Effects of brief mindfulness meditation training on attention and dispositional mindfulness in young adult males.

This study examined the impact of brief mindfulness meditation (BMM) training on attention function and dispositional mindfulness in young males. 126 male participants aged 18-26 from the security industry were recruited, with 66 participants (M = 22.84, SD = 2.41) undergoing 4-week mindfulness meditation training and 60 participants (M = 23.07, SD = 2.29) in the active control group. The intervention was integrated into the participants' schedules. Measures included Five Facets Mindfulness Questionnaires (FFMQ), concentration and assignment attention tasks, Attention Network Test (ANT), and saliva cortisol concentration. Findings indicate that brief mindfulness meditation training led to significant improvements in participants' FFMQ scores), with marginally significant enhancements in the executive control network. However, it had no discernible effect on alertness and orientation networks. Additionally, brief mindfulness meditation training enhanced attention allocation to light stimulation and prolonged individual attention. Surprisingly, there was no observed decrease in saliva cortisol concentration among meditation training participants. However, this study did not find a decrease in saliva cortisol concentration in the brief mindfulness meditation group. In conclusion, this study highlights the potential of a 4-week brief mindfulness meditation training program to enhance dispositional mindfulness and specific aspects of attention function in young men, offering practical insights into the benefits of mindfulness meditation practices for this demographic.

Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis.

Tumor is a local tissue hyperplasia resulted from cancerous transformation of normal cells under the action of various physical, chemical and biological factors. The exploration of tumorigenesis mechanism is crucial for early prevention and treatment of tumors. Epigenetic modification is a common and important modification in cells, including DNA methylation, histone modification, non-coding RNA modification and m6A modification. The normal mode of cell death is programmed by cell death-related genes; however, recent researches have revealed some new modes of cell death, including pyroptosis, ferroptosis, cuproptosis and disulfidptosis. Epigenetic regulation of various cell deaths is mainly involved in the regulation of key cell death proteins and affects cell death by up-regulating or down-regulating the expression levels of key proteins. This study aims to investigate the mechanism of epigenetic modifications regulating pyroptosis, ferroptosis, cuproptosis and disulfidptosis of tumor cells, explore possible triggering factors in tumor development from a microscopic point of view, and provide potential targets for tumor therapy and new perspective for the development of antitumor drugs or combination therapies.

Unlocking Genetic Profiles with a Programmable DNA-Powered Decoding Circuit.

Human genetic architecture provides remarkable insights into disease risk prediction and personalized medication. Advances in genomics have boosted the fine-mapping of disease-associated genetic variants across human genome. In healthcare practice, interpreting intricate genetic profiles into actionable medical decisions can improve health outcomes but remains challenging. Here an intelligent genetic decoder is engineered with programmable DNA computation to automate clinical analyses and interpretations. The DNA-based decoder recognizes multiplex genetic information by one-pot ligase-dependent reactions and interprets implicit genetic profiles into explicit decision reports. It is shown that the DNA decoder implements intended computation on genetic profiles and outputs a corresponding answer within hours. Effectiveness in 30 human genomic samples is validated and it is shown that it achieves desirable performance on the interpretation of CYP2C19 genetic profiles into drug responses, with accuracy equivalent to that of Sanger sequencing. Circuit modules of the DNA decoder can also be readily reprogrammed to interpret another pharmacogenetics genes, provide drug dosing recommendations, and implement reliable molecular calculation of polygenic risk score (PRS) and PRS-informed cancer risk assessment. The DNA-powered intelligent decoder provides a general solution to the translation of complex genetic profiles into actionable healthcare decisions and will facilitate personalized healthcare in primary care.

Correlation of serum omentin-1 level with clinical features and major adverse cardiac and cerebral events in patients undergoing continuous ambulatory peritoneal dialysis.

