The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

Exosomes derived from induced cardiopulmonary progenitor cells alleviate acute lung injury in mice.

Cardiopulmonary progenitor cells (CPPs) constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth. This fact offers the possibility for the treatment of pulmonary heart disease (PHD), in which the lung and heart are both damaged. A reliable source of CPPs is urgently needed. In this study, we reprogrammed human cardiac fibroblasts (HCFs) into CPP-like cells (or induced CPPs, iCPPs) and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury (ALI). iCPPs were created in passage 3 primary HCFs by overexpressing GLI1, WNT2, ISL1 and TBX5 (GWIT). Exosomes were isolated from the culture medium of passage 6-8 GWIT-iCPPs. A mouse ALI model was established by intratracheal instillation of LPS. Four hours after LPS instillation, ALI mice were treated with GWIT-iCPP-derived exosomes (5 × 109, 5 × 1010 particles/mL) via intratracheal instillation. We showed that GWIT-iCPPs could differentiate into cell lineages, such as cardiomyocyte-like cells, endothelial cells, smooth muscle cells and alveolar epithelial cells, in vitro. Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development. Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation, promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier. This study provides a potential new method for the prevention and treatment of cardiopulmonary injury, especially lung injury, and provides a new cell model for drug screening.

Cardiopulmonary progenitors facilitate cardiac repair via exosomal transfer of miR-27b-3p targeting the SIK1-CREB1 axis.

Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of death worldwide, and desperately needs effective treatments, such as cell therapy. Cardiopulmonary progenitors (CPPs) are stem cells for both heart and lung, but their repairing role in damaged heart is still unknown. Here, we obtained CPPs from E9.5 mouse embryos, maintained their stemness while expanding, and identified their characteristics by scRNA-seq, flow cytometry, quantitative reverse transcription-polymerase chain reaction, and differentiation assays. Moreover, we employed mouse MI model to investigate whether CPPs could repair the injured heart. Our data identified that CPPs exhibit hybrid fibroblastic, endothelial, and mesenchymal state, and they could differentiate into cell lineages within the cardiopulmonary system. Moreover, intramyocardial injection of CPPs improves cardiac function through CPPs exosomes (CPPs-Exo) by promotion of cardiomyocytic proliferation and vascularization. To uncover the underlying mechanism, we used miRNA-seq, bulk RNA-seq, and bioinformatic approaches, and found the highly expressed miR-27b-3p in CPPs-Exo and its target gene Sik1, which can influence the transcriptional activity of CREB1. Therefore, we postulate that CPPs facilitate cardiac repair partially through the SIK1-CREB1 axis via exosomal miR-27b-3p. Our study offers a novel insight into the role of CPPs-Exo in heart repair and highlights the potential of CPPs-Exo as a promising therapeutic strategy for MI.

Corrigendum: Comparison of the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children and adolescents with newly diagnosed focal epilepsy.

[This corrects the article DOI: 10.3389/fphar.2023.1189058.].

Comparison of the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children and adolescents with newly diagnosed focal epilepsy.

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children's Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%-87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Clinical Trial Registration: Identifier ChiCTR2300074696.

The role of Vps4 in cancer development.

VPS4 series proteins play a crucial role in the endosomal sorting complexes required for the transport (ESCRT) pathway, which is responsible for sorting and trafficking cellular proteins and is involved in various cellular processes, including cytokinesis, membrane repair, and viral budding. VPS4 proteins are ATPases that mediate the final steps of membrane fission and protein sorting as part of the ESCRT machinery. They disassemble ESCRT-III filaments, which are vital for forming multivesicular bodies (MVBs) and the release of intraluminal vesicles (ILVs), ultimately leading to the sorting and degradation of various cellular proteins, including those involved in cancer development and progression. Recent studies have shown a potential relationship between VPS4 series proteins and cancer. Evidence suggests that these proteins may have crucial roles in cancer development and progression. Several experiments have explored the association between VPS4 and different types of cancer, including gastrointestinal and reproductive system tumors, providing insight into the underlying mechanisms. Understanding the structure and function of VPS4 series proteins is critical in assessing their potential role in cancer. The evidence supporting the involvement of VPS4 series proteins in cancer provides a promising avenue for future research and therapeutic development. However, further researches are necessary to fully understand the mechanisms underlying the relationship between VPS4 series proteins and cancer and to develop effective strategies for targeting these proteins in cancer therapy. This article aims to review the structures and functions of VPS4 series proteins and the previous experiments to analyze the relationship between VPS4 series proteins and cancer.

