Recent advances in anti-inflammation via AMPK activation.

Inflammation is a complex physiological phenomenon, which is the body's defensive response, but abnormal inflammation can have adverse effects, and many diseases are related to the inflammatory response. AMPK, as a key sensor of cellular energy status, plays a crucial role in regulating cellular energy homeostasis and glycolipid metabolism. In recent years, the anti-inflammation effect of AMPK and related signalling cascade has begun to enter everyone's field of vision - not least the impact on metabolic diseases. A great number of studies have shown that anti-inflammatory drugs work through AMPK and related pathways. Herein, this article summarises recent advances in compounds that show anti-inflammatory effects by activating AMPK and attempts to comment on them.

Identification of force chains in wet coal dust layer and the effect of porosity on three-body contact stiffness.

Aiming at the three-body contact problem of mechanical rough surface containing wet coal dust interface, the three-body contact model of rough surface containing wet coal dust interface is constructed by comprehensively considering the contact deformation of rough surface and contact characteristics of wet coal dust, and based on the crushing theory. By analysing the contact force, load-bearing particle size and adjacent contact angle thresholds of the wet coal dust layer, the force chain identification criterion is formulated. Finally, quantitative calculations of the force chain characteristics are performed to reveal the effect of different initial porosities on the three-body contact stiffness, which is verified experimentally. The results of the study show that the average contact force of the wet coal dust layer can be used as the force chain contact force threshold, the average particle size can be used as the force chain particle size threshold, and the force chain angle threshold is determined by the particle coordination number. As the initial porosity decreases, the number, length and stiffness of force chains in the wet coal dust layer increase significantly, and the stiffness reaches a maximum value of 2.007 × 108 pa/m at the moment of downward pressure to stabilisation, while the trend of force chain bending varies in the opposite direction, and its minimum bending degree decreases to 20°. The maximum relative error between the simulation and experimental results of three-body contact stiffness is 9.64%, which proves the accuracy of the force chain identification criterion and the quantitative calculation of three-body contact stiffness by force chain.

[Advances in ectoine biosynthesis and biochemical characteristics of key enzymes].

Compatible solutes are highly water-soluble organic osmolytes produced by microorganisms to adapt to extreme environments, such as high salinity and osmotic pressure. Among these, ectoine plays a crucial role in repairing and protecting nucleic acids, protein, biofilms, and cells. As a result, it has found widespread applications in cosmetics, biological agents, the enzyme industry, medicine, and other fields. Currently, the market value of ectoine is around US$ 1 000/kg, with a global demand reaching 15 000 tons per year. Although halophilic bacteria serve as the natural source of ectoine synthesis, its production in high-salinity media presents challenges such as equipment corrosion and high cost for industrial production. Advancements in functional genomics, systems biology, and synthetic biology have paved the way for the development of high-yielding cell factories through metabolic engineering, leading to significant progress. For example, engineered Escherichia coli achieved a maximum ectoine titer of 131.8 g/L, with a productivity of 1.37 g/(L·h). This review aims to explore the biosynthetic pathway, biochemical characteristics of key enzymes, and the biosynthesis of ectoine, shedding light on current research status and offering insights for industrial-scale ectoine production.

[Advances in the synthesis of cytidine-5'-diphosphate choline].

Cytidine-5'-diphosphate choline (CDP-choline) plays a crucial role in the formation of the phospholipid bilamolecular layer in cell membranes and the stabilization of the neurotransmitter system, acting as a precursor to phosphatidylcholine and acetylcholine. CDP-choline has been found effective in treating functional and consciousness disorders resulting from brain injury, Parkinson's disease, depression and glaucoma, and other conditions. As such, CDP-choline is widely utilized in clinical medicine and health care products. The conventional chemical synthesis process of CDP-choline is gradually being replaced by biosynthesis due to the expensive and toxic reagents involved, the production of various by-products, and the high cost of industrial production. Biosynthesis of CDP-choline offers two strategies: microbial fermentation and biocatalysis. Microbial fermentation utilizes inexpensive raw materials but results in a relatively low conversion rate and requires a complex separation and purification process. Biocatalysis, on the other hand, involves two stages: the growth of a living "catalyst" and the conversion of the substrate. Although the synthetic process in biocatalysis is more complex, it offers a higher conversion ratio, and the downstream processing technique for extraction is relatively less costly. Consequently, biocatalysis is currently the primary strategy for the industrial production of CDP-choline. This review aims to summarize the progress made in both chemical synthesis and biosynthesis of CDP-choline, with particular focus on the metabolic pathway and the synthetic processes involved in biocatalysis, in order to provide insights for the industrial production of CDP-choline.

