We further confirmed this finding in a standard fed-batch production assay. Sodium chlorate at 16mM markedly inhibited tyrosine sulfation by more than 50% and had no significant impact on antibody titer or quality. These data suggest that we can control tyrosine sulfation by selecting CHO cell lines based on the expression level of TPST2 and SLC35B2 or adding sodium chlorate in upstream production process.These data suggest that we can control tyrosine sulfation by selecting CHO cell lines based on the expression level of TPST2 and SLC35B2 or adding sodium chlorate in upstream production process.The use of the methylotrophic yeast Pichia pastoris (Komagataella phaffi) to produce heterologous proteins has been largely reported. However, investigations addressing the potential of this yeast to produce bulk chemicals are still scarce. In this study, we have studied the use of P. pastoris as a cell factory to produce the commodity chemical 3-hydroxypropionic acid (3-HP) from glycerol. 3-HP is a chemical platform which can be converted into acrylic acid and to other alternatives to petroleum-based products. To this end, the mcr gene from Chloroflexus aurantiacus was introduced into P. pastoris. This single modification allowed the production of 3-HP from glycerol through the malonyl-CoA pathway. Further enzyme and metabolic engineering modifications aimed at increasing cofactor and metabolic precursors availability allowed a 14-fold increase in the production of 3-HP compared to the initial strain. The best strain (PpHP6) was tested in a fed-batch culture, achieving a final concentration of 3-HP of 24.75 g l-1 , a product yield of 0.13 g g-1 and a volumetric productivity of 0.54 g l-1 h-1 , which, to our knowledge, is the highest volumetric productivity reported in yeast. These results benchmark P. pastoris as a promising platform to produce bulk chemicals for the revalorization of crude glycerol and, in particular, to produce 3-HP.Tetanus is a fatal but vaccine-preventable disease. The currently available tetanus vaccines are tetanus toxoid (TT)-based. Although these vaccines are generally effective, challenges in vaccine development and access remain. A randomized, double-blind, dose escalation, placebo- and positive-controlled, phase 1/2 trial (ChiCTR1800015865) is performed to evaluate the safety and immunogenicity of an alternative recombinant tetanus vaccine based on the Hc domain of tetanus neurotoxin (TeNT-Hc) in healthy adult volunteers. The primary outcome is the safety profile of the recombinant tetanus vaccine, and immunogenicity is the secondary outcome. 150 eligible participants were enrolled and randomly assigned to receive one of the three doses of recombinant tetanus vaccine (TeNT-Hc 10/20/30 µg), TT vaccine, or placebo. The recombinant tetanus vaccine shows a good safety profile. The frequency of any solicited and unsolicited adverse events after each vaccination does not differ across the vaccine and placebo recipients. No serious treatment-related adverse events occur. The recombinant tetanus vaccine shows strong immune responses (seroconversion rates, geometric mean titer, and antigen-specific CD4+/CD8+ T-cell responses), which are roughly comparable to those of the TT vaccine. In conclusion, the findings from this study support that recombinant tetanus vaccine is safe and immunogenic; thereby, it represents a novel vaccine candidate against tetanus.A closed-loop system that can mini-invasively track blood glucose and intelligently treat diabetes is in great demand for modern medicine, yet it remains challenging to realize. Microneedles technologies have recently emerged as powerful tools for transdermal applications with inherent painlessness and biosafety. In this work, for the first time to the authors' knowledge, a fully integrated wearable closed-loop system (IWCS) based on mini-invasive microneedle platform is developed for in situ diabetic sensing and treatment. The IWCS consists of three connected modules 1) a mesoporous microneedle-reverse iontophoretic glucose sensor; 2) a flexible printed circuit board as integrated and control; and 3) a microneedle-iontophoretic insulin delivery component. As the key component, mesoporous microneedles enable the painless penetration of stratum corneum, implementing subcutaneous substance exchange. The coupling with iontophoresis significantly enhances glucose extraction and insulin delivery and enables electrical control. This IWCS is demonstrated to accurately monitor glucose fluctuations, and responsively deliver insulin to regulate hyperglycemia in diabetic rat model. The painless microneedles and wearable design endows this IWCS as a highly promising platform to improve the therapies of diabetic patients.The past few decades have witnessed the tremendous progress of human-machine interface (HMI) in communication, education, and manufacturing fields. However, due to signal acquisition devices' limitations, the research on HMI related to communication aid applications for the disabled is progressing slowly. Here, inspired by frogs' croaking behavior, a bionic triboelectric nanogenerator (TENG)-based ultra-sensitive self-powered electromechanical sensor for muscle-triggered communication HMI application is developed. The sensor possesses a high sensitivity (54.6 mV mm-1 ), a high-intensity signal (± 700 mV), and a wide sensing range (0-5 mm). The signal intensity is 206 times higher than that of traditional biopotential electromyography methods. By leveraging machine learning algorithms and Morse code, the safe, accurate (96.3%), and stable communication aid HMI applications are achieved. Subasumstat datasheet The authors' bionic TENG-based electromechanical sensor provides a valuable toolkit for HMI applications of the disabled, and it brings new insights into the interdisciplinary cross-integration between TENG technology and bionics.Currently, piperazic acid is chemically synthesized using ecologically unfriendly processes. Microbial synthesis from glucose is an attractive alternative to chemical synthesis. In this study, we report the production of L-piperazic acid via microbial fermentation with the first engineered fungal strain of Aureobasidium melanogenum; this strain was constructed by chassis development, genetic element reconstitution and optimization, synthetic rewiring and constitutive genetic circuit reconstitution, to build a robust L-piperazic acid synthetic cascade. These genetic modifications enable A. melanogenum to directly convert glucose to L-piperazic acid without relying on the use of either chemically synthesized precursors or harsh conditions. This bio-based process overcomes the shortcomings of the conventional synthesis routes. The ultimately engineered strain is a very high-efficient cell factory that can excrete 1.12 ± 0.05 g l-1 of L-piperazic acid after a 120-h 10.0-l fed-batch fermentation; this is the highest titre of L-piperazic acid reported using a microbial cell factory.