Combined evaluation of Geriatric nutritional risk index and Neutrophil to lymphocyte ratio for predicting all-cause and cardiovascular mortality in hemodialysis patients.

OBJECTIVE: Malnutrition, accompanied by an inflammatory profile, is a risk factor for poor prognosis in hemodialysis patients. The purpose of this study was to investigate the predictive value of NLR combined with GNRI for all-cause and cardiovascular mortality in hemodialysis patients. METHODS: A total of 240 maintenance hemodialysis (MHD) patients in hemodialysis centers were enrolled in this retrospective study. The influencing factors of all-cause death in hemodialysis patients were analyzed by COX regression. The cut-off values of GNRI and NLR for predicting mortality in enrolled MHD patients were 89.01 and 4, respectively. Based on these cut-off values, the patients were divided into four groups: G1: high GNRI (≥ 89.01) + high NLR (≥ 4) group; G2: high GNRI (≥ 89.01) + low NLR (<4) group, G3: low GNRI (< 89.01) + high NLR (≥4) group; G4: low GNRI (< 89.01) + low NLR (<4). RESULTS: During the follow-up period (average: 58 months), the all-cause mortality was 20.83%(50/240) and the cardiovascular mortality was 12.08%(29/240). Both NLR and GNRI were independent risk factors for the prognosis of MHD patients (P<0.05). Survival analysis showed that patients with low GNRI had a lower survival rate than those with high GNRI, whereas patients with high NLR had a lower survival rate than those with low NLR. Kaplan-Meier curve for all-cause mortality revealed that compared to G1, G2, and G4, G3 had the lowest survival rate, while G2 had the highest survival rate among all groups (P < 0.05). Kaplan-Meier curve for cardiovascular mortality showed that G3 had lower survival than G1, G2, and G4 (P < 0.001). CONCLUSIONS: Our study demonstrates that bothGNRI and NLR are associated with all-cause mortality and cardiovascular mortality in MHD patients. Combining these two factorsmay contribute to a prognostic evaluation for MHD patients.

Transcriptomic analysis reveals the potential biological mechanism of AIS and lung adenocarcinoma.

Introduction: Acute ischemic stroke (AIS) and lung adenocarcinoma (LUAD) are associated with some of the highest morbidity and mortality rates worldwide. Despite reports on their strong correlation, the causal relationship is not fully understood. The study aimed to identify and annotate the biological functions of hub genes with clinical diagnostic efficacy in AIS and LUAD. Methods: Transcriptome and single-cell datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified the differentially expressed genes (DEGs) upregulated in AIS and LUAD and found 372 genes intersecting both datasets. Hub genes were identified using protein-protein interaction (PPI) networks, and the diagnostic and prognostic utility of these hub genes was then investigated using receiver operating characteristic (ROC) curves, survival analysis, and univariable Cox proportional hazard regression. Single-cell analysis was used to detect whether the hub genes were expressed in tumor epithelial cells. The immune microenvironment of AIS and LUAD was assessed using the CIBERSORT algorithm. The protein expression of these hub genes was tracked using the Human Protein Atlas (HPA). We calculated the number of positive cells using the digital pathology software QuPath. Finally, we performed molecular docking after using the Enrichr database to predict possible medicines. Results: We identified the molecular mechanisms underlying hub genes in AIS and LUAD and found that CCNA2, CCNB1, CDKN2A, and CDK1 were highly expressed in AIS and LUAD tissue samples compared to controls. The hub genes were mainly involved in the following pathways: the cell cycle, cellular senescence, and the HIF-1 signaling pathway. Using immunohistochemical slices from the HPA database, we confirmed that these hub genes have a high diagnostic capability for AIS and LUAD. Further, their high expression is associated with poor prognosis. Finally, curcumin was tested as a potential medication using molecular docking modeling. Discussion: Our findings suggest that the hub genes we found in this study contribute to the development and progression of AIS and LUAD by altering the cellular senescence pathway. Thus, they may be promising markers for diagnosis and prognosis.

