Effects of three-dimensional quality assessment nursing intervention on efficacy and disease management of patients undergoing esophageal cancer surgery.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors. The three-dimensional quality structure model is a quality assessment theory that includes three dimensions: Structure, process, and results. AIM: To investigate the effects of nursing interventions with three-dimensional quality assessment on the efficacy and disease management ability of patients undergoing esophageal cancer surgery. METHODS: In this prospective study, the control group received routine nursing, and the intervention group additionally received a three-dimensional quality assessment intervention based on the above routine care. Self-efficacy and patient disease management abilities were evaluated using the General Self-Efficacy Scale (GSES) and Exercise of Self-Care Agency scale, respectively. IBM SPSS Statistics for Windows, version 17.0, was used for the data processing. RESULTS: This study recruited 112 patients who were assigned to the control and experimental groups (n = 56 per group). Before the intervention, there was no significant difference in GSES scores between the two groups (P > 0.05). After the intervention, the GSES scores of both groups increased, with the experimental group showing higher values (P < 0.05). At the time of discharge and three months after discharge, the scores for positive attitudes, self-stress reduction, and total score of health promotion in the experimental group were higher than those in the control group (P < 0.05). CONCLUSION: The implementation of a three-dimensional quality structure model for postoperative patients with esophageal cancer can effectively improve their self-management ability and self-efficacy of postoperative patients.

Advanced lung cancer inflammation index is associated with mortality in critically ill patients with heart failure.

AIMS: Nutrition and inflammation status play a vital role in the prognosis of patients with heart failure (HF). This study aimed to investigate the association between the advanced lung cancer inflammation index (ALI), a novel composite indicator of inflammation and nutrition, and short-term mortality among critically ill patients with HF. METHODS: This retrospective study included 548 critically ill patients with HF from the MIMIC-IV database. ALI was computed using body mass index, serum albumin and neutrophil-lymphocyte ratio. The primary endpoint was all-cause in-hospital mortality, and the secondary endpoint was 90 day mortality. Kaplan-Meier survival curve analysis with long-rank test and Cox proportional hazards regression models were employed to assess the relationship between baseline ALI and short-term mortality risk. The incremental predictive ability of ALI was evaluated by C-statistic, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The average age of 548 patients was 72.2 (61.9, 82.1) years, with 60% being male. Sixty-three patients (11.5%) died in the hospital, and 114 patients (20.8%) died within 90 days of intensive care unit admission. The Kaplan-Meier analysis revealed that the cumulative incidences of both in-hospital and 90 day mortality were significantly higher in patients with lower ALI (log-rank test, in-hospital mortality: P < 0.001; 90 day mortality: P < 0.001). The adjusted Cox proportional hazard model revealed that ALI was inversely associated with both in-hospital and 90 day mortality after adjusting for confounders [hazard ratio (HR) (95% confidence interval) (CI): 0.97 (0.94, 0.99), P = 0.035; HR (95% CI): 0.62 (0.39, 0.99), P = 0.046]. A linear relationship was observed between ALI and in-hospital mortality (P for non-linearity = 0.211). The addition of ALI significantly improved the prognostic ability of GWTG-HF score in the in-hospital mortality [C-statistic improved from 0.62 to 0.68, P = 0.001; continuous NRI (95% CI): 0.44 (0.20, 0.67), P < 0.001; IDI (95% CI): 0.03 (0.01, 0.04), P < 0.001] and 90 day mortality [C-statistic improved from 0.63 to 0.70, P < 0.001; continuous NRI (95% CI): 0.31 (0.11, 0.50), P = 0.002; IDI (95% CI): 0.01 (0.00, 0.02), P = 0.034]. Subgroup analysis revealed stronger correlations between ALI and in-hospital mortality in males and patients aged over 65 years (interaction P = 0.031 and 0.010, respectively). The C-statistic of in-hospital mortality in patients over 65 years was 0.66 (95% CI: 0.58, 0.74). CONCLUSIONS: ALI at baseline can independently predict the risk of short-term mortality in critically ill patients with HF, with lower ALI significantly associated with higher mortality. Further large prospective research with extended follow-up periods is necessary to validate the findings of this study.

