Hybrid Type I and II Polyketide Synthases Yield Distinct Aromatic Polyketides.

Bacterial aromatic polyketides are compounds with multiple aromatic rings synthesized by bacterial type II polyketide synthases (PKSs), some of which have been developed into clinical drugs. Compounds containing aromatic polyketides synthesized by hybrid type I and type II PKSs are extremely rare. Here, we report the discovery of a gene cluster encoding both modular type I and type II PKSs as well as KAS III through extensive bioinformatics analysis, leading to the characterization of the hybrid polyketide, spirocycline A. The structure of spirocycline A is rare among all aromatic polyketides, featuring a unique starter unit and four spirocycles and forming a dimer. Biosynthetic studies indicate that the starter unit of this molecule is synthesized by type I PKS in collaboration with two trans-acting ketoreductase (KR) and enoylreductase (ER). It is then transferred by KAS III to the type II PKS system, which synthesizes the tricyclic aromatic polyketide backbone. The subsequent formation of the spirocycle and dimerization are carried out by four redox enzymes encoded in the gene cluster. Overall, the discovery of spirocycline A provides a new approach for identifying novel aromatic polyketides and offers potential enzymatic tools for the bioengineering of these hybrid polyketides.

Maduraflavacins A-E, Unusual Phenyl Polyene Metabolites Produced by a Rare Marine-Derived Actinomadura sp.

Phenyl polyenes comprise a small family of bacterial natural products with broad and potent bioactivities, primarily found in actinobacteria. Here we report the discovery of five new phenyl polyene metabolites, maduraflavacins A-E (1-5), from a rare, marine-derived actinobacteria strain Actinomadura glauciflava NA03286. The structures of these natural products were determined by NMR spectroscopy, HRESIMS, LC-MS/MS, and chemical derivatization. All of these new maduraflavacins feature methyl substitutions at the polyene side chain, and maduraflavacins A-C (1-3) possessed a 1-N-ß-d-glucosamine-(3 → 1)-O-ß-d-glucopyranosyl-(3 → 1)-O-ß-d-glucopyranosyl-(6 → 1)-O-ß-d-glucopyranoside tetrasaccharide moiety via an amido linkage with a phenyl polyene skeleton. Compounds 1 and 2 showed weak antibacterial activities against the Gram-positive bacteria Staphylococcus aureus Sau 16339 and Micrococcus luteus, respectively.

Potential profiling of self-management skills in older co-morbid patients.

BACKGROUND: Under the general trend of global aging, geriatric comorbidity is increasingly common, which may have some impact on the quality of life of the older people. Self-management can effectively improve patient compliance, subjective initiative, and improve patient quality of life. However, the present situation of self-management in different old people is different. Therefore, this study classifies older co-morbid patients through potential profiling analysis, understands the category characteristics of self-management level of older co-morbid patients, and discusses the influencing factors of self-management level of different categories of older co-morbid patients, which can provide reference for personalized intervention programs for different comorbidity characteristics of elderly people in the future.  METHOD: Through a cross-sectional study, 616 cases of older co-morbid patients in three districts of Zhengzhou City, Henan Province, were selected as survey subjects by using the whole cluster sampling method. The General Information Questionnaire, Chronic Disease Self-Management Scale, Health Literacy Scale, Electronic Health Literacy Scale, Collaborative Social Support Scale, and Health Empowerment Scale were used to conduct the survey. RESULTS: The result of LPA shows that the self-management characteristics of older co-morbid patients should be classified into 3 categories: good self-management (19.4%), medium self-management(27.9%), and low self-management (52.7%). The results of multivariate logistic regression analyses show that literacy, religiosity, health literacy, e-health literacy, appreciative social support, and health empowerment are influential factors for self-management among older co-morbid patients (p < 0.05). CONCLUSION: There is obvious heterogeneity in the self-management level of older co-morbid patients. It is recommended that healthcare professionals give targeted interventions for their weaknesses according to the self-management characteristics of different categories of patients in order to enhance the self-management level of this population and improve their quality of life.

