Oxidant- and Catalyst-Free Synthesis of Sulfonated Benzothiophenes via Electrooxidative Tandem Cyclization.

A green and practical electrochemical method for the synthesis of C-3-sulfonated benzothiophenes from 2-alkynylthioanisoles and sodium sulfinates was developed under oxidant- and catalyst-free conditions. Moderate to good yields of sulfonated benzothiophenes bearing important and useful functional groups have been achieved at a constant current. Preliminary mechanistic studies indicated a tandem radical addition-cyclization pathway. Moreover, the protocol is easy to scale up and exhibits good reaction efficiency.

Aggrecan governs intervertebral discs development by providing critical mechanical cues of the extracellular matrix.

Aggrecan (ACAN) is localized in the intervertebral disc (IVD) in unique compartment-specific patterns where it contributes to the tissue structure and mechanical function together with collagens. The extracellular matrix (ECM) of the IVD undergoes degenerative changes during aging, misuse or trauma, which inevitably alter the biochemical and biomechanical properties of the tissue. A deeper understanding of these processes can be achieved in genetically engineered mouse models, taking into account the multifaceted aspects of IVD development. In this study, we generated aggrecan insertion mutant mice (Acan iE5/iE5 ) by interrupting exon 5 coding for the G1 domain of ACAN, and analyzed the morphological and mechanical properties of the different IVD compartments during embryonic development. Western blotting using an antibody against the total core protein failed to detect ACAN in cartilage extracts, whereas immunohistochemistry by a G1-specific antibody showed weak signals in vertebral tissues of Acan iE5/iE5 mice. Homozygous mutant mice are perinatally lethal and characterized by short snout, cleft palate and disproportionate dwarfism. Whole-mount skeletal staining and µ-CT analysis of Acan iE5/iE5 mice at embryonic day 18.5 revealed compressed vertebral bodies with accelerated mineralization compared to wild type controls. In Acan iE5/iE5 mice, histochemical staining revealed collapsed extracellular matrix with negligible sulfated glycosaminoglycan content accompanied by a high cellular density. Collagen type II deposition was not impaired in the IVD of Acan iE5/iE5 mice, as shown by immunohistochemistry. Mutant mice developed a severe IVD phenotype with deformed nucleus pulposus and thinned cartilaginous endplates accompanied by a disrupted growth plate structure in the vertebral body. Atomic force microscopy (AFM) imaging demonstrated a denser collagen network with thinner fibrils in the mutant IVD zones compared to wild type. Nanoscale AFM indentation revealed bimodal stiffness distribution attributable to the softer proteoglycan moiety and harder collagenous fibrils of the wild type IVD ECM. In Acan iE5/iE5 mice, loss of aggrecan resulted in a marked shift of the Young's modulus to higher values in all IVD zones. In conclusion, we demonstrated that aggrecan is pivotal for the determination and maintenance of the proper stiffness of IVD and vertebral tissues, which in turn could play an essential role in providing developmental biomechanical cues.

Benlysta-Loaded Sodium Alginate Hydrogel and Its Selective Functions in Promoting Skin Cell Growth and Inhibiting Inflammation.

Benlysta is a new drug approved by the US Food and Drug Administration (US FDA) in 2019 for the treatment of systemic lupus erythematosus. In this study, we loaded the benlysta in the traditional sodium alginate (SA) hydrogel to investigate the potential application of the drug-loaded hydrogel for skin dressing or hypodermic drug. Live/dead staining images and the CCK-8 results showed that the benlysta-loaded hydrogel could promote the growth of human epidermal cells (HaCat), fibroblasts (L929), and endothelial cells while inhibiting the aggregation of inflammatory cells (macrophages). In addition, the hydrogel degradation and drug release are slow and controllable, and the gel time of drug-loaded hydrogel can be adjusted by adding sodium alginate ratios according to the requirement. In summary, we prepared a time-dependent drug-loaded hydrogel for potential application in the treatment of skin injury that may be caused by other diseases.

Characterization of Microbial Diversity and Community Structure in Fermentation Pit Mud of Different Ages for Production of Strong-Aroma Baijiu.

