Ruddlesden-Popper Perovskite Nanocrystals as Interface Modification Layer for Efficient Perovskite Solar Cells.

Perovskite nanocrystals are advantageous for interfacial passivation of perovskite solar cells (PSCs), but the insulating long alkyl chain surface ligands impede the charge transfer, while the conventional ligand exchange would possibly introduce surface defects to the nanocrystals. In this work, we reported novel in situ modification of CsPbBr3 nanocrystals using a short chain conjugated molecule 2-methoxyphenylethylammonium iodide (2-MeO-PEAI) for interfacial passivation of PSCs. Transmission electron microscopy studies with atomic resolution unveil the transformation from cubic CsPbBr3 to Ruddlesden-Popper phase (RPP) nanocrystals due to halogen exchange. Synergic passivation by the RPP nanocrystals and 2-MeO-PEA+ has led to suppressed interface defects and enhanced charge carrier transport. Consequently, PSCs with in situ modified RPP nanocrystals achieved a champion power conversion efficiency of 24.39%, along with an improvement in stability. This work brings insights into the microstructural evolution of perovskite nanocrystals, providing a novel and feasible approach for interfacial passivation of PSCs.

Dual-functional Separators Regulating Ion Transport Enabled by 3D-Reinforced Polyimide Microspheres Protective Layer for Dendrite-Free and High-Temperature Lithium Metal Batteries.

High-energy-density lithium metal batteries (LMBs) are confronted with crucial concerns of security and a short cycle lifespan caused by the uncontrollable formation of lithium (Li) dendrites. The poor thermal stability and heterogeneous Li deposition of conventional polyolefin separators often cause battery short circuiting and thermal runaway in LMBs. Herein, a novel dual-functional PE composite separator (PI-COOH/PE) coated by carboxyl polyimide (PI) microspheres is fabricated by an etching-acidification method. The three-dimensional (3D) high-temp PI microsphere with rich carboxyl groups on the surface improve the security of LMBs at extremely high temperatures and facilitate the formation of a stable and uniform SEI layer, which contributes to accelerating the Li+ transport and stabilizing the formation of the SEI layer. Consequently, the Li symmetric cell assembled with the (PI-COOH)/PE separator exhibits stable overpotential over 3000 h, and the corresponding Li//NCM811 full cells also show a high-level discharge capacity of 146.6 mAh g-1 at 5 C. Meanwhile, it also demonstrates outstanding cycling stability and thermal safety, which can survive continuously over 160 min at 140 °C (vs 21 min for PE). The above results indicate the (PI-COOH)/PE separator constructed by a low-cost and industrial-friendly strategy simultaneously addresses high-temperature stability and dendrite resistance.

New implications for prion diseases therapy and prophylaxis.

Prion diseases are rare, fatal, progressive neurodegenerative disorders that affect both animal and human. Human prion diseases mainly present as Creutzfeldt-Jakob disease (CJD). However, there are no curable therapies, and animal prion diseases may negatively affect the ecosystem and human society. Over the past five decades, scientists are devoting to finding available therapeutic or prophylactic agents for prion diseases. Numerous chemical compounds have been shown to be effective in experimental research on prion diseases, but with the limitations of toxicity, poor efficacy, and low pharmacokinetics. The earliest clinical treatments of CJD were almost carried out with anti-infectious agents that had little amelioration of the course. With the discovery of pathogenic misfolding prion protein (PrPSc) and increasing insights into prion biology, amounts of novel technologies have attempted to eliminate PrPSc. This review presents new perspectives on clinical and experimental prion diseases, including immunotherapy, gene therapy, small-molecule drug, and stem cell therapy. It further explores the prospects and challenge associated with these emerging therapeutic approaches for prion diseases.

Role of the NF-kB signalling pathway in heterotopic ossification: biological and therapeutic significance.

