Identification and Biological Characteristics of Mortierella alpina Associated with Chinese Flowering Cherry (Cerasus serrulata) Leaf Blight in China.

The Chinese flowering cherry (Cerasus serrulata), an ornamental tree with established medicinal values, is observed to suffer from leaf blight within Xi'an's greenbelts. This disease threatens both the plant's growth and its ornamental appeal. In this study, 26 isolates were obtained from plants with typical leaf blight, and only 3 isolates (XA-10, XA-15, and XA-18) were found to be pathogenic, causing similar symptoms on the leaves of the host plant. Based on sequence alignment, the ITS and LSU sequences of the three selected isolates were consistent, respectively. Following morphological and molecular analyses, the three selected isolates were further identified as Mortierella alpina. The three selected isolates exhibited similar morphological characteristics, including wavy colonies with dense, milky-white aerial mycelia on PDA medium. Therefore, isolate XA-10 was used as a representative strain for subsequent experiments. The representative strain XA-10 was found to exhibit optimal growth at a temperature of 30 °C and a pH of 7.0. Host range infection tests further revealed that the representative strain XA-10 could also inflict comparable disease symptoms on both the leaves and fruits of three different Rosaceae species (Prunus persica, Pyrus bretschneideri, and Prunus salicina). This study reveals, for the first time, the causative agent of leaf blight disease affecting the Chinese flowering cherry. This provides a deeper understanding of the biology and etiology of M. alpina. This study lays a solid foundation for the sustainable control and management of leaf blight disease in the Chinese flowering cherry.

A CRISPR-Cas12a-based electrochemical biosensor for the detection of microphthalmia-associated transcription factor.

A novel electrochemical biosensor that combines the CRISPR-Cas12a system with a gold electrode is reported for the rapid and sensitive detection of microphthalmia-associated transcription factor (MITF). The biosensor consists of a gold electrode modified with DNA1, which contains the target sequence of MITF and is labeled with ferrocene, an electroactive molecule. The biosensor also includes hairpin DNA, which has a binding site for MITF and can hybridize with helper DNA to form a double-stranded complex that activates CRISPR-Cas12a. When MITF is present, it binds to hairpin DNA and prevents its hybridization with helper DNA, thus inhibiting CRISPR-Cas12a activity and preserving the DPV signal of ferrocene. When MITF is absent, hairpin DNA hybridizes with helper DNA and activates CRISPR-Cas12a, which cleaves DNA1 and releases ferrocene, thus reducing the DPV signal. The biosensor can detect MITF with high sensitivity (with an LOD of 8.14 fM), specificity, and accuracy in various samples, such as cell nuclear extracts and human serum. The biosensor can also diagnose and monitor melanocyte-related diseases and melanin production. This work provides a simple, fast, sensitive, and cost-effective biosensor for MITF detection and a valuable tool for applications in genetic testing, disease diagnosis, and drug screening.

GPX8 regulates pan-apoptosis in gliomas to promote microglial migration and mediate immunotherapy responses.

Introduction: Gliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques. Methods: The prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential. Results: Experimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration. Conclusions: The incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas.

Crestal sinus augmentation in a head back position: Retrospective case series.

Objectives: To evaluate the clinical efficacy of Crestal Sinus Augmentation (CSA) in a head back position (CSA-HBP) for maxillary sinus mucosa elevation. Materials and Methods: We enrolled 209 patients, 246 maxillary sinuses, 348 sites in this study. Complications, maxillary sinus mucosal perforation rate and cumulative survival rate (CSR) data were collected to evaluate the clinical efficacy of CSA-HBP. Maxillary sinus mucosal elevation height (EH) and new bone height (NH) were measured by cone-beam computerized tomography and standard periapical radiographs. The implantation sites of residual bone height (RBH) ≤5 mm and RBH >5 mm were marked as Groups A (n = 81) and B (n = 267), respectively. The implantation sites of the second and third molar sites were marked as Group C (n = 134), and the remaining sites were marked as Group D (n = 214). Results: The RBH before implant placement was 6.63 ± 2.10 mm (95% confidence interval [CI] 6.41- 6.85 mm). The mucosal EH was 4.04 ± 1.86 mm (95% CI 3.85 - 4.24 mm). The NH was 2.36 ± 1.20 mm (95% CI 3.85-4.24 mm). No other complications were found except three cases of postoperative swelling and one case of nasal blood secretions. The overall mucosal perforation rate was 1.44% (5/348, 95% CI 0.2%-2.7%) and the rate of RBH ≤ 5 mm (Group A) was 1.49% (2/134, 95% CI 0%-3.50%). The 8-year CSR was 99.71% (347/348, 95% CI 99.2%-100.0%). Mucosal EH and NH were higher in RBH ≤5 mm (Group A) than in RBH >5 mm (Group B) (P = 0.001 and P = 0.001, Mann-Whitney U-test). There were no significant differences in mucosal EH and perforation rate between second and third molar sites (Group C) and other sites (Group D) (P = 0.77, Mann-Whitney U-test, and P = 0.16, Yates' Chi-square independence test). Conclusions: CSA-HBP is a minimally invasive and reliable technique.