Effect of extracorporeal shock wave therapy for rotator cuff injury: Protocol for a systematic review and meta-analysis.

BACKGROUND: Rotator cuff injury (RCI) is a common musculoskeletal ailment and a major cause of shoulder pain and limited functionality. The ensuing pain and restricted movement significantly impact overall quality of life. This study aims to systematically review the effects of extracorporeal shock wave therapy (ESWT) on RCI. METHODS: This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. A literature search, spanning inception to November 1, 2023, will include databases such as PubMed, Web of Science, the Cochrane Library, Scopus, MEDLINE, EMBASE, EBSCO, and China National Knowledge Infrastructure (CNKI) to identify ESWT studies for RCI treatment. Excluding retrospectives, bias risk will be assessed with the Cochrane tool. Two researchers will independently screen, extract data, and evaluate bias risk. Revman 5.3 software will be used for data analysis. RESULTS: This study aims to objectively and comprehensively evaluate the effectiveness and safety of randomized controlled trials of ESWT in the treatment of RCI, and analyze in detail the effect of ESWT in the treatment of RCI. Results will be analyzed using the Pain Visual Analogue Scale (VAS), Constant-Murley score, University of California Los Angeles score (UCLA), and American Shoulder and Elbow Surgeons form (ASES). If applicable, subgroup analysis will also be performed to divide patients into groups according to the energy level of ESWT, the time of intervention, and the degree of tearing of RCI. Finally, the results are submitted for publication in a peer-reviewed journal. DISCUSSION AND CONCLUSION: There is existing evidence suggesting that ESWT may contribute to the amelioration of pain and functional limitations associated with Rotator Cuff Injury (RCI). This systematic review aims to update, consolidate, and critically evaluate relevant evidence on the effects of ESWT for RCI. The anticipated outcomes may serve as a valuable reference for clinical ESWT practices, covering treatment methods, timing, and intensity. Moreover, this review aspires to provide high-quality evidence addressing the impact of ESWT on RCI-related pain. Simultaneously, the findings of this systematic review are poised to offer guidance to clinicians and rehabilitation therapists. This guidance is intended to enhance the management of pain and functional impairments experienced by individuals with RCI, ultimately leading to improvements in their physical well-being. TRIAL REGISTRATION: Protocol registration number CRD42023441407. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441407.

Effect of extracorporeal shockwave therapy for rotator cuff tendinopathy: a systematic review and meta-analysis.

BACKGROUND: Rotator cuff tendinopathy (RCT) is a widespread musculoskeletal disorder and a primary cause of shoulder pain and limited function. The resulting pain and limited functionality have a detrimental impact on the overall quality of life. The purpose of this study was to perform a systematic review of the effects of extracorporeal shock wave therapy (ESWT) for RCT. METHODS: The literature search was conducted on the following databases from inception to February 20, 2024: PubMed, Web of Science, the Cochrane Library, Scopus, MEDLINE, EMBASE, EBSCO, and China National Knowledge Infrastructure (CNKI) were checked to identify the potential studies exploring the effect of ESWT for the treatment of Rotator cuff tendinopathy (Calcification or non-calcification), control group for sham, other treatments (including placebo), without restriction of date, language. Two researchers independently screened literature, extracted data, evaluated the risk of bias in the included studies, and performed meta-analysis using RevMan 5.3 software. RESULTS: A total of 16 RCTs with 1093 patients were included. The results showed that compared with the control group, ESWT for pain score Visual Analogue Scale/Score (VAS) (SMD = -1.95, 95% CI -2.47, -1.41, P < 0.00001), function score Constant-Murley score (CMS) (SMD = 1.30, 95% CI 0.67, 1.92, P < 0.00001), University of California Los Angeles score (UCLA) (SMD = 2.69, 95% CI 1.64, 3.74, P < 0.00001), American Shoulder and Elbow Surgeons form (ASES) (SMD = 1.29, 95% CI 0.93, 1.65, P < 0.00001), Range of motion (ROM) External rotation (SMD = 1.00, 95% CI 0.29, 1.72, P = 0.02), Total effective rate (TER) (OR = 3.64, 95% CI 1.85, 7.14, P = 0.0002), the differences in the above results were statistically significant. But ROM-Abduction (SMD = 0.72, 95% CI -0.22, 1.66, P = 0.13), the difference was not statistically significant. CONCLUSION: Currently limited evidence suggests that, compared with the control group, ESWT can provide better pain relief, functional recovery, and maintenance of function in patients with RCT.

