Effects of Diet Supplemented With Hydrolyzable Tannin on the Growth Performance, Antioxidant Capacity, and Muscle Nutritional Quality of Juvenile .

In this study, four groups of diet were prepared, with eel commercial diet without hydrolyzable tannin (HT) as the control group (H0), and the other three groups were fed with diet containing 0.05% (H1), 0.1% (H2), and 0.

Design, synthesis and anticancer activity evaluation of 4-(3-1H-indazolyl)amino quinazoline derivatives as PAK4 inhibitors.

A novel series of 4-(3-1H-indazolyl)amino quinazoline derivatives were developed as PAK4 inhibitors based on a scaffold hopping strategy. Compounds 27e, 27g, 27i and 27j were found to exhibit potent inhibitory activity against PAK4 (IC = 10, 13, 11 and 9 nM, respectively). Subsequent cellular assay demonstrated that compound 27e possessed the strongest antiproliferative activity against A549 cells with an IC value of 0.

A DddA ortholog-based and transactivator-assisted nuclear and mitochondrial cytosine base editors with expanded target compatibility.

Bacterial double-stranded DNA (dsDNA) cytosine deaminase DddA-derived cytosine base editor (DdCBE) and its evolved variant, DddA11, guided by transcription-activator-like effector (TALE) proteins, enable mitochondrial DNA (mtDNA) editing at TC or HC (H = A, C, or T) sequence contexts, while it remains relatively unattainable for GC targets. Here, we identified a dsDNA deaminase originated from a Roseburia intestinalis interbacterial toxin (riDddA) and generated CRISPR-mediated nuclear DdCBEs (crDdCBEs) and mitochondrial CBEs (mitoCBEs) using split riDddA, which catalyzed C-to-T editing at both HC and GC targets in nuclear and mitochondrial genes. Moreover, transactivator (VP64, P65, or Rta) fusion to the tail of DddA- or riDddA-mediated crDdCBEs and mitoCBEs substantially improved nuclear and mtDNA editing efficiencies by up to 3.

Cas9-orthologue-mediated cytosine and adenine base editors recognizing NNAAAA PAM sequences.

CRISPR/Cas9 system has been applied as an effective genome-targeting technology. By fusing deaminases with Cas9 nickase (nCas9), various cytosine and adenine base editors (CBEs and ABEs) have been successfully developed that can efficiently induce nucleotide conversions and install pathogenic single nucleotide variants (SNVs) in cultured cells and animal models. However, the applications of BEs are frequently limited by the specific protospacer adjacent motif (PAM) sequences and protein sizes.

Dual guide RNA-mediated concurrent C&G-to-T&A and A&T-to-G&C conversions using CRISPR base editors.

Base editing tools enable precise genome modifications, disease modeling, and promising gene therapy. However, many human genetic diseases are elicited by multi-nucleotide variants (MNVs) with heterogeneous substitutions at the same genomic locus. Based on the adenine and cytosine base editors, dual base editors that can catalyze concurrent C-to-T and A-to-G editing have been developed, while simultaneous C&G-to-T&A and A&T-to-G&C conversions on the same allele have not been achieved at the desirable site.

Synthesis and anticancer activity evaluation of 7-oxygen-substituted and 8,17-epoxydized 1,2-didehydro-3-ox-14-deoxyandrographolide derivatives.

Two novel series of 1,2-didehydro-7-hydroxy-3-ox-14-deoxyandrographolide and 1,2-didehydro-8,17-epoxy-3-ox-14-deoxyandrographolide derivatives were designed, synthesized and evaluated for their cytotoxic activity in vitro against two human cancer cell lines HCT-116 (human colon cancer) and MCF-7 (human breast cancer). Most tested compounds, especially those of the first series, displayed better inhibitory activity on both HCT-116 and MCF-7 cells than andrographolide. HCT-116 cells were found to be more sensitive to tested compounds than MCF-7, and compound 13b exhibited the most potent activity against HCT-116, with an IC value of 7.

[Effect of Mobile Health for Standardized Management on Women with Gestational Diabetes Mellitus].

Objective To explore the performance of mobile health platform for standardized management of pregnant women with gestational diabetes mellitus(GDM). Methods A randomized controlled trial was conducted,in which 295 women with GDM were randomized into two groups(traditional management group and mobile health management group)by a computer-generated sequence.The traditional management group accepted standardized GDM management,and the mobile health management group was supplemented by mobile health management based on the standardized management.

