STING Membrane Prevents Post-Surgery Tissue Adhesion and Tumor Recurrence of Colorectal Cancer.

Surgery is the standard treatment regimen for resectable colorectal cancer (CRC). However, it is very hard to completely remove all cancer cells in clinical practice, leading to the high recurrence rates of the disease. Moreover, the post-surgery tissue adhesion greatly prevents the possibility of reoperation, significantly limiting the long-term surviving of CRC patients. To overcome CRC recurrence and avoid the post-surgery tissue adhesion, this work develops a novel stimulator of interferon genes "STING" membrane based on the coaxial electrospinning technology and hyaluronic acid modification. A reactive oxygen species responsive prodrug of gambogic acid (GB) and a potent STING agonist (CDN) are coloaded in the core-shell structure of the membrane, which endows the loaded drug with sustained and sequential release patterns. The localized delivery of GB and CDN can selectively induce efficient immunogenic cell death of cancer cells and then evoke the systemic anticancer immunity by activating the Cyclic GMP-AMP (cGAMP) synthase/STING pathway. As-designed "STING" membrane not only safely prevents tumor recurrence through the synergistic chemoimmunotherapy but also efficiently avoids the post-surgery tissue adhesion, facilitating the clinical intervention of CRC.

[Optimization of the fermentative production of L-methionine by engineered Escherichia coli].

As the only essential amino acid containing elemental sulphur, L-methionine has important physiological and biochemical functions in living organisms. However, the fermentative production of L-methionine has not met the requirements of industrial production because of its low production level. In this paper, the fermentation process of an efficient L-methionine producing strain E. coli W3110ΔIJAHFEBC trc-fliY trc-malY/PAM glyA-22 metF constructed previously was systematically optimized. Based on the optimal initial glucose concentration, the effects of different fed-batch fermentation processes, including DO-Stat, pH-Stat, controlling residual sugar control at different level and feeding glucose with constant rate, on L-methionine fermentation were studied. It was found that the control of glucose concentration greatly affected the fermentation process. Subsequently, an optimal fed-batch fermentation process was developed, where the L-methionine titer was increased to 31.71 g/L, the highest yield reported to date, while the fermentation time was shortened to 68 h. Meanwhile, a fermentation kinetics model under the optimal fed-batch fermentation conditions was established, which fitted well with the biosynthesis process of L-methionine. This study may facilitate further development of the fermentative production of L-methionine.

[Efficient synthesis of L-methionine by engineering the one carbon module of Escherichia coli].

L-methionine, also known as L-aminomethane, is one of the eight essential amino acids required by the human body and has important applications in the fields of feed, medicine, and food. In this study, an L-methionine high-yielding strain was constructed using a modular metabolic engineering strategy based on the M2 strain (Escherichia coli W3110 ΔIJAHFEBC/PAM) previously constructed in our laboratory. Firstly, the production of one-carbon module methyl donors was enhanced by overexpression of methylenetetrahydrofolate reductase (methylenetetrahydrofolate reductase, MetF) and screening of hydroxymethyltransferase (GlyA) from different sources, optimizing the one-carbon module. Subsequently, cysteamine lyase (hydroxymethyltransferase, MalY) and cysteine internal transporter gene (fliY) were overexpressed to improve the supply of L-homocysteine and L-cysteine, two precursors of the one-carbon module. The production of L-methionine in shake flask fermentation was increased from 2.8 g/L to 4.05 g/L, and up to 18.26 g/L in a 5 L fermenter. The results indicate that the one carbon module has a significant impact on the biosynthesis of L-methionine, and efficient biosynthesis of L-methionine can be achieved through optimizing the one carbon module. This study may facilitate further improvement of microbial fermentation production of L-methionine.

Investigation of the enhancement for Echinocandin B fermentation with methyl oleate from transcription level.