Heterotopic ossification (HO) is a pathological process in which ectopic bone develops in soft tissues within the skeletal system. Endochondral ossification can be divided into the following types of acquired and inherited ossification: traumatic HO (tHO) and fibrodysplasia ossificans progressiva (FOP). Nuclear transcription factor kappa B (NF-κB) signalling is essential during HO. NF-κB signalling can drive initial inflammation through interactions with the NOD-like receptor protein 3 (NLRP3) inflammasome, Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK). In the chondrogenesis stage, NF-κB signalling can promote chondrogenesis through interactions with mechanistic target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K)/AKT (protein kinase B, PKB) and other molecules, including R-spondin 2 (Rspo2) and SRY-box 9 (Sox9). NF-κB expression can modulate osteoblast differentiation by upregulating secreted protein acidic and rich in cysteine (SPARC) and interacting with mTOR signalling, bone morphogenetic protein (BMP) signalling or integrin-mediated signalling under stretch stimulation in the final osteogenic stage. In FOP, mutated ACVR1-induced NF-κB signalling exacerbates inflammation in macrophages and can promote chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs) through interactions with smad signalling and mTOR signalling. This review summarizes the molecular mechanism of NF-κB signalling during HO and highlights potential therapeutics for treating HO.

Revolutionizing Airborne Virus Defense: Electromagnetic MXene-Coated Air Filtration for Superior Aerosol Viral Removal.

The COVID-19 pandemic sparked public health concerns about the transmission of airborne viruses. Current methods mainly capture pathogens without inactivation, leading to potential secondary pollution. Herein, we evaluated the inactivation performance of a model viral species (MS2) in simulated bioaerosol by an electromagnetically enhanced air filtration system under a 300 kHz electromagnetic induction field. A nonwoven fabric filter was coated with a 2D catalyst, MXene (Ti3C2Tx), at a coating density of 4.56 mg·cm-2 to absorb electromagnetic irradiation and produce local heating and electromagnetic field for microbial inactivation. The results showed that the MXene-coated air filter significantly enhanced the viral removal efficiency by achieving a log removal of 3.4 ± 0.15 under an electromagnetic power density of 369 W·cm-2. By contrast, the pristine filter without catalyst coating only garnered a log removal of 0.3 ± 0.04. Though the primary antimicrobial mechanism is the local heating as indicated by the elevated surface temperature of 72.2 ± 4 °C under the electromagnetic field, additional nonthermal effects (e.g., dielectrophoresis) on enhanced viral capture during electromagnetically enhanced filtration were investigated by COMSOL simulation to delineate the potential transmission trajectories of bioaerosol. The results provide unique insights into the mechanisms of pathogen control and thus promote alternative solutions for preventing the transmission of airborne pathogens.

Unraveling the pH-Dependent Oxygen Reduction Performance on Single-Atom Catalysts: From Single- to Dual-Sabatier Optima.

Metal-nitrogen-carbon (M-N-C) single-atom catalysts (SACs) have emerged as a potential substitute for the costly platinum-group catalysts in oxygen reduction reaction (ORR). However, several critical aspects of M-N-C SACs in ORR remain poorly understood, including their pH-dependent activity, selectivity for 2- or 4-electron transfer pathways, and the identification of the rate-determining steps. Herein, by analyzing >100 M-N-C structures and >2000 sets of energetics, we unveil a pH-dependent evolution in ORR activity volcanos─from a single peak in alkaline media to a double peak in acids. We found that this pH-dependent behavior in M-N-C catalysts fundamentally stems from their moderate dipole moments and polarizability for O* and HOO* adsorbates, as well as unique scaling relations among ORR adsorbates. To validate our theoretical discovery, we synthesized a series of molecular M-N-C catalysts, each characterized by well-defined atomic coordination environments. Impressively, the experiments matched our theoretical predictions on kinetic current, Tafel slope, and turnover frequency in both acidic and alkaline environments. These new insights also refine the famous Sabatier principle by emphasizing the need to avoid an "acid trap" while designing M-N-C catalysts for ORR or any other pH-dependent electrochemical applications.