The Beneficial Effects of Lacticaseibacillus paracasei subsp. paracasei DSM 27449 in a Letrozole-Induced Polycystic Ovary Syndrome Rat Model.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age globally. Emerging evidence suggests that the dysregulation of microRNAs (miRNAs) and gut dysbiosis are linked to the development of PCOS. In this study, the effects of Lacticaseibacillus paracasei subsp. paracasei DSM 27449 (DSM 27449) were investigated in a rat model of PCOS induced by letrozole. The administration of DSM 27449 resulted in improved ovarian function, reduced cystic follicles, and lower serum testosterone levels. Alterations in miRNA expressions and increased levels of the pro-apoptotic protein Bax in ovarian tissues were observed in PCOS-like rats. Notably, the administration of DSM 27449 restored the expression of miRNAs, including miR-30a-5p, miR-93-5p, and miR-223-3p, leading to enhanced ovarian function through the downregulation of Bax expressions in ovarian tissues. Additionally, 16S rRNA sequencing showed changes in the gut microbiome composition after letrozole induction. The strong correlation between specific bacterial genera and PCOS-related parameters suggested that the modulation of the gut microbiome by DSM 27449 was associated with the improvement of PCOS symptoms. These findings demonstrate the beneficial effects of DSM 27449 in ameliorating PCOS symptoms in letrozole-induced PCOS-like rats, suggesting that DSM 27449 may serve as a beneficial dietary supplement with the therapeutic potential for alleviating PCOS.

Effectiveness of blended happy age education program (B-HAEP) on active aging promotion among pre-disable community dwelling older adults in Pakistan.

BACKGROUND: Addressing aging related functional declines in older adults has become a top priority for countries around the world. The aim of this study was to investigate the effectiveness of a blended happy age education program in promoting active aging among community-based pre-disable older adults. METHODS: We conducted a two-arm trial study in Khyber Pakhtunkhwa, Pakistan. Participants were randomly assigned into two groups using a computer-generated random sequence of 150 participants. RESULTS: Blended Happy Age Education Program (BHAEP) reduced time for 3 m walk (Estimated mean 19.5 ± 3.4 to 13.7 ± 1.3, effect size ηp² = 0.98, (P < 0.001). The current level of happiness improved in B-HAEP group from 4.7 ± 1.05 scores to 7.8 ± 1.6, P < 0.001, effect size (ηp² = 0.540). Healthy lifestyle significantly improved (P < 0.001, ηp² = 0.4). CONCLUSIONS: B-HAEP can be an effective intervention strategy to promote active aging in older adults with risk for immobility.

P450-Modified Multicyclic Cyclophane-Containing Ribosomally Synthesized and Post-Translationally Modified Peptides.

Cyclic peptides with cyclophane linkers are an attractive compound type owing to the fine-tuned rigid three-dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C-C and C-O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post-translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450-modified multicyclic RiPPs, we set out to find cryptic and unknown P450-modified RiPP biosynthetic gene clusters (BGCs) through genome mining. Synergized bioinformatic analysis reveals that P450-modified RiPP BGCs are broadly distributed in bacteria and can be classified into 11 classes. Focusing on two classes of P450-modified RiPP BGCs where precursor peptides contain multiple conserved aromatic amino acid residues, we characterized 11 novel P450-modified multicyclic RiPPs with different cyclophane linkers through heterologous expression. Further mutation of the key ring-forming residues and combinatorial biosynthesis study revealed the order of bond formation and the specificity of P450s. This study reveals the functional diversity of P450 enzymes involved in the cyclophane-containing RiPPs and indicates that P450 enzymes are promising tools for rapidly obtaining structurally diverse cyclic peptide derivatives.

A Bipolar Membrane-Integrated Electrochlorination Process for Highly Efficient Ammonium Removal in Mature Landfill Leachate: The Importance of ClO• Generation.