Effects of Cerebellar Repetitive Transcranial Magnetic Stimulation in the Treatment of Post-Stroke Dysphagia: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

INTRODUCTION: This study aimed to comprehensively evaluate the therapeutic efficacy of cerebellar repetitive transcranial magnetic stimulation (rTMS) in the rehabilitation of post-stroke dysphagia (PSD). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Cochrane Library, Embase, and Web of Science to identify relevant randomized controlled trials (RCTs) investigating the application of cerebellar rTMS in the treatment of PSD. Inclusion and exclusion criteria were rigorously applied during the screening process, and pertinent characteristics of the included RCTs were meticulously extracted. The I2 statistic was employed to assess heterogeneity, and meta-analysis was conducted using Stata 17 software. The Cochrane Risk of Bias 2 tool and PEDro scale were utilized to evaluate bias risk and literature quality. RESULTS: Our analysis encompassed a total of 5 RCTs involving 673 patients with dysphagia who met the inclusion criteria. The findings indicated a significant positive impact of cerebellar rTMS when combined with traditional swallowing exercises on PSD, demonstrating superior efficacy compared to conventional swallowing exercises in isolation. Furthermore, the study revealed no statistically significant differences based on stimulation site (unilateral vs. bilateral cerebellum), stimulation mode (rTMS vs. intermittent theta-burst stimulation), and stimulation frequency (5 Hz vs. 10 Hz). CONCLUSION: The amalgamation of cerebellar rTMS with conventional swallowing exercises demonstrates notable efficacy, surpassing the outcomes achievable with traditional exercises alone. The sustained effectiveness observed underscores the potential of cerebellar rTMS as an innovative avenue in the field of neurorehabilitation for PSD. This study contributes valuable insights into the prospect of utilizing cerebellar rTMS as an adjunctive therapeutic strategy in the management of PSD, emphasizing its relevance for further exploration and clinical application.

Effect of Cyclotorsion Compensation in Small Incision Lenticule Extraction Surgery for the Correction of Myopic Astigmatism: A Systematic Review and Meta-Analysis.

INTRODUCTION: Small incision lenticule extraction (SMILE) has made notable advancements in addressing myopic astigmatism. Nevertheless, the potential impact of cyclotorsion on surgical outcomes cannot be overlooked. This study aims to assess the effectiveness of cyclotorsion compensation technology in SMILE surgery for the correction of myopic astigmatism, examining its influence on postoperative visual quality. METHODS: A systematic review and meta-analysis were conducted. A comprehensive literature search was performed using databases, including PubMed, Web of Science, EMBASE, Cochrane Library, EBSCO, Scopus, CNKI, VIP, and Wan Fang. Studies meeting the criteria were selected and included. Data were independently extracted by three authors. Clinical outcome parameters were analyzed using Review Manager version 5.3. RESULTS: This meta-analysis included ten studies. The results showed that, compared with the control group (cyclotorsion compensation was not performed in SMILE), the following indicators in the cyclotorsion compensation group were: residual astigmatism (RA) [weighted mean difference (MD) = 0.73, 95% confidence interval (CI) + 0.26 to + 1.19, P = 0.002], spherical equivalent (SE) (MD = 1.99, 95% CI + 0.77 to + 3.21, P = 0.001), coma (MD = -0.06, 95% CI -0.08 to -0.04, P < 0.00001), higher-order aberrations (HOAs) (MD = -0.04, 95% CI -0.06 to -0.02, P < 0.0001), follow-up 6-month angle of error (AE) (MD = -2.67, 95% CI -3.71 to -1.63, P < 0.00001), and follow-up 6-month uncorrected distance visual acuity (UDVA) (MD = -0.05, 95% CI -0.08 to -0.01, P = 0.005), and the differences in results were statistically significant. However, the differences among correction index, index of success (IOS), targeted induced astigmatism (TIA), magnitude of error (ME), and spherical aberration (SA) were not statistically significant. CONCLUSION: Cyclotorsion compensation proves to be effective and predictable for correcting myopic astigmatism. The cyclotorsion compensation group demonstrated advantages over the control group in terms of postoperative residual astigmatism, and it induced fewer coma aberrations. Whether cyclotorsion compensation can lead to better visual quality remains to be seen, and further research on correcting myopic astigmatism through cyclotorsion compensation is warranted.