Echinocandin B (ECB) is the key precursor compound of the antifungal drug Anidulafungin. The effects of the five precursor amino acids on ECB biosynthesis were firstly investigated. It showed that although L-threonine was a main compound of the hexapeptide scaffold of ECB, exogenous addition of L-threonine had no significant effect on the increase of ECB fermentation titer. Meanwhile, the ECB fermentation titer with methyl oleate showed two times higher than that of the other carbon sources. Transcription level analysis of the key genes for ECB biosynthesis indicated that the gene an655543 related to L-threonine biosynthesis showed higher value during the fermentation process, therefore, the exogenous addition of L-threonine had no obvious affection. Furthermore, it indicated that the transcription level of gene ecdA might be the main restriction factor for the ECB biosynthesis. The study provided the research foundation for the modification of the ECB producing strains in the following work.

Attribute-based multi-user collaborative searchable encryption in COVID-19.

With the outbreak of COVID-19, the government has been forced to collect a large amount of detailed information about patients in order to effectively curb the epidemic of the disease, including private data of patients. Searchable encryption is an essential technology for ciphertext retrieval in cloud computing environments, and many searchable encryption schemes are based on attributes to control user's search permissions to protect their data privacy. The existing attribute-based searchable encryption (ABSE) scheme can only implement the situation where the search permission of one person meets the search policy and does not support users to obtain the search permission through collaboration. In this paper, we proposed a new attribute-based collaborative searchable encryption scheme in multi-user setting (ABCSE-MU), which takes the access tree as the access policy and introduces the translation nodes to implement collaborative search. The cooperation can only be reached on the translation node and the flexibility of search permission is achieved on the premise of data security. ABCSE-MU scheme solves the problem that a single user has insufficient search permissions but still needs to search, making the user's access policy more flexible. We use random blinding to ensure the confidentiality and security of the secret key, further prove that our scheme is secure under the Decisional Bilinear Diffie-Hellman (DBDH) assumption. Security analysis further shows that the scheme can ensure the confidentiality of data under chosen-keyword attacks and resist collusion attacks.

Dexmedetomidine attenuates postoperative spatial memory impairment after surgery by reducing cytochrome C.

BACKGROUND: Anesthesia and surgery can induce perioperative neurocognitive disorders (PND). Mitochondrial dysfunction has been proposed to be one of the earliest triggering events in surgery-induced neuronal damage. Dexmedetomidine has been demonstrated to attenuate the impairment of cognition in aged rats induced by surgery in our previous study. METHODS: Male Sprague-Dawley rats underwent hepatic apex resection under anesthesia with propofol to clinically mimic human abdominal surgery. The rats were divided into three groups: Control group, Model group and Dexmedetomidine (Dex) group. Cognitive function was evaluated with the Morris water maze (MWM), Open Field Test (OFT)and Novel object recognition task (NOR). Ultrastructural change in neuronal mitochondria was measured by transmission electron microscopy. Mitochondrial function was measured by mitochondrial membrane potential and activities of mitochondrial complexes. Neuronal morphology was observed with H&E staining and the activation of glial cells was observed by immunohistochemistry in the hippocampus. Protein levels were measured by Western blot (WB) and immunofluorescence at 3 and 7 days after surgery. RESULTS: Surgery-induced cognitive decline lasts three days, but not seven days after surgery in the model group. Transmission electron microscope showed the mitochondrial structure damage in the model group, similar changes were not induced in the Dex group. Dexmedetomidine may reverse the decrease in mitochondrial membrane potential and mitochondrial complex activity. Compared with the Control group, the expression of cytochrome c was significantly increased in model group by Western blot and immunofluorescence on days 3, but not day 7. Rats from the Model group expressed significantly greater levels of Iba-1 and GFAP compared with the Control group and the Dex group. CONCLUSION: Dexmedetomidine appears to reverse surgery-induced behavior, mitigate the higher density of Iba-1 and GFAP, reduce the damage of mitochondrial structure and function by alleviating oxidative stress and protect mitochondrial respiratory chain, thus increasing cytochrome c oxidase (COX) expression and downregulate the expression of cytochrome c protein in the hippocampus of rats.

