ED50 and ED95 of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal endoscopy: A prospective dose-finding study using up-and-down sequential allocation method.

WHAT IS KNOWN AND OBJECTIVE: Propofol and esketamine are routine anaesthetics used in sedation or general anaesthesia for paediatric procedures. Coadministration could reduce the dose of either propofol or esketamine required and lower the incidence of drug-related adverse events. We designed a four-arm randomized controlled trial in children undergoing diagnostic upper gastrointestinal endoscopy to investigate the dose of propofol with different doses of esketamine inducing appropriate depth of anaesthesia in 50% patients (median effective dose, ED50 ). METHODS: After getting the approval of the research ethics committee and informed consent, 92 paediatric patients planning for upper gastrointestinal endoscopy were divided into four groups randomly: esketamine 0, 0.25, 0.5 and 1 mg/kg groups (n = 23/group). Propofol doses followed the Dixon and Massey up-and-down method with different starting and interval doses between groups. During the first attempt of endoscope insertion, if patients' reactions prevented the insertion, it would be considered as a failure. The awakening time, total propofol doses, as well as the perioperative and post-procedure adverse events were evaluated and recorded for each patient. RESULTS AND DISCUSSION: The ED50 (median, 95% confidence interval) of propofol was significantly greater in esketamine 0 and 0.25 mg/kg groups in comparison with the esketamine 0.5 and 1 mg/kg groups (4.1 [3.3-4.9]; 3.1 [2.5-3.8] mg/kg vs. 1.8 [1.1-2.4]; 0.8 [0.2-1.3] mg/kg, respectively, p < .05). The total doses of propofol in esketamine 0.5 and 1 mg/kg groups were statistically lower than these in esketamine 0 and 0.25 mg/kg group (p < .01). The mean blood pressure was lower in the esketamine 0 mg/kg group than that in 1 mg/kg group after administration and during the procedure (p < .01). The esketamine 1 mg/kg group showed a higher incidence of vomiting and visual disturbances than the other three groups (p < .001). WHAT IS NEW AND CONCLUSION: In children who accomplished diagnostic paediatric upper gastrointestinal endoscopy under deep sedation/anaesthesia, the total dosage of propofol needed was reduced significantly in esketamine 0.5 and 1 mg/kg groups with a corresponding reduce in propofol-related hemodynamic changes. However, a higher incidence of esketamine-related adverse effects was found in esketamine 1 mg/kg group.

Preemptive analgesic effectiveness of single dose intravenous ibuprofen in infants undergoing cleft palate repair: a randomized controlled trial.

BACKGROUND: Correction surgery for cleft palate is recommended between 9 and 18 months of age. Patients suffer from acute pain after palatoplasty. Clinicians are hesitant to use opioids for analgesia concerning the potential high risk of respiratory adverse events. Intravenous ibuprofen perhaps be a suitable adjuvant to pain relief. We try to assess whether preoperative administration of intravenous ibuprofen can decrease opioid requirements following cleft palate repair in infants. METHODS: This single center prospective randomized clinical trial was performed from February to April 2021 at Department of Anesthesiology in Shanghai Children's Medical Center. Forty patients ASA I-II, aged 9-24 months with isolated cleft palate and undergoing palatoplasty were randomized in a 1:1 ratio to receive either a single dose of 10 mg/kg ibuprofen intravenously or normal saline at induction. Children and infants postoperative pain scale (CHIPPS) was used for pain assessment. Those patients CHIPPS pain score equal or higher than 4 received analgesic rescue with titrating intravenous fentanyl 0.5 µg/kg and repeated in 10 min if required. The primary outcome was the amount of postoperative fentanyl used for rescue analgesia in postanesthesia care unit (PACU). RESULTS: Patients (n = 20 in each group) in IV-Ibuprofen group required less postoperative fentanyl than those in placebo group (p<0.001). There was no significant difference between two groups in first rescue analgesia time (p = 0.079) and surgical blood loss (p = 0.194). No incidence of obvious adverse events had been found within the first 24 h after surgery in both groups. CONCLUSIONS: Preemptive intravenous administration ibuprofen 10 mg/kg at induction had a significant opioid sparing effect in early postoperative period without obvious adverse effects in infants undergoing palatoplasty. TRIAL REGISTRATION: CHICTR, CTR2100043718, 27/02/2021 http://www.chictr.org.cn/showproj.aspx?proj=122187.