Effects of Carrier's sex on the outcome of embryos and pregnancies in 412 couples undergoing preimplantation genetic testing for structural rearrangements.

STUDY DESIGN: To ascertain whether the carrier's sex affects the outcome of embryos and pregnancies in couples undergoing preimplantation genetic testing for structural rearrangements (PGT-SR). METHODS: This retrospective study comprised 412 couples with reciprocal translocations (RecT), Robertsonian translocations (RobT), or inversions (INV) between January 2017 and October 2022. We applied next-generation sequencing (NGS) on 2588 embryos after trophectoderm (TE) biopsy. RESULTS: Genetically transferable blastocyst rate was higher in the male carrier group (34.0 % vs 31.7 %, P = 0.013) relative to the female carrier group whereas other embryo and pregnancy outcomes remained similar. Further analysis revealed that this result was primarily due to the alteration of segregation patterns in the RobT subgroup, in which the proportion of alternate segregation was higher (84.3 % vs 66.4 %, P < 0.001) in male carriers compared with female carriers. In the RecT subgroup, the genetically transferable blastocyst rate between male and female carriers was similar although the segregation models also changed, such that the frequency of the adjacent-1 segregation pattern was higher in male carriers than in female carriers (42.5 % vs 34.7 %, P = 0.002). In addition, interchromosomal effect (ICE) did not differ between male and female carriers although ICE was lower in male carriers of the RobT subgroup (pure ICE: 35.50 % vs 44.30 %, P = 0.14; total ICE: 35.50 % vs 40.30 %, P = 0.32) and higher in male carriers of the INV subgroup (pure ICE: 42.3 % vs 37.20 %, P = 0.33; total ICE: 40.90 % vs 36.00 %, P = 0.36). CONCLUSIONS: The carrier's sex was closely associated with the genetically transferable embryo rate in couples undergoing PGT-SR, principally resulted from the change in segregation pattern in the RobT subgroup but not in the RecT and INV subgroups.

Utility of Radiographic Parameter in Assessing Bone Density and Subsequent Fractures in Patients With Osteoporotic Vertebral Compression Fracture.

OBJECTIVE: To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF). METHODS: A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis. RESULTS: CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023-0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97-43.22; p < 0.01). CONCLUSION: CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.

Activity of the Caged Xanthone Morellic Acid against Vancomycin-Resistant Enterococcus Infection by Targeting the Bacterial Membrane.

Vancomycin-resistant Enterococcus (VRE) is an important nosocomial opportunistic pathogen that is associated with multidrug resistance. Here, we demonstrate that morellic acid inhibits VRE by restoring its sensitivity to vancomycin and ampicillin with low drug resistance and efficient biofilm clearance effects. Morellic acid binds to inner membrane phospholipids, such as phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) of VRE, such that the fluidity and proton-motive force (PMF) interfere with the damaged inner membrane, causing intracellular reactive oxygen species (ROS) accumulation and bacterial death. Transcriptional analyses supported this effect on inner membrane-related pathways such as fatty acid biosynthesis and glycerophospholipid metabolism. Moreover, morellic acid significantly eliminated residual bacteria in the spleen, liver, kidneys, and abdominal effusion in mice. Our findings indicate the potential applications of morellic acid as an antibacterial agent or adjuvant for treating VRE infections.

Influence of stem and leaf phenotypes, physiological responses and cellular ultrastructure on defoliated sugarcane cultivars.

Defoliation is a primary agronomic traits, its variation depends on different plant species or cultivars. The present article assess the leaf morphological responses, oxidative metabolites and enzymatic activities at sheath base of sugarcane cultivars during defoliation stage of plant leaves. The mature leaf sheath of GT47 strongly wrapped to the stem, and no stem was exposed. The upper and lower edges of the immature fusing abscission zone were parallel, and slightly lower browning area (+ 3 to + 7 leaf position). The ROC22 cultivar was monitored highest leaf sheath-based cellulose and lignin content, followed by GT60 and GT47. Peroxidase activity was higher in leaf sheath base edge (ROC22) as compare to other cultivars. The malondialdehyde content was found highest in GT60, followed by ROC22, and GT47. The exo-ß-1,4-glucanase/ cellobiohydrolase activity was found highest in the margin of GT47 than lateral and medial axis of ROC22 and GT60. The axis activity increased exponentially, and ROC22 gradually decreased from the periphery of the mid-axis and lower than GT47 and GT60 in the lateral and mid-axis of leaf. In conclusion, the mature leaves are easy to defoliate mainly loose leaf sheaths, large leaf sheath inclination angles, more deformation during the growth period of the abscission zone, early with large cracks, and slow browning process. Leaf sheaths with high fibre and lignin content showed significant hardness and thickness. The sugarcane cultivars showed positive correlation between peroxidase and malondialdehyde content with the browning process at the base of mature leaf sheaths.