Genetic basis of the oil biosynthesis in ultra-high-oil maize grains with an oil content exceeding 20.

Vegetable oil is an important part of the human diet and has multiple industrial uses. The rapid increase in vegetable oil consumption has necessitated the development of viable methods for optimizing the oil content of plants. The key genes regulating the biosynthesis of maize grain oil remain mostly uncharacterized. In this study, by analyzing oil contents and performing bulked segregant RNA sequencing and mapping analyses, we determined that su1 and sh2-R mediate the shrinkage of ultra-high-oil maize grains and contribute to the increase in the grain oil content. Functional kompetitive allele-specific PCR (KASP) markers developed for su1 and sh2-R detected su1su1Sh2Sh2, Su1Su1sh2sh2, and su1su1sh2sh2 mutants among 183 sweet maize inbred lines. An RNA sequencing (RNA-seq) analysis indicated that genes differentially expressed between two conventional sweet maize lines and two ultra-high-oil maize lines were significantly associated with linoleic acid metabolism, cyanoamino acid metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, and nitrogen metabolism. A bulk segregant analysis and sequencing (BSA-seq) analysis identified another 88 genomic intervals related to grain oil content, 16 of which overlapped previously reported maize grain oil-related QTLs. The combined analysis of BSA-seq and RNA-seq data enabled the identification of candidate genes. The KASP markers for GRMZM2G176998 (putative WD40-like beta propeller repeat family protein), GRMZM2G021339 (homeobox-transcription factor 115), and GRMZM2G167438 (3-ketoacyl-CoA synthase) were significantly related to maize grain oil content. Another candidate gene, GRMZM2G099802 (GDSL-like lipase/acylhydrolase), catalyzes the final step of the triacylglycerol synthesis pathway and was expressed at significantly higher levels in the two ultra-high-oil maize lines than in the two conventional sweet maize lines. These novel findings will help clarify the genetic basis of the increased oil production in ultra-high-oil maize lines with grain oil contents exceeding 20%. The KASP markers developed in this study may be useful for breeding new high-oil sweet maize varieties.

Podoplanin: A potential therapeutic target for thrombotic diseases.

As a specific lymphatic marker and a key ligand of C-type lectin-like receptor 2 (CLEC-2), podoplanin (Pdpn) is involved in various physiological and pathological processes such as growth and development, respiration, blood coagulation, lymphangiogenesis, angiogenesis, and inflammation. Thrombotic diseases constitute a major cause of disability and mortality in adults, in which thrombosis and inflammation play a crucial role. Recently, increasing evidence demonstrates the distribution and function of this glycoprotein in thrombotic diseases such as atherosclerosis, ischemic stroke, venous thrombosis, ischemic-reperfusion injury (IRI) of kidney and liver, and myocardial infarction. Evidence showed that after ischemia, Pdpn can be acquired over time by a heterogeneous cell population, which may not express Pdpn in normal conditions. In this review, the research progresses in understanding the roles and mechanisms of podoplanin in thromobotic diseases are summarized. The challenges of podoplanin-targeted approaches for disease prognosis and preventions are also discussed.