Omentin-1 shows a critical protective role of cardiovascular events in chronic kidney disease. This study aimed to further assess serum omentin-1 level and its relationship with clinical features and accumulating major adverse cardiac/cerebral events (MACCE) risk in end-stage renal disease patients undergoing continuous ambulatory peritoneal dialysis (CAPD-ESRD). Totally, 290 CAPD-ESRD patients and 50 healthy controls (HCs) were recruited, and their serum omentin-1 levels were measured by enzyme-linked immunosorbent assay. All CAPD-ESRD patients were followed up for 36 months to assess accumulating MACCE rate. Omentin-1 level in CAPD-ESRD patients was lower than that in HCs [median (interquartile range): 229.350 (153.575-355.550) vs. 449.800 (354.125-527.450) pg/mL] (p < 0.001). Moreover, omentin-1 level was inversely related to C-reactive protein (CRP) (p = 0.028), total cholesterol (p = 0.023), and low-density lipoprotein cholesterol (p = 0.005), while there was no correlation in omentin-1 level with other clinical features in CAPD-ESRD patients. The accumulating MACCE rate was 4.5%, 13.1%, and 15.5% in the first, second, and third years respectively, and it was lower in CAPD-ESRD patients with high level of omentin-1 than those with low level of omentin-1 (p = 0.004). Furthermore, omentin-1 (hazard ratio (HR)=0.422, p = 0.013) and high-density lipoprotein cholesterol (HR = 0.396, p = 0.010) were independently associated with reduced accumulating MACCE rate; while age (HR = 3.034, p = 0.006), peritoneal dialysis duration (HR = 2.741, p = 0.006), CRP (HR = 2.289, p = 0.026), serum uric acid (HR = 2.538, p = 0.008) were independently related to higher accumulating MACCE rate in CAPD-ESRD patients. In conclusion, serum high omentin-1 level is associated with decreased inflammation, lipid levels, and accumulating MACCE risk in CAPD-ESRD patients.

Activating One/Two-Photon Excited Red Fluorescence on Carbon Dots: Emerging n→π Photon Transition Induced by Amino Protonation.

Due to the complicated nature of carbon dots (CDs), fluorescence mechanism of red fluorescent CDs is still unrevealed and features highly controversial. Reliable and effective strategies for manipulating the red fluorescence of CDs are urgently needed. Herein, CDs with one-photon excited (622 nm, QYs ≈ 17%) and two-photon (629 nm) excited red fluorescence are prepared by acidifying o-phenylenediamine-based reaction sediments. Systematic analysis reveals that the protonation of amino groups increases the particle surface potential, disperse the bulk sediments into nano-scale CDs. In the meanwhile, amino protonation of pyridinic nitrogen (-N=) structure inserts numerous n orbital energy levels between the π → π* transition, narrows the gap distance for photon transition, and induces red fluorescence emission on CDs. Present research reveals an effective pathway to activate CDs reaction sediments and trigger red emission, thus may open a new avenue for developing CDs with ideal optical properties and promising application prospects.

Molybdopterin biosynthesis pathway contributes to the regulation of SaeRS two-component system by ClpP in Staphylococcus aureus.

In Staphylococcus aureus, the SaeRS two-component system is essential for the bacterium's hemolytic activity and virulence. The Newman strain of S. aureus contains a variant of SaeS sensor kinase, SaeS L18P. Previously, we showed that, in the strain Newman, SaeS L18P is degraded by the membrane-bound protease FtsH. Intriguingly, the knockout mutation of clpP, encoding the cytoplasmic protease ClpP, greatly reduces the expression of SaeS L18P. Here, we report that, in the strain Newman, the positive regulatory role of ClpP on the SaeS L18P expression is due to its destabilizing effect on FtsH and degradation of MoeA, a molybdopterin biosynthesis protein. Although the transcription of ftsH was not affected by ClpP, the expression level of FtsH was increased in the clpP mutant. The destabilizing effect appears to be indirect because ClpXP did not directly degrade FtsH in an in vitro assay. Through transposon mutagenesis, we found out that the moeA gene, encoding the molybdopterin biosynthesis protein A, suppresses the hemolytic activity of S. aureus along with the transcription and expression of SaeS L18P. In a proteolysis assay, ClpXP directly degraded MoeA, demonstrating that MoeA is a substrate of the protease. In a murine bloodstream infection model, the moeA mutant displayed reduced virulence and lower survival compared with the WT strain. Based on these results, we concluded that ClpP positively controls the expression of SaeS L18P in an FtsH and MoeA-dependent manner, and the physiological role of MoeA outweighs its suppressive effect on the SaeRS TCS during infection.