Five New Species of Wood-Decaying Brown-Rot Fungi within Postiaceae (Polyporales, Basidiomycota) from Xinjiang, Northwest China.

Brown-rot fungi are an important group of wood-decaying fungi, but there has been limited research on the species diversity of brown-rot fungi in Xinjiang, China. During an investigation of brown-rot fungi in Xinjiang, from July 2018 to July 2023, five new species belonging to the family Postiaceae were discovered based on morphological and molecular evidence. Amaropostia altaiensis is characterized by a conchate pileus, circular pores (5-8 per mm), and growing on Populus. Amaropostia tianshanensis is characterized by a flabelliform-to-conchate pileus, angular pores (5-6 per mm), and growing on Picfea. Cyanosporus latisporus is characterized by a hirsute and dark greyish blue pileal surface with fresh, larger pores (3-6 per mm) and broad basidiospores (4.3-5.9 × 1.4-2 µm). Cyanosporus tianshanensis is characterized by a smooth and white-to-cream pileal surface with fresh, smaller pores (6-9 per mm). Osteina altaiensis is characterized by a light mouse-grey-to-honey-yellow pileal surface, smaller pores (4-6 per mm), and slightly wide basidiospores (5-6 × 1.7-2.2 µm). Each of these five new species form independent lineages in phylogenetic analyses based on the seven gene loci (ITS + nLSU + nSSU + mtSSU + TEF1 + RPB1 + RPB2). This research enriches the diversity of brown-rot fungi species, while also demonstrating the substantial discovery potential and research value of brown-rot fungi in Xinjiang.

Roseobacter weihaiensis sp. nov., a cellulose-degrading bacterium isolated from intestinal content of Nipponacmea schrenckii collected from golden beach in Weihai, China.

A Gram-staining-negative, dark pink, rod-shaped, amastigote and cellulose-degrading strain, designated H9T, was isolated from intestinal contents of Nipponacmea schrenckii. The isolate was able to grow at 4-42 °C (optimum, 25 °C), at pH 6.5-9.0 (optimum, pH 7.0), and with 0.0-11.0% (w/v) NaCl (optimum, 3.0-5.0%). Phylogenetic analysis of the 16S rRNA gene sequence suggested that isolate H9T belongs to the genus Roseobacter, neighboring Roseobacter insulae YSTF-M11T, Roseobacter cerasinus AI77T and Roseobacter ponti MM-7 T, and the pairwise sequence showed the highest similarity of 99.1% to Roseobacter insulae YSTF-M11T. The major fatty acid was summed feature 8 (C18:1ω7c and/or C18:1ω6c; 81.08%). The predominant respiratory quinone was Q-10. The polar lipids consisted of phosphatidylcholine, phosphatidylglycerol, an unknown lipid, and a small amount of an unknown phospholipid. The genome of strain H9T was 5,351,685 bp in length, and the DNA G + C content was 59.8%. The average amino acid identity (AAI), average nucleotide identity (ANI), and digital DNA hybridization (dDDH) values between strain H9T and closely related strains were 63.4-76.8%, 74.7-78.8%, and 13.4-19.7%, respectively. On the basis of the phenotypic, chemical taxonomic, and phylogenetic data, it is suggested that strain H9T should represent a novel species in the genus Roseobacter, for which the name Roseobacter weihaiensis sp. nov. is proposed. The type strain is H9T (= KCTC 82507 T = MCCC 1K04354T).

Transfer learning-enabled outcome prediction for guiding CRRT treatment of the pediatric patients with sepsis.