Effect of serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte ratio on pregnancy and neonatal outcomes in women undergoing ICSI cycle.

BACKGROUND: The serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte (P/MII) ratio might be a more predictable indicator of pregnancy and neonatal outcomes as compare to P/estradiol (E2) or P alone. Hence, we conducted a larger population study to compare the pregnancy and neonatal outcomes in the low and high P/MII ratio. METHODS: A retrospective, single-center, larger population cohort study between January 2015 and August 2021. Calculate the threshold effect of P/MII ratio on clinical pregnancy rate according to the construct smooth curve fitting. Divide data into two groups by threshold for comparison. RESULTS: 3566 fresh ICSI-ET cycles were included, in which 929 singleton delivery and 676 twin deliveries. Compare to P/MII ≤ 0.367 group, it indicated that the P/MII > 0.367 group had a lower clinical pregnancy rate and live birth rate, furthermore, a significantly higher rate of LBW and SGA were observed in the singleton and twin deliveries. No deleterious impact of high P/MII ratio on embryo quality and undesirable pregnancy outcomes was shown. CONCLUSIONS: When P/MII is higher than 0.367, may have adverse impacts on pregnancy and neonatal outcomes for ICSI cycle.

[Determination of eight cannabinoids in foods with enhanced matrix removal-lipid adsorbent by ultra performance liquid chromatography-tandem mass spectrometry].

A novel method was developed for the simultaneous determination of eight cannabinoids in six types of food matrices, including chocolate, fondant, biscuit, beverage, cookie and baijiu, using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The sample extraction and cleanup steps were optimized, and various purification methods were investigated to remove the oil matrix and glue in chocolate and fudge, respectively. Enhanced matrix removal-lipid adsorbent (EMR-Lipid) provided efficient, selective cleanup of the evaluated matrices. The sample was extracted using acetonitrile, followed by EMR-Lipid cleanup, and then dried using anhydrous sodium sulfate. The acetonitrile layer was concentrated by nitrogen to near-dry after 100 µL 10% glycerol in methanol was added to improve the recovery by reducing loss during concentration under the stream of nitrogen gas. Eight cannabinoids were separated using a Waters ACQUITY UPLC BEH Shield RP18 column (100 mm×3.0 mm, 1.7 µm). The responses of the cannabinoids in the positive and negative ionization modes were investigated and optimized, and the responses were superior in the negative ion mode compared to those in the positive ion mode. MS detection was performed in the multi-reaction monitoring (MRM) mode using an electrospray source in the negative ion mode. The cannabinoids were quantified using an external standard with matrix calibration curves to reduce the influences of the matrix effects on the quantitative results. The developed method was verified, and the conditions of sample pretreatment were also optimized. The calibration curves of tetrahydrocannabinol, cannabidivarin, tetrahydrocannabivarin, and cannabigerol and those of cannabidiol, cannabinol, cannabidiolic acid, and tetrahydrocannabinolic acid exhibited good linearities, with r>0.995, in the ranges of 2-200 and 0.4-40 ng/mL, respectively. The respective limits of detection (LODs, S/N=3) and quantification (LOQs, S/N=10) of tetrahydrocannabinol, cannabidivarin, tetrahydrocannabivarin, and cannabigerol were 4 and 10 µg/kg, and those of cannabidiol, cannabinol, cannabidiolic acid, and tetrahydrocannabinolic acid were 0.8 and 2 µg/kg. The average recoveries of the cannabinoids were 82.0%-114.9% under three spiked levels with corresponding relative standard deviations (RSDs) of <15% (n=6). EMR-Lipid provided efficient, selective cleanups of food matrices with good accuracy. The method is sensitive, rapid, accurate, simple to execute, and it is suitable for the determination of cannabinol compounds in typical food matrices.

Value of neutrophil-to-lymphocyte ratio for diagnosing sarcopenia in patients undergoing maintenance hemodialysis and efficacy of Baduanjin exercise combined with nutritional support.