Jiawei guomin decoction regulates the degranulation of mast cells in atopic dermatitis mice via the HIS/PAR-2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Guomin decoction (GMD) is a traditional Chinese medicine commonly used in clinical practice. It has traditionally been used to treat all allergic diseases. Currently, Jiawei Guomin Decoction (JWGMD) is used to treat sensitive skin after initial therapy. Although it has a significant clinical therapeutic effect, the exact role of mast cell degranulation in treating atopic dermatitis (AD) is still unclear. AIM OF THE STUDY: GMD and JWGMD can both treat allergic diseases, while JWGMD focuses on skin allergies. This study aims to explore the potential effect of JWGMD on the degranulation of mast cells in an AD mouse model induced by 2,4-dinitrofluorobenzene (DNFB) and investigate the effectiveness of JWGMD in alleviating disease progression to further provide specific therapeutic targets for treating AD. MATERIALS AND METHODS: The scratching times and skin lesions of model mice induced by DNFB were observed, and skin tissues were collected for subsequent measurement. Histopathological changes in the back skin of mice were observed by haematoxylin eosin (H&E) staining, Toluidine blue staining was used to detect the degranulation of mouse skin mast cells, and the relationship between the expression of histamine (HIS), mast cell tryptase (MCT) and mast cell degranulation was analysed by enzyme-linked immunosorbent assay (ELISA). The expression of protease-activated receptor-2 (PAR-2), histamine 1 receptor (H1R), H2R, H4R and MCT proteins in AD mice was detected by Western blot (WB). Immunofluorescence assay (IFA) further confirmed the localization of PAR-2, H1R, H2R, H4R, and MCT proteins in the skin. Quantitative real-time PCR (qPCR) was used to determine PAR-2, H1R, H2R and H4R mRNA levels in skin lesions to further clarify the mechanism by which JWGMD amplifies mast cell degranulation in AD. In addition, a reliable ultrahigh-performance liquid chromatography-quadrupole electrostatic field orbitrap mass spectrometry (UPLC-QE-MS) nontargeted metabolomics analysis was performed to analyse the differences in metabolite abundance between GMD and JWGMD, and these results were used to identify the active components in JWGMD that may have antipruritic and anti-inflammatory properties and inhibit mast cell degranulation. RESULTS: After intermittent stimulation with DNFB, the skin lesions showed extensive desquamation, dryness, scabbing, skin thickening, and slight bleeding. Both treatments alleviated this phenomenon and reduced the number of scratches, with JWGMD being the most effective. JWGMD can significantly reduce inflammatory cell infiltration, oedema, and some capillary neogenesis in mice and reduce the degranulation of mast cells. The ELISA results showed that JWGMD can increase the levels of MCT and HIS proteins. The WB and IFA results demonstrated that JWGMD reduced the expression levels of PAR-2, H1R, H4R, and MCT proteins in skin lesions, with protein localization mainly in the epidermal layer, while H2R protein levels were increased and mainly localized in the dermis. In addition, JWGMD downregulates the mRNA expression of PAR-2, H1R, H2R, and H4R. Interestingly, through UPLC-QE-MS nontargeted metabolomic analysis, we detected the anti-inflammatory and antiallergy active substances in JWGMD, such as methyl eugenol, dictamnine and sinapine. CONCLUSIONS: JWGMD may alleviate itching through methyl syringol, dictamnine, sinapine and other substances, and its mechanism may be related to inhibiting the HIS/PAR-2 pathway in AD model mice and further regulating the self-amplification of mast cell degranulation. JWGMD is a potential drug for treating AD. Therefore, it deserves continuous attention and research.

N6-methyladenosine modification promotes hepatocarcinogenesis through circ-CDYL-enriched and EpCAM-positive liver tumor-initiating exosomes.