Continuous renal replacement therapy (CRRT) is a life-saving procedure for sepsis but the benefit of CRRT varies and prediction of clinical outcomes is valuable in efficient treatment planning. This study aimed to use machine learning (ML) models trained using MIMIC III data for identifying sepsis patients who would benefit from CRRT. We first selected patients with sepsis and CRRT in the ICU setting and their gender, and an array of routine lab results were included as features to train machine learning models using 30-day mortality as the primary outcome. A total of 4161 patients were included for analysis, among whom there were 1342 deaths within 30 days. Without data augmentation, extreme gradient boosting (XGBoost) showed an accuracy of 64.2% with AUC-ROC of 0.61. Data augmentation using a conditional generative adversarial neural network (c-GAN) resulted in a significantly improved accuracy (82%) and ROC-AUC (0.78%). To enable prediction on pediatric patients, we adopted transfer learning approaches, where the weights of all but the last hidden layer were fixed, followed by fine-tuning of the weights of the last hidden layer using pediatric data of 200 patients as the inputs. A significant improvement was observed using the transfer learning approach (AUCROC = 0.76) compared to direct training on the pediatric cohort (AUCROC = 0.62). Through this transfer-learning-facilitated patient outcome prediction, our study showed that ML can aid in clinical decision-making by predicting patient responses to CRRT for managing pediatric sepsis.

Comparative analysis of the complete chloroplast genomes of thirteen Bougainvillea cultivars from South China with implications for their genome structures and phylogenetic relationships.

Bougainvillea spp., belonging to the Nyctaginaceae family, have high economic and horticultural value in South China. Despite the high similarity in terms of leaf appearance and hybridization among Bougainvillea species, especially Bougainvillea × buttiana, their phylogenetic relationships are very complicated and controversial. In this study, we sequenced, assembled and analyzed thirteen complete chloroplast genomes of Bougainvillea cultivars from South China, including ten B. × buttiana cultivars and three other Bougainvillea cultivars, and identified their phylogenetic relationships within the Bougainvillea genus and other species of the Nyctaginaceae family for the first time. These 13 chloroplast genomes had typical quadripartite structures, comprising a large single-copy (LSC) region (85,169-85,695 bp), a small single-copy (SSC) region (18,050-21,789 bp), and a pair of inverted-repeat (IR) regions (25,377-25,426 bp). These genomes each contained 112 different genes, including 79 protein-coding genes, 29 tRNAs and 4 rRNAs. The gene content, codon usage, simple sequence repeats (SSRs), and long repeats were essentially conserved among these 13 genomes. Single-nucleotide polymorphisms (SNPs) and insertions/deletions (indels) were detected among these 13 genomes. Four divergent regions, namely, trnH-GUG_psbA, trnS-GCU_trnG-UCC-exon1, trnS-GGA_rps4, and ccsA_ndhD, were identified from the comparative analysis of 16 Bougainvillea cultivar genomes. Among the 46 chloroplast genomes of the Nyctaginaceae family, nine genes, namely, rps12, rbcL, ndhF, rpoB, rpoC2, ndhI, psbT, ycf2, and ycf3, were found to be under positive selection at the amino acid site level. Phylogenetic relationships within the Bougainvillea genus and other species of the Nyctaginaceae family based on complete chloroplast genomes and protein-coding genes revealed that the Bougainvillea genus was a sister to the Belemia genus with strong support and that 35 Bougainvillea individuals were divided into 4 strongly supported clades, namely, Clades Ⅰ, Ⅱ, Ⅲ and Ⅳ. Clade Ⅰ included 6 individuals, which contained 2 cultivars, namely, B. × buttiana 'Gautama's Red' and B. spectabilis 'Flame'. Clades Ⅱ only contained Bougainvillea spinosa. Clade Ⅲ comprised 7 individuals of wild species. Clade Ⅳ included 21 individuals and contained 11 cultivars, namely, B. × buttiana 'Mahara', B. × buttiana 'California Gold', B. × buttiana 'Double Salmon', B. × buttiana 'Double Yellow', B. × buttiana 'Los Banos Beauty', B. × buttiana 'Big Chitra', B. × buttiana 'San Diego Red', B. × buttiana 'Barbara Karst', B. glabra 'White Stripe', B. spectabilis 'Splendens' and B. × buttiana 'Miss Manila' sp. 1. In conclusion, this study not only provided valuable genome resources but also helped to identify Bougainvillea cultivars and understand the chloroplast genome evolution of the Nyctaginaceae family.