Evaluation of commercial nanofiltration and reverse osmosis membrane filtration to remove per-and polyfluoroalkyl substances (PFAS): Effects of transmembrane pressures and water matrices.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are now widely found in aquatic ecosystems, including sources of drinking water and portable water, due to their increasing prevalence. Among different PFAS treatment or separation technologies, nanofiltration (NF) and reverse osmosis (RO) both yield high rejection efficiencies (>95%) of diverse PFAS in water; however, both technologies are affected by many intrinsic and extrinsic factors. This study evaluated the rejection of PFAS of different carbon chain length (e.g., PFOA and PFBA) by two commercial RO and NF membranes under different operational conditions (e.g., applied pressure and initial PFAS concentration) and feed solution matrixes, such as pH (4-10), salinity (0- to 1000-mM NaCl), and organic matters (0-10 mM). We further performed principal component analysis (PCA) to demonstrate the interrelationships of molecular weight (213-499 g·mol-1 ), membrane characteristics (RO or NF), feed water matrices, and operational conditions on PFAS rejection. Our results confirmed that size exclusion is a primary mechanism of PFAS rejection by RO and NF, as well as the fact that electrostatic interactions are important when PFAS molecules have sizes less than the NF membrane pores. PRACTITIONER POINTS: Two commercial RO and NF membranes were both evaluated to remove 10 different PFAS. High transmembrane pressures facilitated permeate recovery and PFAS rejection by RO. Electrostatic repulsion and pore size exclusion are dominant rejection mechanisms for PFAS removal. pH, ionic strength, and organic matters affected PFAS rejection. Mechanisms of PFAS rejection with RO/NF membranes were explained by PCA analysis.

Integrated microbiome and metabolomics revealed the protective effect of baicalin on alveolar bone inflammatory resorption in aging.

BACKGROUND: With the growing aging population and longer life expectancy, periodontitis and tooth loss have become major health concerns. The gut microbiota, as a key regulator in bone homeostasis, has gathered immense interest. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis Georgi, has shown antioxidant and anti-inflammatory activities. PURPOSE: This study investigated, for the first time, the protective mechanism of baicalin against alveolar bone inflammatory resorption in aging mice by regulating intestinal flora and metabolites, as well as intestinal barrier function. METHODS: A ligature-induced periodontitis model was established in d-galactose (D-gal)-induced aging mice, and baicalin was administered at different dosages for 13 weeks. Body weight was measured weekly. The antioxidant and anti-inflammatory activity of baicalin were evaluated using serum superoxide dismutase (SOD), malonaldehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. The immune capability was assessed by thymus and spleen indices. Histopathological changes were observed in the heart, liver, ileum, and periodontal tissues. Alveolar bone absorption of maxillary second molars was examined, and osteoclasts were counted by tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, fecal samples were analyzed using 16S rRNA sequencing and non-targeted metabolomics to identify differences in intestinal bacterial composition and metabolites. RESULTS: Baicalin exhibited anti-aging properties, as evidenced by increased SOD activity and decreased levels of MDA, IL-6, and TNF-α in serum compared to the control group. Baicalin also ameliorated alveolar bone loss in the d-gal-induced aging-periodontitis group (p < 0.05). Furthermore, baicalin restored ileal permeability by up-regulating the expression of ZO-1 and occludin in aging-periodontitis groups (p < 0.05). Alpha diversity analysis indicated that baicalin-treated mice harbored a higher diversity of gut microbe. PCoA and ANOSIM results revealed significant dissimilarity between groups. The Firmicutes/Bacteroidetes (F/B) ratio, which decreased in periodontitis mice, was restored by baicalin treatment. Additionally, medium-dosage baicalin promoted the production of beneficial flavonoids, and enriched short-chain fatty acids (SCFAs)-producing bacteria. CONCLUSION: Intestinal homeostasis is a potential avenue for treating age-related alveolar bone loss. Baicalin exerts anti-inflammatory, antioxidant, and osteo-protective properties by regulating the gut microbiota and metabolites.

Identifying Stable Electrocatalysts Initialized by Data Mining: Sb2 WO6 for Oxygen Reduction.