Electroacupuncture ameliorates surgery-induced spatial memory deficits by promoting mitophagy in rats.

Background: This study sought to explore the mechanism underlying the therapeutic effects of electroacupuncture (EA) on spatial memory deficits caused by surgery. Methods: Hepatic apex resection was performed under propofol-based total intravenous anesthesia. Male Sprague-Dawley rats were subjected to EA treatment or EA + mitochondrial division inhibitor-1 (mdivi-1) treatment once a day for three consecutive days after surgery. The Morris water maze test was used to evaluate the spatial memory of the rats after surgery. Tissue from the hippocampus of each rat was frozen and used for transcriptomic and proteomic analyses to identify potential targets for EA treatment. Western blotting was used to confirm the protein expression levels. The levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were detected using commercial kits. The rat mitochondria were then isolated, and the activity of mitochondrial complex V was assessed. Results: EA attenuated surgery-induced spatial memory deficits on postoperative day 3, while these effects were reversed by treatment with the mdivi-1 (P<0.05). Ribonucleic acid (RNA)-sequencing revealed that EA upregulated multiple metabolic pathways and the phosphatidylinositol 3­kinas/protein kinase B signaling pathway. The proteomic and western blotting results suggested that the EA treatment substantially downregulated coiled-coil-helix-coiled-coil-helix domain containing 3 (ChChd3) expression in the hippocampus. The EA treatment significantly increased the autophagy-related protein levels, including phosphatase and tensin homolog-induced kinase 1, Parkin, MAP1LC3 (LC3), and Beclin1, and inhibited the production of ROS and inflammatory cytokine interleukin-1ß in the hippocampus (P<0.05). Conclusions: These results suggest that EA ameliorates postoperative spatial memory deficits and protects hippocampus from oxidative stress and inflammation through enhanced autophagy in an animal model of perioperative neurocognitive disorders (PNDs).

High-Level Production of l-Methionine by Dynamic Deregulation of Metabolism with Engineered Nonauxotroph Escherichia coli.

l-Methionine is the only sulfur-containing amino acid among the essential amino acids, and it is mainly produced by the chemical method in industry so far. The fermentation production of l-methionine by genetically engineered strains is an attractive alternative. Due to the complex metabolic mechanism and multilevel regulation of the synthesis pathway in the organism, the fermentation production of l-methionine by genetically engineered strains was still not satisfied. In this study, the biosynthesis pathway of l-methionine was regulated based on the previous studies. As the competitive pathway and an essential amino acid for cell growth, the biosynthesis pathway of l-lysine was first repaired by complementation of the lysA gene in situ on the genome and then replaced the in situ promoter with the dynamically regulated promoter PfliA to construct a nonauxotroph strain. In addition, the central metabolic pathway and l-cysteine catabolism pathway were further modified to promote the cell growth and enhance the l-methionine production. Finally, the l-methionine fermentation yield in a 5 L bioreactor reached 17.74 g/L without adding exogenous amino acids. These strategies can effectively balance the contradiction between cell growth and l-methionine production and alleviate the complexity of fermentation operation and the cost with auxotroph strains, which provide a reference for the industrial production of l-methionine by microbial fermentation.

Alpiniae oxyphylla fructus extract promotes longevity and stress resistance of C. elegans via DAF-16 and SKN-1.