CircRNAs play multiple roles in a variety of cellular processes. We found that Circ-CDYL is highly enriched in early HCC plasma exosomes. Moreover, EpCAM+ HCC cells and exosomes had significant Circ-CDYL levels. We postulated that Circ-CDYL-enriched and EpCAM-positive exosomes would function as liver tumor-initiating exosomes (LTi-Exos). As predicted, intercellular transfer of LTi-Exos activates the HDGF-PI3K-AKT-mTOR and HIF1AN-NOTCH2 axes in recipient cells, promoting malignancy. Upstream, we found that the N6-methyladenosine (m6A) modification of Circ-CDYL exerted its action in HCC cells through a dual mechanism. First, it stimulated back-splicing processes via YTHDC1 to promote Circ-CDYL biogenesis. Second, it facilitates the active sorting of Circ-CDYL into exosomes via hnRNPA2/B1. Clinically, the combination of LTi-Exos and plasma alpha-fetoprotein (AFP) provides a promising early diagnostic biomarker for HCC with an AUC of 0.896. This study highlights the effect and mechanism by which m6A modification promotes hepatocarcinogenesis via modulation of the tumor microenvironment by LTi-Exos.

Efficacy of probiotics in pediatric atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis (AD) is a prevailing skin disease in childhood. Several studies have appraised probiotics as a strategy for treating AD. We aimed to assess the validity of probiotics in the treatment of AD in children. METHODS: We systematically searched the PubMed/MEDLINE, Embase, Scopus, EBSCO, Web of Science and Cochrane library databases for randomized controlled trials (RCTs) that assessed the effect of probiotic treatment on SCORAD value in pediatric patients with AD compared with a placebo group between 1 January 2010 and 1 January 2023. The risk of bias and the certainty of evidence were assessed using Cochrane ROB 2.0. RESULTS: A total of 10 outcomes from 9 RCTs involving 1000 patients were included. Three of these outcomes were analyzed as dichotomous variables in 373 patients. The other seven were analyzed for continuous variables in 627 patients. A meta-analysis of the random-effect model of the dichotomous variables demonstrated no significant difference between the probiotic and control groups [OR = 1.75, 95% confidence interval (CI) (0.70, 4.35), p = 0.23, I2  = 68%]. A meta-analysis of the random-effect model of continuous variables demonstrated significant differences between the probiotic and control groups [MD = -4.24, 95% CI (-7.78, -0.71), p = 0.002, I2  = 71%]. Subgroup analysis of continuous variables showed that the effects of children's age, treatment duration and probiotic species on the SCORAD value were not statistically significant. CONCLUSION: Evidence on the improvement effect of probiotics on pediatric patients with AD is limited. This study showed that single-strain probiotic treatment exerts a positive effect on AD. Restricted to the quantity and quality of incorporated studies, these conclusions have yet to be validated by high-quality studies.

Effect of Kinesio tape and Compression sleeves on delayed onset of muscle soreness: a single-blinded randomized controlled trial.

BACKGROUND: Both Kinesio Tape (KT) and Compression Sleeves (CS) can relieve Delayed Onset Muscle Soreness (DOMS) to a certain extent, but there is no study report on the difference in the effectiveness of the KT and CS whether the effect is better when used at the same time. The purpose of this study was to compare the effects of KT and CS on the recovery of muscle soreness, isokinetic strength, and body fatigue after DOMS. METHODS: In this single-blinded randomized controlled trial, 32 participants aged 18 to 24 years were randomly divided into Control group (CG), Compression Sleeves group (CSG), Kinesio Tape group (KTG), Compression Sleeves and Kinesio Tape group (CSKTG), between October 2021 and January 2022. KTG uses Kinesio Tape, CSG wears Compression Sleeves, and CSKTG uses both Compression Sleeves and Kinesio Tape. Outcomes were performed at five-time points (baseline, 0 h, 24 h, 48 h, 72 h), Primary outcome was pain level Visual Analogue Scale (VAS), and Secondary outcomes were Interleukin 6, Peak Torque/Body Weight, Work Fatigue. Statistical analyses were performed using the repeated measures analysis of variance method. SETTING: Laboratory. RESULTS: After the intervention, VAS reached the highest at 24 h after exercise-induced muscle soreness, while the KTG and CSG at each time point were less than CG, and the scores of CSKTG at 24 h and 48 h were less than those of KTG and CSG in the same period (P < 0.05). Interleukin 6, at 24 h, CSKTG is lower than KTG 0.71(95%CI: 0.43 to 1.86) and CG 1.68(95%CI: 0.06 to 3.29). Peak Torque/Body Weight, at 24 h, CG was lower than CSKTG 0.99(95%CI: 0.42 to 1.56), KTG 0.94(95%CI: 0.37 to 1.52), and CSG 0.72(95%CI: 0.14 to 1.29); at 72 h, CG was lower than CSKTG 0.65(95%CI: 0.13 to 1.17) and KTG 0.58(95%CI: 0.06 to 1.10). Work Fatigue, at 24 h, CG was lower than KTG 0.10(95%CI: 0.02 to 1.78) and CSKTG 0.01(95%CI: -0.07 to 0.09). At 48 h, CG was lower than KTG 0.10(95%CI: 0.13 to 1.17) and CSKTG 0.11(95%CI: 0.03 to 0.18). CONCLUSIONS: Kinesio Tape can significantly reduce DOMS pain, and Kinesio Tape has a better recovery effect on Delayed Onset Muscle Soreness than Compression Sleeves. Kinesio Tape combined with Compression Sleeves is helpful to alleviate the Delayed Onset Muscle Soreness pain, speeding up the recovery of muscle strength, and shortening the recovery time after Delayed Onset Muscle Soreness. TRIAL REGISTRATION: Registration number: This study was also registered on 11/10/2021, at the Chinese Clinical Trial Registry (ChiCTR2100051973).

