Transcriptomic analysis uncovers a biphasic response to precocious Eimeria acervulina infection in chicken duodenal tissue.

Live anticoccidial vaccines, either formulated with unattenuated or attenuated Eimeria parasites, are powerful stimulators of chicken intestinal immunity. Little is known about the dynamics of gene expression and the corresponding biological processes of chicken responses against infection with precocious line (PL) of Eimeria parasites. In the present study, we performed a time-series transcriptomic analysis of chicken duodenum across 15 time points from 6 to 156 hours post-infection (p.i.) with PL of E. acervulina. A high-quality profile showing two distinct changes in chicken duodenum mRNA expression was generated during the infection of Eimeria. Early response revealed that activation of the chicken immune response was detectable from 6 h.p.i., prominent genes triggered during the initiation of asexual and sexual parasite growth encompass immune regulatory effects, such as interferon gamma (IFN-γ), interferon regulatory factor 1 (IRF1), and interleukin-10 (IL10). The late response was identified significantly associating with maintaining cellular structure and activating lipid metabolic pathways. These analyses provide a detailed depiction of the biological response landscape in chickens infected by the PL of E. acervulina, contributing significant insights for the investigation of the host-parasite interactions and the management of parasitic diseases.

Propensity score-matched analysis examining the role of obesity on outcomes in retroperitoneal laparoscopic adrenalectomy: a cohort study.

Background: There is inconsistent evidence regarding obesity's effect on surgical outcomes following retroperitoneal laparoscopic adrenalectomy (RLA). This study aimed to investigate the influence of obesity on surgical outcomes in patients undergoing RLA, with an emphasis on operative time, drainage tube removal time, postoperative hospital stays and perioperative complications. Methods: In this retrospective, single-center, observational study, all consecutive cases of unilateral RLA for adrenal disease from January 2012 to December 2021 were incorporated. The patients were divided into two groups based on their body mass index (BMI) of 28 kg/m2. To mitigate selection bias, propensity score matching (PSM) was conducted, using logistic regression to calculate propensity scores for balancing baseline characteristics. A multivariate logistic regression analysis was performed to assess how obesity affects operative time and intraoperative blood loss as well. The linear correlation between BMI and surgical outcomes, including prolonged operative time and increased intraoperative blood loss, was also examined using restricted cubic spline (RCS) analysis. Results: A total of 569 patients who underwent RLA were included. After PSM, 122 patients were apportioned to each group. Statistically significant differences were observed between the obese and non-obese group in operative time (97.5 vs. 115 min, P<0.001). There were no statistically significant differences between the two groups regarding hospital stay (6.7 vs. 6.8 days, P=0.58), drainage tube removal time (3.0 vs. 3.0 days, P=0.19), nor postoperative complications (9.0% vs. 12.3%, P=0.41). Furthermore, univariate logistic regression analysis revealed that, obese patients undergoing RLA were linked to prolonged operative time and increased intraoperative blood loss. After adjusting for potential confounders, the obese group showed a 67% increased risk of prolonged operative time and a 69% increased intraoperative blood loss. The RCS analysis revealed that BMI had a linear relationship with operative time (P for nonlinearity =0.47) and blood loss during surgery (P for linearity =0.89). Conclusions: In patients undergoing RLA, obesity exerts a significant influence on surgical outcomes, particularly with regard to operative time and intraoperative blood loss, as shown in multivariable logistic regression analysis and PSM to balance baseline characteristics.

Wnt/ß-catenin signaling pathway as an important mediator in muscle and bone crosstalk: A systematic review.