Objective: To investigate the value of neutrophil-to-lymphocyte ratio (NLR) for diagnosing sarcopenia in patients undergoing maintenance hemodialysis (MHD) and efficacy of Baduanjin exercise combined with nutritional support on MHD patients with sarcopenia. Methods: A total of 220 patients undergoing MHD in MHD centers were selected, among which 84 had occurred with sarcopenia confirmed by measurements from the Asian Working Group for Sarcopenia. Data were collected for analyzing the influencing factors that lead to the onset of sarcopenia in MHD patients with the use of one-way analysis of variance and multivariate logistic regression. The role of NLR in the diagnosis of sarcopenia was explored, and its correlation with relevant diagnostic measurement performance such as grip strength, gait speed and skeletal muscle mass index was analyzed. In the end, some 74 patients with sarcopenia that qualify for further intervention and observation standards were divided into observation group (Baduanjin exercise plus nutritional support) and control group (nutritional support only), which were both intervened for 12 weeks. A total of 68 patients finished all interventions, with 33 patients in the observation group and 35 in the control group. The grip strength, gait speed, skeletal muscle mass index as well as the NLR were compared between the two groups. Results: With the employment of multivariate logistic regression analysis, it was found that age, hemodialysis duration and NLR were risk factors for the onset of sarcopenia in MHD patients (P < 0.05). The area under ROC curve for NLR of MHD patients with sarcopenia was 0.695, and NLR was negatively correlated with a biochemical indicator-human blood albumin (P < 0.05). NLR was also negatively correlated with patient's grip strength, gait speed and skeletal muscle mass index, with the same correlation found in sarcopenia patients (all P < 0.05). After intervention, patient's grip strength and gait speed were both higher, and the NLR lower in the observation group than those in the control group (P < 0.05). Conclusion: The occurrence of sarcopenia in MHD patients is associated with patient's age, hemodialysis duration and NLR. Therefore, it has been concluded that NLR has certain values in the diagnosis of sarcopenia in patients undergoing MHD. Moreover, the muscular strength can be enhanced and inflammation decreased in sarcopenia patients through nutritional support and physical exercise, i.e., Bajinduan exercise.

Regulating the Electronic Structure of Cu-Nx Active Sites for Efficient and Durable Oxygen Reduction Catalysis to Improve Microbial Fuel Cell Performance.

The efficient and durable oxygen reduction reaction (ORR) catalyst is of great significance to boost power generation and pollutant degradation in microbial fuel cells (MFCs). Although transition metal-nitrogen-codoped carbon materials are an important class of ORR catalysts, copper-nitrogen-codoped carbon is not considered a suitable MFC cathode catalyst due to the insufficient performance and especially instability. Herein, we report a three-dimensional (3D) hierarchical porous copper, nitrogen, and boron codoped carbon (3DHP Cu-N/B-C) catalyst synthesized by the dual template method. The introduced B atom as an electron donor increases the electron density around the Cu-Nx active site, which significantly promotes the efficiency of the ORR process and stabilizes the active site by preventing demetallization. Thus, the 3DHP Cu-N/B-C catalyst exhibited excellent ORR performance with the half-wave potential of 0.83 V (vs reversible hydrogen electrode (RHE)) in a 0.1 M KOH electrolyte and 0.68 V (vs RHE) in a 50 mM PBS electrolyte. Meanwhile, 3DHP Cu-N/B-C had satisfactory stability with 94.16% current retention after 24 h of chronoamperometry test, which is better than that of 20% Pt/C. The MFCs using 3DHP Cu-N/B-C not only showed a maximum power density of up to 760.14 ± 19.03 mW m-2 but also operating durability of more than 50 days. Moreover, the 16S rDNA sequencing results presented that the 3DHP Cu-N/B-C catalyst had a positive effect on the microbial community of the MFC with more anaerobic electroactive bacteria in the anode biofilm and fewer aerobic bacteria in the cathode biofilm. This study provides a new approach for the development of Cu-based ORR electrocatalysts as well as guidance for the rational design of high-performance MFCs.

Differential Physiological, Transcriptomic, and Metabolomic Responses of Paspalum wettsteinii Under High-Temperature Stress.

