Elucidating the chemical interaction effects of herb pair Danshen-Chuanxiong and its anti-ischemic stroke activities evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge (Danshen) and Ligusticum chuanxiong Hort. (Chuanxiong) is the core herb pair in traditional Chinese medicines (TCMs) formulae for treating ischemic stroke. However, the synergistic effect of Danshen-Chuanxiong against anti-ischemic stroke and its compatibility mechanism remains unclear. AIM OF THE STUDY: This study aimed to uncover the compatibility mechanism of Danshen-Chuanxiong against ischemic stroke through chemical profiling, pharmacodynamics evaluation, network pharmacology and experimental validation. MATERIALS AND METHODS: Ultra-high performance liquid chromatography (UHPLC) combined with quadrupole time-of-flight tandem mass spectrometry (QTOF-MS) and UHPLC connected with tandem triple quadrupole mass spectrometry (QQQ-MS) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of Danshen-Chuanxiong against ischemic stroke were comprehensively evaluated by the middle cerebral artery occlusion reperfusion (MCAO/R) mice model, zebrafish ischemic stroke model and glutamic acid-induced PC12 cells injury model. Afterwards, network pharmacology and molecular docking were applied to dissect the significant active compounds and potential mechanisms. Finally, the key target proteins were experimentally validated by Western blot. RESULTS: 83 compounds were characterized in Danshen-Chuanxiong by UHPLC-QTOF-MS analysis, and 4 compounds were tentatively identified for the first time. The quantification results (24 accurately identified compounds) in 13 proportions of Danshen-Chuanxiong revealed that Danshen significantly increased the dissolution of most phthalides (from Chuanxiong), while Chuanxiong facilitated the dissolution of most phenolic acids (from Danshen) in solution. The anti-ischemic stroke effects of Danshen-Chuanxiong were significantly better than Danshen or Chuanxiong in attenuating infarct size, reducing brain edema and neurological scores in MCAO/R mice. Also, compared with single herbs, this herb pair exerted better effects of suppressing the incidence of cerebral thrombosis in zebrafish, and increasing the cell viability of glutamic acid-induced PC12 cells. In network pharmacology, 7 effective compounds (rosmarinic acid, chlorogenic acid, salvianolic acid B, (Z)-ligustilide, ferulic acid, caffeic acid, tanshinone IIA) and 5 hub targets (AKT, TNF-α, IL-1ß, CASP3 and BCL2) as well as 4 key pathways were predicted. Western blot results showed that Danshen-Chuanxiong exert therapeutic effects mainly through decreasing the protein expressions of TNF-α, IL-1ß and Cleaved-CASP3, elevating the levels of p-AKT and BCL2. CONCLUSIONS: This work provided an integration strategy for uncovering the synergistic effects and compatibility mechanism of Danshen-Chuanxiong herb pair for treating ischemic stroke, and laid foundation for the further development and utilization of this herb pair.

Influence of Lithium Diffusion into Copper Current Collectors on Lithium Electrodeposition in Anode-Free Lithium-Metal Batteries.

The development of "anode-free" lithium-metal batteries with high energy densities is, at present, mainly limited by the poor control of the nucleation of lithium directly on the copper current collector, especially in conventional carbonate electrolytes. It is therefore essential to improve the understanding of the lithium nucleation process and its interactions with the copper substrate. In this study, it is shown that diffusion of lithium into the copper substrate, most likely via the grain boundaries, can significantly influence the nucleation process. Such diffusion makes it more difficult to obtain a great number of homogeneously distributed lithium nuclei on the copper surface and thus leads to inhomogeneous electrodeposition. It is, however, demonstrated that the nucleation of lithium on copper is significantly improved if an initial chemical prelithiation of the copper surface is performed. This prelithiation saturates the copper surface with lithium and hence decreases the influence of lithium diffusion via the grain boundaries. In this way, the lithium nucleation can be made to take place more homogenously, especially when a short potentiostatic nucleation pulse that can generate a large number of nuclei on the surface of the copper substrate is applied.

Automated Workflow for Calculating the Collective and Average Effective Doses of Galactic Cosmic Radiation Received by Pilots in Taiwan from 2006 to 2021.

