Alteration of intestinal microbiota-intestinal barrier interaction interferes with intestinal health after microcystin-LR exposure in Lithobates catesbeianus tadpoles.

There remains uncertainty regarding the influence of microcystin-leucine arginine (MC-LR) on amphibian intestinal health, specifically how MC-LR interferes with intestinal microbiota following exposure to environmental concentrations. In this study, Lithobates catesbeianus tadpoles were exposed to varying MC-LR concentrations (0, 0.5, and 2 µg/L) over a 30-day period.

Acoustic modulation on a fiber laser based on dissipative coupling of a microcavity.

Imparting information on a light wave by signal modulation is fundamental for all forms of optical sensors. Here, we use a microfiber coupled whispering-gallery microcavity as a feedback element and experimentally demonstrate the intensity modulation on a fiber laser based on dissipative acousto-optic interaction where the acoustic wave modulates the coupling strength of suspended microfiber and microcavity, and accordingly modulates the decay rate of laser cavity. As high as 35% modulation depth is realized and the laser is then explored for the sensitive detection of an acoustic wave in air and a noise equivalent pressure of less than 0.

Discovery of the Clinical Candidate Sonrotoclax (BGB-11417), a Highly Potent and Selective Inhibitor for Both WT and G101V Mutant Bcl-2.

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax's limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g.

Fiber laser cascaded with an MZ interferometer for simultaneous measurement of temperature and refractive index.

A fiber laser with strong spontaneous emission and high signal-to-noise ratio is proposed and experimentally demonstrated for simultaneous measurement of temperature and refractive index (RI). By cascading a single MZ interferometer, the power and the emission spectrum of the fiber laser are modulated by surrounding temperature and RI. The dual parameters are determined from the measured power change and interference dip shift.

Discovery of BGB-8035, a Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase for B-Cell Malignancies and Autoimmune Diseases.

Bruton's tyrosine kinase (BTK) plays an essential role in B-cell receptor (BCR)-mediated signaling as well as the downstream signaling pathway for Fc receptors (FcRs). Targeting BTK for B-cell malignancies by interfering with BCR signaling has been clinically validated by some covalent inhibitors, but suboptimal kinase selectivity may lead to some adverse effects, which also makes the clinical development of autoimmune disease therapy more challenging. The structure-activity relationship (SAR) starting from zanubrutinib (-) leads to a series of highly selective BTK inhibitors, in which - is located in the ATP binding pocket and has similar hinge binding to ATP but exhibits high selectivity over other kinases (EGFR, Tec, etc.

Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase.

Aberrant activation of Bruton's tyrosine kinase (BTK) plays an important role in pathogenesis of B-cell lymphomas, suggesting that inhibition of BTK is useful in the treatment of hematological malignancies. The discovery of a more selective on-target covalent BTK inhibitor is of high value. Herein, we disclose the discovery and preclinical characterization of a potent, selective, and irreversible BTK inhibitor as our clinical candidate by using in vitro potency, selectivity, pharmacokinetics (PK), and in vivo pharmacodynamic for prioritizing compounds.

Detailed studies on the enantioselective synthesis and HPLC enantioseparation of N-protected 3-hydroxyglutarimides.

An analytical HPLC method using CHIREX (S)-LEU/(S)-alpha-NEA column was developed for the determination of the enantiomeric excesses of N-protected (S)-3-hydroxyglutarimides. Using this method, detailed studies on the base-promoted ring-expansion reaction of the amidolactones, derived from l-glutamic acid, were undertaken.