Background: The interaction between muscle and bone is shown to be clinically important but the underlying mechanisms are largely unknown. The canonical Wnt/ß-catenin signaling pathway is reported to be involved in muscle-bone crosstalk, but its detailed function remains unclear. This systematic review aims to investigate and elucidate the role of the Wnt/ß-catenin signaling pathways in muscle-bone crosstalk. Methods: We conducted a literature search on the Web of Science, PubMed, EBSCO and Embase with keywords "Wnt*", "bone*" and "muscle*". A systematic review was completed according to the guideline of preferred reporting items of systematic reviews and meta-analyses (PRISMA). Data synthesis included species (human, animal or cell type used), treatments involved, outcome measures and key findings with respect to Wnts. Results: Seventeen papers were published from 2007 to 2021 and were extracted from a total of 1529 search results in the databases of Web of Science (468 papers), PubMed (457 papers), EBSCO (371) and Embase (233). 12 Wnt family members were investigated in the papers, including Wnt1, Wnt2, Wnt2b, Wnt3a, Wnt4, Wnt5a, Wnt8a, Wnt8b, Wnt9a, Wnt10a, Wnt10b and Wnt16. Many studies showed that muscles were able to increase or decrease osteogenesis of bone, while bone increased myogenesis of muscle through Wnt/ß-catenin signaling pathways. Wnt3a, Wnt4 and Wnt10b were shown to play important roles in the crosstalk between muscle and bone. Conclusions: Wnt3a, Wnt4 and Wnt10b are found to play important mediatory roles in muscle-bone crosstalk. The role of Wnt4 was mostly found to regulate muscle from the bone side. Whilst the role of Wnt10b during muscle ageing was proposed, current evidence is insufficient to clarify the specific role of Wnt/ß-catenin signaling in the interplay between sarcopenia and osteoporosis. More future studies are required to investigate the exact regulatory roles of Wnts in muscle-bone crosstalk in musculoskeletal disease models such as sarcopenia and osteoporosis. Translational potential of this article: The systematic review provides an extensive overview to reveal the roles of Wnt/ß-catenin signaling pathways in muscle-bone crosstalk. These results provide novel research directions to further understand the underlying mechanism of sarcopenia, osteoporosis, and their crosstalk, finally helping the future development of new therapeutic interventions.

Sclerostin inhibition in rare bone diseases: Molecular understanding and therapeutic perspectives.

Sclerostin emerges as a novel target for bone anabolic therapy in bone diseases. Osteogenesis imperfecta (OI) and X-linked hypophosphatemia (XLH) are rare bone diseases in which therapeutic potential of sclerostin inhibition cannot be ignored. In OI, genetic/pharmacologic sclerostin inhibition promoted bone formation of mice, but responses varied by genotype and age. Serum sclerostin levels were higher in young OI-I patients, while lower in adult OI-I/III/IV. It's worth investigating whether therapeutic response of OI to sclerostin inhibition could be clinically predicted by genotype and age. In XLH, preclinical/clinical data suggested factors other than identified FGF23 contributing to XLH. Higher levels of circulating sclerostin were detected in XLH. Sclerostin inhibition promoted bone formation in Hyp mice, while restored phosphate homeostasis in age-/gender-dependent manner. The role of sclerostin in regulating phosphate metabolism deserves investigation. Sclerostin/FGF23 levels of XLH patients with/without response to FGF23-antibody warrants study to develop precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy. Notably, OI patients were associated with cardiovascular abnormalities, so were XLH patients receiving conventional therapy. Targeting sclerostin loop3 promoted bone formation without cardiovascular risks. Further, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety. The Translational Potential of this Article. Preclinical data on the molecular understanding of sclerostin inhibition in OI and therapeutic efficacy in mouse models of different genotypes, as well as clinical data on serum sclerostin levels in patients with different phenotypes of OI, were reviewed and discussed. Translationally, it would facilitate to develop clinical prediction strategies (e.g. based on genotype and age, not just phenotype) for OI patients responsive to sclerostin inhibition. Both preclinical and clinical data suggested sclerostin as another factor contributing to XLH, in addition to the identified FGF23. The molecular understanding and therapeutic effects of sclerostin inhibition on both promoting bone anabolism and improving phosphate homostasis in Hyp mice were reviewed and discussed. Translationaly, it would facilitate the development of precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy for the treatment of XLH. Cardiovascular risk could not be ruled out during sclerostin inhibition treatment, especially for OI and XLH patients with cardiovascular diseases history and cardiovascular abnormalities. Studies on the role of sclerostin in inhiting bone formation and protecting cardiovascular system were reviewed and discussed. Translationaly, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.

Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling. AIM: To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved. METHODS: Human vaginal wall collagen content was assessed by Masson's trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules. RESULTS: In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 µg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression. CONCLUSION: HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.