In the traditional fermentation process of strong-aroma Baijiu, a fermentation pit mud (FPM) provides many genera of microorganisms for fermentation. However, the functional microorganisms that have an important effect on the quality of Baijiu and their changes with the age of fermentation pit (FP) are poorly understood. Herein, the Roche 454 pyrosequencing technique and a phospholipid fatty-acid analysis were employed to reveal the structure and diversity of prokaryotic communities in FPM samples that have been aged for 5, 30, and 100 years. The results revealed an increase in total prokaryotic biomass with an FP age; however, Shannon's diversity index decreased significantly (p < 0.01). These results suggested that a unique microbial community structure evolved with uninterrupted use of the FP. The number of functional microorganisms, which could produce the flavor compounds of strong-aroma Baijiu, increased with the FP age. Among them, Clostridium and Ruminococcaceae are microorganisms that directly produce caproic acid. The increase of their relative abundance in the FPM might have improved the quality of strong-aroma Baijiu. Syntrophomonas, Methanobacterium, and Methanocorpusculum might also be beneficial to caproic acid production. They are not directly involved but provide possible environmental factors for caproic acid production. Overall, our study results indicated that an uninterrupted use of the FP shapes the particular microbial community structure in the FPM. This research provides scientific support for the concept that the aged FP yields a high-quality Baijiu.In the traditional fermentation process of strong-aroma Baijiu, a fermentation pit mud (FPM) provides many genera of microorganisms for fermentation. However, the functional microorganisms that have an important effect on the quality of Baijiu and their changes with the age of fermentation pit (FP) are poorly understood. Herein, the Roche 454 pyrosequencing technique and a phospholipid fatty-acid analysis were employed to reveal the structure and diversity of prokaryotic communities in FPM samples that have been aged for 5, 30, and 100 years. The results revealed an increase in total prokaryotic biomass with an FP age; however, Shannon's diversity index decreased significantly (p < 0.01). These results suggested that a unique microbial community structure evolved with uninterrupted use of the FP. The number of functional microorganisms, which could produce the flavor compounds of strong-aroma Baijiu, increased with the FP age. Among them, Clostridium and Ruminococcaceae are microorganisms that directly produce caproic acid. The increase of their relative abundance in the FPM might have improved the quality of strong-aroma Baijiu. Syntrophomonas, Methanobacterium, and Methanocorpusculum might also be beneficial to caproic acid production. They are not directly involved but provide possible environmental factors for caproic acid production. Overall, our study results indicated that an uninterrupted use of the FP shapes the particular microbial community structure in the FPM. This research provides scientific support for the concept that the aged FP yields a high-quality Baijiu.

Dynamic alterations of the levels of tumor necrosis factor-α, interleukin-6, and interleukin-1ß in rat primary motor cortex during transhemispheric functional reorganization after contralateral seventh cervical spinal nerve root transfer following brachial plexus avulsion injuries.

The transfer of a contralateral healthy seventh cervical spinal nerve root (cC7) to the recipient nerve in the injured side is considered a reliable and effective procedure for restoration of the physiological functions of an injured hand after brachial plexus root avulsion injury (BPAI). Growing evidence shows that the transhemispheric cortical reorganization is induced after cC7 nerve transfer surgery. However, little is known about the underlying molecular mechanism. Proinflammatory cytokines reportedly play an important role in the neural plasticity. We hypothesize that proinflammatory cytokines are involved in the transhemispheric functional reorganization after cC7 transfer. In the present study, we investigated the level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in the rat primary motor cortex after cC7 transfer following BPAI by enzyme-linked immunosorbent assay. The results showed that, in the sham group, no statistical significance was observed between the level of TNF-α, IL-6, and IL-1ß at each time point after the operation compared with that at day 0, respectively. However, in the unrepaired and repaired groups, the level of TNF-α, IL-6, and IL-1ß changed dynamically. The study is the first to provide evidence for the involvement of proinflammatory cytokines in transhemispheric functional reorganization after cC7 transfer following BPAI, which are useful for understanding the underlying mechanism.