Comparison of the ED50 propofol requirements during the insertion of laryngeal mask airway Ambu AuraFlex with Ambu AuraOnce in children undergoing strabismus surgery.

WHAT IS KNOWN AND OBJECTIVE: Optimal airway management is crucial in strabismus surgery due to the inaccessibility of the airway throughout the procedure. Laryngeal mask airway offers advantages over tracheal intubation in ophthalmic surgery as it does not increase the intraocular pressure. The purpose of this study was to determine the median effective dose of propofol required, when combined with 0.2 µg/kg of sufentanil, for smooth insertion of Ambu AuraFlex in the first attempt in children undergoing strabismus surgery, and to compare it with that for Ambu AuraOnce. METHODS: Forty-three paediatric patients undergoing strabismus surgery under general anaesthesia were recruited. For induction, the initial dosage of propofol was 2 mg/kg in the AuraOnce group or 3 mg/kg in the AuraFlex group. In accordance with Dixon's up-and-down method, the dose of propofol for consecutive patients in each group was adjusted in increments or decrements of 0.25 mg/kg based on the previous patient's "three-point, six-category scale" response to the first attempt of insertion of the randomized device. Insertion of the device was attempted when the bispectral index was ≤60 for 5 s after propofol administration without the use of neuromuscular blocking agents. RESULTS AND DISCUSSION: The median effective dose (95% confidence interval) of propofol was significantly lower in the Ambu AuraOnce group than in the Ambu AuraFlex group (1.92 [1.50-2.32] mg/kg vs. 2.98 [2.49-3.94] mg/kg; p = 0.002). The incidence of dislodgement of the device was significantly higher with the use of the Ambu AuraOnce than with the use of AuraFlex (p = 0.023), whereas insignificant differences were observed between the two groups in the incidence of other perioperative adverse events. WHAT IS NEW AND CONCLUSION: Ambu AuraFlex requires a significantly higher dose of propofol for insertion and provides more effective and stable airway management in strabismus surgery than AuraOnce.

Opportunities for pharmacists to integrate pharmacogenomics into clinical practice.

Many medical centers in the United States have implemented pharmacogenomics (PGx) programs to integrate PGx into clinical practice. The roles of pharmacists in optimizing medication use based on genetic testing results are emergently evolving. A literature search was conducted to assess pharmacists' roles in pharmacogenetics/pharmacogenomics or precision/personalized medicine programs. Fifteen PGx pharmacy practice models implemented in eleven hospitals and one community pharmacy in the U.S. were selected for evaluation. Pharmacists perform results interpretation, genotype-guided medication selection and adjustment, medication acquisition, adverse reactions monitoring, and patient education. Institutions that are interested in implementing a PGx program should plan the strategies to overcome the challenges, such as educational knowledge gaps, informatics, and reimbursement issues. Strong institutional support, well-defined goals, standardized procedures, and strategies to educate clinicians and patients are the prerequisites to comprehensively deliver genomic data for individualized drug therapy.

Effect of recorded maternal voice on emergence agitation in children undergoing bilateral ophthalmic surgery: A randomised controlled trial.