Global warming has far-reaching effects on plant growth and development. As a warm-season forage grass, Paspalum wettsteinii is highly adaptable to high temperatures. However, the response mechanism of P. wettsteinii under high-temperature stress is still unclear. Therefore, we investigated the physiological indicators, transcriptome and metabolome of P. wettsteinii under different heat stress treatments. Plant height, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the contents of soluble sugar, proline, chlorophyll a, and chlorophyll b increased and then decreased, while the malondialdehyde (MDA) content decreased and then increased with increasing heat stress. Transcriptomic analysis revealed that genes related to energy and carbohydrate metabolism, heat shock proteins (HSPs), and transcription factors (TFs), secondary metabolite biosynthesis and the antioxidant system significantly changed to varying degrees. Metabolomic analysis showed that only free fatty acids were downregulated, while amino acids and their derivatives, organic acids, flavonoids, and sugars were both up- and downregulated under heat stress. These combined analyses revealed that growth was promoted at 25-40°C, while at 45°C, excess reactive oxygen species (ROS) damage reduced antioxidant and osmoregulatory effects and inactivated genes associated with the light and electron transport chains (ETCs), as well as damaged the PS II system and inhibited photosynthesis. A small number of genes and metabolites were upregulated to maintain the basic growth of P. wettsteinii. The physiological and biochemical changes in response to high-temperature stress were revealed, and the important metabolites and key genes involved in the response to high temperature were identified, providing an important reference for the physiological and molecular regulation of high-temperature stress in plants.

Y-splitting medial rectus muscle and recession in treatment for convergence excess esotropia.

AIM: To evaluate the surgical outcome of medial rectus (MR) recession with Y-splitting procedure in treatment of esotropia with convergence excess. METHODS: Medical records were retrospectively reviewed for those patients who underwent surgical treatment for their convergence excess esotropia (CEET) between January 2018 and December 2020. Refractive error was examined by the equipment of the VS100 (Welch Allyn). The surgical approach was bilateral MR recession with Y-splitting. The amount of recession was calculated according to the deviation angle at distance. Ocular movement and ocular alignment at distance and near were evaluated pre- and post-operatively. Binocular sensory status was evaluated by the Bagolini striated glasses at near and distance, and by stereoacuity assessment at near using the Titmus test. RESULTS: Six patients with CEET were included in this study. Four of them were hyperopia and two of them were myopia. A mean of eso-deviation angle at distance had been changed from 27.3±13.02 prism diopters (PD) preoperatively to 1.83±1.60 PD postoperatively (P<0.05), while a mean of eso-deviation angle at near had been changed from 50.00±20.74 PD preoperatively to 6.83±0.98 PD postoperatively (P<0.05). Patients had obtained binocular vision postoperatively. CONCLUSION: The surgical approach of Y-splitting MR and recession is effective in treatment of CEET.

Circular RNAs as Diagnostic and Prognostic Indicators of Colorectal Cancer: A Pooled Analysis of Individual Studies.

Background: Circular RNAs (circRNAs) have proven as a special subset of endogenous RNAs that are implicated in the tumorigenesis of various cancers. This study sought to evaluate the role of circRNAs in the diagnosis and prognosis of colorectal cancer (CRC). Methods: The online databases were searched for collecting relevant studies on circRNAs as diagnostic and prognostic biomarkers of CRC. Two researchers independently screened literature, extracted data, and evaluated the bias and risks of included studies. The diagnostic and prognostic indicators were merged and analyzed using STATA 12.0 software, and sources of heterogeneity were traced by the sensitivity analysis and the meta-regression test. Results: A total of 29 articles representing 2639 CRC patients were included. The pooled sensitivity, specificity, and area under the curve (AUC) of circRNAs in differentiating CRC from non-tumor control were 0.75 (95% CI: 0.69-0.80) and 0.74 (95% CI: 0.69-0.78) and 0.81, respectively. The survival analysis showed that up-regulations of up-regulated circRNAs were significantly related to dismal survival in CRC patients (HR = 2.38, p < 0.001). A stratified analysis showed that the comprehensive diagnostic value of up-regualted circRNAs in CRC was higher than that of down-regualted circRNAs (AUC: 0.83 vs. 0.77; Z test, p < 0.05). The efficacy of tissue-derived circRNAs in the diagnosis of CRC was equal to that of plasma/serum-derived ones (AUC: 0.81 vs. 0.82; Z test, p > 0.05). Conclusion: Abnormally expressed circRNAs as auxiliary biomarkers present underlying value in the diagnosis and prognosis prediction of CRC.