[Hypothetical Alcohol Consumption Interventions and Hepatic Steatosis: A Longitudinal Study in a Large Cohort]. / æ¨¡æ‹Ÿé¥®é ’å¹²é¢„ä¸Žè‚è„‚è‚ªå˜æ€§ï¼šä¸€é¡¹å¤§åž‹é˜Ÿåˆ—çš„çºµå‘ç ”ç©¶.

Objective: Non-alcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (ALD) are the most common chronic liver diseases. Hepatic steatosis is an early histological subtype of both NAFLD and ALD. Excessive alcohol consumption is widely known to lead to hepatic steatosis and subsequent liver damage. However, reported findings concerning the association between moderate alcohol consumption and hepatic steatosis remain inconsistent. Notably, alcohol consumption as a modifiable lifestyle behavior is likely to change over time, but most previous studies covered alcohol intake only once at baseline. These inconsistent findings from existing studies do not inform decision-making concerning policies and clinical guidelines, which are of greater interest to health policymakers and clinician-scientists. Additionally, recommendations on the types of alcoholic beverages are not available. Usually, assessing the effects of two or more hypothetical alcohol consumption interventions on hepatic steatosis provides answers to questions concerning the population risk of hepatic steatosis if everyone changes from heavy drinking to abstinence, or if everyone keeps on drinking moderately, or if everyone of the drinking population switches from red wine to beer? Thus, we simulated a target trial to estimate the effects of several hypothetical interventions, including changes in the amount of alcohol consumption or the types of alcoholic beverages consumed, on hepatic steatosis using longitudinal data, to inform decisions about alcohol-related policymaking and clinical care. Methods: This longitudinal study included 12687 participants from the UK Biobank (UKB), all of whom participated in both baseline and repeat surveys. We excluded participants with missing data related to components of alcohol consumption and fatty liver index (FLI) in the baseline and the repeat surveys, as well as those who had reported liver diseases or cancer at the baseline survey. We used FLI as an outcome indicator and divided the participants into non-, moderate, and heavy drinkers. The surrogate marker FLI has been endorsed by many international organizations' guidelines, such as the European Association for the Study of the Liver. The calculation of FLI was based on laboratory and anthropometric data, including triglyceride, gamma-glutamyl transferase, body mass index, and waist circumference. Participants responded to questions about the types of alcoholic beverages, which were defined in 5 categories, including red wine, white wine/fortified wine/champagne, beer or cider, spirits, and mixed liqueurs, along with the average weekly or monthly amounts of alcohol consumed. Alcohol consumption was defined as pure alcohol consumed per week and was calculated according to the amount of alcoholic beverages consumed per week and the average ethanol content by volume in each alcoholic beverage. Participants were categorized as non-drinkers, moderate drinkers, and heavy drinkers according to the amount of their alcohol consumption. Moderate drinking was defined as consuming no more than 210 g of alcohol per week for men and 140 g of alcohol per week for women. We defined the following hypothetical interventions for the amount of alcohol consumed: sustaining a certain level of alcohol consumption from baseline to the repeat survey (e.g., none to none, moderate to moderate, heavy to heavy) and changing from one alcohol consumption level to another (e.g., none to moderate, moderate to heavy). The hypothetical interventions for the types of alcoholic beverages were defined in a similar way to those for the amount of alcohol consumed (e.g., red wine to red wine, red wine to beer/cider). We applied the parametric g-formula to estimate the effect of each hypothetical alcohol consumption intervention on the FLI. To implement the parametric g-formula, we first modeled the probability of time-varying confounders and FLI conditional on covariates. We then used these conditional probabilities to estimate the FLI value if the alcohol consumption level of each participant was under a specific hypothetical intervention. The confidence interval was obtained by 200 bootstrap samples. Results: For the alcohol consumption from baseline to the repeat surveys, 6.65% of the participants were sustained non-drinkers, 63.68% were sustained moderate drinkers, and 14.74% were sustained heavy drinkers, while 8.39% changed from heavy drinking to moderate drinking. Regarding the types of alcoholic beverages from baseline to the repeat surveys, 27.06% of the drinkers sustained their intake of red wine. Whatever the baseline alcohol consumption level, the hypothetical interventions for increasing alcohol consumption from the baseline alcohol consumption were associated with a higher FLI than that of the sustained baseline alcohol consumption level. When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to moderate drinking, the mean ratio of FLI was 1.027 (95% confidence interval [CI]: 0.997-1.057). When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to heavy drinking, the mean ratio of FLI was 1.075 (95% CI: 1.042-1.108). When comparing sustained heavy drinking with the hypothetical intervention of changing from heavy drinking to moderate drinking, the mean ratio of FLI was 0.953 (95% CI: 0.938-0.968). The hypothetical intervention of changing to red wine in the UKB was associated with lower FLI levels, compared with sustained consumption of other types of alcoholic beverages. For example, when comparing sustaining spirits with the hypothetical intervention of changing from spirits to red wine, the mean ratio of FLI was 0.981 (95% CI: 0.948-1.014). Conclusions: Regardless of the current level of alcohol consumption, interventions that increase alcohol consumption could raise the risk of hepatic steatosis in Western populations. The findings of this study could inform the formulation of future practice guidelines and health policies. If quitting drinking is challenging, red wine may be a better option than other types of alcoholic beverages in Western populations.