Electrochemical oxidation has been demonstrated to be a useful method for removing biorefractory organic pollutants in mature landfill leachate but suffers from low efficiency in eliminating ammonium because of its resistance to being oxidized by HO• or free chlorine (FC) at decreased pH. Here, we propose a new bipolar membrane-electrochlorination (BPM-EC) process to address this issue. We found that the BPM-EC system was significantly superior to both the undivided and divided reactors with monopolar membranes in terms of elevated rate of ammonium removal, attenuated generation of byproducts (e.g., nitrate and chloramines), increased Faradaic efficiency, and decreased energy consumption. Mechanistic studies revealed that the integration of BPM was helpful in creating alkaline environments in the vicinity of the anode, which facilitated production of surface-bound HO• and FC and eventually promoted in situ generation of ClO•, a crucial reactive species mainly responsible for accelerating ammonium oxidation and selective transformation to nitrogen. The efficacy of BPM-EC in treating landfill leachates with different ammonium concentrations was verified under batch and continuous-flow conditions. A kinetic model that incorporates the key parameters was developed, which can successfully predict the optimal number of BPM-EC reactors (e.g., 2 and 5 for leachates containing 589.4 ± 5.5 and 1258.1 ± 9.6 mg L-1 NH4+-N, respectively) necessary for complete removal of ammonium. These findings reveal that the BPM-EC process shows promise in treating ammonium-containing wastewater, with advantages that include effectiveness, adaptability, and flexibility.

Boosting Ammonium Oxidation in Wastewater by the BiOCl-Functionalized Anode.

Mixed metal oxide (MMO) anodes are commonly used for electrochlorination of ammonium (NH4+) in wastewater treatment, but they suffer from low efficiency due to inadequate chlorine generation at low Cl- concentrations and sluggish reaction kinetics between free chlorine and NH4+ under acidic pH conditions. To address this challenge, we develop a straightforward wet chemistry approach to synthesize BiOCl-functionalized MMO electrodes using the MMO as an efficient Ohmic contact for electron transfer. Our study demonstrates that the BiOCl@MMO anode outperforms the pristine MMO anode, exhibiting higher free chlorine generation (24.6-60.0 mg Cl2 L-1), increased Faradaic efficiency (75.5 vs 31.0%), and improved rate constant of NH4+ oxidation (2.41 vs 0.76 mg L-1 min-1) at 50 mM Cl- concentration. Characterization techniques including electron paramagnetic resonance and in situ transient absorption spectra confirm the production of chlorine radicals (Cl• and Cl2•-) by the BiOCl/MMO anode. Laser flash photolysis reveals significantly higher apparent second-order rate constants ((4.3-4.9) × 106 M-1 s-1 at pH 2.0-4.0) for the reaction between NH4+ and Cl•, compared to the undetectable reaction between NH4+ and Cl2•-, as well as the slower reaction between NH4+ and free chlorine (102 M-1 s-1 at pH < 4.0) within the same pH range, emphasizing the significance of Cl• in enhancing NH4+ oxidation. Mechanistic studies provide compelling evidence of the capacity of BiOCl for Cl- adsorption, facilitating chlorine evolution and Cl• generation. Importantly, the BiOCl@MMO anode exhibits excellent long-term stability and high catalytic activity for NH4+-N removal in a real landfill leachate. These findings offer valuable insights into the rational design of electrodes to improve electrocatalytic NH4+ abatement, which holds great promise for wastewater treatment applications.

Mechanisms of Epichloë bromicola to Promote Plant Growth and Its Potential Application for Coix lacryma-jobi L. Cultivation.

Endophytic fungi play important roles in regulating plant growth and development and usually used as a promising strategy to enhance the biosynthesis of host valuable secondary metabolite, but the underlying growth-promoting mechanisms are only partly understood. In this study, the wild-type Arabidopsis thaliana seedlings co-cultured with fungal endophyte Epichloë bromicola showed auxin (IAA)-stimulated phenotypes, and the growth-promoting effects caused by E. bromicola were further verified by the experiments of spatially separated co-culture and fungal extract treatment. IAA was detected and identified in the extract of E. bromicola culture by LC-HRMS/MS, whereas 2,3-butanediol was confirmed to be the predominant volatile active compound in the diethyl ether and ethyl acetate extracts by GC-MS. Further study observed that IAA-related genes including synthesis key enzyme genes (CYP79B2, CYP79B3, NIT1, TAA1 and YUCCA1) and controlling polar transport genes (AUX1, BIG, EIR1, AXR3 and ARF1), were highly expressed at different periods after E. bromicola inoculation. More importantly, the introduction of fungal endophyte E. bromicola could effectively promote the growth and accumulation of coixol in Coix under soil conditions. Our study showed that endophytic fungus E. bromicola might be considered as a potential inoculant for improving medicinal plant growth.