Targeting erythrocyte-mediated hypoxia to alleviate lung injury induced by pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PAs) are widely distributed natural toxins and have been extensively studied for their hepatotoxicity. However, PA-induced pulmonary toxicity remains less studied regarding the initiating mechanism and treatment approaches. Our previous study demonstrated the formation of pyrrole-hemoglobin adducts after PA exposure in vivo, which is suspected to affect the oxygen-carrying capacity of erythrocytes [red blood cells (RBCs)] consequently. The present study aimed to investigate the effects of PAs on the oxygen-carrying capacity of RBCs and the potential of targeting RBC-mediated hypoxia to alleviate PA-induced lung injury. First, rats were treated with retrorsine (RTS) or monocrotaline (MCT) intravenously at 0.2 mmol/kg. The results of Raman spectrometry analysis on blood samples revealed both RTS and MCT significantly reduced the oxygen-carrying capacity of RBCs. Further, MCT (0.2 mmol/kg) was orally given to the rats with or without pretreatment with two doses of erythropoietin (Epo, 500 IU/kg/dose every other day), an RBC-stimulating agent. Biochemical and histological results showed pretreatment with Epo effectively reduced the cardiopulmonary toxicity induced by MCT. These findings provide the first evidence that adduction on hemoglobin, and the resulting RBC damage and impaired oxygen-carrying capacity, are the major initiating mechanism underlying PA-induced pulmonary arterial hypertension (PAH), while targeting the RBC damage is a potential therapeutic approach for PA-induced lung injury.

Optical coherence tomography classifications of diabetic macular edema and response to aflibercept: One-year follow-up outcomes in a Chinese population.

To evaluate the effect of intravitreal aflibercept on different classifications of diabetic macular edema (DME) by spectral-domain optical coherence tomography. This hospital-based retrospective study included 95 consecutive patients (130 eyes) diagnosed with DME. Three groups were defined: diffuse retinal thickening (DRT), cystoid macular edema and serous retinal detachment. All eyes received intravitreal aflibercept (0.05 mL/2 mg) 5 times monthly. Best corrected visual acuity (BCVA) in (logarithm of the minimum angle of resolution) units and central macular thickness (CMT) on optical coherence tomography were recorded at months 1, 2, 3, 4, 6, and 12 after the injections. There was no significant baseline difference in BCVA (P = .273) or CMT (P = .115) among the 3 groups. Over 12 months, the BCVA of the DRT group significantly improved from baseline (P = .013). The BCVA of the cystoid macular edema (P = .062) and serous retinal detachment groups (P = .073) improved slightly from baseline. The DRT group had the greatest BCVA improvement (P = .021). Over 12 months, the CMTs of all 3 groups significantly decreased from baseline (P = .016, P = .025, P = .031). The CMT decreased more in the DRT group than in the other 2 groups (P = .009). The CMT changes were most evident in the DRT group (P = .022). Binary logistic regression analysis showed that DME type, disorganization of the retinal inner layers, ellipsoid zone disruption and external limiting membrane disruption independently predicted the effect of aflibercept treatment in DME patients (P = .006, P = .001, P = .004, P = .001). Aflibercept therapy improved anatomical structure and visual acuity in every type of DME; DRT responded best in terms of both BCVA and CMT. Furthermore, DME, disorganization of the retinal inner layers, external limiting membrane disruption and ellipsoid zone disruption independently predicted the effect of aflibercept treatment in DME patients.

Manipulation of PD-L1 Endosomal Trafficking Promotes Anticancer Immunity.

The aberrant regulation of PD-L1 in tumor cells remains poorly understood. Here, the authors systematically investigate the endosomal trafficking of plasma membrane PD-L1 in tumor cells. They show that plasma membrane PD-L1 is continuously internalized, and then trafficked from early endosomes to multivesicular bodies/late endosomes, recycling endosomes, lysosomes, and/or extracellular vesicles (EVs). This constitutive endocytic trafficking of PD-L1 is Rab5- and clathrin-dependent. Triazine compound 6J1 blocks the endosomal trafficking of PD-L1 and induces its accumulation in endocytic vesicles by activating Rab5. 6J1 also promotes exosomal PD-L1 secretion by activating Rab27. Together, these effects result in a decrease in the membrane level of PD-L1 in 6J1-treated tumor cells and enables tumor cells to be more susceptible to the tumor-killing activity of T cells in vitro. 6J1 also increases tumor-infiltrating cytotoxic T cells and promotes chemokines secretion in the tumor microenvironment. Rab27 knockdown abolishes 6J1-induced PD-L1 secretion in EVs and revokes the exhausted tumor-infiltrating T cells in tumors, thereby improving the anticancer efficacy of 6J1. Furthermore, a combination of 6J1 and an anti-PD-1 antibody significantly improves the anticancer immune response. Therefore, manipulating PD-L1 endosomal trafficking provides a promising means to promote an anticancer immune response in addition to the immune checkpoint-blocking antibody therapy.