ABSTRACT: On the basis of statistical data obtained from publicly available annual civil aviation reports, we developed an automated workflow for estimating the overall radiation exposure of aircraft pilots caused by galactic cosmic radiation. The workflow comprises several data-processing scripts that work with the batch analysis capability built in the NTHU Flight Dose Calculator. This method can quickly provide best possible estimates of the annual collective and average effective doses received by pilots of various airlines because all passenger, cargo, and charter flights operated that year were considered rather than some selected flights. The workflow and its implementation as well as analysis of results for the period of 2006-2021 are discussed herein. The results revealed that in 2019, six airlines in Taiwan operated 479 separate flight segments with 226 aircraft. The collective effective dose received by all 2,986 pilots was approximately 5,536 person-mSv; hence, the average individual effective dose was 1.85 mSv. During the COVID-19 pandemic, the doses decreased by more than half. In 2020, the collective effective dose received by all 2,936 pilots decreased sharply to 2,527 person-mSv, corresponding to an average effective dose per pilot of only 0.86 mSv. During 2006-2019, the annual average effective dose per pilot in Taiwan was between 1.65 and 2.71 mSv, and the average effective dose rate per flight hour was 3.15 µSv h.-1.

Dietary risk assessment of benzophenone derivatives using bread consumption estimates in a Taiwanese population.

Listed as endocrine-disrupting chemicals, benzophenone (BP) and its nine analogues (BPs) are an emerging group of contaminants. The migration of BPs from ultraviolet inks to food has been investigated in many studies; however, few studies have investigated BPs in foods and the risks of human exposure to BPs. We validated a trace and multi-residue method for simultaneously determining 10 BPs, including BP, BP-1, BP-2, BP-3, BP-8, 4-MBP, 2-OHBP, 4-OHBP, M2BB, and PBZ. Eighty-one bread samples were analyzed using stable isotope labeling and ultrahigh-performance liquid chromatography-electrospray ionization tandem mass spectrometry with solid-liquid extraction. We determined the estimated daily intake of BPs, non-cancer risks, and lifetime cancer risks (LTCRs) from daily bread consumption for seven age groups using a Monte Carlo simulation. The method demonstrated robust linearity (R2 ≥ 0.991), low limits of detection (0.04-2 ng/g), and satisfactory precision. The intra- and interday relative standard deviation ranges were 0.6%-9% and 3%-20%, respectively. BP, 4-MBP, 2-OHBP, BP-1, and BP-3 were detected in 97%, 67%, 59%, 24%, and 23% of the samples, respectively. 2-OHBP had the highest mean (range) value of 18.3 (

Comparison of senhance and da vinci robotic radical prostatectomy: short-term outcomes, learning curve, and cost analysis.

BACKGROUND: The Senhance® Robotic System is a new laparoscopy-based platform that has been increasingly used in radical prostatectomy (RP) procedures. The purpose of this study is to compare the outcome of Senhance RP (SRP) with da Vinci RP (DRP) cases. METHODS: From August 2019 to April 2022, we prospectively recruited 63 cases of SRP. We compared the perioperative data, postoperative complication rates, short-term surgical outcomes (3-month postoperative undetectable prostate-specific antigen (PSA) and incontinence rates), learning curves, and cost analysis with data from 63 matched da Vinci Xi RP cases. RESULTS: There was no difference in BL (180 versus 180 ml, p = 0.86) and postoperative surgical complication rate (Clavient -Dindo grade I-IV, 25.3 versus 22.2%, p = 0.21) between the SRP cases and the DRP. Regarding the oncologic and continence function, there was no difference between positive margin rate (36.5% versus 41.3%, p = 0.58), rate of undetectable PSA level at postoperative 3 months (68.3 versus 66.7%, p = 0.85), and incontinence rate (14.3 versus 15.9%, p = 1.0) at postoperative 3 months between the two cohorts. The learning curve showed a quick downward slope for laparoscopic experienced surgeons. The median pocket cost for SRP patients in our hospital was $4170, which was lower than $7675 for the DRP patients. CONCLUSIONS: Safety and short-term outcomes are comparable between SRP and DRP. For experienced LRP surgeons, using the Senhance system to perform RP is straightforward. With a more affordable price as its biggest advantage, the Senhance system may serve as a safe and effective alternative for robotic RP.

Long-term survival after major trauma: a retrospective nationwide cohort study from the National Health Insurance Research Database.