Assessment of fall-associated risk factors in the Muslim community-dwelling older adults of Peshawar, Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Falls are the third-leading cause of disability among the elderly population worldwide. It is multifactorial, and the occurrence of falls depends on different factors, which can be different from context to context, and individual to individual. Therefore, regular assessment of fall risk factors is required to develop a strategy for fall prevention. The study aimed to identify fall-related risk factors in Pakistani healthy older adults at risk of developing physical disabilities. It also aimed to create a risk-predictive model for fall occurrence, offering evidence for preventive strategies. METHODS: Data were collected from 140 Muslim older adults from two residential areas of Peshawar, Khyber Pakhtunkhwa, from July 2022 to August 25, 2022, after obtaining permission from the Zhengzhou University Ethical Review Board (ZZUIRB #202,254), and the District Health Department Office (DHO #14,207). Participants were informed, and consent was obtained before data collection. Data were collected using the Time Up and Go Test (TUGT) checklist, the Cognitive Screening Scores (CS-10) checklist, interviews regarding the prayer practice, fall history in the last six months, visual equity questions, and demographic variables. RESULTS: Factors associated with falls were; age, gender, education, cognitive status, poor walking speed, lack of physical activity, poor vision, and history of falls in the last six months, with a significant P value of (P. < 0.05) in the Pearson correlation coefficient test. Poor cognition, low visual equity, poor walking speed, and lack of exercise increase the risk of falling in the future, with a prediction value of (P < 0.005) in Omnibus, Lemeshow score of (0.77). CONCLUSION: Hence, our study provides a road map for future risk assessment of falls by adding the four mentioned risk factors in the proposed model to facilitate timely action to prevent fall-related infirmities in Pakistani healthy older adults.

The translation process of the culturally sensitive active aging scale for community-dwelling older adults in Pakistan.

BACKGROUND: The assessment of active aging levels in Pakistani older adults is crucial yet; research tools are scarce in the local language. Therefore, this study aims to translate and validate the English version of an Active Aging Scale into a cross-culturally sensitive Urdu version to assess active aging levels in Pakistani older adults. METHODS: To translate and validate the scale, we used the ISPOR (International Society for Pharmacy Economic and Outcome Research) standards. Reliability, concurrent validity, construct validity, convergent validity, and discriminatory validity were checked on a total sample of 160 community-dwelling older adults. After two weeks, the test-retest reliability was examined. AMOS version 23 and SPSS version 23 were used to analyze the data. RESULTS: The average content validity index for clarity was 0.91 and relevancy was 0.80. The total variance in the pilot study of all items secured > 0.3 variances except for two items scored < 0.30 that were omitted before the validity and reliability test. The remaining items explained 65.46% of the overall variation and had factor loadings ranging from 0.46 to 0.90 in the principal factor analysis (PFA). The confirmatory factor analysis of the Active Aging Scale revealed that the model fit was good with a Chi-square value (418.18 (DF = 2.2) which is less than 3.00. This is further evidenced by the root mean square error of approximation (RMSEA) of 0.042, goodness of fit index (GFI) of 0.92, adjusted goodness of fit index (AGFI) of 0.94, and comparative fit index (CFI) values of 0.92 and 0.96 (unstandardized and standardized, respectively). The scale's Cronbach's alpha coefficient was 0.88, indicating dependability and its test-retest reliability with the significance of (P. < 0.05). CONCLUSION: The Urdu version of the Active Aging Scale was successfully translated and validated in a culturally sensitive manner, and can be used to evaluate the effectiveness of various active aging interventions for older adults in Pakistan.