Background: Alpiniae Oxyphylla Fructus (AOF) is Traditional Chinese medicine and a dietary supplements for centuries, which posseses cardiotonic, neuroprotective, antioxidant, warming the kidney and nourish the spleen, these biological fuction is related to potential anti-aging properties. However, little is known about their effects on aging. This work aimed to investigate the effects of extracts of AOF on longevity and stress resistance in Caenorhabditis elegans (C. elegans) and the mechanisms that underlie its effects. Methods: Wild-type (WT) strand of C.elegans (N2)worms were cultured in growth medium with or without AOF. First, we examined the effects of AOF on lifespan, reproduction and healthspan assay, stress resistance and oxidative analysis, lipofuscin levels. Second, The levels of ROS and MDA, the antioxidant enzyme activities were examined to explore the underlying mechanism of AOF. Finally, the expression of the longevity-related genes were investigated to further understand the AOF's underlying mechanism. Results: The lifespan of C. elegans was prolonged by 23.44% after treatment with high-dose AOF (100 ug/ml). AOF alleviated aging-related declines in C. elegans health and enhanced resistance to heat shock. Furthermore, AOF decreased reactive oxygen species and malondialdehyde, increased the activities of superoxide dismutase and catalase, and reduced accumulation of fat. AOF upregulated the expression of sod-3, gst-4, daf-16, and skn-1 but downregulated the expression of daf-2 and age-1 and accelerated the translocation of DAF-16 into the nucleus. The extended lifespan induced by AOF was reversed in daf-16(mu86) and skn-1(zu135) mutants, indicating that this gene is involved in AOF-regulated longevity. Conclusion: Our findings demonstrated that AOF extends lifespan and healthspan and enhances stress via boosting the activity of the antioxidant enzyme and controlling the expression of genes associated with insulin/IGF signaling and SKN-1 pathways. As a result, this work suggested AOF as a possible candidate to reduce the signs of aging by activating and inhibiting target genes.

B-cell receptor associated protein 31 deficiency decreases the expression of adhesion molecule CD11b/CD18 and PSGL-1 in neutrophils to ameliorate acute lung injury.

Acute lung injury (ALI) and its more severe condition acute respiratory distress syndrome (ARDS) are critical life-threatening disorders characterized by an excessive influx of neutrophils into the alveolar space. Neutrophil infiltration is a multi-step process involving the sequential engagement of adhesion molecules. The adhesion molecule CD11b/CD18 acts as an important role in the recruitment of neutrophils to lung tissues in the ALI model. B-cell receptor associated protein 31 (BAP31), an endoplasmic reticulum transmembrane protein, has been reported to regulate the cellular anterograde transport of CD11b/CD18 in human neutrophils. To explore how BAP31 regulates CD11b/CD18 in mouse neutrophils, we constructed myeloid-specific BAP31 knockdown mice in this study. Biological investigations indicated that BAP31 deficiency could significantly alleviated lung injury, as evidenced by the improved histopathological morphology, reduced pulmonary wet/dry weight ratio, inhibited myeloperoxidase level and decreased neutrophil counts in the bronchoalveolar lavage fluid. Further studies clarified that BAP31 deficiency obviously down-regulated the expression of CD11b/CD18 and P-selectin glycoprotein ligand-1 (PSGL-1) by deactivating the nuclear factor kappa B (NF-κB) signaling pathway. Collectively, our results revealed that BAP31 depletion exerted a protective effect on ALI, which was possibly dependent on the attenuation of neutrophil adhesion and infiltration by blocking the expression of adhesion molecules CD11b/CD18 and PSGL-1. These findings implied the potential of BAP31 as an appealing protein to mediate the occurrence of ALI.

Network pharmacology-based approach uncovers the JAK/STAT signaling mechanism underlying paederia scandens extract treatment of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease. Paederia scandens (Lour.) Merr is a common folk remedy used in Hainan, China, to dispel the wind and dampness associated with RA. METHODS: The active components of Paederia scandens were extracted using network pharmacology. The potential targets of active components were used to determine activated pathways, and the in vitro effects of Paederia scandens extracts were verified in RA fibroblast-like synoviocytes (HFLS-RA). RESULTS: We identified 27 active components using ultra-high-performance liquid chromatography (UHPLC)-quadrupole time-of-flight (QTOF)-mass spectrometry (MS). Among the major target genes with high connectivity, IL-1ß, PI3K, TNF, and JAK2 are known to play key roles in RA development. High-affinity interactions were identified between active compounds in Paederia scandens extract and Janus kinase JAK 2, which are key components of the JAK-signal transducer and activator of transcription (STAT) signaling pathway. In HFLS-RA cells, Paederia scandens extract treatment reduced the mRNA levels of IL-6, IL-1ß, and IL-17. Paederia scandens extract treatment also significantly inhibited the phosphorylation of JAK 2 and STAT3, regulating cell proliferation. CONCLUSIONS: Based on these results, we confirmed that Paederia scandens has potential for application as a therapeutic and preventive food and acts through the modulation and suppression of JAK-STAT pathway activation to control the inflammatory response in RA.