Data mining from computational materials database has become a popular strategy to identify unexplored catalysts. Herein, the opportunities and challenges of this strategy are analyzed by investigating a discrepancy between data mining and experiments in identifying low-cost metal oxide (MO) electrocatalysts. Based on a search engine capable of identifying stable MOs at the pH and potentials of interest, a series of MO electrocatalysts is identified as potential candidates for various reactions. Sb2 WO6 attracted the attention among the identified stable MOs in acid. Based on the aqueous stability diagram, Sb2 WO6 is stable under oxygen reduction reaction (ORR) in acidic media but rather unstable under high-pH ORR conditions. However, this contradicts to the subsequent experimental observation in alkaline ORR conditions. Based on the post-catalysis characterizations, surface state analysis, and an advanced pH-field coupled microkinetic modeling, it is found that the Sb2 WO6 surface will undergo electrochemical passivation under ORR potentials and form a stable and 4e-ORR active surface. The results presented here suggest that though data mining is promising for exploring electrocatalysts, a refined strategy needs to be further developed by considering the electrochemistry-induced surface stability and activity.

Single-cell RNA-seq reveals MIF-(CD74 + CXCR4) dependent inhibition of macrophages in metastatic papillary thyroid carcinoma.

BACKGROUND: The mechanism promoting papillary thyroid carcinoma (PTC) metastasis remains unclear. We aimed to investigate the potential metastatic mechanisms at a single-cell resolution. METHODS: We performed single-cell RNA-seq (scRNA-seq) profiling of thyroid tumour (TT), adjacent normal thyroid (NT) and lymph node metastasized tumour (LN) from a young female with PTC. Validation of our results was conducted in 31 tumours with metastasis and 30 without metastasis. RESULTS: ScRNA-seq analysis generated data on 38,215 genes and 0.14 billion transcripts from 28,839 cells, classified into 18 clusters, each annotated to represent 10 cell types. PTC cells were found to originate from epithelial cells. Epithelial cells and macrophages emerged as the strongest signal emitters and receivers, respectively. After reclustering epithelial cells and macrophages, our analysis, incorporating gene set variation analysis (GSVA), SCENIC analysis, and pseudotime trajectory analysis, indicated that subcluster 0 of epithelial cells (EP_0) showed a more malignant phenotype, and subclusters 3 and 4 of macrophages (M_3 and M_4) demonstrated heightened activity. Further analysis suggested that EP_0 may suppress the activity of M_3 and M_4 via MIF - (CD74 + CXCR4) in the MIF pathway. After analysing the expression of the 4 genes in the MIF pathway in both the TCGA cohort and our cohort (n = 61), CD74 was identified as significantly overexpressed in PTC tumours particularly those with lymph node metastasis. CONCLUSION: Our study revealed that PTC may facilitate lymph node metastasis by inhibiting macrophages via MIF signalling. It is suggested that malignant PTC cells may suppress the immune activity of macrophages by consistently releasing signals to them via MIF-(CD74 + CXCR4).

LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation.

Ferroptosis, a unique type of non-apoptotic cell death resulting from iron-dependent lipid peroxidation, has a potential physiological function in tumor suppression, but its underlying mechanisms have not been fully elucidated. Here, we report that the long non-coding RNA (lncRNA) LncFASA increases the susceptibility of triple-negative breast cancer (TNBC) to ferroptosis. As a tumor suppressor, LncFASA drives the formation of droplets containing peroxiredoxin1 (PRDX1), a member of the peroxidase family, resulting in the accumulation of lipid peroxidation via the SLC7A11-GPX4 axis. Mechanistically, LncFASA directly binds to the Ahpc-TSA domain of PRDX1, inhibiting its peroxidase activity by driving liquid-liquid phase separation, which disrupts intracellular ROS homeostasis. Notably, high LncFASA expression indicates favorable overall survival in individuals with breast cancer, and LncFASA impairs the growth of breast xenograft tumors by modulating ferroptosis. Together, our findings illustrate the crucial role of this lncRNA in ferroptosis-mediated cancer development and provide new insights into therapeutic strategies for breast cancer.