Prevalence, Causes, and Risk Factors of Presenting Visual Impairment and Presenting Blindness in Adults Presenting to an Examination Center in Suzhou, China.

Purpose: To evaluate the prevalence, causes, and risk factors of presenting visual impairment (PVI) and presenting blindness among adults in Suzhou, China. Methods: A total of 43927 subjects were included in this cross-sectional study. Each subject underwent ophthalmic examinations, including presenting visual acuity (PVA), intraocular pressure (IOP), slit-lamp examination, and fundus examination under the small pupils of each eye. Results: Using the World Health Organization (WHO) definition, the prevalence of bilateral PVI, bilateral presenting blindness, monocular PVI, and monocular presenting blindness was 1.59% (95% CI, 1.51-1.67), 0.002% (95% CI, 0.0019-0.0021), 3.87% (95% CI, 3.68-4.06), and 0.19% (95% CI, 0.18-0.20), respectively. Using the United States (US) definition, the prevalence of bilateral PVI, bilateral presenting blindness, monocular PVI, and monocular presenting blindness was 5.83% (95% CI, 5.54-6.12), 0.04% (95% CI, 0.038-0.042), 7.43% (95% CI, 7.06-7.80), and 0.45% (95% CI, 0.43-0.47), respectively. The prevalence of PVI was higher in females (WHO criteria, 2.06%, 95% CI, 1.96-2.16; US criteria, 7.27%, 95% CI, 6.91-7.63) than in males (WHO criteria, 1.2%, 95 CI%, 1.14-1.26; US criteria, 4.65%, 95% CI, 4.42-4.89). The leading cause of PVI is an uncorrected refractive error, followed by cataracts and age-related macular degeneration (AMD). Multivariate analysis proved that the prevalence of visual impairment (PVA, better eye, WHO criteria) increased significantly with older age, higher mean arterial pressure (MAP), higher globulin level, and higher fasting blood glucose (FBG). In addition, it also increased significantly with lower hemoglobin, a lower body mass index (BMI), and a lower arterial stiffness index. In this study, serum creatinine, blood urea nitrogen, uric acid, triglycerides, and the systemic immune-inflammation index (SII) showed no association with visual impairment. Conclusion: The leading causes of PVI in Suzhou were uncorrected refractive error and cataracts. The prevalence of PVI increased with females, older age, higher MAP, higher FBG, higher globulin, lower hemoglobin, lower BMI, and lower arterial stiffness index.

Determining the effective dose of esketamine for mitigating pain during propofol injection by Dixon's up-and-down method: a double-blind, prospective clinical study of drug dose response.