Intraperitoneal ozone injection prevents REM sleep deprivation - induced spatial learning and memory deficits by suppressing the expression of Sema3A in the hippocampus in rats.

Objectives: Sleep deprivation is a common health problem in modern society and is negatively associated with deleterious effects on cognitive functions such as learning and memory ability. This study was undertaken to provide a detailed account of the effect of chronic ozone intraperitoneal injection on the deleterious effects of sleep deprivation on brain function in rats. Materials and Methods: Sleep deprivation was induced using the modified multiple platform model. The rats received REM sleep deprivation with an intraperitoneal injection of ozone or midazolam for 28 days. The effects of ozone on REM sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by the following approaches: Morris water maze (MWM) tests were used to evaluate spatial learning and memory of rats. Morphological changes in the brain were evaluated using hematoxylin and eosin (HE) staining. RNA-sequence was performed to seek a common mechanism. The expression of the targeted gene was examined by qPCR and Western blotting. Results: Ozone intraperitoneal injection reversed spatial learning and memory deficits associated with REM sleep deprivation, ameliorating pathological brain damage and down-regulating the hippocampal expression of Sema3A in rats after REM sleep deprivation. Conclusion: Ozone intraperitoneal injection alleviated sleep deprivation-induced spatial learning and memory deficits by protecting hippocampal neurons via down-regulation of the expression of Sema3A in the hippocampus.

Screening of potential key ferroptosis-related genes in sepsis.

Background: Sepsis leads to multiple organ dysfunction caused by a dysregulated host response to infection with a high incidence and mortality. The effect of ferroptosis on the development of sepsis remains unclear. In this study, we aimed to identify the key ferroptosis-related genes involved in sepsis and further explore the potential biological functions of these ferroptosis-related genes in sepsis using bioinformatics analysis. Methods: The GSE13904 (from children) and GSE28750 (from adults) datasets were downloaded from the Gene Expression Omnibus (GEO). The ferroptosis-related genes were obtained from the FerrDb database. The ferroptosis-related differentially expressed genes (DEGs) were screened by the limma R package. The DAVID online database or clusterProfiler R package was used for the functional enrichment analysis. Then, the STRING database was used to predict the interactions of proteins, and the CytoHubba plugin of Cytoscape was used to confirm key clustering modules. Then, the miRNAs and lncRNAs associated with the key clustering modules were predicted by miRWalk 2.0 and LncBase v.2 respectively. Finally, we generated a cecal ligation and puncture (CLP) polymicrobial sepsis model in C57 male mice and examined the expression of the mRNAs and noncoding RNAs of interest in peripheral blood leukocytes by PCR during the acute inflammation phase. Results: In total, 34 ferroptosis-related DEGs were identified in both adult and pediatric septic patients. These ferroptosis-related DEGs were mainly enriched in inflammatory pathways. Then, a significant clustering module containing eight genes was identified. Among them, the following five genes were closely associated with the MAPK signaling pathway: MAPK14, MAPK8, DUSP1, MAP3K5 and MAPK1. Then, crucial miRNAs and lncRNAs associated with biomarker MAPK-related genes were also identified. In particular, let-7b-5p and NEAT1 were selected as noncoding RNAs of interest because of their correlation with ferroptosis in previous studies. Finally, we examined the mRNAs, miRNAs and lncRNAs of interest using CLP-induced sepsis in peripheral blood leukocytes of mice. The results showed that MAPK14, MAPK8, MAP3K5, MAPK1 and NEAT1 were upregulated, while DUSP1 and let-7b-5p were downregulated in the CLP group compared with the sham group. Conclusions: The MAPK signaling pathway may play a key role in regulating ferroptosis during sepsis. This study provides a valuable resource for future studies investigating the mechanism of MAPK-related ferroptosis in sepsis.