A new therapeutic strategy for infectious diseases against intracellular multidrug-resistant bacteria.

Bacterial infections result in 7,700,000 deaths per year globally, with intracellular bacteria causing repeated and resistant infection. No drug is currently licenced for the treatment of intracellular bacteria. A new screening platform mimicking the host milieu has been established to explore phytochemical antibiotic adjuvants. Previously neglected isoprenylated flavonoids were found to be effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Specifically, the synergistic effect between glabrol and streptomycin against intracellular bacteria was observed for the first time. The glabrol-streptomycin combination targets bacterial inner membrane phospholipids, disrupts arginine biosynthesis, inhibits cell wall proteins and biofilm formation genes (agrA/B/C/D), and promotes ROS production, causing subsequent membrane and wall damage. To enhance the selective uptake of combination drug into infected cells, hyaluronic acid-streptomycin-lipoic acid-glabrol nanoparticles (HSLGS-S) were designed and synthesized to trigger the intracellular delivery of the glabrol-streptomycin combination. Thus, the treatment can be transported into the infected intracellular region and selectively release the glabrol-streptomycin combination to the bacterial at site. The bioactivity of HSLGS-S in clearing intracellular bacteria was 20-fold higher than that of the glabrol-streptomycin combination alone in vitro and 2- to 10-fold higher in vivo.

Non-Linear Association Between Climatic Parameters and Bell's Palsy Prevalence of Hospital Outpatients: An Ecological Proof in Kunshan, Suzhou, China.

Objective: This study aimed to explore the relationship between climatic parameters and the daily cases of Bell's palsy (BP) among hospital outpatients, providing ecological evidence for understanding BP etiology and prevention. Methods: Retrospective analysis was conducted on data from 2187 BP patients who attended Kunshan First People's Hospital Outpatient Clinic from January 1, 2020, to December 31, 2022. Meteorological data, including temperature, relative humidity, precipitation, wind speed, sunshine duration, and atmospheric pressure, were collected and combined with daily BP case records. Additionally, air quality index was used as a covariate. Results: The number of new BP cases among outpatients showed a negative correlation with average daily temperature. A nonlinear relationship between daily average temperature and BP cases was observed through the generalized additive model (GAM). A significant negative correlation was identified between daily average temperature and BP cases, with inflection points at temperatures above 4.2°C, suggesting a potential decrease in BP risk with temperature rise beyond this threshold. Conclusion: This study provides ecological evidence of a link between climatic factors and BP occurrence. Temperature demonstrated a significant nonlinear negative correlation with daily BP incidence, highlighting temperature and cold exposure as key targets for BP prevention in Kunshan.

Quercus dentata Thunb. leaves extract inhibits CaOx crystallization and ameliorates ethylene glycol-induced CaOx kidney stones via the OPN/CD44 and NLRP3 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus, with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones (Lin Zheng). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine. AIM OF STUDY: This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones. MATERIALS AND METHODS: The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD3 were compared in vivo. Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis. RESULTS: There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L-Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy (P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways. CONCLUSION: The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD.

GREM1 Negatively Regulates Osteo-/Dentinogenic Differentiation of Dental Pulp Stem Cells via Association with YWHAH.

OBJECTIVE: To investigate the biological regulatory function of Gremlin1 (GREM1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) in dental pulp stem cells (DPSCs), and determine the underlying molecular mechanism involved. METHODS: Alkaline phosphatase (ALP) activity, alizarin red staining, scratch migration assays and in vitro and in vivo osteo-/dentinogenic marker detection of bone-like tissue generation in nude mice were used to assess osteo-/dentinogenic differentiation. Coimmunoprecipitation and polypeptide microarray assays were employed to detect the molecular mechanisms involved. RESULTS: The data revealed that knockdown of GREM1 promoted ALP activity, mineralisation in vitro and the expression of osteo-/dentinogenic differentiation markers and enhanced osteo-/ dentinogenesis of DPSCs in vivo. GREM1 bound to YWHAH in DPSCs, and the binding site was also identified. Knockdown of YWHAH suppressed the osteo-/dentinogenesis of DPSCs in vitro, and overexpression of YWHAH promoted the osteo-/dentinogenesis of DPSCs in vitro and in vivo. CONCLUSION: Taken together, the findings highlight the critical roles of GREM1-YWHAH in the osteo-/dentinogenesis of DPSCs.

