2 and post-unwound D1D2:single-stranded RNA complex, and the structure of a D2:dsRNA complex that is thought to represent a pre-unwound state.

The molecular mechanism of dsRNA processing by a bacterial Dicer.

Members of the ribonuclease (RNase) III family regulate gene expression by processing dsRNAs. It was previously shown that Escherichia coli (Ec) RNase III recognizes dsRNA with little sequence specificity and the cleavage products are mainly 11 nucleotides (nt) long. It was also shown that the mutation of a glutamate (EcE38) to an alanine promotes generation of siRNA-like products typically 22 nt long.

Cytomegalovirus infective gastritis in an immunocompetent host misdiagnosed as malignancy on upper gastrointestinal endoscopy: a case report and review of literature.

Primary cytomegalovirus (CMV) infection is rare in immunocompetent hosts and generally asymptomatic. CMV infective gastritis in patients without immunosuppression is very unusual. A 44-year-old man presented with complaints of intermittent epigastric pain.

Structure and function of Rnt1p: An alternative to RNAi for targeted RNA degradation.

The double-stranded RNA-binding protein (dsRBP) family controls RNA editing, stability, and function in all eukaryotes. The central feature of this family is the recognition of a generic RNA duplex using highly conserved double-stranded RNA-binding domain (dsRBD) that recognizes the characteristic distance between the minor grooves created by the RNA helix. Variations on this theme that confer species and functional specificities have been reported but most dsRBPs retain their capacity to bind generic dsRNA.

Design, synthesis, and anticancer activity evaluation of irreversible allosteric inhibitors of the ubiquitin-conjugating enzyme Ube2g2.

The RING finger-dependent ubiquitin ligase (E3) gp78, known as the tumor autocrine motility factor receptor, contributes to tumor progression. The protein interacts with its cognate ubiquitin-conjugating enzyme (E2), Ube2g2, its RING domain and a unique region called G2BR that strongly binds to E2. The binding of G2BR to Ube2g2 allosterically enhances the binding of RING to E2, and the binding of RING triggers the departure of G2BR from E2 also in an allosteric fashion.

Nitrogen dioxide air pollution and preterm birth in Shanghai, China.

Background: Nitrogen dioxide (NO) is a typical indicator of traffic-related air pollution, and few studies with exposure assessment of high resolution have been conducted to explore its association with preterm birth in China.

Objectives: To investigate the association between NO exposure based on a land use regression (LUR) model and preterm birth in Shanghai, China.

Methods: A retrospective cohort study was performed among 25,493 singleton pregnancies in a major maternity hospital in Shanghai, China, from 2014 to 2015.