BACKGROUND: Propofol is an intravenous (IV) anesthetic medication widely used for procedural sedation, operative anesthesia, and in intensive care unit (ICU), but the incidence of pain during IV infusion can reach 28-90%. Ketamine can attenuate pain associated with IV propofol injection through local and central analgesic effects. Ketamine is gradually being transitioned to its S-enantiomer, esketamine, which has a similar mechanism of action. The purpose of our study is to determine the half effective dose (ED50), 95% effective dose (ED95), and 99% effective dose (ED99) of esketamine for attenuating propofol injection pain using Dixon's up-and-down method to provide a reference for optimal dose selection for surgeries and procedures. METHODS: Thirty gynecological patients undergoing hysteroscopic surgery were enrolled in a sequential method to determine the effective dose of esticketamine for analgesic propofol injection in order of operation. This study was based on the sequential allocation up-and-down rule designed by Dixon, and each patient was induced by esticketamine combined with propofol. During induction, the target dose of esketamine was first given via venous access in the left hand of the patient, and 30 s later, a fixed dose of 2 mg/kg (1 ml/s) of propofol was given. Patient perception of pain was scored with the verbal rating scale (VRS) every 5 s after the start of the propofol infusion, and the evaluation was stopped once the patient became unresponsive. The dosage of esketamine was increased or decreased up or down according to the patient's pain response. The initial dose of esketamine was 0.2 mg/kg, and the gradient of adjacent dose was 0.02 mg/kg. If the pain response assessment of the upper patient was positive (+), the dose of esselketamine in the next patient was increased by 0.02 mg/kg; if the pain response assessment of the upper patient was negative (-), the dose of esselketamine in the next patient was decreased by 0.02 mg/kg. The tests were carried out sequentially, with the pain response changing from positive to negative or from negative to positive, and the tests were stopped after at least 6 crossover points, and the effective dose of esticketamine was calculated using probit probability regression analysis. RESULTS: The ineffective group comprised patients with a positive pain response and the effective group comprised patients with a negative pain response. The 95% CI was set as the confidence interval of effective dose ED value，and we found esketamine's ED50 = 0.143 mg/kg (0.120, 0.162 mg/kg), ED95 = 0.176 mg/kg (0.159, 0.320 mg/kg), and ED99 = 0.189 mg/kg (0.167, 0.394 mg/kg). The esketamine dose and VRS score during propofol injection were significantly different between the two groups (P < 0.05), whereas surgical duration, emergence time, visual analogue scale (VAS) score of postoperative uterine contraction pain, and Riker sedation/anxiety scale (SAS) score were not significantly different. Bradycardia occurred in only one patient during anesthesia induction, while hemodynamics was stable in the rest of the patients without obvious adverse reactions. CONCLUSION: Small doses of esketamine combined with propofol can be safely and effectively used for hysteroscopic surgery. We recommended a dose of 0.2 mg/kg IV esketamine before induction of anesthesia to reduce the pain of propofol injection. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048951. Date of registration: July 19, 2021.

Influential factors and transcriptome analyses of immature diploid embryo anthocyanin accumulation in maize.

BACKGROUND: Anthocyanins are widely applied as a marker for haploid identification after haploid induction in maize. However, the factors affecting anthocyanin biosynthesis in immature embryos and the genes regulating this process remain unclear. RESULTS: In this study, we analyzed the influence of genetic background of the male and female parents, embryo age and light exposure on anthocyanin accumulation in embryos. The results showed that light exposure was the most crucial factor enhancing the pigmentation of immature embryos. The identification accuracy of haploid embryos reached 96.4% after light exposure, but was only 11.0% following dark treatment. The total anthocyanin content was 7-fold higher in immature embryos cultured for 24 h under light conditions compared to embryos cultured in the dark. Transcriptome analysis revealed that the differentially expressed genes between immature embryos cultured for 24 h in dark and light chambers were significantly enriched in the pathways of flavonoid, flavone, flavonol and anthocyanin biosynthesis. Among the genes involved in anthocyanin biosynthesis, five up-regulated genes were identified: F3H, DFR, ANS, F3'H and the MYB transcription factor-encoding gene C1. The expression patterns of 14 selected genes were confirmed using quantitative reverse transcription-polymerase chain reaction. CONCLUSION: Light is the most important factor facilitating anthocyanin accumulation in immature embryos. After 24 h of exposure to light, the expression levels of the structural genes F3H, DFR, ANS, F3'H and transcription factor gene C1 were significantly up-regulated. This study provides new insight into the factors and key genes regulating anthocyanin biosynthesis in immature embryos, and supports improved efficiency of immature haploid embryo selection during doubled haploid breeding of maize.