Extracellular DNA released by glycine-auxotrophic Staphylococcus epidermidis small colony variant facilitates catheter-related infections.

Though a definitive link between small colony variants (SCVs) and implant-related staphylococcal infections has been well-established, the specific underlying mechanism remains an ill-explored field. The present study analyzes the role SCVs play in catheter infection by performing genomic and metabolic analyses, as well as analyzing biofilm formation and impacts of glycine on growth and peptidoglycan-linking rate, on a clinically typical Staphylococcus epidermidis case harboring stable SCV, normal counterpart (NC) and nonstable SCV. Our findings reveal that S. epidermidis stable SCV carries mutations involved in various metabolic processes. Metabolome analyses demonstrate that two biosynthetic pathways are apparently disturbed in SCV. One is glycine biosynthesis, which contributes to remarkable glycine shortage, and supplementation of glycine restores growth and peptidoglycan-linking rate of SCV. The other is overflow of pyruvic acid and acetyl-CoA, leading to excessive acetate. SCV demonstrates higher biofilm-forming ability due to rapid autolysis and subsequent eDNA release. Despite a remarkable decline in cell viability, SCV can facilitate in vitro biofilm formation and in vivo survival of NC when co-infected with its normal counterparts. This work illustrates an intriguing strategy utilized by a glycine-auxotrophic clinical S. epidermidis SCV isolate to facilitate biofilm-related infections, and casts a new light on the role of SCV in persistent infections.

Staphylococcus epidermidis clones express Staphylococcus aureus-type wall teichoic acid to shift from a commensal to pathogen lifestyle.

Most clonal lineages of Staphylococcus epidermidis are commensals present on human skin and in the nose. However, some globally spreading healthcare-associated and methicillin-resistant S. epidermidis (HA-MRSE) clones are major causes of difficult-to-treat implant or bloodstream infections. The molecular determinants that alter the lifestyle of S. epidermidis have remained elusive, and their identification might provide therapeutic targets. We reasoned that changes in surface-exposed wall teichoic acid (WTA) polymers of S. epidermidis, which potentially shape host interactions, may be linked to differences between colonization and infection abilities of different clones. We used a combined epidemiological and functional approach to show that while commensal clones express poly-glycerolphosphate WTA, S. epidermidis multilocus sequence type 23, which emerged in the past 15 years and is one of the main infection-causing HA-MRSE clones, contains an accessory genetic element, tarIJLM, that leads to the production of a second, Staphylococcus aureus-type WTA (poly-ribitolphosphate (RboP)). Production of RboP-WTA by S. epidermidis impaired in vivo colonization but augmented endothelial attachment and host mortality in a mouse sepsis model. tarIJLM was absent from commensal human sequence types but was found in several other HA-MRSE clones. Moreover, RboP-WTA enabled S. epidermidis to exchange DNA with S. aureus via siphovirus bacteriophages, thereby creating a possible route for the inter-species exchange of methicillin resistance, virulence and colonization factors. We conclude that tarIJLM alters the lifestyle of S. epidermidis from commensal to pathogenic and propose that RboP-WTA might be a robust target for preventive and therapeutic interventions against MRSE infections.

Current status of oxacillin-susceptible mecA-positive Staphylococcus aureus infection in Shanghai, China: A multicenter study.

BACKGROUND: Oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) represents an important issue, as its oxacillin susceptibility has contributed to misidentification by conventional susceptibility tests and consequently potential therapeutic failure, but limited data on the current status of OS-MRSA infection in Chinese hospitals are available. METHODS: This multicenter study performed a battery of susceptibility tests and diagnostic tests for 956 S. aureus isolates from 10 hospitals, including automated susceptibility testing on VITEK 2, broth microdilution, disk diffusion, and detection of PBB2a, mecA gene and mecC gene. For all identified OS-MRSA, multi-locus sequence typing (MLST), together with spa typing, SCCmec typing and PVL detecting, was carried out. RESULTS: OS-MRSA, most of which were from pediatric inpatients, represented 1.8% (17/956) of total isolates. Of these 17 OS-MRSA, 10 were ST59, followed by ST965 (3/17), and 11 carried SCCmec type IV, while 5 carried SCCmec type V, but only one was Panton-Valentine leucocidin (PVL)-positive, also, 16 had one or two point mutations within mecA promoter. OS-MRSA had inducible oxacillin resistance and significantly lower MDR (Multi-Drug Resistant) rate. We observed that the VITEK 2 system exhibited some deficiency in OS-MRSA detection, whereas cefoxitin disk diffusion was shown to be a reliable and cost-saving alternative and should be supplemented in detecting S. aureus with borderline oxacillin susceptible MICs. CONCLUSION: This study has characterized phenotypically and molecularly OS-MRSA in China, and provided insights into more effective management of OS-MRSA.

