Background Acupuncture is gaining in popularity as a treatment for chronic low back pain (cLBP); however, its therapeutic mechanisms remain controversial, partly because of the absence of an objective way of measuring subjective pain. Resting-state functional MRI (rsfMRI) has demonstrated aberrant default mode network (DMN) connectivity in patients with chronic pain, and also shown that acupuncture increases DMN connectivity in pain-modulator and affective-emotional brain regions of healthy subjects. Objective This study sought to explore how cLBP influences the DMN and whether, and how, the altered DMN connectivity is reversed after acupuncture for clinical pain. Methods RsfMRI data from 20 patients with cLBP, before and after 4 weeks of treatment, and 10 age-and gender-matched healthy controls (without treatment) were analysed using independent components analyses to determine connectivity within the DMN, and combined with correlation analyses to compute covariance between changes in DMN connectivity and changes in clinical pain. Visual analogue scale data were assessed to rate clinical pain levels. Results Less connectivity within the DMN was found in patients with cLBP than in healthy controls, mainly in the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate gyrus and precuneus. After acupuncture, patients' connectivities were restored almost to the levels seen in healthy controls. Furthermore, reductions in clinical pain were correlated with increases in DMN connectivity. Conclusions This result suggests that modulation of the DMN by acupuncture is related to its therapeutic effects on cLBP. Imaging of the DMN provides an objective method for assessment of the effects of acupuncture-induced analgesia.

Muconic acid is a platform chemical and an important intermediate in the degradation process of a series of aromatic compounds. Herein, a plasmid-free synthetic pathway in Pseudomonas chlororaphis HT66 is constructed for the enhanced biosynthesis of muconic acid by connecting endogenous ubiquinone biosynthesis pathway with protocatechuate degradation pathway using chromosomal integration. Instead of being plasmid and inducer dependent, the engineered strains could steadily produce the high muconic acid using glycerol as a carbon source. The engineered strain HT66-MA6 achieved a 3376 mg/L muconic acid production with a yield of 187.56 mg/g glycerol via the following strategies: (1) block muconic acid conversion and enhance muconic acid efflux pumping with phenazine biosynthesis cluster; (2) increase the muconic acid precursors supply through overexpressing the rate-limiting step, and (3) coexpress the "3-dehydroshikimate-derived" route in parallel with the "4-hydroxybenzoic acid-derived" route to create a synthetic "metabolic funnel". Finally, on the basis of the glycerol feeding strategies, the muconic acid yield reached 0.122 mol/mol glycerol. The results suggest that the construction of synthetic pathway with a plasmid-free strategy in P. chlororaphis displays a high biotechnological perspective.

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4-Hydroxybenzoic acid (4-HBA) has recently emerged as a promising intermediate for several value-added bioproducts with potential biotechnological applications in food, cosmetics, pharmacy, fungicides, etc. Over the past years, a variety of biosynthetic techniques have been developed for producing the 4-HBA and 4-HBA-based products. At this juncture, synthetic biology and metabolic engineering approaches enabled the biosynthesis of 4-HBA to address the increasing demand for high-value bioproducts. This review summarizes the biosynthesis of a variety of industrially pertinent compounds such as resveratrol, muconic acid, gastrodin, xiamenmycin, and vanillyl alcohol using 4-HBA as the starting feedstock. Moreover, potential research activities with a close-up look at the future perspectives to produce new compounds using 4-HBA have also been discussed.