Stroke risk with vegetarian, low-animal and high-animal diets: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Vegetarian and prudent diets are associated with several health benefits but their role in stroke epidemiology is not as clear. This study aimed to evaluate stroke risk with vegetarian, low-animal, and high-animal diets. METHODS AND STUDY DESIGN: Studies reporting stroke risk with high versus low use of vegetarian or low/high-animal diets were identified by conducting literature search in Ebsco, Ovid, PubMed, Science Direct, and Web of Science databases. Relative risks (RRs) of stroke between high and low use of vegetarian, low-animal, and high-animal were pooled to achieve overall estimates. Relationship between stroke risk and increasing quantiles of dietary patterns was sought by performing metaregression analyses. RESULTS: 17 studies (932545 individuals; follow-up 11.7 years [95% confidence interval (CI): 9.5, 13.9]) were included. Compared to low use, high use of vegetarian and low-animal diets was associated with lower risk of hemorrhagic stroke (RR: 0.71 [95% CI: 0.47, 0.96] and 0.82 [95% CI: 0.64, 0.99]), ischemic stroke (RR: 0.78 [95% CI: 0.66, 0.91] and 0.70 [95% CI: 0.45, 0.95]) and total stroke (RR: 0.84 [95% CI: 0.71, 0.96] and 0.72 [95% CI: 0.61, 0.83]) respectively. Dose-response analyses further supported these findings. High use of high-animal diet was associated with relatively higher risk of stroke [RR: 1.12 [95%CI: 0.94, 1.29]. In vegetarians, relative to high use of vegetables, high use of fruits posed lower risk of stroke. CONCLUSIONS: Stroke risk is lower with more use of a vegetarian or low-animal diet but relatively higher with more use of a high-animal diet.

A newly characterized allele of ZmR1 increases anthocyanin content in whole maize plant and the regulation mechanism of different ZmR1 alleles.

KEY MESSAGE: The novel ZmR1CQ01 allele for maize anthocyanin synthesis was identified, and the biological function and regulatory molecular mechanisms of three ZmR1 alleles were unveiled. Anthocyanins in maize are valuable to human health. The R1 gene family is one of the important regulatory genes for the tissue-specific distribution of anthocyanins. R1 gene allelic variations are abundant and its biological function and regulatory molecular mechanisms are not fully understood. By exploiting genetic mapping and transgenic verification, we found that anthocyanin pigmentation in maize leaf midrib was controlled by ZmR1 on chromosome 10. Allelism test of maize zmr1 EMS mutants confirmed that anthocyanin pigmentation in leaf sheath was also controlled by ZmR1. ZmR1CQ01 was a novel ZmR1 allelic variation obtained from purple maize. Its overexpression caused the whole maize plant to turn purple. ZmR1B73 allele confers anthocyanin accumulation in near ground leaf sheath rather than in leaf midribs. The mRNA expression level of ZmR1B73 was low in leaf midribs, resulting in no anthocyanin accumulation. ZmR1B73 overexpression promoted anthocyanin accumulation in leaf midribs. Loss of exon 5 resulted in ZmR1ZN3 allele function destruction and no anthocyanin accumulation in leaf midrib and leaf sheath. DNA affinity purification sequencing revealed 1010 genes targeted by ZmR1CQ01, including the bz2 in anthocyanin synthesis pathway. RNA-seq analysis showed 55 genes targeted by ZmR1CQ01 changed the expression level significantly, and the expression of genes encoding key enzymes in flavonoid and phenylpropanoid biosynthesis pathways were significantly up-regulated. ZmR1 functional molecular marker was developed. These results revealed the effects of transcriptional regulation and sequence variation on ZmR1 function and identified the genes targeted by ZmR1CQ01 at the genome-wide level.

Effect of additional equipotent fentanyl or sufentanil administration on recovery profiles during propofol-remifentanil-based anaesthesia in patients undergoing gynaecologic laparoscopic surgery: a randomized clinical trial.