Dynamic Changes of Staphylococcus aureus Susceptibility to Vancomycin, Teicoplanin, and Linezolid in a Central Teaching Hospital in Shanghai, China, 2008-2018.

Vancomycin, teicoplanin, and linezolid are the major treatment options for methicillin-resistant Staphylococcus aureus (MRSA). The phenomenon of progressive increase in the value of vancomycin minimum inhibitory concentration (MIC) for S. aureus (i.e., vancomycin MIC "creep"), has been reported; however, it is still a controversial concept because the results of research remain inconclusive. In this study, we conducted a retrospective epidemiologic investigation for more than 10 years to elucidate the dynamic changes of the MICs of vancomycin, teicoplanin, and linezolid in S. aureus in a central teaching hospital in Shanghai, China. A total of 2911 S. aureus isolates was recovered from 2008 to 2018, to which the MICs of three antimicrobials were tested by the E-test method and subsequently correlated with the characteristics of oxacillin susceptibility, clonotypes, and antimicrobial consumption during the study period. The proportion of MRSA dramatically decreased from 2008 to 2018 (from 84 to 49%, p < 0.001). Vancomycin MIC decline was identified both in MRSA and methicillin-sensitive S. aureus (MSSA) (both with p < 0.001), and both the dominating MRSA clone ST5 and pre-dominating MRSA clone ST239 displayed vancomycin MIC decline (p < 0.001, p = 0.040), while teicoplanin MIC decline was only identified in MRSA (p = 0.037). Linezolid MIC creep was identified in total S. aureus (p < 0.001), but linezolid in MRSA as well as teicoplanin and linezolid in MSSA displayed no statistically distinct trends of MIC creep or decline. Clinical consumption of linezolid increased significantly from 2012 to 2018 (p = 0.003), which correlated with vancomycin MIC decline in S. aureus (p = 0.005). The results of this study clearly demonstrate the dynamic changes of the MICs of these three primary antimicrobials in S. aureus, and suggest that changes in clinical antibiotic use may affect bacterial resistance.

Skin microbiota analysis-inspired development of novel anti-infectives.

BACKGROUND: The alarming spread of antimicrobial resistance requires the development of novel anti-infective drugs. Despite the recent research focus on the human microbiome and its likely value to understand and exploit inter-bacterial inhibitory phenomena as a source for antimicrobial strategies, the human microbiota has barely been investigated for the purpose of drug development. RESULTS: We performed a large screen analyzing over 3000 human skin isolates to evaluate bacterial competition within the human skin microbiota as a basis for the development of anti-infective therapeutics. We discovered a Staphylococcus hominis strain with strong and broad activity against Gram-positive pathogens that was mediated by the bacteriocin micrococcin P1 (MP1). In "probiotic" approaches, this strain led to reduced Staphylococcus aureus infection and accelerated closure of S. aureus-infected wounds. Furthermore, we used a nanoparticle strategy to overcome the physico-chemical limitations often encountered with natural substances such as MP1 and demonstrate a significant reduction of S. aureus infection by MP1-loaded nanoparticles. CONCLUSIONS: Our study gives examples of how analysis of bacterial interactions in the human microbiota can be explored for the development of novel, effective anti-infective strategies. Video Abstract.

Development of a practical prediction scoring system for severe acute organophosphate poisoning.