BACKGROUND: Most trauma-related studies are focused on short-term survival and complications within the index admission, and the long-term outcomes beyond discharge are mainly unknown. The purpose of this study was to analyze the data from the National Health Insurance Research Database (NHIRD) and to assess the long-term survival of major trauma patients after being discharged from the index admission. MATERIAL AND METHODS: This retrospective, observational study included all patients with major trauma (injury severity score ≥16) in Taiwan from 2003 to 2007, and a 10-year follow-up was conducted on this cohort. Patients aged 18-70 who survived the index admission were enrolled. Patients who survived less than one year after discharge (short survival, SS) and those who survived for more than one year (long survival, LS) were compared. Variables, including preexisting factors, injury types, and short-term outcomes and complications, were analyzed, and the 10-year Kaplan-Meier survival analysis was conducted. RESULTS: In our study, 9896 patients were included, with 2736 in the SS group and 7160 in the LS group. Age, sex, comorbidities, low income, cardiopulmonary resuscitation event, prolonged mechanical ventilation, prolonged ICU length of stay (LOS), and prolonged hospital LOS were identified as the independent risk factors of SS. The 10-year cumulative survival for major trauma patients was 63.71%, and the most mortality (27.64%) occurred within the first year after discharge. CONCLUSION: 27.64% of patients would die one year after being discharged from major trauma. Major trauma patients who survived the index admission still had significantly worse long-term survival than the general population, but the curve flattened and resembled the general population after one year.

Prenatal to preschool exposure of nonylphenol and bisphenol A exposure and neurodevelopment in young children.

BACKGROUND: Nonylphenol (NP) and bisphenol A (BPA) are produced in large quantities worldwide as multipurpose agents. However, studies on relations between NP and BPA exposure and childhood neurodevelopment are few, and the results are inconsistent. This study aimed to investigate associations between prenatal and early childhood NP and BPA exposure and neurodevelopment in mother-child pairs. METHODS: Pregnant women at 27-38 weeks' gestation were recruited, as were children 2-3 years of age (n = 94) and 4-6 years of age (n = 56) years. Urine was collected to assess NP and BPA exposure. Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), Wechsler Preschool and Primary Scale of Intelligence (4th edition), and the Full Scale Intelligence Quotient (WPPSI-IV-FSIQ) were used to assess the neurodevelopment of the children. RESULTS: The detection rate and concentration of NP and BPA in the urine of children 4-6 years old were higher than in those 2-3 years old. Children were divided into a high concentration group (3rd tertile) and a reference group (1st and 2nd tertiles) based on natural log-transformed urine concentration of NP and BPA. Girls' Bayley-III motor scores in the high concentration group were higher than those of the BPA reference group of urine of mothers (ß = 6.85, 95% confidence interval [CI]: 1.58-12.13). Boys' FSIQ in the higher concentration group were significantly lower than those in children 2-3 years old in the NP reference group (ß = -11.29, 95% CI: -18.62 to -3.96) (all, p < 0.05). CONCLUSIONS: Prenatal and childhood exposure to NP and BPA may have different effects on the neurodevelopment of young children, and there are no consistent effects between boys and girls.

Whole genome analysis of Bacillus amyloliquefaciens TA-1, a promising biocontrol agent against Cercospora arachidicola pathogen of early leaf spot in Arachis hypogaea L.

BACKGROUND: Early leaf spot disease, caused by Cercospora arachidicola, is a devastating peanut disease that has severely impacted peanut production and quality. Chemical fungicides pollute the environment; however, Bacillus bacteria can be used as an environmentally friendly alternative to chemical fungicides. To understand the novel bacterial strain and unravel its molecular mechanism, De novo whole-genome sequencing emerges as a rapid and efficient omics approach. RESULTS: In the current study, we identified an antagonistic strain, Bacillus amyloliquefaciens TA-1. In-vitro assay showed that the TA-1 strain was a strong antagonist against C. arachidicola, with an inhibition zone of 88.9 mm. In a greenhouse assay, results showed that the TA-1 strain had a significant biocontrol effect of 95% on peanut early leaf spot disease. De novo whole-genome sequencing analysis, shows that strain TA-1 has a single circular chromosome with 4172 protein-coding genes and a 45.91% guanine and cytosine (GC) content. Gene function was annotated using non-redundant proteins from the National Center for Biotechnology Information (NCBI), Swiss-Prot, the Kyoto Encyclopedia of Genes and Genomes (KEGG), clusters of orthologous groups of proteins, gene ontology, pathogen-host interactions, and carbohydrate-active enZYmes. antiSMASH analysis predicted that strain TA-1 can produce the secondary metabolites siderophore, tailcyclized peptide, myxochelin, bacillibactin, paenibactin, myxochelin, griseobactin, benarthin, tailcyclized, and samylocyclicin. CONCLUSION: The strain TA-1 had a significant biological control effect against peanut early leaf spot disease in-vitro and in greenhouse assays. Whole genome analysis revealed that, TA-1 strain belongs to B. amyloliquefaciens and could produce the antifungal secondary metabolites.