BACKGROUND: In clinical practice, sufentanil has a stronger sedative effect on patients than fentanyl at equivalent doses. This study hypothesized that, at equivalent doses, patients undergoing gynaecologic laparoscopic surgery (GLS) receiving fentanyl would have an earlier emergence from anaesthesia (EA), a shorter time to extubation (TE), and a better degree of wakefulness. Therefore, this study evaluated the effects of equipotent doses of fentanyl and sufentanil on the quality of emergence in patients undergoing GLS. METHODS: One hundred seven patients scheduled for GLS under general anaesthesia were randomly divided into two groups and were induced with 0.35 µg/kg sufentanil (Group S; n = 55) or 3.5 µg/kg fentanyl (Group F; n = 52). When the GLS was almost over, the patient's abdominal cavity was flushed with warm saline, and 5 µg of sufentanil or 50 µg of fentanyl in a double-blind manner was intravenously injected into the patients. The primary outcomes of the study included EA, TE, the rate of leaving the surgical bed voluntarily and the incidence of endotracheal tube tolerance. The Ramsay Sedation Scale (RSS), and Verbal Rating Scale (VRS) scores at 15 and 30 min in the postanaesthesia care unit (PACU), as well as other adverse events, including nausea and vomiting, itching, delirium, dizziness, chills, and respiratory depression (SpO2 < 95%) in the PACU, were evaluated as secondary outcomes. RESULTS: There were no statistically significant dissimilarities between the two groups with respect to baseline characteristics. For recovery, the EA (9.0 ± 4.8 min vs. 8.9 ± 3.0 min; P = 0. 146), TE (9.5 ± 4.7 min vs. 9.0 ± 3.0 min; P = 0.135), rate of leaving the surgical bed voluntarily (31.18% vs. 38.46%; P = 0.976), and incidence of endotracheal tube tolerance (94.55% vs. 96.15%; P = 0.694) were not significantly different between the two groups. In the PACU, the 15-min RSS score (2.07 ± 0.38 vs. 2.15 ± 0.36; P = 0.125), the 30-min RSS score (2.02 ± 0.13 vs. 2.04 ± 0.19; P = 0.207), the 15-min VRS score (0.50 ± 0.57 vs. 0.67 ± 0.55; P = 0.295), and the 30-min VRS score (0.45 ± 0.50 vs. 0.75 ± 0.52; P = 0.102) were not significantly different between Groups S and F. No adverse events, such as nausea, vomiting, pruritus, delirium, and tremors, occurred in either group. The rates of respiratory depression (1.82% vs. 1.92%; P = 0.968) and dizziness (0.00% vs. 4.85%; P = 0.142) were not different between Groups S and F in the PACU. CONCLUSIONS: The majority of patients scheduled for GLS were able to rapidly and smoothly emerge from anaesthesia. After surgery, similar outcomes, including EA, TE, the incidence of endotracheal tube tolerance, the rate of leaving the surgical bed voluntarily, RSS scores, VRS scores, and adverse events in the PACU, were achieved for the patients between the two anaesthetic protocols.

Whole-genome analysis reveals the hybrid formation of Chinese indigenous DHB pig following human migration.

Hybridization is widespread in nature and is a valuable tool in domestic breeding. The DHB (DaHuaBai) pig in South China is the product of such a breeding strategy, resulting in increased body weight compared with other pigs in the surrounding area. We analyzed genomic data from 20 Chinese pig breeds and investigated the genomic architecture after breed formation of DHB. The breed showed inconsistency in genotype and body weight phenotype, in line with selection after hybridization. By quantifying introgression with a haplotype-based approach, we proposed a two-step introgression from large-sized pigs into small-sized pigs to produce DHB, consistent with the human migration events in Chinese history. Combining with gene prioritization and allele frequency analysis, we identify candidate genes that showed selection after introgression and that may affect body weight, such as IGF1R, SRC, and PCM1. Our research provides an example of a hybrid formation of domestic breeds along with human migration patterns.

LINC00943 acts as miR-338-3p sponge to promote MPP+-induced SK-N-SH cell injury by directly targeting SP1 in Parkinson's disease.