LncRNA LINK-A Remodels Tissue Inflammatory Microenvironments to Promote Obesity.

High-fat diet (HFD)-induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study has used genetic screening to identify an obesity-associated human lncRNA LINK-A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD-induced obesity knock-in (KI) mouse model. Mechanistically, HFD LINK-A KI mice induce the infiltration of inflammatory factors, including IL-1ß and CXCL16, through the LINK-A/HB-EGF/HIF1α feedback loop axis in a self-amplified manner, thereby promoting the adipose tissue microenvironment remodeling and adaptive thermogenesis disorder, ultimately leading to obesity and insulin resistance. Notably, LINK-A expression is positively correlated with inflammatory factor expression in individuals who are overweight. Of note, targeting LINK-A via nucleic acid drug antisense oligonucleotides (ASO) attenuate HFD-induced obesity and metabolic syndrome, pointing out LINK-A as a valuable and effective therapeutic target for treating HFD-induced obesity. Briefly, the results reveale the roles of lncRNAs (such as LINK-A) in remodeling tissue inflammatory microenvironments to promote HFD-induced obesity.

Comparative Efficacy and Safety of Measures for the Treatment of Adults with Isolated Calf Muscular Vein Thrombosis: A Systematic Review and Network Meta-analysis.

BACKGROUND: Isolated calf muscular vein thrombosis (ICMVT) can result in pulmonary embolism, but the treatment of ICMVT remains controversial. Therefore, the purpose of the present study was to investigate the optimal treatment for the ICMVT by comparing the efficacy and safety of different treatments. METHODS: A network meta-analysis was conducted to search for studies published from database inception to April 30, 2022, that compared the outcomes of 2 or more treatments for ICMVT. The primary outcomes were efficacy (resolution rate) and safety (adverse reactions). Data were extracted following predefined hierarchy and the Cochrane Collaboration risk of bias tool was used to evaluate the methodological quality of the included studies. We estimated summary odds ratios with 95% credibility intervals using Bayesian network meta-analysis with random effects. RESULTS: A total of 16 studies were enrolled in the study. In terms of efficacy and safety, urokinase thrombolysis combined with low-molecular-weight heparin (LMWH) was most effective but had the lowest safety, while physical therapy was safest but had the lowest efficacy. More important, direct oral factor Xa inhibitors were most likely to be second most effective and safe compared with other treatments. For the duration of treatment, anticoagulant therapy for at least 3 months could effectively increase the resolution rate of ICMVT. CONCLUSIONS: Considering both efficacy and safety, taking direct oral factor Xa inhibitors for at least 3 months was the optimal treatment compared to LMWH, urokinase thrombolysis combined LMWH, physical therapy and warfarin for patients with ICMVT.

Higher Cumulative Blood Pressure in Midlife Predicts an Increased Risk of Atrial Fibrillation: Evidence From the Atherosclerosis Risk in Communities Study.

BACKGROUND: Elevated blood pressure (BP) is reportedly associated with an increased risk of atrial fibrillation (AF). However, the association between cumulative BP exposure in midlife and incident AF in mid-to-late life remains unclear. METHODS AND RESULTS: Participants enrolled in the ARIC (Atherosclerosis Risk in Communities) study with 4 consecutive BP measurements and no prevalent AF at baseline were included. Cumulative BP was calculated as the area under the curve from visit 1 to visit 4. Incident AF was identified by study visit ECGs, hospital discharge codes, or death certificates. A total of 9892 participants were included (44.6% men and mean age 62.9±5.7 years at visit 4) with 1550 (15.7%) individuals who developed new-onset AF during an average follow-up of 15.4 years. The incidence rates of AF per 1000 person-years across the 4 quartiles of cumulative systolic BP were 7.9, 9.2, 12.5, and 16.9, respectively. After multivariable adjustment, the hazard ratios for incident AF among participants in the highest quartile of cumulative systolic BP, pulse pressure, and mean arterial pressure were 1.48 (95% CI, 1.27-1.72), 1.81 (95% CI, 1.53-2.13), and 1.22 (95% CI, 1.05-1.41), respectively, compared with those in the lowest quartile. The addition of cumulative systolic BP or pulse pressure slightly improved the ability to predict new-onset AF. CONCLUSIONS: Higher exposure to cumulative systolic BP, pulse pressure, and mean arterial pressure was significantly associated with increased risk of incident AF.