AIM: This study was designed to investigate whether the playing-back of the recorded maternal voice through the headphones to children undergoing bilateral ophthalmic surgery has clinical effects on the incidence of emergence agitation, and the anaesthesia recovery course. METHODS: In this prospective, blinded and randomised study, 127 children, aged 2-8 years and undergoing bilateral ophthalmic surgery were randomly allocated to one of the two groups: group T (treatment group, listening to recorded mother's voice via headphones) or group C (control group, wearing headphones without auditory stimuli). The primary outcome was the incidence of emergence agitation, and the secondary outcomes were the awakening time, and the post-anaesthesia care unit (PACU) stay time. RESULTS: Children in the group of listening recorded mother's voice exhibited significantly low incidence of emergence agitation compared with those in the control group (32.8 vs. 55.6%; odds ratio (95% confidence interval): 0.39(0.19-0.80); P = 0.010). The awakening time was shorter in group T as compared to that in group C (22.9 (10.4) vs. 27.3 (13.7); P = 0.048). As results, the group T had significantly less PACU stay time with early discharge than the group C did (29.7 (12.1) vs. 34.8 (14.1); P = 0.031). CONCLUSIONS: Recorded mother's voice is an efficient method to reduce emergence agitation in children undergoing bilateral ophthalmic surgery with sevoflurane anaesthesia. Also, patients woke faster and PACU stay time was shorter in the mother's voice group as compared with the control group.

Synthesis, biological evaluation and molecular docking of benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives as novel tubulin polymerization inhibitors.

Tubulin-targeting drugs have increasingly become the focus of anticancer drugs research. Twenty-five novel benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives were synthesized and evaluated for bioactivity as potential tubulin polymerization inhibitors. Among them, compound 30 showed the most excellent inhibition against tubulin assembly (IC50 = 1.52 µM) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC50 = 0.15, 0.21, 0.33 and 0.17 µM, respectively for A549, Hela, HepG2 and MCF-7). It could also validly induce A549 cell apoptosis, cause cell cycle arrest in G2/M phase and disrupt the cellular microtubule network. These results, along with molecular docking data, provided an important basis for further optimization of compound 30 as a potential anticancer agent.

A Brief Review of Bioactive Metabolites Derived from Deep-Sea Fungi.

Deep-sea fungi, the fungi that inhabit the sea and the sediment at depths of over 1000 m below the surface, have become an important source of industrial, agricultural, and nutraceutical compounds based on their diversities in both structure and function. Since the first study of deep-sea fungi in the Atlantic Ocean at a depth of 4450 m was conducted approximately 50 years ago, hundreds of isolates of deep-sea fungi have been reported based on culture-dependent methods. To date more than 180 bioactive secondary metabolites derived from deep-sea fungi have been documented in the literature. These include compounds with anticancer, antimicrobial, antifungal, antiprotozoal, and antiviral activities. In this review, we summarize the structures and bioactivities of these metabolites to provide help for novel drug development.

Chaperone heat shock protein 70 in nucleus accumbens core: a novel biological target of behavioural sensitization to morphine in rats.

Drug addiction is a major public health issue, yet the underlying adaptation of neural networks by drugs of abuse is not fully understood. We have previously linked chaperone heat shock protein 70 (Hsp70) to drug-induced adaptations. Focusing on the NAc core and shell, the present study aims to provide further findings for our understanding of the relation between behavioural sensitization to morphine and Hsp70 at transcriptional and functional levels in rats. Firstly, we delineated the characteristics of behavioural sensitization induced by a single morphine exposure (1-10 mg/kg, s.c.). Secondly, Hsp70 protein expression in the NAc core was time- and dose-relatedly induced during the development of behavioural sensitization to a single morphine exposure in rats, and Pearson analysis indicated a positive correlation between behavioural sensitization and Hsp70 expression in NAc core. Thirdly, at the transcriptional level, intra-NAc core injection of the specific heat shock factor-I (HSF-I) inhibitor N-Formyl-3,4-methylenedioxy-benzylidine-γ-butyrolactam (KNK437) suppressed Hsp70 expression and the development of behavioural sensitization, while the HSF-I specific inducer geranylgeranylacetone (GGA) promoted both of them. Interestingly, intra-NAc shell injection of KNK437 or GGA did not affect the development of behavioural sensitization. Finally, both the functional inhibition of Hsp70 ATPase activity by methylene blue (MB), and the antagonism of Hsp70 substrate binding site (SBD) activity by pifithrin-µ (PES) impaired the development of behavioural sensitization when they were microinjected into the NAc core. Taken together, the critical involvement of chaperone Hsp70 in behavioural sensitization to morphine identifies a biological target for long-lasting adaptations with relevance to addiction.