Design, synthesis, and anticancer evaluation of novel andrographolide derivatives bearing an α,β-unsaturated ketone moiety.

A series of 1,2-didehydro-3-ox-andrographolide derivatives based on two Michael acceptors were designed, synthesized and evaluated for their anticancer activity against two human cancer cell lines (HCT116 and MCF-7). All tested compounds exhibited significant growth inhibitory effect on HCT116 and moderate to good inhibitory effect on MCF-7 cell proliferation. Compound 10b displayed the best inhibitory activities against both HCT116 and MCF-7 cell lines, with IC values of 2.

Effect of mobile health based peripartum management of gestational diabetes mellitus on postpartum diabetes: A randomized controlled trial.

Aims: To investigate the effects of mobile health based peripartum management of gestational diabetes mellitus (GDM) on postpartum diabetes and factors associated with postpartum diabetes.

Methods: Women with GDM (n = 309) were randomly assigned to receive standard management (SM) or mobile management (MM). 75-g OGTT was performed at 6 weeks postpartum.

Glycemic qualification rate and frequency of self-monitoring blood glucose glycemic qualification rate and frequency of self-monitoring blood glucose (SMBG) in women with gestational diabetes mellitus (GDM).

Aims: To explore the relationship between blood glucose (BG) control rate and self-monitoring blood glucose (SMBG) compliance of women with gestational diabetes mellitus (GDM).

Methods: Women with GDM (n = 309) were randomized to receive routine clinical prenatal care or additional online management. Follow-up visits were conducted every two weeks (noted here as T) from enrollment to delivery.

Synthesis of -Cleistanthane Diterpenoid Spruceanol: Construction of an Aromatic C Ring Lewis Acid-Controlled Regioselective Diels-Alder Cycloaddition.

The first synthesis of -cleistanthane-type diterpenoid spruceanol with significant anticancer activity is described. A chiral pool approach was employed with a linear sequence of 13 steps beginning from readily available and inexpensive andrographolide. The approach features the construction of an aromatic ring with hydroxyl and methyl groups at C-12 and C-13 of the target compound, respectively, Lewis acid-controlled regioselective Diels-Alder cycloaddition and the regioselective removal of the primary hydroxyl group of the Diels-Alder adduct.

Discovery and evaluation of new compounds targeting ribosomal protein S1 in antibiotic-resistant Mycobacterium Tuberculosis.

The emergence of antibiotic-resistant Mycobacterium Tuberculosis (Mtb) infections compels new treatment strategies, of which targeting trans-translation is promising. During the trans-translation process, the ribosomal protein S1 (RpsA) plays a key role, and the Ala438 mutant is related to pyrazinamide (PZA) resistance, which shows its effects after being hydrolysed to pyrazinoic acid (POA). In this study, based on the structure of the RpsA C-terminal domain (RpsA-CTD) and POA complex, new compounds were designed.

Synthesis and anti-fibrosis activity study of 14-deoxyandrographolide-19-oic acid and 14-deoxydidehydroandrographolide-19-oic acid derivatives.

A series of 14-deoxyandrographolide-19-oic acid and 14-deoxy-11,12 (or 14,15)-didehydroandrographolide-19-oic acid derivatives were designed, synthesized and screened in vitro against the mouse fibroblast cell lines NIH-3T3. Thirteen compounds 8a-f, 14a-c, 14e-f, and 18a-b were found to exhibit better anti-fibrotic activities than andrographolide, with compounds 8b and 14e displaying best activity with IC values of 12.86 and 13.

A potent peptide as adiponectin receptor 1 agonist to against fibrosis.

Fibrotic diseases have become a major cause of death in the developed world. AdipoR1 agonists are potent inhibitors of fibrotic responses. Here, we focused on the in silico identification of novel AdipoR1 peptide agonists.

Hepatoprotective effects of AdipoRon against d-galactosamine-induced liver injury in mice.

Adiponectin is an antidiabetic and antiatherogenic adipokine, which plays distinct roles in the balance of energy homoeostasis. As an insulin sensitizing hormone, adiponectin exerts multiple biological effects by the specific receptors (AdipoR1 and AdipoR2), through activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)α pathways. AdipoRon, an orally active synthetic small-molecule AdipoR agonist, shows very similar effects to adiponectin in vitro and in vivo, which could be a promising therapeutic approach for obesity-related disorders.