Investigating the molecular mechanism of Compound Danshen Dropping Pills for the treatment of epilepsy by utilizing network pharmacology and molecular docking technology.

Background: Compound Danshen Dropping Pills (CDDP) is widely used in clinical treatment of epilepsy. But the underlying active ingredients and molecular mechanisms are unclear. Our study aims to investigate the active components and functional mechanisms of CDDP in treating epilepsy using a network pharmacology approach. Methods: Candidate constituents and targets of CDDP were searched on the Traditional Chinese Medicine Systems Pharmacology database. NCBI and Genecards were used to establish a database of epilepsy targets. Next, used Cytoscape software, the interactive network diagram of "drug-active component-target" was drawn. Based on the STRING database we constructed protein-protein interaction network and analyzed protein-protein interaction relationships. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for the common targets. Molecular docking provided an evaluation tool for verifying the combination of components and targets, which was performed using Auto-dock. Results: Sixty bioactive components, corresponding to 79 therapeutic targets for epilepsy, were successfully identified. Functional enrichment analysis showed that CDDP plays a pharmacological role in the treatment of epilepsy by regulating serotonergic synapses, morphine addiction, nicotine addiction and other pathways, as well as the NF-κB signaling pathway. Molecular docking analysis showed that representative components may be closely bound to key targets. Conclusions: This network pharmacology study revealed the synergistic effects of multiple components, targets, and pathways of CDDP in the treatment of epilepsy, which will deepen our understanding of the underlying molecular mechanisms of CDDP in the treatment of epilepsy and lay the foundation for further experimental studies.

The Multivariate Effect of Ketamine on PTSD: Systematic Review and Meta-Analysis.

Background: Post-traumatic stress disorder (PTSD) is a serious stress-related disorder caused by traumatic experiences. However, identifying a key therapy that can be used for PTSD treatment remains difficult. Ketamine, a well-known dissociative anesthetic, is considered safe to be used in anesthesia, pain management, and antidepressant actions since 1970. At present, it is still controversial whether PTSD can be treated with ketamine. The authors performed a meta-analysis to determine whether the use of perioperative ketamine lowers the incidence of PTSD. Methods: Cochrane Central Register of Controlled Trials, Embase, PubMed, and Web of Science were searched to examine the use of ketamine for the treatment of PTSD among soldiers with combating experience. Studies were included if they were randomized placebo-controlled, case-control, and cohort studies. The primary outcome was the incidence of PTSD in the later stage of the wounded or burn soldiers. The secondary outcome was the influence of ketamine on PTSD-scale scores for early and chronic PTSD, respectively. Results: Our search yielded a total of three studies (n = 503 patients) comparing the use of ketamine (n = 349) to control (n = 154). The available evidence showed no significant difference in the incidence of PTSD between combatant soldiers on the battlefield with or without ketamine treatment (risk ratio = 0.81, 95% CI, 0.63-1.04; P = 0.10). In 65 patients from three trials, ketamine was not only ineffective in treating early PTSD but also lead to exacerbation of the disease (risk ratio = 2.45, 95% CI, 1.33-3.58; P < 0.001). However, in 91 patients from the other three trials, ketamine is effective in treating chronic PTSD (risk ratio = -3.66, 95% CI, -7.05 to -0.27; P = 0.03). Conclusion: Ketamine was not effective on lower the PTSD incidence for soldiers on the battlefield, nor on the PTSD-scale scores in early PTSD patients. However, it may improve the PTSD-scale scores for chronic conditions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255516, PROSPERO, identifier: CRD42021255516.