Three-dimensional human bile duct formation from chemically induced human liver progenitor cells.

Background: The intrahepatic bile ducts (BDs) play an important role in the modification and transport of bile, and the integration between the BD and hepatocytes is the basis of the liver function. However, the lack of a source of cholangiocytes limits in vitro research. The aim of the present study was to establish three-dimensional BDs combined with human mature hepatocytes (hMHs) in vitro using chemically induced human liver progenitor cells (hCLiPs) derived from hMHs. Methods: In this study, we formed functional BDs from hCLiPs using hepatocyte growth factor and extracellular matrix. BDs expressed the typical biliary markers CK-7, GGT1, CFTR and EpCAM and were able to transport the bile-like substance rhodamine 123 into the lumen. The established three-dimensional BDs were cocultured with hMHs. These cells were able to bind to the BDs, and the bile acid analog CLF was transported from the culture medium through the hMHs and accumulated in the lumen of the BDs. The BDs generated from the hCLiPs showed a BD function and a physiological system (e.g., the transport of bile within the liver) when they were connected to the hMHs. Conclusion: We present a novel in vitro three-dimensional BD combined with hMHs for study, drug screening and the therapeutic modulation of the cholangiocyte function.

Epidemiological and Clinical Characteristics of COVID-19 Outbreak in a Mental Hospital in Wenzhou, China, December 2022-January 2023.

Background: Coronavirus disease (COVID-19) mainly caused by the Omicron virus strain currently is still prevalent worldwide, and many medical institutions have experienced COVID-19 outbreaks in the past three years. Objective: This article reported COVID-19 outbreak among health care workers in a mental hospital to clarify the epidemiological and clinical characteristics of COVID-19 outbreak in a medical institution, to assess the susceptible factors related to COVID-19 among these personnel and to evaluate the effect of COVID-19 vaccine on the medical workers. Methods: A uniform questionnaire was used to investigate all employees, including age, gender, department, time of onset, clinical symptoms, vaccination status. At the same, the results of laboratory testing, chest computed tomography (CT) and/or X-ray examination were collected. Results: Among 1047 hospital employees, 842 cases were diagnosed as COVID-19, with a total attack rate of 80.42%. The attack rate of doctors, nurses, medical technicians, and administrators (83.50-90.67%) was higher than that of logistics departments (56.81%). Out of the 842 patients, 9 were hospitalized; 833 were non-hospitalized patients who belong to mild or moderate cases. No deaths were reported. The full vaccination rate and booster rate of COVID-19 vaccine were 78.26% and 80.87%, respectively. There was no significant correlation between the attack rate and COVID-19 vaccine (χ2 = 3.41 P > 0.05). Conclusion: This is an outbreak of COVID-19 with a high attack rate among employees in a mental hospital. The attack rate of medical personnel is higher than that of logistics personnel, which may be related to opportunities and duration of contact with infected individuals. COVID-19 vaccine has no significant protective effect on patients with mild or moderate symptoms 13 months after the full vaccination. It is suggested that they should be timely boostered with COVID-19 vaccine to maintain their immunity to the disease.

Intraoperative Blood Pressure Lability Acts as a Key Mediator of the Impact of Goal-Directed Fluid Therapy on Postoperative Complications among Patients Undergoing Major Spine Surgery.