Synthesis, biological evaluation and molecular modeling of 1,3,4-thiadiazol-2-amide derivatives as novel antitubulin agents.

A series of 1,3,4-thiadiazol-2-amide derivatives (6a-w) were designed and synthesized as potential inhibitors of tubulin polymerization and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 6f exhibited the most potent anticancer activity against A549, MCF-7 and HepG2 cancer cell lines with IC50 values of 0.03 µM, 0.06 µM and 0.05 µM, respectively. Compound 6f also exhibited significant tubulin polymerization inhibitory activity (IC50=1.73 µM), which was superior to the positive control. The obtained results, along with a 3D-QSAR study and molecular docking that were used for investigating the probable binding mode, could provide an important basis for further optimization of compound 6f as a novel anticancer agent.

Brucine suppresses ethanol intake and preference in alcohol-preferring Fawn-Hooded rats.

AIM: Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse. METHODS: Alcohol-preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg, sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference (CPP) was conducted to assess conditioned reinforcing effect. RESULTS: In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg) administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose (10%) responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU (30 mg/kg) completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20, and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion. CONCLUSION: BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.

Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Molecular chaperone heat shock protein 70 participates in the labile phase of the development of behavioural sensitization induced by a single morphine exposure in mice.

De-novo protein synthesis is required in the development of behavioural sensitization. A prior screening test from our laboratory has implicated heat shock protein 70 (Hsp70) as one of the proteins required in this behavioural plasticity. Thus, this study was designed to extend our understanding of the role of Hsp70 in the development of behavioural sensitization induced by a single morphine exposure in mice. First, by employing transcription inhibitor actinomycin D (AD) and protein synthesis inhibitor cycloheximide (CHX), we identified a protein synthesis-dependent labile phase (within 4 h after the first morphine injection) in the development of behavioural sensitization to a single morphine exposure. Second, Hsp70 protein expression in the nucleus accumbens correlated positively with locomotor responses of sensitized mice and, more importantly, the expression of Hsp70 increased within 1 h after the first morphine injection. Third, AD and CHX both prevented expression of Hsp70 and disrupted the development of the single morphine induced behavioural sensitization, which further implied Hsp70 was highly associated with behavioural sensitization. Finally, the selective Hsp70 inhibitor pifithrin-µ (PES) i.c.v. injected in mice prevented the development of behavioural sensitization and, critically, this inhibitory effect occurred only when PES was given within 1 h after the first morphine injection, which was within the labile phase of the development period. Taken together, we draw the conclusion that Hsp70 is crucially involved in the labile phase of the development of behavioural sensitization induced by a single morphine exposure, probably functioning as a molecular chaperone.

Synthesis and antioxidant activity of novel Mannich base of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan.

A new series of Mannich base of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan (6a-6ae) were synthesized and characterized by (1)H NMR, ESI-MS and elemental analysis. The structure of 6b was further confirmed by single crystal X-ray diffraction. All these novel compounds were screened for their in vitro antioxidant activity employing 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+)) and ferric reducing antioxidant power (FRAP) scavenging assays. Due to the combination of 1,4-benzodioxan, 1,3,4-oxadiazoles and substituted phenyl ring, most of them exhibited nice antioxidant activities. In all of these three assays mentioned above, compounds 6f and 6e showed significant radical scavenging ability comparable to the commonly used antioxidants, BHT and Trolox. Seven compounds with representative substituents or activities were selected for further assays in chemical simulation biological systems-inhibition of microsomal lipid peroxidation (LPO) and protection against 2,2'-azobis (2-amidinopropane hydrochloride) (AAPH) induced DNA strand breakage, in which, 6f and 6e were demonstrated to be of the most potent antioxidant activities.

[Clinical survey and analysis of persistent submacular fluid on optical coherence tomography after surgery for rhegmatogenous retinal detachment].