Morphological, transcriptomic and metabolomic analyses of Sophora davidii mutants for plant height.

Sophora davidii is an important plant resource in the karst region of Southwest China, but S. davidii plant-height mutants are rarely reported. Therefore, we performed phenotypic, anatomic structural, transcriptomic and metabolomic analyses to study the mechanisms responsible for S. davidii plant-height mutants. Phenotypic and anatomical observations showed that compared to the wild type, the dwarf mutant displayed a significant decrease in plant height, while the tall mutant displayed a significant increase in plant height. The dwarf mutant cells were smaller and more densely arranged, while those of the wild type and the tall mutant were larger and loosely arranged. Transcriptomic analysis revealed that differentially expressed genes (DEGs) involved in cell wall biosynthesis, expansion, phytohormone biosynthesis, signal transduction pathways, flavonoid biosynthesis and phenylpropanoid biosynthesis were significantly enriched in the S. davidii plant-height mutants. Metabolomic analysis revealed 57 significantly differential metabolites screened from both the dwarf and tall mutants. A total of 8 significantly different flavonoid compounds were annotated to LIPID MAPS, and three metabolites (chlorogenic acid, kaempferol and scopoletin) were involved in phenylpropanoid biosynthesis and flavonoid biosynthesis. These results shed light on the molecular mechanisms of plant height in S. davidii mutants and provide insight for further molecular breeding programs.

Transcriptomic and Metabolomic Analyses Reveal Key Metabolites, Pathways and Candidate Genes in Sophora davidii (Franch.) Skeels Seedlings Under Drought Stress.

Soil aridification and desertification are particularly prominent in China's karst areas, severely limiting crop yields and vegetation restoration. Therefore, it is very important to identify naturally drought-tolerant plant species. Sophora davidii (Franch.) Skeels is resistant to drought and soil infertility, is deeply rooted and is an excellent plant material for soil and water conservation. We studied the transcriptomic and metabolomic changes in S. davidii in response to drought stress (CK, control; LD, mild drought stress; MD, moderate drought stress; and SD, severe drought stress). Sophora davidii grew normally under LD and MD stress but was inhibited under SD stress; the malondialdehyde (MDA), hydrogen peroxide (H2O2), soluble sugar, proline, chlorophyll a, chlorophyll b and carotenoid contents and ascorbate peroxidase (APX) activity significantly increased, while the superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities and soluble protein content significantly decreased. In the LD/CK, MD/CK and SD/CK comparison groups, there were 318, 734 and 1779 DEGs, respectively, and 100, 168 and 281 differentially accumulated metabolites, respectively. Combined analysis of the transcriptomic and metabolomic data revealed the metabolic regulation of S. davidii in response to drought stress. First, key candidate genes such as PRR7, PRR5, GI, ELF3, PsbQ, PsaK, INV, AMY, E2.4.1.13, E3.2.1.2, NCED, PP2C, PYL, ABF, WRKY33, P5CS, PRODH, AOC3, HPD, GPX, GST, CAT and SOD1 may govern the drought resistance of S. davidii. Second, three metabolites (oxidised glutathione, abscisic acid and phenylalanine) were found to be related to drought tolerance. Third, several key candidate genes and metabolites involved in 10 metabolic pathways were identified, indicating that these metabolic pathways play an important role in the response to drought in S. davidii and possibly other plant species.

Co, N co-doped hierarchical porous carbon as efficient cathode electrocatalyst and its impact on microbial community of anode biofilm in microbial fuel cell.