Neuroprotective Effects of Lactobacillus plantarum PS128 in a Mouse Model of Parkinson's Disease: The Role of Gut Microbiota and MicroRNAs.

Parkinson's disease (PD) is a neurodegenerative disease characterized by motor deficits and marked neuroinflammation in various brain regions. The pathophysiology of PD is complex and mounting evidence has suggested an association with the dysregulation of microRNAs (miRNAs) and gut dysbiosis. Using a rotenone-induced PD mouse model, we observed that administration of Lactobacillus plantarum PS128 (PS128) significantly improved motor deficits in PD-like mice, accompanied by an increased level of dopamine, reduced dopaminergic neuron loss, reduced microglial activation, reduced levels of inflammatory factors, and enhanced expression of neurotrophic factor in the brain. Notably, the inflammation-related expression of miR-155-5p was significantly upregulated in the proximal colon, midbrain, and striatum of PD-like mice. PS128 reduced the level of miR-155-5p, whereas it increased the expression of suppressor of cytokine signaling 1 (SOCS1), a direct target of miR-155-5p and a critical inhibitor of the inflammatory response in the brain. Alteration of the fecal microbiota in PD-like mice was partially restored by PS128 administration. Among them, Bifidobacterium, Ruminiclostridium_6, Bacteroides, and Alistipes were statistically correlated with the improvement of rotenone-induced motor deficits and the expression of miR-155-5p and SOCS1. Our findings suggested that PS128 ameliorates motor deficits and exerts neuroprotective effects by regulating the gut microbiota and miR-155-5p/SOCS1 pathway in rotenone-induced PD-like mice.

Evaluation of adsorption performance and mechanisms of a highly effective 3D boron-doped graphene composite for amitriptyline pharmaceutical removal.

Three-dimensional heteroatom-doped graphene presents a state-of-the-art approach for effective remediation of pharmaceutical wastewater on account of its distinguished adsorption and physicochemical attributes. Amitriptyline is an emerging tricyclic antidepressant pollutant posing severe risks to living habitats through water supply and food chain. With ultra-large surface area and plentiful chemical functional groups, graphene oxide is a favorable adsorbent for decontaminating polluted water. Herein, a new boron-doped graphene oxide composite reinforced with carboxymethyl cellulose was successfully developed via solution-based synthesis. Characterization study revealed that the adsorbent was formed by graphene sheets intertwined into a porous network and engrafted with 13.37 at% of boron. The adsorbent has a zero charge at pH 6 and contained various chemical functional groups favoring the attachment of amitriptyline. It was also found that a mere 10 mg of adsorbent was able to achieve relatively high amitriptyline removal (89.31%) at 50 ppm solution concentration and 30 °C. The amitriptyline adsorption attained equilibrium within 60 min across solution concentrations ranging from 10 to 300 ppm. The kinetic and equilibrium of amitriptyline adsorption were well correlated to the pseudo-second-order and Langmuir models, respectively, portraying the highest Langmuir adsorption capacity of 737.4 mg/g. Notably, the predominant mechanism was chemisorption assisted by physisorption that contributed to the outstanding removal of amitriptyline. The saturated adsorbent was sufficiently regenerated using ethanol eluent. The results highlighted the impressive performance of the as-synthesized boron-doped adsorbent in treating amitriptyline-containing waste effluent.

Sleep quality is associated with the weight of newborns after in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI).