OBJECTIVE: To investigate the incidence, duration and consequences of persistent submacular fluid after pars plana vitrectomy (PPV) and scleral buckling surgery (SB) in rhegmatogenous retinal detachment, thus to explore the clinical association between persistent SMF and different surgical methods, and simultaneously, to study the effect of persistent submacular fluid on visual outcome. METHODS: It was a retrospective case-series study. Ninety-two qualified eyes including 54 eyes of males and 38 eyes of females with rhegmatogenous retinal detachment which had been performed PPV or SB were recruited. The average age of the patients was (45.8 ± 15.3) years with a age-range from 15 to 76 years. The inclusion criteria was as follows, the macula-off rhegmatogenous retinal detachments without macular hole and obvious proliferative vitreoretinopathy, the retina was completely reattached 1 month after operation and no redetachment was found by ophthalmoscope and B scan till the last follow-up, the minimal follow-up time was 1 year and the submacular fluid must have been dissolved for at least 6 months. All patients underwent thorough ophthalmologic examinations before and after operation, Those patients in whom a persistent submacular fluid was seen on optical coherence tomography (OCT) at 1 month after operation performed follow-up with repeat of the investigations at 3, 6 and 12 months after surgery, If the abnormality resolved, further observations were continued to undertake for 6 months or more till the last follow-up.Rank-sum test, χ²-test and Fisher exact test were applied respectively to analyze for statistical analysis. RESULTS: The incidence of persistent submacular fluid at 1 month after surgery in the PPV and SB group was 13.9% (5/36) and 48.2% (27/56).Six months later however, the figure expressed as percentage was 2.8% (1/36) and 23.2% (18/28) correspondingly. Persistent submacular fluid was more frequent in eyes with inferior breaks (64.3%) than that with superior ones (13.9%), making a significant differences (χ² = 17.38, P < 0.01) . The persistent submacular fluid group showed worse best-corrected visual acuity than no persistent submacular fluid group 6 and 12 months after surgery (t = 2.525, t = 2.254, both P < 0.05). Comparing the visual acuity (VA) between the eyes with or without persistent submacular fluid 6, 12 months after surgery and the latest followed-up among the ever suffered eyes, a statistically significant differences presented in late stages(average VA: 0.47 ± 0.29, 0.30 ± 0.16; 0.44 ± 0.28, 0.27 ± 0.15;0.42 ± 0.22, 0.27 ± 0.19; t = 2.114, 2.207, 2.068; all P < 0.05), though there were no significant differences in the first three months (average VA: 0.70 ± 0.33, 0.63 ± 0.37; 0.50 ± 0.25,0.45 ± 0.22; t = 0.556, 0.601; both P > 0.05). CONCLUSIONS: Persistent submacular fluid presents in both surgical procedures but it is more frequent after buckling surgery than vitrectomy, the selection of patients, the location of retinal breaks and the duration of detachment may be the potential influencing factors. Persistent submacular fluid after retinal detachment surgery is responsible for delayed recovery, and may affect the final visual outcome. The longer it lasts, the more harm may it do.

The Disease Experience of Women with Granulomatous Lobular Mastitis. A Qualitative Interview Study.