Objective Although goal-directed fluid therapy has been proven to be effective in reducing the incidence of postoperative complications, the underlying mechanisms remain unknown. The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between goal-directed fluid therapy (GDFT) and the incidence of postoperative complications. We further tested the role of this mediation effect using mean arterial pressure, a hemodynamic indicator.Methods This is a secondary analysis of a completed nonrandomized controlled study purposed to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis. We used a simple mediation model to test whether the mediation effect of average real variability (ARV) between the association of GDFT and postoperative complication exists. Mediation analysis was conducted using the mediation package in R (version 3.1.2), based on 5,000 bootstrapped samples, adjusting for covariates.Results Among the 300 patients in the study, 40% (120/300) developed postoperative complications within 30 days. GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders (odds ratio: 0.460, 95% CI: 0.278, 0.761; P = 0.003). The total effect of GDFT on postoperative complications was -0.18 (95% CI: -0.28, -0.07; P < 0.01). The average causal mediation effect was -0.08 (95% CI: -0.15, -0.04; P < 0.01). The average direct effect was -0.09 (95% CI: -0.20, 0.03; P = 0.17). The proportion mediated was 49.9% (95% CI; 18.3%, 140.0%). Conclusions The intraoperative blood pressure lability mediated the relationship between GDFT and the incidence of postoperative complications. Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.

Hypso- or bathochromic phosphorescent mechanochromic mononuclear Cu(I) complexes with a bis(2-diphenylphosphinophenyl)ether auxiliary ligand.

Six phosphorescence-emitting metal-organic mononuclear Cu(I) complexes, namely four quinoline-containing three-coordinate Cu(I) complexes and two N-heterocyclic carbene-containing four-coordinate Cu(I) complexes, have been successfully developed and fully characterized. All these Cu(I) complexes include the same bis(2-diphenylphosphinophenyl)ether bidentate auxiliary ligand. Significantly, four-coordinate Cu(I) complexes 1 and 2 display typical aggregation-induced emission phenomena. Their solid samples of luminogenic complexes 1-6 emit a variety of different phosphorescence. Furthermore, solid-state phosphorescence of these Cu(I) complexes can be effectively manipulated by external mechanical force. Remarkably, luminophores 1, 2 and 5 exhibit blue-shifted mechanoluminochromism responses, while luminophores 3, 4 and 6 present red-shifted mechanoluminochromism characteristics. All of the observed mechano-responsive phosphorescence changes of solids 1-6 are reversible by the method of solvent fuming. Powder X-ray diffraction results confirm that the reversible mechanically induced phosphorescence changes of complexes 1-6 are due to the mutual transformation of ordered crystalline and metastable amorphous states.

Antihypertensive peptide resources map of ribulose-1,5-bisphosphate carboxylase/oxygenases (RuBisCO) in angiosperms: Revealed by an integrated in silico and in vitro approach.

As the most abundant protein on earth, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) has been considered a promising resource of functional foods. This study aimed to explore the full potential of plant RuBisCO proteins as precursors of antihypertensive peptides on a large scale. In total, 12,766 RuBisCO large subunit and 1,020 RuBisCO small subunit sequences of angiosperms were collected for simulated proteolysis and evaluation of antihypertensive potential, revealing a vast reservoir of antihypertensive peptides. Moreover, RuBisCO-derived novel antihypertensive peptides TTVW, TMW, and VPCL were identified with in vitro IC50 of 12.89 ± 0.82, 23.97 ± 1.02, and 339.12 ± 21.64 µM, respectively. Notably, TTVW and TMW are noncompetitive inhibitors predicted to bound adjacent to the catalytic region of ACE, while VPCL is a competitive inhibitor predicted to bound to the central active site inside ACE. Overall, this work provides a powerful theoretical guidance in developing antihypertensive functional foods utilizing plant RuBisCO.

Evaluation of a two-test strategy for HIV screening in a low-prevalence setting and the indications for optimizing clinical management.