Experiences and prospects for national survey of terrestrial wildlife resources in China.

Wildlife resources are strategic resources of a country, and the investigation of which is a key task for effective management in protection and utilization. Since the 1990s, two national surveys of terrestrial wildlife resources have been carried out in China, and the situation of wildlife resources has been known to a certain extent. Due to the complexity and difficulty of national wildlife survey, we are still not able to grasp the background and dynamics of wildlife resources as a whole promptly and effectively. The results and effectiveness of wildlife resources investigation will directly affect the decision-making related in wildlife protection. According to Law of the People's Republic of China on the Protection of Wildlife and Regulations of the People's Republic of China for the Implementation of the Protection of Terrestrial Wildlife, it is imperative to carry out the third national survey of terrestrial wildlife resources, and to be integrated with the national strategy of ecological civilization construction. The aims of this review were to summarize the earlier experiences in time, to further improve the investigation scheme and technical methods, to serve the third national survey of terrestrial wildlife resources, in addition to obtain more comprehensive and reliable data of wildlife resources, grasp the development trend of domestic wildlife resources, and provide more effective supports for the wildlife conservation in China.

Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma.

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Benzo(a)pyrene exposure during pregnancy leads to germ cell apoptosis in male mice offspring via affecting histone modifications and oxidative stress levels.

Infertility has gradually become a global health concern, and evidence suggests that exposure to environmental endocrine-disrupting chemicals (EDCs) represent one of the key causes of infertility. Benzo(a)pyrene (BaP) is a typical EDC that is widespread in the environment. Previous studies have detected BaP in human urine, semen, cervical mucus, oocytes and follicular fluid, resulting in reduced fertility and irreversible reproductive damage. However, the mechanisms underlying the effects of gestational BaP exposure on offspring fertility in male mice have not been fully explored. In this study, pregnant mice were administered BaP at doses of 0, 5, 10 and 20 mg/kg/day via gavage from Days 7.5 to 12.5 of gestation. The results revealed that BaP exposure during pregnancy disrupted the structural integrity of testicular tissue, causing a disorganized arrangement of spermatogenic cells, compromised sperm quality, elevated levels of histone modifications and increased apoptosis in the testicular tissue of F1 male mice. Furthermore, oxidative stress was also increased in the testicular tissue of F1 male mice. BaP activated the AhR/ERα signaling pathway, affected H3K4me3 expression and induced apoptosis in testicular tissue. AhR and Cyp1a1 were overexpressed, and the expression of key molecules in the antioxidant pathway, including Keap1 and Nrf2, was reduced. The combined effects of these molecules led to apoptosis in testicular tissues, damaging and compromising sperm quality. This impairment in testicular cells further contributed to compromised testicular tissues, ultimately impacting the reproductive health of F1 male mice.

Characterization of Ucp1-iCre knockin mice reveals the recombination activity in male germ cells.