Background: The incidence of granulomatous lobular mastitis (GLM) is increasing year by year, and the breast wounds of women patients with GLM can develop into abscesses, fistulas, sinuses, and sometimes orange-like degeneration similar to malignant tumors, which seriously affects the quality of life of women patients with GLM. In China, breast wounds in women patients with GLM have not been better managed. Therefore, the purpose of this study is to explore the disease experience of women patients with GLM, to provide a basis for the development of precise intervention and support strategies for women patients with GLM, and to further improve the quality of nursing management and enrich the research types of GLM. Methods: In this study, 10 cases of GLM women patients from a tertiary hospital in Hangzhou, Zhejiang Province were selected by purposive sampling. After obtaining the informed consent of GLM women patients, semi-structured interviews were conducted with GLM women patients using the interview outline to collect qualitative data. The interview was recorded, transcribed verbatim in the local language, and then translated into English, and the content analysis method was used to analyze the data. The Consolidated Criteria for Reporting Qualitative Research (CORE-Q) checklist follows the report 's findings. Results: Our study identified six themes: (a) Perception of the disease, (b) Emotional discomfort (c) Variety of changes (d) Lack of specific skills (e) Coping strategies adopted to rebuild health, (f) Expectation. Conclusion: The experience of women with GLM is characterized by diversity and specificity. After experiencing physical trauma, most patients use support systems to change negative attitudes and rebuild physical and mental health. Family, hospital and society should be fully linked to strengthen the prevention of GLM and the popularization of nursing management knowledge; nurses should provide targeted nursing services. Nursing leaders should improve the medical security system, broaden the medical channels, and reduce the pain experience and pressure of patients.

Calpain: the regulatory point of myocardial ischemia-reperfusion injury.

Calpain is a conserved cysteine protease readily expressed in several mammalian tissues, which is usually activated by Ca2+ and with maximum activity at neutral pH. The activity of calpain is tightly regulated because its aberrant activation will nonspecifically cleave various proteins in cells. Abnormally elevation of Ca2+ promotes the abnormal activation of calpain during myocardial ischemia-reperfusion, resulting in myocardial injury and cardiac dysfunction. In this paper, we mainly reviewed the effects of calpain in various programmed cell death (such as apoptosis, mitochondrial-mediated necrosis, autophagy-dependent cell death, and parthanatos) in myocardial ischemia-reperfusion. In addition, we also discussed the abnormal activation of calpain during myocardial ischemia-reperfusion, the effect of calpain on myocardial repair, and the possible future research directions of calpain.

The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases.

Morbidity and mortality of cardiovascular diseases (CVDs) are exceedingly high worldwide. Researchers have found that the occurrence and development of CVDs are closely related to intestinal microecology. Imbalances in intestinal microecology caused by changes in the composition of the intestinal microbiota will eventually alter intestinal metabolites, thus transforming the host physiological state from healthy mode to pathological mode. Trimethylamine N-oxide (TMAO) is produced from the metabolism of dietary choline and L-carnitine by intestinal microbiota, and many studies have shown that this important product inhibits cholesterol metabolism, induces platelet aggregation and thrombosis, and promotes atherosclerosis. TMAO is directly or indirectly involved in the pathogenesis of CVDs and is an important risk factor affecting the occurrence and even prognosis of CVDs. This review presents the biological and chemical characteristics of TMAO, and the process of TMAO produced by gut microbiota. In particular, the review focuses on summarizing how the increase of gut microbial metabolite TMAO affects CVDs including atherosclerosis, heart failure, hypertension, arrhythmia, coronary artery disease, and other CVD-related diseases. Understanding the mechanism of how increases in TMAO promotes CVDs will potentially facilitate the identification and development of targeted therapy for CVDs.

Characterization and expression pattern of KIFC1-like kinesin gene in the testis of the Macrobrachium nipponense with discussion of its relationship with structure lamellar complex (LCx) and acroframosome (AFS).