Objectives: To evaluate a two-test strategy for HIV screening in the low-prevalence population and to assess the feasibility of utilizing the optimal signal-to-cutoff (S/CO) threshold on the chemiluminescence immunoassay(CMIA) and an additional rapid test on the gold immune-chromatography assay (GICA) for screening positive patients and optimization of clinical management. Methods: We conducted a retrospective study of samples analyzed by the fourth-generation Architect HIV Ag/Ab combo assay (CMIA) in a large medical center between June 2017 and August 2020. Reactive samples underwent a second screening test using the rapid test GICA, followed by Western blot (WB) as the confirmatory test. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal S/CO. We calculated sensitivity, specificity, and predictive value based on our population. The performance of the single-test strategy (CMIA) was compared with that of the two-test strategy (CMIA and GICA). Logistic regression was used to analyze the factors of clinical characteristics leading to false positive results. Results: A total of 220558 samples were screened by CMIA, and 429 patients met the inclusion criteria. Of these, CMIA produced 199 false-positive results with a median S/CO of 1.93(IQR1.45-3.68) and 230 positive results with a median S/CO of 455.1 (IQR169.3-709.7). The optimal S/CO of the single-test strategy was 8.82, which achieved a sensitivity of 100% and a positive predictive value (PPV) of 90.9%. The two-test strategy (CMIA and GICA) provided a sensitivity of 100% and a PPV of 98.7%, which best correlated with the confirmatory test WB. The combination of S/CO 8.82 on the CMIA assay and additional test results of GICA can be defined as four types used to interpret HIV serostatus. The false positive rate (FPR) was high in the female, the age≤18 group, the pre-operative patients, and the patients from the clinical departments of Pediatrics, Gynecology and Obstetrics, and Oncology, etc. Conclusions: The false positive rate is high in the low-prevalence setting by using CMIA. The two-test strategy (CMIA and GICA) is recommended for HIV screening in hospitals. Hopefully, the clinicians will be able to interpret HIV serostatus and facilitate clinical decision-making while waiting for the confirmatory results.

Development and validation of a nomogram to predict non-response to 5-aminosalicylic acid in patients with ulcerative colitis.

BACKGROUND: There are some patients with UC who have non-response (NR) to 5-ASA. To promote individualized treatment in UC patients, it is crucial to identify valid predictors to estimate NR to 5-ASA. Therefore, we aimed to identify the predictive value of clinical and biochemical markers and to construct a nomogram model predicting NR to 5-ASA in patients with UC. METHODS: Data of patients diagnosed with UC in the First Hospital of China Medical University between January 2012 and December 2020 were retrospectively analysed. Primary outcome was the proportion of NR to 5-ASA. Multivariable logistic regression was used to construct prediction models. Area under the curve (AUC), calibration and decision curve analyses (DCA) were assessed in the validation cohort. RESULTS: Of 284 UC patients who were treatment-naive, 86 (30.3%) had NR to 5-ASA. Univariate regressions showed that disease classification (DC) (p = 0.008), monocytes (MONO) (p = 0.041), platelet distribution width (PDW) (p = 0.027), serum total cholesterol (TC) (p = 0.031), and α1 globulin (p < 0.001) were strongly associated with NR to 5-ASA. ROC analysis indicated the AUC was 0.852, it showed that this model has a good degree of discrimination. The DCA curve showed that the predicted probability is 0.0%-96.0%. CONCLUSION: Our study developed a predictive model with good discrimination and calibration, and high clinical validity, which can effectively estimate the risk of NR to 5-ASA. DC, MONO, PDW, TC, and α1 globulin can be used as predictors for NR to 5-ASA in UC patients.

Living prosthetic breast for promoting tissue regeneration and inhibiting tumor recurrence.

Developing a living prosthetic breast to inhibit potential breast cancer recurrence and simultaneously promote breast reconstruction would be a promising strategy for clinical treatment of breast cancer after mastectomy. Here, a living prosthetic breast in the form of injectable gelatin methacryloyl microspheres is prepared, where they encapsulated zeolitic imidazolate framework (ZIF) nanoparticles loaded with small molecules urolithin C (Uro-C) and adipose-derived stem cells (ADSCs). Taking advantage of the acidic tumor microenvironment, the ZIF triggered a pH-sensitive drug release in situ so that Uro-C can induce tumor cell apoptosis via reactive oxygen species (ROS) generation. Meanwhile, the ADSCs proliferate in situ to promote tissue regeneration. Using such a design, our data showed that the ADSCs maintained viable and proliferate under the inhibitory effect of Uro-C in vitro. Through ROS generation, Uro-C also activated a suppressive tumor microenvironment in mice by both re-polarizing M2 macrophages to M1 macrophages for elevated inflammatory responses, and increasing the ratio between CD8 and CD4 T cells for tumor recurrence inhibition, significantly promoting new adipose tissue formation. Altogether, our results demonstrate that the prepared living prosthetic breast with bifunctional properties can be a promising candidate in clinic involving tumor treatment and tissue engineering in synergy.