Pinibarreniales, a new order of Sordariomycetes from pine barrens ecosystem.

Pinibarrenia chlamydospora, sp. nov. isolated from the roots of highbush blueberry in the New Jersey Pine Barrens, is described and illustrated. Based on multigene phylogenetic analysis, as well as morphological and ecological characteristics, Pinibarreniales and Pinibarreniaceae are established to accommodate this novel lineage in Sordariomycetidae, Sordariomycetes. Pinibarreniales, Tracyllalales, and Vermiculariopsiellales are proposed to be included in the subclass Sordariomycetidae. Pinibarreniales likely have a wide distribution and forms association with Ericaceae plants that live in acidic and oligotrophic environments because its DNA barcode matches with environmental sequences from other independent ecological studies. The plant-fungal interaction experiment revealed negative impacts on Arabidopsis, indicating its pathogenicity. This uncovered new fungal lineage will contribute to a better understanding of the diversity and systematics of Sordariomycetes.

CircCFL1 Promotes TNBC Stemness and Immunoescape via Deacetylation-Mediated c-Myc Deubiquitylation to Facilitate Mutant TP53 Transcription.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%-80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c-Myc, further promoting the stability of c-Myc via deacetylation-mediated inhibition of K48-linked ubiquitylation. Stably expressed c-Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p-AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD-L1 and suppressing the antitumor immunity of CD8+ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c-Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

Efficient enrichment and sensitive detection of polychlorinated biphenyls using nanoflower MIL-on-UiO as solid-phase microextraction fiber coating.

The sensitive detection of polychlorinated biphenyls (PCBs) is crucial for protecting the environment and human health. Herein, we constructed a Materials Institute Lavoisier 88B (MIL-88B)-on-University of Oslo 66 (UiO-66) composite (MIL-on-UiO) with a unique nanoflower morphology, in which highly stable UiO-66 is the precursor, with MIL-88B grown on its surface. MIL-on-UiO was used as a fiber coating for headspace solid-phase microextraction to enrich PCBs. Experimental results demonstrated that MIL-on-UiO provided better enrichment performance for PCBs than single components due to multiple interactions, including π-π stacking, halogen bonding, pore-filling, and steric hindrance effects. The method established using the MIL-on-UiO-based SPME fiber coating provided a good linear relationship in the range of 0.001-50 ng·mL-1, with limits of detection ranging from 0.0002 to 0.002 ng·mL-1 and enrichment factors between 3530 and 7420. In addition, the method was used to detect trace PCBs in water and orange juice achieving satisfactory recoveries (81%-111%).

A prediction nomogram for fractured vertebra re-collapse after posterior reduction and pedicle screw fixation in thoracolumbar fractures.