BACKGROUND: Sleep disorders are thought to be common in women with in vitro fertilization and embryo transfer (IVF-ET) conception. Although a few studies have investigated the association between maternal sleep quality and infant birth weight, it is unclear to what extent birth weight is associated with sleep quality during pregnancy among these women. Therefore, we conducted a cohort study to assess sleep quality among women receiving IVF-ET during the subsequent pregnancy and investigated the association of self-report sleep quality on infant birth weight. METHODS: This study was a prospective cohort study recruiting women who were to receive assisted reproductive technology (ART). Sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI) before oocyte retrieval and in the first trimester, second trimester, and third trimester during pregnancy. A generalized estimating equation (GEE) model was applied to evaluate the associations between sleep quality at specific times and infant birth weight. A general linear model was conducted to explore which component of the PSQI questionnaire was most associated with infant birth weight. RESULTS: Between August 2016 and August 2020, a total of 1344 women who had singleton births with IVF conception were included in the analysis. PSQI scores in the first trimester were highest (4.59 ± 2.47) but had no significant relationship with birth weight. After accounting for potential influencing factors, we found that poor maternal sleep quality in the second trimester was significantly associated with small for gestational age (SGA) among female infants (OR = 3.03, 95% CI = 1.04 to 9.71, P = 0.044), while no association was observed between sleep quality and birth weight in male infants (OR = 1.64, 95% CI = 0.68 to 3.99, P = 0.271). CONCLUSIONS: These findings suggest that the sleep quality of women with IVF pregnancies may influence fetal weight in a trimester- and sex-specific manner.

The relationship between using estrogen and/or progesterone and the risk of mammary gland hyperplasia in women: a meta-analysis.

BACKGROUND: As reported that the usage of estrogen and/or progesterone increases the risk of mammary gland hyperplasia (MGH) with conflicting results. Therefore, we conducted a meta-analysis to higher elucidate the relationship between hormones and MGH. METHOD: PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, and Wan-fang database were searched for studies until April 28, 2021. RESULTS: Nine related studies were included in the present meta-analysis. We found that the usage of estrogen and/or progesterone had a significant association with increasing the risk of MGH (RR = 1.56, 95% CI: 1.13-2.15, p = .000). The subgroup results showed that the risk of MGH increased in the Mix population (RR = 1.72, CI: 1.58-1.88, p < .001) but no significant difference in the Asian population. Meanwhile, as for using estrogen plus progesterone (EPP) and postmenopausal women the risk of MGH, respectively, increased (RR = 1.74, CI: 1.22-2.47, p = .002) and (RR = 1.75, CI: 1.24-2.47, p = .001) but no significant different for using estrogen alone and premenopausal women. CONCLUSIONS: This study findings indicated that using estrogen and/or progesterone might increase the risk of MGH in premenopausal and postmenopausal women.

Screening and analysis of RNAs associated with activated memory CD4 and CD8 T cells in liver cancer.

BACKGROUND: Liver cancer is one of the most common malignant tumors in the world. T cell-mediated antitumor immune response is the basis of liver cancer immunotherapy. OBJECTIVE: To screen and analyze the RNAs associated with activated memory CD4 T cells and CD8 T cells in liver cancer. METHODS: ESTIMATE was used to calculate the stromal and immune scores of tumor samples, which were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed genes (DEGs) in high and low stromal and immune scores were screened, followed by functional enrichment of overlapped DEGs. We then conducted a survival analysis to identify immune-related prognostic indicators and constructed protein-protein interaction (PPI) networks and ceRNA networks. Finally, chemical small-molecule-target interaction pairs associated with liver cancer were screened. RESULTS: A total of 55,955 stromal-related DEGs and 1811 immune-related DEGs were obtained. The 1238 overlapped DEGs were enriched in 1457 biological process terms and 74 KEGG pathways. In addition, a total of 120 activated memory CD4 T cell-related genes and 309 CD8 T cell-related genes were identified. The survival analysis revealed that upregulated expression of T cell-related genes including EOMES, CST7, and CD5L indicated the favorable prognosis of liver cancer. EOMES was regulated by has-miR-23b-3p and has-miR-23b-3p was regulated by lncRNA AC104820.2 in the ceRNA network of activated memory CD4 T cell-related genes. In addition, EOMES was regulated by has-miR-23a-3p and has-miR-23a-3p was regulated by lncRNA AC000476.1 in the ceRNA network of CD8 T cells. CONCLUSION: T cell-related RNAs EOMES, CST7, CD5L, has-miR-23b-3p, and has-miR-23a-3p may be associated with the prognosis of liver cancer. And the molecular characteristics of these T cell-related genes were plotted.

Dexmedetomidine combined with ropivacaine for erector spinae plane block after posterior lumbar spine surgery: a randomized controlled trial.