The exploration of low-cost, long-term stable, and highly electrochemically active cathode catalysts is important for the practical application of microbial fuel cell (MFC). In this work, a series of the 3D hierarchical porous Co-N-C (3DHP Co-N-C) materials are designed and synthesized by a metal-organic framework ZIF-67 as a precursor and SiO2 sphere of different sizes as the hard template. The 3DHP Co-N-C-2 with 129 nm macropore exhibits excellent ORR performance in 0.1 M KOH solution with a half-wave potential of 0.80 V vs. RHE and superior durability than Pt/C (20%) due to the specific macropore-mesopore-micropore structure that exposes a large number of active sites and accelerates the electrolyte transport and oxygen diffusion. The MFC with 3DHP Co-N-C-2 as the cathode catalysts shows excellent performance with a maximum power density of 426.9±7.87 mW m-2 and favorable durability after 50 d of operation. In addition, 16s rDNA results reveal the presence of different dominant electrogenic bacteria and different abundance of important non-electrogenic bacteria in the anode biofilm in MFCs using cathode catalysts with different ORR activity. And 3DHP Co-N-C-2 was found to be beneficial to the synergistic effect of electrogenic and non-electrogenic bacteria. This study explores electrocatalysts in terms of both electrocatalytic activity and anode microorganisms, providing new and comprehensive insights into the power generation of MFC.

Temperature might increase the hospital admission risk for rheumatoid arthritis patients in Anqing, China: a time-series study.

Temperature has been studied in relation to many health outcomes. However, few studies have explored its effect on the risk of hospital admission for rheumatoid arthritis (RA). A distributed lag non-linear model (DLNM) was used to analyze associations between mean temperature, diurnal temperature range (DTR), temperature change between neighboring days (TCN), and daily admissions for RA from 2015 to 2019 in Anqing, China. Subgroup analyses based on age, gender, rheumatoid factors, and admission route were performed. In total, 1456 patients with RA were hospitalized. Regarding the cumulative-lag effects of extreme cold temperature (5th percentile = 3℃), the risks of admissions for RA were increased and highest at lag 0-11 (RR = 2.68, 95% CI: 1.23-5.86). Exposing to low (5th percentile = 1.9℃) and high (95th percentile = 14.2℃) DTRs both had increased risks of RA admission, with highest RRs of 1.40 (95% CI: 1.03-1.91) and 1.24 (95% CI: 1.0-1.53) at lag 0 day, respectively. As for TCN, the marginal risk of admission in RA patients was found when exposed to high TCN (95th percentile = 2.9℃) with the largest single-day effect at lag 10 (RR = 1.11, 95% CI: 1.01-1.23). In subgroup analyses, females were more susceptible to extreme cold temperature, low and high DTRs, and high TCN. In regard to extreme cold temperature, significant risk of hospital admission in females only appeared at lag 2 (RR = 1.48, 95% CI: 1.02-2.15) and lag 0-2 (RR = 2.35, 95% CI: 1.11-4.95). It is clear that RA patients exposed to changing temperature may increase risks of admission.

Selective and predicable amine conjugation sites by kinetic characterization under excess reagents.

The site selectivity for lysine conjugation on a native protein is difficult to control and characterize. Here, we applied mass spectrometry to examine the conjugation kinetics of Trastuzumab-IgG (Her-IgG) and α-lactalbumin under excess linker concentration ([L]0) based on the modified Michaelis-Menten equation, in which the initial rate constant per amine (kNH2 = Vmax/NH2/KM) was determined by the maximum reaction rate (Vmax/NH2) under saturated accessible sites and initial amine-linker affinity (1/KM). Reductive amination (RA) displayed 3-4 times greater Vmax/NH2 and a different panel of conjugation sites than that observed for N-hydroxysuccinimide ester (NHS) chemistry using the same length of polyethylene glycol (PEG) linkers. Moreover, faster conversion power rendered RA site selectivity among accessible amine groups and a greater tunable range of linker/protein ratio for aldehyde-linkers compared to those of the same length of NHS-linkers. Single conjugation with high yield or poly-conjugations with site homogeneity was demonstrated by controlling [L]0 or gradual addition to minimize the [L]0/KM ratio. Formaldehyde, the shortest aldehyde-linker with the greatest 1/KM, exhibited the highest selectivity and was shown to be a suitable probe to predict conjugation profile of aldehyde-linkers. Four linkers on the few probe-predicted hot spots were elucidated by kinetically controlled RA with conserved drug efficacy when conjugated with the payload. This study provides insights into controlling factors for homogenous and predictable amine bioconjugation.