OBJECTIVE: This study aimed to establish a predictive nomogram model for re-collapse of fractured vertebra after posterior pedicle screw fixation in thoracolumbar fractures (TLFs). METHODS: Patients undergoing posterior pedicle screw fixation for TLFs at our hospital between January 2016 and December 2021 were retrospectively reviewed. Patients were divided into two groups according to the presence or absence of re-collapse of the fractured vertebra at the final follow-up. The predictors for fractured vertebra re-collapse were identified by univariate and multivariable logistic regression analysis, and a nomogram model was developed. The prediction performance and internal validation were established. RESULTS: A total of 224 patients were included in this study. Of these, 46 (20.5%) patients developed re-collapse of fractured vertebra. Age, thoracic and lumbar injury severity score (TLICS), screw distribution in the fractured vertebra, and anterior vertebral height compression (AVHC) ratio were associated with vertebral re-collapse. These predictors were used to construct a predictive nomogram. The area under the receiver operating characteristic curve (AUC) of the nomogram model was 0.891. The concordance index (C-index) was 0.891, and it was 0.877 with bootstrapping validation. The calibration curves and decision curve analysis (DCA)also suggested that the nomogram model had excellent predictive performances for fractured vertebra re-collapse. CONCLUSIONS: A clinical nomogram incorporating four variables was constructed to predict fractured vertebra re-collapse after posterior pedicle screw fixation for TLFs. The nomogram demonstrated good calibration and discriminative abilities, which may help clinicians to make better treatment decisions.

Fungal biofilm formation and its regulatory mechanism.

Fungal biofilm is a microbial community composed of fungal cells and extracellular polymeric substances (EPS). In recent years, fungal biofilms have played an increasingly important role in many fields. However, there are few studies on fungal biofilms and their related applications and development are still far from enough. Therefore, this review summarizes the composition and function of EPS in fungal biofilms, and improves and refines the formation process of fungal biofilms according to the latest viewpoints. Moreover, based on the study of Saccharomyces cerevisiae and Candida albicans, this review summarizes the gene regulation network of fungal biofilm synthesis, which is crucial for systematically understanding the molecular mechanism of fungal biofilm formation. It is of great significance to further develop effective methods at the molecular level to control harmful biofilms or enhance and regulate the formation of beneficial biofilms. Finally, the quorum sensing factors and mixed biofilms formed by fungi in the current research of fungal biofilms are summarized. These results will help to deepen the understanding of the formation process and internal regulation mechanism of fungal biofilm, provide reference for the study of EPS composition and structure, formation, regulation, group behavior and mixed biofilm formation of other fungal biofilms, and provide strategies and theoretical basis for the control, development and utilization of fungal biofilms.

Transcriptomic and proteomic investigations identify PI3K-akt pathway targets for hyperthyroidism management in rats via polar iridoids from radix Scrophularia.

High-polarity iridoids from Radix Scrophulariae (R. Scrophulariae) offer a range of benefits, including anti-inflammatory, antioxidant, antitumour, antibacterial, antiviral, and antiallergic effects. Although previous studies have indicated the potential of R. Scrophulariae for hyperthyroidism prevention and treatment, the specific active compounds involved and their mechanisms of action are not fully understood. This study explored the effects of high-polarity iridoid glycosides from R. Scrophulariae on hyperthyroidism induced in rats by levothyroxine sodium. The experimental design included a control group, a hyperthyroidism model group, and a group treated with iridoid glycosides. Serum triiodothyronine (T3) and thyroxine (T4) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Transcriptomic and proteomic analyses were applied to liver samples to identify differentially expressed genes and proteins. These analyses were complemented by trend analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The effectiveness of key factors was further examined through molecular biology techniques. ELISA results indicated a notable increase in T3 and T4 in the hyperthyroid rats, which was significantly mitigated by treatment with iridoid glycosides. Transcriptomic analysis revealed 6 upregulated and 6 downregulated genes in the model group, showing marked improvement following treatment. Proteomic analysis revealed changes in 30 upregulated and 50 downregulated proteins, with improvements observed upon treatment. The PI3K-Akt signalling pathway was investigated through KEGG enrichment analysis. Molecular biology methods verified the upregulation of Spp1, Thbs1, PI3K, and Akt in the model group, which was reversed in the treatment group. This study revealed that highly polar iridoids from R. Scrophulariae can modulate the Spp1 gene and Thbs1 protein via the PI3K-Akt signalling pathway, suggesting a therapeutic benefit for hyperthyroidism and providing a basis for drug development targeting this condition.