PURPOSE: Due to lumbar spinal surgery is frequently accompanied with moderate-to-severe postoperative pain, it is necessary to find an effective postoperative analgesia for patients with this surgery. This study aimed to observe the analgesic effect of dexmedetomidine combined with ropivacaine erector spinae plane block (ESPB) used in posterior lumbar spine surgery. METHODS: In this clinical trial, patients undergoing posterior lumbar spine surgery were recruited and randomly divided into two groups: intervention and control. The intervention group (Group E) received 0.375% ropivacaine with 1 µg/kg dexmedetomidine in a total of 20 ml for ESPB; the control group (Group C) received 20 ml ropivacaine 0.375% for ESPB. US-guided ESPB was performed preoperatively in all patients. Demographics, anesthesia time, surgery time, and ASA grade from the participants were recorded at baseline. The primary clinical outcome measures were 2-, 4-, 8-, 12-, 24-and 48-h visual analog scale (VAS) pain scores after surgery at rest and movement state. Other end points included opioid consumption, number of PCIA presses, flurbiprofen-axetil consumption, quality of recovery and pain management after surgery. RESULTS: One hundred twenty patients were enrolled in the study (mean [SD] ages: Group E, 54.77 [8.61] years old; Group C,56.40 [7.87] years old; P = 0.280). The mean anesthesia time was 152.55 (15.37) min in Group E and 152.60 (16.47) min in Group C (P = 0.986). Additionally, the surgery time was 141.70 (15.71) min in Group E compared to 141.48 (17.13) min in Group C (P = 0.943). In addition, we found that the VAS pain scores in the resting state during the postoperative period at 8-48 h were lower in Group E than in Group C. However, the VAS pain scores in the active state were lower in Group E at 12-48 h (P < 0.05). More importantly, the consumption of opioids and flurbiprofen-axetil after surgery was also lower in Group E (P < 0.05). Subsequently, we administered questionnaires on the quality of recovery and pain management after surgery that were positively correlated with the postoperative analgesic effect. It was worth affirming that the QoR-15 scores and APS-POQ-R questionnaire results were different between the two groups, further confirming that the combination of drugs not only could obtain an ideal analgesic effect but also had no obvious adverse reactions (P < 0.05). CONCLUSIONS: All the findings suggested that dexmedetomidine could significantly relieve postoperative pain and reduce the consumption of opioids in patients undergoing posterior lumbar spine surgery without obvious adverse reactions as a local anesthetic adjuvant. Further studies with larger sample sizes and different drug dosages may be useful in understanding the potential clinical benefits of dexmedetomidine.

Fetal exposure of Aristolochic Acid I undermines ovarian reserve by disturbing primordial folliculogenesis.

The primordial follicle pool established in early life determines the ovarian reserve in the female reproductive lifespan. Premature exhaustion of primordial follicles contributes to primary ovarian insufficiency (POI), that is dependent by the initial size of the primordial follicle pool and by the rate of its activation and depletion. AAI, a powerful nephrotoxin with carcinogenic potential, is present in the Aristolochiaceae species, which can release AAI into soil as a persistent pollutant. In order to assess the potential risk of Aristolochic Acid I (AAI) exposure on mammalian oogenesis, we uncovered its adverse effect on primordial folliculogenesis in the neonatal mouse ovary and its effect on female fertility in adulthood. Pregnant mice were orally administrated with doses of AAI without hepatic or renal toxicity during late-gestation. Ovaries from offspring of administered female displayed gross aberrations during primordial folliculogenesis. Also, unenclosed oocytes in germ-cell cysts showed increased DNA damage. Furthermore, several key factors, including NANOS3, SOX9, KLF4, that govern early gonad's differentiation were abnormally expressed in the exposed ovary, while the follicle formation was partially restored by knockdown of Nanos3 or sox9. In adulthood, these aberrations evolved into a significant reduction in offspring number and impaired ovarian reserve. Together, our results show that AAI influences primordial folliculogenesis and, importantly, affected female fertility. This study shows that administration of drugs herbs or consumption of vegetables that contain AAs during pregnancy may adversely influence the fertility of offspring.

