Achieving robust synthetic tolerance in industrial E. coli through negative auto-regulation of a DsrA-Hfq module.

In industrial fermentation processes, microorganisms often encounter acid stress, which significantly impact their productivity. This study focused on the acid-resistant module composed of small RNA (sRNA) DsrA and the sRNA chaperone Hfq. Our previous study had shown that this module improved the cell growth of Escherichia coli MG1655 at low pH, but failed to obtain this desired phenotype in industrial strains. Here, we performed a quantitative analysis of DsrA-Hfq module to determine the optimal expression mode. We then assessed the potential of the CymR-based negative auto-regulation (NAR) circuit for industrial application, under different media, strains and pH levels. Growth assay at pH 4.5 revealed that NAR-05D04H circuit was the best acid-resistant circuit to improve the cell growth of E. coli MG1655. This circuit was robust and worked well in the industrial lysine-producing strain E. coli SCEcL3 at a starting pH of 6.8 and without pH control, resulting in a 250 % increase in lysine titer and comparable biomass in shaking flask fermentation compared to the parent strain. This study showed the practical application of NAR circuit in regulating DsrA-Hfq module, effectively and robustly improving the acid tolerance of industrial strains, which provides a new approach for breeding industrial strains with tolerance phenotype.

Effectiveness of Baduanjin (a Type of Qigong) on Physical, Cognitive, and Mental Health Outcomes: A Comprehensive Review.

Objectives: The aim of this study is to comprehensively review empirical evidence on the effectiveness of Baduanjin exercise, one type of mind-body focused qigong exercise, on individuals' physical, cognitive, and mental well-being; outline potential mechanisms; and, suggest potential implication strategies for using Baduanjin in clinical practices and for future research. Methods: Recent randomized-controlled studies and systematic reviews/meta-analyses published in English were searched in PubMed, PsycINFO, and Scopus up to July 2022. The search terms include Baduanjin and sleep, chronic illness, cognition, mental health, etc. We only selected papers that specifically studied the health effects of Baduanjin, excluding those that involved other forms of Qigong or other traditional Chinese medical practices. Since many RCT studies have already been included in the review papers that we selected, only those not covered in the review papers were selected to avoid repetition. Results: 19 recent randomized-controlled studies and 8 systematic reviews were identified. In general, the effectiveness of Baduanjin exercise on individuals' physical, cognitive, and mental health is evident. Baduanjin has proven to be effective in improving sleep quality, including reducing difficulties in getting asleep and reducing daytime sleepiness. It also reduces fatigue and improves the quality of life for patients with other physical health issues, such as cancer, musculoskeletal pain, and chronic illnesses. The effectiveness of Baduanjin exercise is also evident in cognition, improving executive functions, and slowing down age-related cognitive deterioration. Similarly, Baduanjin alleviates various types of mental illnesses, increases patients' social competence, and enhances emotional regulation. Conclusion: There is initial evidence on the safety and efficacy of Baduanjin in improving individuals' various aspects of health and well-being, suggesting that Baduanjin may serve as an effective adjunct to conventional treatments for a variety of clinical health benefits. More research is needed to confirm the efficacy and safety of Baduanjin in other non-Chinese ethnic populations.

Engineering of the Small Noncoding RNA (sRNA) DsrA Together with the sRNA Chaperone Hfq Enhances the Acid Tolerance of Escherichia coli.

Acid tolerance of microorganisms is a desirable phenotype for many industrial fermentation applications. In Escherichia coli, the stress response sigma factor RpoS is a promising target for engineering acid-tolerant phenotypes. However, the simple overexpression of RpoS alone is insufficient to confer these phenotypes. In this study, we show that the simultaneous overexpression of the noncoding small RNA (sRNA) DsrA and the sRNA chaperone Hfq, which act as RpoS activators, significantly increased acid tolerance in terms of cell growth under modest acidic pH, as well as cell survival upon extreme acid shock. Directed evolution of the DsrA-Hfq module further improved the acid tolerance, with the best mutants showing a 51 to 72% increase in growth performance at pH 4.5 compared with the starting strain, MG1655. Further analyses found that the improved acid tolerance of these DsrA-Hfq strains coincided with activation of genes associated with proton-consuming acid resistance system 2 (AR2), protein chaperone HdeB, and reactive oxygen species (ROS) removal in the exponential phase. This study illustrated that the fine-tuning of sRNAs and their chaperones can be a novel strategy for improving the acid tolerance of E. coliIMPORTANCE Many of the traditional studies on bacterial acid tolerance generally focused on improving cell survival under extreme-pH conditions, but cell growth under less harsh acidic conditions is more relevant to industrial applications. Under normal conditions, the general stress response sigma factor RpoS is maintained at low levels in the growth phase through a number of mechanisms. This study showed that RpoS can be activated prior to the stationary phase via engineering its activators, the sRNA DsrA and the sRNA chaperone Hfq, resulting in significantly improved cell growth at modest acidic pH. This work suggests that the sigma factors and likely other transcription factors can be retuned or retimed by manipulating the respective regulatory sRNAs along with the sufficient supply of the respective sRNA chaperones (i.e., Hfq). This provides a novel avenue for strain engineering of microbes.

Complementary medicine in chronic cancer care.

Although advancements in cancer care have led to increased cure rates and survival times, those coping with the long-term sequelae of a cancer diagnosis often report high levels of distress, poor health-related quality of life, and unmet psychosocial needs. The shortcomings of the conventional biomedical system at sufficiently addressing these chronic illness issues are a primary reason that many patients turn to complementary and alternative medicine (CAM). Although patients usually use such treatments in addition to conventional care, they often do not discuss doing so with their conventional physicians, who are perceived as being unreceptive to the topic. Physicians may feel uninformed about CAM treatments, especially given the relatively small amount of data on the topic available in the medical literature. This article reviews a few CAM modalities commonly used by cancer survivors and those with chronic cancer illness, with a particular focus on familiarizing physicians with treatments that may potentially complement regular oncologic care by decreasing stress and enhancing health-related quality of life.