Enhancing Efficiency and Durability of Perovskite Solar Cells with Chlorine-Functionalized Fully Conjugated Porous Aromatic Framework.

Non-radiative recombination, caused by trap states, significantly hampers the efficiency and stability of perovskite solar cells (PSCs). The emerging porous organic polymers (POPs) show promise as a platform for designing novel defect passivation agents due to their rigid and porous structure. However, the POPs reported so far lack either sufficient stability or clear sites of interactions with the defects. Herein, two chlorine-functionalized, fully conjugated porous aromatic frameworks (PAFs) were constructed via a decarbonylation reaction. The chlorinated PAFs feature unique long-range conjugated networks bearing multiple chlorine atoms, significantly improving the photovoltaic performance and stability of doped solar cells. Combined experimental and theoretical analyses confirmed the strong passivation effects of conjugated structure to the defect through Cl sites. Specifically, PAF-159, bearing a triphenylamine moiety, demonstrated stronger Cl-Pb bonding and higher passivation efficiency due to the presence of π* anti-bonding orbitals, which elevate the HOMO energy level and facilitate Cl-Pb charge transfer. Consequently, we obtained high-performance PAF-159-doped devices with advanced PCE (24.3%), good storage stability (retaining 86% after 3000 hours), and good long-term operational stability (retaining 92% after 350 hours).

Temporal relationship between hepatic steatosis and fasting blood glucose elevation: a longitudinal analysis from China and UK.

BACKGROUND: The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect. METHODS: This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects. RESULTS: In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (ßCMEC = 0.068, ßUK-Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (ßCMEC = 0.027, ßUK-Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D. CONCLUSIONS: Our findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well.

The influence of ferroptosis on the in vitro OGD/R model in rat microglia.

OBJECTIVE: We aimed to explore the influence of ferroptosis on an oxygen-glucose deprivation/reoxygenation (OGD/R) model in primary rat microglia. METHODS: Primary microglia were extracted from rats and cultured in vitro. The cells were subjected to a hypoxic environment for 6 h in a glucose-free medium, and then re-oxygenated for 24 h in DMEM/F12. Rat microglia were pretreated with the ferroptosis activator erastin and the ferroptosis inhibitor ferrostatin 1 for 24 h, followed by detection of cell cycle progression and apoptosis by flow cytometry. Intracellular total iron levels were measured. In addition, the relative levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were determined using enzyme-linked immunosorbent assay. The protein levels of 15-lox2, GPX4, SLC7A11, ACSL4, and TFR1 were examined by western blotting. RESULTS: Compared with rat microglia subjected to OGD/R, pretreatment with erastin did not influence cell apoptosis but significantly enhanced total iron levels, MDA, and ROS levels, whereas it reduced SOD levels. Moreover, it upregulated ACSL4, TFR1, and 15-lox2 and downregulated GPX4 and SLC7A11. Pretreatment with ferrostatin 1 significantly inhibited cell apoptosis and cell cycle arrest in the G0/G1 phase. It significantly reduced total iron levels, MDA, and ROS levels and enhanced SOD levels, which also downregulated ACSL4, TFR1, and 15-lox2, and upregulated GPX4 and SLC7A11. CONCLUSION: Our study showed that inhibition of ferroptosis is favorable against potential OGD/R-induced damage in rat microglia.

Assessment of Ammoniacal Leaching Agents for Metal Cation Extraction from Construction Wastes in Mineral Carbonation.