[Effects of electroacupuncture on gait and proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle].

OBJECTIVE: To observe the effects of electroacupuncture on threshold of pain, gait, proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle, and to explore the possible mechanism of electroacupuncture in promoting the repair of acute injury of skeletal muscle. METHODS: A total of 48 SD rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an electroacupuncture group (18 rats). In the model group and the electroacupuncture group, the model of acute blunt trauma of gastrocnemius muscle was established by self-made impactor. In the electroacupuncture group, electroacupuncture was applied at "Chengshan" (BL 57) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once a day, 30 min each time. Electroacupuncture intervention was performed for 3, 7 and 14 days according to the sampling time. On the 1st, 3rd, 7th and 14th days after modeling, the mechanical withdrawal pain threshold of hindfoot was detected by Von Frey method; the standing time and the maximum contact area of the right hindfoot were recorded by Cat Walk XTTM animal gait analysis instrument; the morphology of the right gastrocnemius muscle and the number of inflammatory cells were observed by HE staining; the positive expression of paired box gene 7 (Pax7) and myogenic differentiation (MyoD) of the right gastrocnemius muscle was detected by immunofluorescence. RESULTS: After modeling, the muscle fiber rupture and massive infiltration of red blood cells and inflammatory cells were observed in the right gastrocnemius muscle; after electroacupuncture intervention, the morphology of muscle fiber was intact and the infiltration of inflammatory cells was improved. Compared with the blank group, in the model group, the differences of mechanical withdrawal pain threshold between the left and right foot were increased (P<0.05), the standing time was shortened and the maximum contact area of the right hindfoot was decreased (P<0.05), the number of inflammatory cells and the positive expression of Pax7 and MyoD of the right gastrocnemius muscle were increased (P<0.05) on the 1st, 3rd, 7th and 14th days after modeling. Compared with the model group, in the electroacupuncture group, the differences of mechanical withdrawal pain threshold were decreased (P<0.05), the standing time was prolonged (P<0.05), the number of inflammatory cells of right gastrocnemius muscle was decreased (P<0.05) on the 7th and 14th days after modeling; the maximum contact area of the right hindfoot was increased (P<0.05), the positive expression of MyoD of the right gastrocnemius muscle was increased (P<0.05) on the 3rd, 7th and 14th days after modeling; the positive expression of Pax7 of the right gastrocnemius muscle was increased (P<0.05) on the 3rd day after modeling. CONCLUSION: Electroacupuncture can effectively improve the pain threshold and gait in rats with acute blunt trauma of gastrocnemius muscle, and promote the repair of skeletal muscle injury, the mechanism may be related to the up-regulation of Pax7 and MyoD, so as to promoting the proliferation and differentiation of muscle satellite cell.

MAVS integrates glucose metabolism and RIG-I-like receptor signaling.

MAVS is an adapter protein involved in RIG-I-like receptor (RLR) signaling in mitochondria, peroxisomes, and mitochondria-associated ER membranes (MAMs). However, the role of MAVS in glucose metabolism and RLR signaling cross-regulation and how these signaling pathways are coordinated among these organelles have not been defined. This study reports that RLR action drives a switch from glycolysis to the pentose phosphate pathway (PPP) and the hexosamine biosynthesis pathway (HBP) through MAVS. We show that peroxisomal MAVS is responsible for glucose flux shift into PPP and type III interferon (IFN) expression, whereas MAMs-located MAVS is responsible for glucose flux shift into HBP and type I IFN expression. Mechanistically, peroxisomal MAVS interacts with G6PD and the MAVS signalosome forms at peroxisomes by recruiting TNF receptor-associated factor 6 (TRAF6) and interferon regulatory factor 1 (IRF1). By contrast, MAMs-located MAVS interact with glutamine-fructose-6-phosphate transaminase, and the MAVS signalosome forms at MAMs by recruiting TRAF6 and TRAF2. Our findings suggest that MAVS mediates the interaction of RLR signaling and glucose metabolism.