Integrating Enzyme Evolution and Metabolic Engineering to Improve the Productivity of Γ-Aminobutyric Acid by Whole-Cell Biosynthesis in Escherichia Coli.

γ-Aminobutyric acid (GABA) is used widely in various fields, such as agriculture, food, pharmaceuticals, and biobased chemicals. Based on glutamate decarboxylase (GadBM4) derived from our previous work, three mutants, GadM4-2, GadM4-8, and GadM4-31, were obtained by integrating enzyme evolution and high-throughput screening methods. The GABA productivity obtained through whole-cell bioconversion using recombinant Escherichia coli cells harboring mutant GadBM4-2 was enhanced by 20.27% compared to that of the original GadBM4. Further introduction of the central regulator GadE of the acid resistance system and the enzymes from the deoxyxylulose-5-phosphate-independent pyridoxal 5'-phosphate biosynthesis pathway resulted in a 24.92% improvement in GABA productivity, reaching 76.70 g/L/h without any cofactor addition with a greater than 99% conversion ratio. Finally, when one-step bioconversion was applied for the whole-cell catalysis in a 5 L bioreactor, the titer of GABA reached 307.5 ± 5.94 g/L with a productivity of 61.49 g/L/h by using crude l-glutamic acid (l-Glu) as the substrate. Thus, the biocatalyst constructed above combined with the whole-cell bioconversion method represents an effective approach for industrial GABA production.

Efficacy of Robot-Assisted Training on Rehabilitation of Upper Limb Function in Patients With Stroke: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically evaluate the effect of robot-assisted training (RAT) on upper limb function recovery in patients with stroke, providing the evidence-based medical basis for the clinical application of RAT. DATA SOURCES: We searched online electronic databases up to June 2022, including PubMed, The Cochrane Library, Scopus, Web of Science, EMBASE, WanFang Data, CNKI, and VIP full-text databases. STUDY SELECTION: Randomized controlled trials of the effect of RAT on upper extremity functional recovery in patients with stroke. DATA EXTRACTION: The Cochrane Collaboration Tool for Assessing the Risk of Bias was used to assess study quality and risk of bias. DATA SYNTHESIS: Fourteen randomized controlled trials involving 1275 patients were included for review. Compared with the control group, RAT significantly improved upper limb motor function and daily living ability. The overall differences were statistically significant, Fugl-Meyer Assessment for the Upper Extremity (FMA-UE; standard mean difference=0.69; 95% confidence interval, 0.34, 1.05; P=.0001), modified Barthel Index (standard mean difference=0.95; 95% confidence interval, 0.75, 1.15; P<.00001), whereas the differences in modified Ashworth Scale, FIM, and Wolf Motor Function Test scores were not statistically significant. SUBGROUP ANALYSIS: Compared with the control group, the differences between FMA-UE and modified Barthel Index at 4 and 12 weeks of RAT, there were statistically significant, the differences of FMA-UE and modified Ashworth Scale in patients with stroke in the acute and chronic phases were statistically significant. CONCLUSION: The present study showed that RAT can significantly enhance the upper limb motor function and activities of daily life in patients with stroke undergoing upper limb rehabilitation.

[Advances in physiological activities and synthesis of ß-nicotinamide mononucleotide].