'Single-shot' pulmonary vein isolation using a novel lotos pulsed field ablation catheter: a pre-clinical evaluation of feasibility, safety, and 30-day efficacy.

AIMS: Pulsed field ablation (PFA) is emerging as a non-thermal, tissue-specific technique for pulmonary vein isolation (PVI) in atrial fibrillation therapy. This pre-clinical study aims to investigate the feasibility and safety of PVI using a novel PFA system including a nanosecond-scale PFA generator, a novel lotos PFA catheter, and a customized 12 Fr steerable sheath. METHODS AND RESULTS: A total of 11 Yorkshire swine were included in this study, with 4 in the acute cohort and 7 in the chronic cohort. Under general anaesthesia, transseptal puncture and pulmonary vein (PV) angiography was initially performed. The PFA catheter was navigated to position at the right and left PV antrum after the electroanatomic reconstruction of the left atrium. Biphasic PFA applications were performed on PVs in both the spindle-shaped and the lotos-shaped poses. Pulmonary vein isolation and PFA-associated safety were assessed 30 min after ablation in both cohorts and 30 days later in the chronic cohort. Detailed necropsy and histopathology were performed. Additional intracardiac echocardiography and coronary angiogram were evaluated for safety. All target PVs (n = 20) were successfully isolated on the first attempt. No spasm of coronary artery or microbubble was seen during the procedure. Eleven of 12 PVs (91.6%) remained in isolation at the 30-day invasive study. No evidence of PV stenosis was observed in any targets. However, transient diaphragm capture occurred in 17.6%. Histopathological examinations showed no evidence of collateral injury. CONCLUSION: This study provides scientific evidence demonstrating the safety and efficacy of the novel PFA catheter and system for single-shot PVI, which shows great potential.

Role of Ideal Cardiovascular Health Metrics in Reducing Risk of Incident Arrhythmias.

AIMS: Cardiovascular health (CVH) has been proved to reduce cardiovascular disease burden and mortality, but data are lacking regarding cardiac arrhythmias. The aim of this study was to assess the association between CVH metrics and atrial fibrillation/flutter (AF), ventricular arrhythmias and bradyarrhythmias. METHODS AND RESULTS: This study analyzed data from the ARIC (Atherosclerosis Risk in Communities) cohort, with participants recruited from four different communities across the United States. CVH metrics were scored at baseline (1987 to 1989) following the AHA's recommendations and categorized as poor, intermediate, or ideal. Arrhythmia episodes were diagnosed by ICD-9 code. Adjusted associations were estimated using Cox models and event rates and population attributable fractions were calculated by CVH metrics category. The study population consisted of 13078 participants, with 2548 AF, 1363 ventricular arrhythmias, and 706 bradyarrhythmias occurred. The adjusted hazard ratios (HRs) for ideal (vs. poor) CVH metrics were 0.59 (95% confidence interval [CI]: 0.50 to 0.69) for AF, 0.38 (95% CI: 0.28 to 0.51) for ventricular arrhythmias, and 0.70 (95% CI: 0.51 to 0.97) for bradyarrhythmia. The risk of incident arrhythmias decreased steadily as the CVH metrics improved from 0 to 14 scores. The adjusted population attributable fractions were calculated to be 29.9% for AF, 54.4% for ventricular arrhythmias, and 21.9% for bradyarrhythmia, respectively. The association between CVH metrics and incident arrhythmias was also seen in people who remained free of coronary heart disease over the follow-up. CONCLUSION: Achieving ideal CVH metrics recommendations by AHA in midlife was associated with a lower risk of incident arrhythmias later in life.