Ucp1 promoter-driven Cre transgenic mice are useful in the manipulation of gene expression specifically in thermogenic adipose tissues. However, the wildly used Ucp1-Cre line was generated by random insertion into the genome and showed ectopic activity in some tissues beyond adipose tissues. Here, we characterized a knockin mouse line Ucp1-iCre generated by targeting IRES-Cre cassette immediately downstream the stop codon of the Ucp1 gene. The Cre insertion had little to no effect on uncoupling protein 1 (UCP1) levels in brown adipose tissue. Ucp1-iCre mice of both genders exhibited normal thermogenesis and cold tolerance. When crossed with Rosa-tdTomato reporter mice, Ucp1-iCre mice showed robust Cre activity in thermogenic adipose tissues. In addition, limited Cre activity was sparsely present in the ventromedial hypothalamus (VMH), choroid plexus, kidney, adrenal glands, ovary, and testis in Ucp1-iCre mice, albeit to a much lesser extent and with reduced intensity compared with the conventional Ucp1-Cre line. Single-cell transcriptome analysis revealed Ucp1 mRNA expression in male spermatocytes. Moreover, male Ucp1-iCre mice displayed a high frequency of Cre-mediated recombination in the germline, whereas no such effect was observed in female Ucp1-iCre mice. These findings suggest that Ucp1-iCre mice offer promising utility in the context of conditional gene manipulation in thermogenic adipose tissues, while also highlighting the need for caution in mouse mating and genotyping procedures.NEW & NOTEWORTHY Ucp1 promoter-driven Cre transgenic mice are useful in the manipulation of gene expression specifically in thermogenic adipose tissues. The widely used Ucp1-Cre mouse line (Ucp1-CreEvdr), which was generated using the bacterial artificial chromosome (BAC) strategy, exhibits major brown and white fat transcriptomic dysregulation and ectopic activity beyond adipose tissues. Here, we comprehensively validate Ucp1-iCre knockin mice, which serve as another optional model besides Ucp1-CreEvdr mice for specific genetic manipulation in thermogenic tissue.

Synthesis of Indolyl Isothiocyanate and Its Inhibitory Activity against Fungi.

Based on previous research, this study synthesized 24 compounds by splicing the substructures of the indolyl group and the isothiocyanate group. Alternaria alternata, Phytophthora capsici, Botrytis cinerea, and Valsa mali were used to test the activity of the target compounds. At 100 µg/mL, compounds 8, 13, 14, and 17 exhibited excellent inhibitory effects of more than 80% on P. capsici, B. cinerea, and V. mail. The EC50 values of compounds 13 and 14 were 0.64 and 2.08 µg/mL, respectively. Potted antifungal activity demonstrated that compounds 13 and 14 had a protective effect of around 80% against B. cinerea at 200 µg/mL. Further physiological and biochemical studies on B. cinerea revealed that compound 13 thickened cell walls and caused mitochondrial vacuolization. Moreover, theoretical calculations indicated that the charge distribution of indolyl isothiocyanate compounds played a crucial role in the observed fungicidal activity. In summary, this study provided fundamental reference data for the derivative synthesis of these indolyl isothiocyanate compounds.

Vericiguat in heart failure with reduced ejection fraction patients on guideline-directed medical therapy: Insights from a 6-month real-world study.

BACKGROUND: Vericiguat has demonstrated efficacy in improving the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) following recent clinical deterioration. However, its real-world impact on reducing N-terminal B-type natriuretic peptide (NT-proBNP) levels and improving ventricular remodeling remains uncertain in stable HFrEF patients receiving guideline-directed medical therapy (GDMT) over the short term. METHODS: This multicenter, observational cohort study included 200 HFrEF patients. Patients were grouped based on their preference for vericiguat use. We evaluated the impact of vericiguat on HFrEF patients by analyzing the difference in the proportion of patients with NT-proBNP levels ≤1000 pg/ml between two groups after a 6-month follow-up, using logistic regression and covariance analysis. Changes in echocardiographic parameters, left ventricular reverse remodeling (LVRR) ratio, and safety outcomes were also evaluated. RESULTS: During the 6-month follow-up, 105 patients (82.68 %) in the vericiguat group and 46 patients (63.01 %) in the control group reached the primary endpoint. Multivariate logistic regression confirmed vericiguat as a significant factor in reducing NT-proBNP levels (Model 2: odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.24-5.77, P = 0.013), but it showed no significant association with LVRR (Model 2: OR = 0.52, 95 % CI: 0.24-1.13, P = 0.097). The safety analysis indicated a higher incidence of mild to moderate gastrointestinal symptoms in the vericiguat group compared to the control group (23.62 % vs. 2.74 %, P < 0.001). CONCLUSIONS: Vericiguat significantly reduced NT-proBNP levels in patients with chronic HErEF under GDMT but was ineffective for LVRR during the 6-month follow-up.