BACKGROUND: Abnormal expression of long non-coding RNA (lncRNA) is associated with the progression of Parkinson's disease (PD). LINC00943 has been proved to play an important role in the development of PD, so its role and mechanism in PD progression are worth further exploration. METHODS: MPTP was used to construct PD mice model, and its active ingredient MPP+ was used to construct PD cell model. Cell proliferation and apoptosis were determined by MTT assay, EdU staining and flow cytometry. The protein levels of Cyclin D1, Bcl-2 and specificity protein 1 (SP1) were tested by western blot analysis. The concentrations of inflammation factors were examined by ELISA assay. The expression levels of LINC00943, microRNA (miR)-338-3p and SP1 were measured using quantitative real-time PCR. The interaction between miR-338-3p and LINC00943 or SP1 was confirmed using dual-luciferase reporter assay and RIP assay. RESULTS: Our data showed that LINC00943 was highly expressed in the brain tissues of MPTP-treated mice and MPP+-induced SK-N-SH cells. Knockdown of LINC00943 could promote the proliferation, while inhibit the apoptosis and inflammation of MPP+-induced SK-N-SH cells to alleviate cell injury. In terms of mechanism, we pointed out that LINC00943 could sponge miR-338-3p, and miR-338-3p could target SP1. The negative regulation of si-LINC00943 on MPP+-induced SK-N-SH cell injury could be reversed by miR-338-3p inhibitor. Moreover, miR-338-3p had a protective effect on SK-N-SH cells from MPP+-induced injury, which could be reversed by SP1 overexpression. Additionally, we confirmed that LINC00943 positively regulated SP1 via sponging miR-338-3p. CONCLUSION: To sum up, our data revealed that knockdown LINC00943 might alleviate PD progression through regulating the miR-338-3p/SP1 axis.

Polymer amendment regulates cadmium migration in cadmium contaminated cotton field: Insights from genetic adaptation and phenotypic plasticity.

Polymer materials have been widely used in the remediation of soil heavy metal contamination for their good performance in the absorption of metal ions. To reveal the effect of polymer amendment (PA) on the remediation of cadmium-contaminated cotton fields, the cadmium (Cd) fractions in soil, Cd concentration in cotton organs, bioconcentration factor (BCF) of Cd, translocation factor (TF) of Cd, and the antioxidant capacity and photosynthesis of functional leaves were evaluated combining with the transcriptomic and metabolomic analyses, in barrel experiments in the field at the flowering and boll-forming stage of cotton. The results showed that, cotton improved the tolerance to Cd through self-regulation in Cd-contaminated soil. The expression of oxoglutaric acid and jasmonic acid were down-regulated by the application of PA to improve the photosynthetic rate (7.71%-46.20%), chlorophyll content (17.59%-63.18%), chlorophyll fluorescence (7.66%-32.25%), and antioxidant enzyme activity (15.49%-45.50%) of functional leaves, and the down-regulation of the expression of jasmonic acid and up-regulation of the expression of stearic acid reduced the exchangeable Cd concentration in the soil, which reduced the transport of Cd from the root to the bolls (54.39%). Thereby, the balance of the genetic adaptation and phenotypic plasticity of cotton was achieved, and the cell structure of leaves was restored. This study deepens our understanding of the molecular mechanism of PA in the remediation of Cd contamination in cotton fields, and provides guidance for the remediation of heavy metal contamination in farmland soil and agricultural safety under drip irrigation.

Fasting augments pyrrolizidine alkaloid-induced hepatotoxicity.

Pyrrolizidine alkaloids (PAs) are phytotoxins widely present in various natural products and foodstuffs. The present study aims to investigate the effects of fasting on PA-induced hepatotoxicity and the underlying biochemical mechanisms. The results of hepatotoxic study showed that 15-h overnight fasting significantly exacerbated the hepatotoxicity of retrorsine (RTS, a representative toxic PA) in fasted rats compared to fed rats, as indicated by remarkably elevated plasma ALT and bilirubin levels and obvious liver histological changes. Further toxicokinetic studies revealed that fasting significantly enhanced cytochromes P450 enzymes (CYPs)-mediated metabolic activation of RTS leading to increased formation of pyrrole-protein adducts and thus decreased the in vivo exposure and excretion of both parent RTS and its N-oxide metabolite. Metabolic studies demonstrated that fasting induced enzyme activities of CYP1A2, CYP2B6 and CYP2E1 that participated in catalyzing RTS to its reactive pyrrolic metabolites. Moreover, fasting also dramatically decreased hepatic glutathione (GSH) content, which restricted the detoxification of GSH by neutralizing the reactive pyrrolic metabolite of RTS, further contributing to the enhanced hepatotoxicity. The present findings may have an impact on future PA toxicity tests with different dietary styles and/or risk assessment of metabolite-mediated toxins by considering the profound effects of fasting.