Nicotinamide mononucleotide (NMN) is one of the key precursors of coenzyme Ⅰ (NAD+). NMN exists widely in a variety of organisms, and ß isomer is its active form. Studies have shown that ß-NMN plays a key role in a variety of physiological and metabolic processes. As a potential active substance in anti-aging and improving degenerative and metabolic diseases, the application value of ß-NMN has been deeply explored, and it is imminent to achieve large-scale production. Biosynthesis has become the preferred method to synthesize ß-NMN because of its high stereoselectivity, mild reaction conditions, and fewer by-products. This paper reviews the physiological activity, chemical synthesis as well as biosynthesis of ß-NMN, highlighting the metabolic pathways involved in biosynthesis. This review aims to explore the potential of improving the production strategy of ß-NMN by using synthetic biology and provide a theoretical basis for the research of metabolic pathways as well as efficient production of ß-NMN.

Adaptive evolutionary strategy coupled with an optimized biosynthesis process for the efficient production of pyrroloquinoline quinone from methanol.

BACKGROUND: Pyrroloquinoline quinone (PQQ), a cofactor for bacterial dehydrogenases, is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. Due to the extremely high cost of chemical synthesis and low yield of microbial synthesis, the election of effective strains and the development of dynamic fermentation strategies for enhancing PQQ production are meaningful movements to meet the large-scale industrial requirements. RESULTS: A high-titer PQQ-producing mutant strain, Hyphomicrobium denitrificans FJNU-A26, was obtained by integrating ARTP (atmospheric and room­temperature plasma) mutagenesis, adaptive laboratory evolution and high-throughput screening strategies. Afterward, the systematic optimization of the fermentation medium was conducted using a one-factor-at-a-time strategy and response surface methodology to increase the PQQ concentration from 1.02 to 1.37 g/L. The transcriptional analysis using qRT-PCR revealed that the expression of genes involved in PQQ biosynthesis were significantly upregulated when the ARTP-ALE-derived mutant was applied. Furthermore, a novel two-stage pH control strategy was introduced to address the inconsistent effects of the pH value on cell growth and PQQ production. These combined strategies led to a 148% increase in the PQQ concentration compared with that of the initial strain FJNU-6, reaching 1.52 g/L with a yield of 40.3 mg/g DCW after 144 h of fed-batch fermentation in a 5-L fermenter. CONCLUSION: The characteristics above suggest that FJNU-A26 represents an effective candidate as an industrial PQQ producer, and the integrated strategies can be readily extended to other microorganisms for the large-scale production of PQQ.

Efficacy of rehabilitation robot-assisted gait training on lower extremity dyskinesia in patients with Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Robot-assisted training is used as a new rehabilitation training method for the treatment of motor dysfunction in neurological diseases. Robot-assisted gait training (RAGT) has been reported to treat motor dysfunction in patients with Parkinson's disease (PD). The purpose of this study was to summarize previous clinical studies comparing the effectiveness of RAGT and conventional training for lower extremity dyskinesia in PD patients. METHODS: PubMed, Cochrane library, Scopus, Embase, EBSCO, Web of Science, CNKI, and Wanfang databases were searched. This study included all randomized controlled trials (RCTs) compared lower extremity RAGT with conventional training on motor impairment in PD patients. The retrieval time limit is from the establishment of the database to October 2022. Two researchers independently screened the literature, extracted data, assessed the risk of bias of included studies, and then used RevMan 5.3 software for meta-analysis. RESULTS: A total of 14 RCTs with 572 patients were included. The results showed that compared with the control group, RAGT significantly improved the motor function evaluation-related indicators 10MWT, 6MWT, TUG and UPDRS III, 10MWT [MD= 0.08, 95 % CI (0.01, 0.14), P = 0.03], 6MWT [MD= 42.83, 95 % CI (22.05, 63.62), P < 0.0001], TUG[MD= -1.81, 95 % CI (-2.55, -1.08), P < 0.0001], UPDRS III [MD= - 3.82, 95 % CI (-4.27, -3.37), P < 0.00001]; For the balance function evaluation index BBS [MD= 3.33, 95 % CI (2.76, 3.89), P < 0.00001], the above results were significantly different significance. CONCLUSION: The currently limited evidence suggests that RAGT provides evidence for the effectiveness of lower extremity motor function and balance dysfunction, and RAGT can significantly improve motor and balance function in PD patients.