Acute organophosphorus poisoning (AOPP) is a serious public health issue, especially in the rural areas. This study was designed to establish a scoring system to assess the risk of cases with severe AOPP. A retrospective cohort study was conducted at two independent hospitals. The derivation cohort included 444 patients with AOPP and the validation cohort included 274 patients. A risk score for patients with severe AOPP was developed. The rates of severe AOPP cases were 20.7% and 20.1% in the derivation and validation cohorts, respectively. A scoring system for severe AOPP risk was developed that included: (1) age >50 years, (2) white blood cell count of >15 × 109 /L, (3) plasma cholinesterase of <360 U/L, (4) plasma albumin of <35 g/L, (5) blood pH <7.3, and (6) lactic acid >3.0 mmol/L. The predicted score in severe cases of AOPP had good accuracy in both the derivation (area under the receiver operating characteristic curve [AUC] 0.88, 95% confidence interval [CI], 0.85-0.92) and validation cohorts (AUC 0.83, 95% CI, 0.77-0.90). A practical bedside prediction scoring system was developed for patients with severe AOPP. The routine use of this scoring system could rapidly assist in identifying patients at higher risk who require more intensive care or transfer to a larger better-equipped hospital.

Staphylococcus epidermidis Contributes to Healthy Maturation of the Nasal Microbiome by Stimulating Antimicrobial Peptide Production.

The composition of the human microbiome profoundly impacts human well-being. However, the mechanisms underlying microbiome maturation are poorly understood. The nasal microbiome is of particular importance as a source of many respiratory infections. Here, we performed a large sequencing and culture-based analysis of the human nasal microbiota from different age groups. We observed a significant decline of pathogenic bacteria before adulthood, with an increase of the commensal Staphylococcus epidermidis. In seniors, this effect was partially reversed. In vitro, many S. epidermidis isolates stimulated nasal epithelia to produce antimicrobial peptides, killing pathogenic competitors, while S. epidermidis itself proved highly resistant owing to its exceptional capacity to form biofilms. Furthermore, S. epidermidis isolates with high antimicrobial peptide-inducing and biofilm-forming capacities outcompeted pathogenic bacteria during nasal colonization in vivo. Our study identifies a pivotal role of S. epidermidis in healthy maturation of the nasal microbiome, which is achieved at least in part by symbiotic cooperation with innate host defense.

Unilateral Axilla-Bilateral Areola Approach for Thyroidectomy by da Vinci Robot: 500 Cases Treated by the Same Surgeon.

Objective: To investigate the efficacy and safety of da Vinci robot-assisted thyroidectomy via an unilateral axilla-bilateral areola (UABA) approach. Methods: The clinical data of 500 patients undergoing robotic thyroidectomy via an UABA approach from July 2014 to April 2018 were retrospectively analyzed. All 500 patients were operated on by the same surgeon and divided into two groups by the time sequence. The efficacy and complications were compared between the two groups. Results: Robotic thyroidectomy via an UABA approach was performed successfully in 500 cases, including 196 cases of benign thyroid diseases with a lesion diameter of 3.1 ± 1.3 cm (0.4 - 8.2 cm) and 304 cases of thyroid cancer with a tumor diameter of 1.2 ± 0.7 cm (0.4 - 4.4 cm). Surgical procedures included unilateral lobectomy and total thyroidectomy with or without central lymph node dissection. Among the 500 patients, 9 (1.8%) had transient recurrent laryngeal nerve injury, 1 (0.2%) had permanent unilateral recurrent laryngeal nerve injury, 12 (2.4%) had subcutaneous hemorrhage of the trajectory area, and 6 (1.2%) had subcutaneous infection of the trajectory area after surgery. Among 239 thyroid cancer patients undergoing total thyroidectomy, 45 (18.8%) had transient hypoparathyroidism and 5 (2.1%) had permanent hypoparathyroidism. The incidence of permanent hypoparathyroidism was 1.9% (4/212) among the patients undergoing total thyroidectomy plus unilateral central lymph node dissection, and 3.7% (1/27) among the patients undergoing total thyroidectomy plus bilateral central lymph node dissection. During the follow-up of median 17 months, all patients were satisfied with postoperative appearance of the neck and no structural recurrence or metastases occurred. There was no significant difference in efficacy between the two groups (P > 0.05), while the complication rate in phase 2 was significantly lower than that in phase 1 (P < 0.05) as the surgeon became more proficient in the UABA approach. Conclusion: Robotic thyroidectomy via an UABA approach is simple, safe, and minimally invasive, suitable for radical resection of large benign tumors and early thyroid cancer and central lymph node dissection.