(1) Intermediate and ideal levels of cardiovascular health metrics are associated with a markedly reduced risk of developing incident arrhythmias, including atrial fibrillation/flutter, ventricular arrhythmias and bradyarrhythmia, independent of coronary heart disease. (2) A majority of incident arrhythmias could be prevented if the risk profile of the entire population were optimized. (3) These findings emphasize the significance of public health policies that improve cardiovascular health to reduce the social and economic burden of arrhythmias.

Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. METHODS: Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. RESULTS: F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. CONCLUSIONS: Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.

A prediction nomogram for deep venous thrombosis risk in patients undergoing primary total hip and knee arthroplasty: a retrospective study.

INTRODUCTION: Deep venous thrombosis (DVT) prediction after total hip and knee arthroplasty remains challenging. Early diagnosis and treatment of DVT are crucial. This research aimed to develop a nomogram for early DVT prediction. METHODS: A total of 317 patients undergoing primary total hip and knee arthroplasty in Sun Yat-sen Memorial Hospital were enrolled between May 2020 and September 2022. Data from May 2020 to February 2022 were used as the development datasets to build the nomogram model (n = 238). Using multivariate logistic regression, independent variables and a nomogram for predicting the occurrence of DVT were identified. Datasets used to validate the model for internal validation ranged from March 2022 to September 2022 (n = 79). The nomogram's capacity for prediction was also compared with the Caprini score. RESULTS: For both the development and validation datasets, DVT was found in a total of 38 (15.97%) and 9 patients (11.39%) on post-operative day 7 (pod7), respectively. 59.6% patients were symptomatic DVT (leg swelling). The multivariate analysis revealed that surgical site (Knee vs. Hip), leg swelling and thrombin-antithrombin complex (TAT) were associated with DVT. The previously indicated variables were used to build the nomogram, and for the development and validation datasets, respectively. In development and validation datasets, the area under the receiver operating characteristic curve was 0.836 and 0.957, respectively. In both datasets, the predictive value of the Nomogram is greater than the Caprini score. CONCLUSIONS: A proposed nomogram incorporating surgical site (Knee vs. Hip), leg swelling, and thrombin antithrombin complex (TAT) may facilitate the identification of patients who are more prone to develop DVT on pod7.

Comparison of Transcriptome between Tolerant and Susceptible Rice Cultivar Reveals Positive and Negative Regulators of Response to Rhizoctonia solani in Rice.

Rice (Oryza sativa L.) is one of the world's most crucial food crops, as it currently supports more than half of the world's population. However, the presence of sheath blight (SB) caused by Rhizoctonia solani has become a significant issue for rice agriculture. This disease is responsible for causing severe yield losses each year and is a threat to global food security. The breeding of SB-resistant rice varieties requires a thorough understanding of the molecular mechanisms involved and the exploration of immune genes in rice. To this end, we conducted a screening of rice cultivars for resistance to SB and compared the transcriptome based on RNA-seq between the most tolerant and susceptible cultivars. Our study revealed significant transcriptomic differences between the tolerant cultivar ZhengDao 22 (ZD) and the most susceptible cultivar XinZhi No.1 (XZ) in response to R. solani invasion. Specifically, the tolerant cultivar showed 7066 differentially expressed genes (DEGs), while the susceptible cultivar showed only 60 DEGs. In further analysis, we observed clear differences in gene category between up- and down-regulated expression of genes (uDEGs and dDEGs) based on Gene Ontology (GO) classes in response to infection in the tolerant cultivar ZD, and then identified uDEGs related to cell surface pattern recognition receptors, the Ca2+ ion signaling pathway, and the Mitogen-Activated Protein Kinase (MAPK) cascade that play a positive role against R. solani. In addition, DEGs of the jasmonic acid and ethylene signaling pathways were mainly positively regulated, whereas DEGs of the auxin signaling pathway were mainly negatively regulated. Transcription factors were involved in the immune response as either positive or negative regulators of the response to this pathogen. Furthermore, our results showed that chloroplasts play a crucial role and that reduced photosynthetic capacity is a critical feature of this response. The results of this research have important implications for better characterization of the molecular mechanism of SB resistance and for the development of resistant cultivars through molecular breeding methods.