Regeneration of Thyroid Glands in the Spleen Restores Homeostasis in Thyroidectomy Mice.

Surgical removal of the thyroid gland (TG) for treating thyroid disorders leaves the patients on lifelong hormone replacement that partially compensates the physiological needs, but regenerating TG is challenging. Here, an approach is reported to regenerate TG within the spleen for fully restoring the thyroid's functions in mice, by transplanting thyroid tissue blocks to the spleen. Within 48 h, the transplanted tissue efficiently revascularizes, forming thyroid follicles similar to the native gland after 4 weeks. Structurally, the ectopically generated thyroid integrates with the surrounding splenic tissue while maintaining its integrity, separate from the lymphatic tissue. Functionally, it fully restores the native functions of the TG in hormone regulation in response to physiological stimuli, outperforming the established method of oral levothyroxine therapy in maintaining systemic homeostasis. The study demonstrates the full restoration of thyroid functions post-thyroidectomy by intrasplenic TG regeneration, providing fresh insights for designing novel therapies for thyroid-related disorders.

Heavy-ion mutagenesis significantly enhances enduracidin production by Streptomyces fungicidicus.

To improve fermentative production of enduracidin, heavy-ion beams generated by the Heavy Ion Research Facility in Lanzhou (HIRFL), China, were employed for the first time to generate mutations in Streptomyces fungicidicus. Initial screening detected 44 positive mutants with larger inhibition zone, which were subsequently tested based on flask fermentation. Finally, 20 mutants showed 20% increase in enduracidin production, when compared with the original strain. Among them, enduracidin production by the three mutants (M13, M30, and M34) was significantly higher than that by the original strain. In particular, mutant M30 exhibited highest enduracidin production, which was 114% higher than that obtained with the original strain. Following culture optimization, the maximal enduracidin yield obtained by M30 reached 918.5 mg/L in 10 days, which was 34% higher than that noted in the control.

Enhanced production of l-lactic acid by Lactobacillus thermophilus SRZ50 mutant generated by high-linear energy transfer heavy ion mutagenesis.

The aim of this study was to improve l-lactic acid production of Lactobacillus thermophilus SRZ50. For this purpose, high efficient heavy-ion mutagenesis technique was performed using SRZ50 as the original strain. To enhance the screening efficiency for high yield l-lactic acid producers, a scale-down from shake flask to microtiter plate was developed. The results showed that 24-well U-bottom MTPs could well alternate shake flasks for L. thermophilus cultivation as a scale-down tool due to its a very good comparability to the shake flasks. Based on this microtiter plate screening method, two high l-lactic acid productivity mutants, A59 and A69, were successfully screened out, which presented, respectively, 15.8 and 16.2% higher productivities than that of the original strain. Based on fed-batch fermentation, the A69 mutant can accumulate 114.2 g/L l-lactic acid at 96 h. Hence, the proposed traditional microbial breeding method with efficient high-throughput screening assay was proved to be an appropriate strategy to obtain lactic acid-overproducing strain.

Mechanistic origin of chemoselectivity in thiolate-catalyzed Tishchenko reactions.

The thiolate-catalyzed Tishchenko reaction has shown high chemoselectivity for the formation of double aromatic-substituted esters. In the present study, the detailed reaction mechanism and, in particular, the origin of the observed high chemoselectivity, have been studied with DFT calculations. The catalytic cycle mainly consisted of three steps: 1,2-addition, hydride transfer, and acyl transfer steps. The calculation results reproduce the experimental observations that 4-chlorobenzaldehyde acts as the hydrogen donor (carbonyl part in the ester product), while 2-methoxybenzaldehyde acts as the hydrogen acceptor (alcohol part in the product). The two main factors are responsible for such chemoselectivity: 1) in the rate-determining hydride transfer step, the para-chloride substituent facilitates the hydride-donating process by weakening the steric hindrance, and 2) the ortho-methoxy substituent facilitates the hydride-accepting process by stabilizing the magnesium center (by compensating for the electron deficiency).

The conjugates of gold nanorods and chlorin e6 for enhancing the fluorescence detection and photodynamic therapy of cancers.

Gold nanorods (AuNRs) were conjugated with chlorin e6 (Ce6), a commonly used photosensitizer, to form AuNRs-Ce6 by electrostatic binding. Due to the strong surface plasmon resonance coupling, the fluorescence of conjugated Ce6 was enhanced 3-fold and the production of singlet oxygen was increased 1.4-fold. AuNRs-Ce6 were taken up by the HeLa and KB cell lines more easily than free Ce6, enhancing the intracellular delivery of Ce6. The increased cellular amount of Ce6 leads to a 3-fold more efficient photodynamic killing of these two cell lines. This demonstrates the potential of this approach to improve photodynamic detection and therapy of cancers.