Synthesis of CDDO-amino acid-nitric oxide donor trihybrids as potential antitumor agents against both drug-sensitive and drug-resistant colon cancer.

Seventeen CDDO-amino acid-NO donor trihybrids (4a-q) were designed and synthesized. Biological evaluation indicated that the most active compound 4c produced high levels of NO and inhibited the proliferation of drug-sensitive (HCT-8, IC50 = 0.294 μM) and drug-resistant (HCT-8/5-FU, IC50 = 0.

Synthesis and anticancer activity of some novel indolo[3,2-b]andrographolide derivatives as apoptosis-inducing agents.

A series of novel indolo[3,2-b]andrographolide derivatives were designed, synthesized and screened in vitro against three human cancer cell lines MCF7 (human breast cancer), HCT116 (human colon cancer), and DU145 (human prostate cancer). Fourteen compounds 6b, 6e, 6i, 6j, 6l, 6m, 6n, 12a, 12b, 13a, 13b, 15a, 17a, and 17b exhibited better anti-cancer activities than andrographolide for all three human cancer lines, with compound 6l displaying best activity with IC50 values of 1.85, 1.

Synthesis and in vitro cytotoxicity of andrographolide-19-oic acid analogues as anti-cancer agents.

The synthesis of a series of andrographolide-19-oic acid derivatives was described and their in vitro anti-tumor activity against two human cell lines was evaluated. Most compounds were found to exhibit significant cytotoxicity, better than andrographolide, and compounds 9d and 9b were identified as the most potent with IC50 values of 1.18 and 6.

Design, synthesis, and biological evaluation of novel histone deacetylase 1 inhibitors through click chemistry.

We report the design, synthesis, and biological evaluation of a new series of HDAC1 inhibitors using click chemistry. Compound 17 bearing a phenyl ring at meta-position was identified to show much better selectivity for HDAC1 over HDAC7 than SAHA. The compond 17 also showed better in vitro anticancer activities against several cancer cell lines than that of SAHA.

Enthalpy (DeltaH) and entropy (DeltaS) for pi-stacking interactions in near-sandwich configurations: relative importance of electrostatic, dispersive, and charge-transfer effects.

Interactions between two aromatic rings with various substituents in a near-sandwich configuration have been quantitatively studied by using the triptycene derived molecular models. This model system allows a stacking arrangement of two arenes to assume a near-perfect face-to-face configuration in its ground state conformation. Comparing to our previous study of the parallel displaced configuration, repulsive interactions are predominant for most arenes currently studied.

A threshold for charge transfer in aromatic interactions? A quantitative study of pi-stacking interactions.

[structure: see text] Attractive interactions between substituted arenes in the parallel displaced configuration have been quantitatively studied using triptycene-derived molecular conformational reporters. Charge-transfer bands are observed for models where the interactions are between strong donor and acceptors. Substituent effects on the strength of the aromatic interaction follow opposite trends for strongly electron-deficient arenes and mildly perturbed arenes.

Off-center oxygen-arene interactions in solution: a quantitative study.

[reaction: see text] Triptycenes with C1-MeO/RCOO (R = H, Me, Et, i-Pr, CF3) and C9-XC6H4CH2 (X = Me, H, F, CN, CF3) have been prepared to determine lone pair-arene interactions in the off-center configuration. The ratios of the syn and anti conformers were determined by low-temperature NMR spectroscopy. The syn conformer allows the attached arene and the MeO/ester to interact with each other while the anti conformer does not.

The strength of parallel-displaced arene-arene interactions in chloroform.

[reaction: see text] Triptycene-derived compounds have been prepared to serve as conformational equilibrium reporters for direct measurements of arene-arene interactions in the parallel-displaced orientation. A series of such compounds bearing arenes with different substituents were synthesized, and the ratios of the syn and anti conformers were determined by variable-temperature NMR spectroscopy. The syn conformer allows attached arenes to interact with each other while the anti conformer does not.

The origin of diastereofacial control in allylboration reactions using tartrate ester derived allylboronates: attractive interactions between the Lewis acid coordinated aldehyde carbonyl group and an ester carbonyl oxygen.

Transition-state structures for the allylboration reaction between the tartrate ester and tartramide modified allylboronates and acetaldehyde are located at the B3LYP/6-31G* level of theory. An attractive interaction between the boron-activated aldehyde and the ester or amide carbonyl oxygen lone pair is found to play a major role in the favored transition states 11a and 13. This attractive interaction appears to be electrostatic in origin.