Serum ubiquitin C-terminal hydrolase L1 predicts cognitive impairment in patients with acute organophosphorus pesticide poisoning.

BACKGROUND: To assess the usefulness of serum C-terminal hydrolase L1 (UCH-L1) level as a biomarker for predicting cognitive impairment in patients with acute organophosphorus pesticide poisoning (AOPP). METHODS: Two hundred and seven adult patients with AOPP were included in this study. Serum UCH-L1 levels were assessed on admission (Day 1 postpoisoning) and on Days 3 and 7 postpoisoning. The associations between serum UCH-L1 levels, other clinical predictors, and cognitive function evaluated on Day 30 postpoisoning were investigated. RESULTS: On multivariate analysis, serum UCH-L1 levels on admission (odds ratio [OR] 1.889, 95% confidence interval [CI] 1.609-3.082, P = 0.002) and 24-hour APACHE II score (OR 1.736, 95% CI 1.264-3.272, P = 0.012) were independent predictors of cognitive impairment on Day 30 postpoisoning. Based on the receiver operating characteristic curve, serum UCH-L1 levels >5.9 ng/mL on admission predicted cognitive impairment on Day 30 postpoisoning with 86.1% sensitivity and 72.5% specificity (area under the curve, 0.869; 95% CI 0.815-0.923). On admission [8.51 (6.53-10.22) ng/mL vs 4.25 (2.57-6.31) ng/mL, P < 0.001] and Day 3 [9.31 (7.92-10.98) ng/mL vs 3.32 (2.25-5.13) ng/mL, P < 0.001] and Day 7 [4.96 (3.28-7.26) ng/mL vs 2.27 (1.55-3.24) ng/mL, P < 0.001] postpoisoning, serum UCH-L1 concentration was significantly higher in patients that developed cognitive impairment compared to those that did not. CONCLUSION: This study demonstrates that serum UCH-L1 level has potential as a novel biomarker for predicting cognitive impairment 30 days after AOPP.

Decreasing methicillin-resistant Staphylococcus aureus (MRSA) infections is attributable to the disappearance of predominant MRSA ST239 clones, Shanghai, 2008-2017.

A consistently decreasing prevalence of MRSA infections in China has been reported, however, the underlying mechanism of molecular processes responsible for this decline in MRSA infections has been poorly understood. We conducted an epidemiologic investigation to determine the dynamic changes of Staphylococcus aureus infections. A total of 3695 S. aureus isolates was recovered from 2008 to 2017, and subsequently characterized by infection types, resistance profile, and clone types. The frequency of respiratory infection decreased over the study period from 76% to 52%. The proportion of MRSA remarkably decreased (from 83.5% to 54.2%, 2008-2017) (p < .0001). The prevalence of predominant healthcare-associated MRSA (HA-MRSA) clones, ST239-t030 and ST239-t037, significantly decreased (from 20.3% to 1% and 18.4% to 0.5%, 2008-2017, respectively); both of them were replaced by the continually growing ST5-t2460 clone (from 0% to 17.3%, 2008-2017). Epidemic community-acquired MRSA (CA-MRSA) ST59 and ST398 clones also increased (from 1.0% to 5.8% and 1.8% to 10.5%, 2008-2017, respectively). These results demonstrated a significant decrease in the previously dominant HA-MRSA ST239 clones, leading to a marked decrease in the prevalence of MRSA over the past decade, and shed new light on the complex competition of S. aureus clones predominating within the health-care environment.

Multifaceted regulation and functions of replication factor C family in human cancers.

Replication factor C (RFC) family is a complex comprised of the RFC1, RFC2, RFC3, RFC4, and RFC5 subunits, which acts as a primer recognition factor for DNA polymerase. It is reported that RFC, biologically active in various malignant tumors, may play an important role in the proliferation, progression, invasion, and metastasis of cancer cells. It could act as an oncogene or tumor suppressor gene based on the cellular and histological characteristics of the tumor. In this review, we summarized the updated researches on the structure, physiological function, and expression pattern of RFC in a variety of tumors, the underlying mechanisms on carcinogenesis, and the potentials of RFC family members in the diagnosis and prognosis prediction.