Treatment of Femoral Head Osteonecrosis with Ozone Therapy: Pilot Trial of a New Therapeutic Approach.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a progressive and painful disorder due to impaired blood supply to the femoral head, yet little is known about the effect of ozone therapy in femoral head necrosis. OBJECTIVES: We aimed to evaluate the clinical and radiographic outcomes of ozone therapy in the treatment of ONFH. STUDY DESIGN: Nonrandomized clinical trial. SETTINGS: The study was conducted in a single-center, academic institution. METHODS: A total of 71 patients (107 hip joints) with Association Research Circulation Osseous (ARCO) stage-I, II, III, and IV ONFH were included and assigned to undergo either intraarticular O2-O3 mixture hip injections with ozonated autohemotherapy (ozone therapy group, n = 39, 58 hip joints) or protected weight bearing (control group, n = 32, 49 hip joints). The primary outcomes included the Visual Analog Scale (VAS) for pain intensity and Harris Hip Score (HHS) for hip function. The secondary outcomes included bone marrow edema examination, and conversion to total hip arthroplasty (THA). RESULTS: Ozone therapy effectively improves VAS for pain intensity and HHS during the follow-up period compared to the control group. Ozone therapy showed a significant resolution of bone marrow edema of the femoral head compared to the control group (P < 0.001). Thirteen of the 49 hips (26.53%) in the control group underwent THA, whereas only 6 hips (10.34%) in the ozone therapy group required THA during a 30-month follow-up (P = 0.041). The cumulative analysis revealed a low rate of conversion to THA in the ozone therapy group (logrank test; P = 0.022). LIMITATIONS: The study is limited by a single treatment protocol in addition to the lack of a randomized design. CONCLUSIONS: Ozone therapy was associated with significant pain relief, improvement in hip function, and bone marrow edema resolution that may delay the need for THA in patients affected by ONFH.Institutional Review Board (IRB) approval number: HK2018-10-28.Clinical trials registration number: ChiCTR1900023449.

[Advances in the biosynthesis of L-homoserine and its derivatives by metabolic engineering of Escherichia coli].

L-homoserine and its derivatives (O-succinyl-L-homoserine and O-acetyl-L-homoserine) are precursors for the biosynthesis of L-methionine, and various C4 compounds (isobutanol, γ-butyrolactone, 1, 4-butanediol, 2, 4-dihydroxybutyric acid) and L-phosphinothricin. Therefore, the fermentative production of L-homoserine and its derivatives became the research hotspot in recent years. However, the low fermentation yield and conversion rate, and the unclear regulation mechanism for the biosynthesis of L-homoserine and its derivatives, hamper the development of an efficient production process for L-homoserine and its derivatives. This review summarized the advances in the biosynthesis of L-homoserine and its derivatives by metabolic engineering of Escherichia coli from the aspects of substrate uptake, redirection of carbon flow at the key nodes, recycle of NADPH and export of target products. This review may facilitate subsequent metabolic engineering and biotechnological production of L-homoserine and its derivatives.

[Development and practice of national first-class undergraduate course "bioengineering equipment"].

As a strategic emerging industry of China, the biotechnology industry develops rapidly in recent years, which significantly increased the demand for creative and capable talents. As a core curriculum of bioengineering specialty, biotechnology equipment plays an important role in fostering such talents. To address the problems in biotechnology equipment course teaching such as limited equipment availability, limited engineering practice, and lack of learning motivations, curriculum reform and optimization were performed based on curriculum resource development, virtual reality-physical combined engineering training, and boosting learning motivations. The optimized teaching contents focus on fostering morality, intelligence, and creative practice abilities by connecting new requirements of social development, introducing new progress in biotechnology research, as well as new practices in research and development (R & D). Measures such as teaching methods innovation, assessment and evaluation methods optimization, cutting-edge R & D progress, diverse resources integration, and online-offline combined teaching, were developed to boost the learning motivation and foster the innovation competence of students. By above exploration and practice, the practice and innovation competence of students were significantly enhanced.