The use of carbon mineralization to produce carbonates from alkaline industrial wastes is gaining traction as a method to decarbonize the built environment. One of the environmental concerns during this process is the use of acids, which are required to extract Ca2+ or Mg2+ from the alkaline waste to produce carbonates. Conventionally, acids such as hydrochloric, nitric, or sulfuric are used which allow for the highest material recovery but are corrosive and difficult to regenerate as they are utilized in a linear fashion and generate additional process waste. An alternative is to use regenerable protonatable salts of ammonia, such as ammonium chloride (AC) or ammonium sulfate, the former of which is used globally during the Solvay process as a reversible proton shuttle. In this study, we show that regenerable ammonium salts, such as AC (NH4Cl) and ammonium bisulfate (NH4HSO4), can be effectively used for material recovery and the production of calcium carbonate during the leaching of waste cement paste as an alternative to conventional acids such as HCl. Leaching kinetics, postreaction residue, and carbonate characterization were performed to assess the productivity of this system and potential uses of these materials downstream. The stabilization of vaterite was observed in the case of AC leaching, suggesting its importance in the kinetic stability of vaterite and suppression of calcite nucleation. Overall, this study motivates the use of alternative leaching agents, such as salts of ammonia, to facilitate material recovery and carbon capture from alkaline industrial wastes.

A Case of Rapidly Diagnosed Mycobacterium intracellulare in a Frail Geriatric Patient With Multimorbidity.

The prevalence of non-tuberculous mycobacteria (NTM) infections has been on the rise in recent years, especially among the elderly population and other immunocompromised groups. Risk factors for NTM infections include advanced age, preexisting pulmonary diseases, and low body mass index. This study presents a case of NTM pulmonary disease attributed to Mycobacterium intracellulare, which was rapidly identified using metagenomic next-generation sequencing (mNGS). An 82-year-old male presented with persistent fever, cough, and shortness of breath. Initial assessments revealed an elevated white blood cell count and high-sensitivity C-reactive protein, with chest CT showing newly formed nodular shadows and cavity formation. Sputum tests confirmed NTM infection through positive acid-fast staining and mNGS, which rapidly identified M. intracellulare within 48 hours. Subsequent sputum samples confirmed the diagnosis using traditional methods. The patient had a complex medical history, including pulmonary tuberculosis, chronic pancreatitis, chronic hepatitis B, diabetes, and malnutrition. The patient was treated with a combination of cefotaxime, moxifloxacin, clarithromycin, and acetylcysteine, in addition to receiving nutritional support. After the treatment, there was an improvement in symptoms, normalization of body temperature, and a decrease in cough and sputum production. This case highlights the significance of mNGS in promptly diagnosing and treating NTM pulmonary disease, especially in elderly patients with various underlying health conditions. The collaborative effort among different medical specialties enabled more thorough patient care, ultimately leading to better outcomes. Incorporating cutting-edge diagnostic techniques such as mNGS alongside a holistic treatment approach is crucial for the successful management of NTM infections in at-risk populations.

Syndromic Surveillance Tracks COVID-19 Cases in University and County Settings: Retrospective Observational Study.

Background: Syndromic surveillance represents a potentially inexpensive supplement to test-based COVID-19 surveillance. By strengthening surveillance of COVID-19-like illness (CLI), targeted and rapid interventions can be facilitated that prevent COVID-19 outbreaks without primary reliance on testing. Objective: This study aims to assess the temporal relationship between confirmed SARS-CoV-2 infections and self-reported and health care provider-reported CLI in university and county settings, respectively. Methods: We collected aggregated COVID-19 testing and symptom reporting surveillance data from Cornell University (2020-2021) and Tompkins County Health Department (2020-2022). We used negative binomial and linear regression models to correlate confirmed COVID-19 case counts and positive test rates with CLI rate time series, lagged COVID-19 cases or rates, and day of the week as independent variables. Optimal lag periods were identified using Granger causality and likelihood ratio tests. Results: In modeling undergraduate student cases, the CLI rate (P=.003) and rate of exposure to CLI (P<.001) were significantly correlated with the COVID-19 test positivity rate with no lag in the linear models. At the county level, the health care provider-reported CLI rate was significantly correlated with SARS-CoV-2 test positivity with a 3-day lag in both the linear (P<.001) and negative binomial model (P=.005). Conclusions: The real-time correlation between syndromic surveillance and COVID-19 cases on a university campus suggests symptom reporting is a viable alternative or supplement to COVID-19 surveillance testing. At the county level, syndromic surveillance is also a leading indicator of COVID-19 cases, enabling quick action to reduce transmission. Further research should investigate COVID-19 risk using syndromic surveillance in other settings, such as low-resource settings like low- and middle-income countries.