Spermiogenesis is a developmental process undergoing continuous differentiation to drive a diploid spermatogonium towards a haploid sperm cell. This striking transformation from spermatogonium to spermatozoa is made possible by the stage-specific adaption of cytoskeleton and associated molecular motor proteins. KIFC1 is a C-terminal kinesin motor found to boast essential roles in acrosome biogenesis and nuclear reshaping during spermiogenesis in rat. To explore its functions during the same process in Macrobrachium nipponense, we have cloned and sequenced the cDNA of a mammalian KIFC1 homologue (termed mn-KIFC1) from the total RNA of the testis. The 2,296 bp mn-KIFC1 cDNA contained a 87 bp 5' untranslated region, a 211 bp 3' untranslated region and a 1,998 bp open reading frame. Protein alignment demonstrated that mn-KIFC1 had 37.7, 58.7, 38.4, 37.2, 38.9 and 37.8% identity with its homologues in Salmo salar, Eriocheir sinensis, Homo sapiens, Mus musculus, Danio rerio and Xenopus laevis respectively. The phylogenetic tree revealed that mn-KIFC1 is most related to E. Sinensis KIFC1 among the examined species. Tissue expression analysis showed the presence of mn-KIFC1 in the testis, hepatopancreas, gill, muscle and heart. In situ hybridization showed that the mn-KIFC1 mRNA was localized at the periphery of the nuclear membrane and in the proacrosomal vesicle in early and middle spermatids. In late spermatids and spermatozoa, mn-KIFC1 was expressed in the acrosome and in the spike. In situ hybridization also indicated that KIFC1 works together with lamellar complex (LCx) and acroframosome (AFS) to drive acrosome formation and cellular transformation. LCx and AFS have both been previously proved to have essential roles during spermiogenesis in M. nipponense. In conclusion, the expression of mn-kifc1 at specific stages of spermiogenesis suggests a role in cellular transformations in M. nipponense.

Characterization of Tibetan kefir grain-fermented milk whey and its suppression of melanin synthesis.

Tibetan kefir grain as the starter of milk fermentation has been applied as functional food with many bioactive characteristics. In this study, the milk whey product (TKG-MW) was obtained through the milk fermentation of Tibetan kefir grain containing the dominant Lactobacillus, Acetobacter, and Bacillus after 3 and 6 days of cultivation. Antioxidant, anti-inflammatory, and melanogenesis inhibition capacities under TKG-MW treatment were analyzed. Results revealed that the antioxidation of TKG-MW at 6 days of fermentation was higher than that at 3 days of fermentation according to the DPPH and ABTS+ radical scavenging analysis. However, the anti-inflammation of TKG-MW was only observed at 6 days of fermentation by using lipopolysaccharide-stimulated RAW 264.7 macrophages. The inhibition of mushroom tyrosinase activity by TKG-MW was demonstrated. The decrease of melanin content was verified using α-melanocyte-stimulating hormone-stimulated B16-F10 cell. The real-time quantitative reverse transcription polymerase chain reaction result indicated that the mRNA levels of Tyr, Trp-1, and Trp-2 of the B16 cell involved in melanin synthesis were down-regulated over a two-fold change by the TKG-MW treatment. Additionally, the protein expressions of Tyr, Trp-1, Trp-2, and Mitf of the B16 cell were reduced with the TKG-MW treatment. Organic acids, such as lactic acid, succinic acid, 3-phenyllactic acid, l-pyroglutamic acid, and malic acid, were identified by liquid chromatography-mass spectrometry in TKG-MW and were found to significantly inhibit tyrosinase activity. To the best of our knowledge, this work is the first to report melanogenesis suppression by TKG-MW. Results suggested that the fermentation product of TKG could be applied as a depigmenting agent in food and cosmetics.

Enhancing Smart Sensor Tag Sensing Performance-Based on Modified Plasma-Assisted Electrochemical Exfoliated Graphite Nanosheet.

Water that penetrates through cracks in concrete can corrode steel bars. There is a need for reliable and practical seepage sensing technology to prevent failure and determine the necessary maintenance for a concrete structure. Therefore, we propose a modified plasma-assisted electrochemical exfoliated graphite (MPGE) nanosheet smart tag. We conducted a comparative study of standard and modified RFID smart tags with sensor technology for seepage detection in concrete. The performance of both smart tags was tested and verified for seepage sensing in concrete, characterized by sensor code and frequency values. Seepage was simulated by cracking the concrete samples, immersing them for a designated time, and repeating the immersing phase with increasing durations. The test showed that the modified smart tag with 3% MPGE and an additional crosslinking agent provided the best sensitivity compared with the other nanosheet compositions. The presence of 3D segregated structures on the smart tag's sensing area successfully enhanced the sensitivity performance of seepage detection in concrete structures and is expected to benefit structural health monitoring as a novel non-destructive test method.