Efficacy of traditional Chinese exercise for sarcopenia: A systematic review and meta-analysis of randomized controlled trials.

Objective: To conduct a systematic review and meta-analysis to evaluate the effectiveness of Traditional Chinese Exercise (TCE) for sarcopenia. Methods: A literature search was conducted in eight online databases from inception until September 2022. Based on the Cochrane risk of bias tool, randomized controlled trials (RCTs) with RoB score ≥ 4 were included for further analyses. The primary outcome was muscle strength and physical function, and the secondary outcomes were adverse events. Data collection and analyses were conducted by RevMan 5.4 Software. GRADE system was used to evaluate the certainty of evidence. Results: A total of 13 eligible RCTs with 718 subjects were identified and included in this study. Among them, 10 RCTs involved Yijinjing; 2 involved Tai Chi; and 1 involved Baduanjin. Meta-analyses showed that TCE had better clinical effects than control measures in the chair stand test (P < 0.00001, I2 = 38%; Certainty of evidence: Moderate), squatting-to-standing test (P < 0.00001, I2 = 0%; Certainty of evidence: Moderate), 6-m gait speed (P < 0.00001, I2 = 13%; Certainty of evidence: Moderate), Time Up and Go Test (P = 0.03, I2 = 81%; Certainty of evidence: Low), peak torque of the extensors (P = 0.03, I2 = 0%; Certainty of evidence: Moderate), total work of the extensors (P = 0.03, I2 = 35%; Certainty of evidence: Moderate), peak torque of the flexors (P = 0.03, I2 = 47%; Certainty of evidence: Low), total work of the flexors (P = 0.02, I2 = 42%; Certainty of evidence: Low), the average power of the flexors (P = 0.03, I2 = 30%; Certainty of evidence: Moderate), and balance function (P < 0.00001, I2 = 53%; Certainty of evidence: Low). In additional, no adverse events were reported in participants who receive TCE. Conclusion: The findings of the present systematic review, at least to a certain extent, provided supporting evidence for the routine use of TCE for sarcopenia.

Optimization of traditional Chinese medicine rolling manipulation and pressure attenuation.

BACKGROUND: Traditional Chinese Medicine (TCM) massage utilizes mechanical force stimulation, and the amount of mechanical force influences therapeutic outcome. This amount is determined by pressure, frequency, and duration; however, there are no standard definitions for these measures. METHODS: An orthogonal design was used to evaluate massage efficacy using muscle tension as an index. Pressure (2, 4, 6 kg), duration (5, 10, 15 min), frequency (60, 120, 180 repetitions/min), pain (mild, medium, severe), weight (<60, 60-75, >75 kg), and sex (male, female) were evaluated. Additionally, a porcine model of muscle tension was used to construct pressure-time curves for muscle tissues under static and dynamic pressure. RESULTS: We identified an interaction among the six massage measures (P<0.05). Of these measures, only two were individually significant: manipulation frequency and patient pain level (P<0.05). Specifically, 120 repetitions/min improved muscle tension significantly more than 60 or 180 repetitions/min (P<0.05), and patients with severe pain had significantly improved muscle tension compared to those with medium or mild pain (P<0.05). In the porcine muscle model, both static and dynamic pressure were attenuated by approximately 12.5% per cm. This attenuation dropped to 10% per cm when the pressure sensor was placed below tissues with different thicknesses instead of being inserted into tissues at different levels. CONCLUSION: Manipulation frequency and patient pain level were primarily responsible for the therapeutic effects of TCM massage. Mechanistically, pressure was attenuated by nearly 75% at a depth of 2 cm from the muscle surface during TCM massage.