The immediate meniscal allograft transplantation achieved better chondroprotection and less meniscus degeneration than the conventional delayed transplantation in the long-term.

PURPOSE: The purpose of this study was to compare the long-term clinical and radiological outcomes between the immediate and delayed meniscus allograft transplantation (MAT). METHODS: Nine menisci were transplanted immediately after total meniscectomy (immediate group, IM), and 10 menisci were delayed transplanted in patients with the median of 35 months (range 9-92 months) after total meniscectomy (delayed group, DE). Patient's subjective clinical outcomes including VAS, IKDC, Lysholm and Tegner scores as well as muscle strength measures were compared. Joint degeneration was evaluated by both radiographs to assess joint space width narrowing, Kellegren-Lawrence (KL) grade and MRI with T2 mapping sequences to quantitatively analyze both cartilage and meniscal allograft degeneration. RESULTS: The median follow-up time was 10.8 years (range 10-14 years). The IKDC (IM vs DE, 89.8 vs 80.9, n.s.) and Lysholm scores (IM vs DE, 87.7 vs 78.0, n.s.) were close in two groups, while the IM group showed slightly lower VAS (IM vs DE, 0.2 vs 1.5, p = 0.031), higher Tegner score (IM vs DE, 7 vs 3.5 p = 0.021) and better quadriceps muscle strength. The IM group had less joint space narrowing (IM vs DE, 0.35 mm vs 0.71 mm, n.s.), less KL grade progression (IM vs DE, 0.6 vs 1.7, p = 0.041) on radiographs and less chondral lesions development on MRIs (Cartilage Degeneration Index, IM vs DE, 252 vs 2038, p = 0.025). All meniscal grafts exhibited degeneration by showing grade 3 signal on MRI, and 4 (4/9) in the IM group and 8 (8/10) cases in the DE group. The T2 value of cartilage and meniscal allograft in the IM group was close to that of the healthy control and was significantly lower than that of the DE group. CONCLUSION: Compared to the conventional delayed MAT, the immediate MAT achieved better cartilage and meniscus protection in the long-term, while its superiority in patient-reported outcomes was limited. LEVEL OF EVIDENCE: IV.

Synthesis of a highly recoverable 3D MnO2/rGO hybrid aerogel for efficient adsorptive separation of pharmaceutical residue.

Water contamination by non-steroidal anti-inflammatory drugs, such as acetaminophen, is an emerging ecological concern. In this study, a new three-dimensional manganese dioxide-engrafted reduced graphene oxide (3D MnO2/rGO) hybrid aerogel was developed for acetaminophen sequestration. The synthesis involved firstly the self-assembly of GO aerogel, followed by thermal reduction and in-situ MnO2 growth by redox-reaction. The aerogel demonstrated interlinked planes with smooth surfaces deposited with MnO2 nanospheres and pores of 138.4 - 235.3 µm width. The influences of adsorbent dosage, initial pH, acetaminophen concentration, temperature and contact time were investigated. It was determined that the adsorption of acetaminophen occurred on uniform sorption sites in the aerogel, as suggested by the best fit of data to the Langmuir isotherm, yielding a maximum adsorption capacity of 252.87 mg/g. This highest adsorption performance of the 3D MnO2/rGO aerogel was attained at a dosage of 0.6 g/L, initial pH of 6.2 and temperature of 40°C. The process kinetics were in-line with the pseudo-first-order and pseudo-second-order kinetics at 10 and 20 - 500 mg/L concentrations, respectively. Thermodynamic assay showed the spontaneity and endothermicity features of the 3D MnO2/rGO-acetaminophen system. The acetaminophen adsorption mechanisms were mainly hydrogen bonding and pore entrapment. Moreover, the as-synthesised aerogel was effectively regenerated using acetone and re-utilised in four adsorption-desorption cycles. Overall, the results highly recommend the implementation of the 3D MnO2/rGO hybrid aerogel for purification of wastewater polluted by acetaminophen residue.