Spatial multiomics atlas reveals smooth muscle phenotypic transformation and metabolic reprogramming in diabetic macroangiopathy.

BACKGROUND: Diabetic macroangiopathy has been the main cause of death and disability in diabetic patients. The mechanisms underlying smooth muscle cell transformation and metabolic reprogramming other than abnormal glucose and lipid metabolism remain to be further explored. METHOD: Single-cell transcriptome, spatial transcriptome and spatial metabolome sequencing were performed on anterior tibial artery from 11 diabetic patients with amputation. Multi-omics integration, cell communication analysis, time series analysis, network analysis, enrichment analysis, and gene expression analysis were performed to elucidate the potential molecular features. RESULT: We constructed a spatial multiomics map of diabetic blood vessels based on multiomics integration, indicating single-cell and spatial landscape of transcriptome and spatial landscape of metabolome. At the same time, the characteristics of cell composition and biological function of calcified regions were obtained by integrating spatial omics and single cell omics. On this basis, our study provides favorable evidence for the cellular fate of smooth muscle cells, which can be transformed into pro-inflammatory chemotactic smooth muscle cells, macrophage-like smooth muscle cells/foam-like smooth muscle cells, and fibroblast/chondroblast smooth muscle cells in the anterior tibial artery of diabetic patients. The smooth muscle cell phenotypic transformation is driven by transcription factors net including KDM5B, DDIT3, etc. In addition, in order to focus on metabolic reprogramming apart from abnormal glucose and lipid metabolism, we constructed a metabolic network of diabetic vascular activation, and found that HNMT and CYP27A1 participate in diabetic vascular metabolic reprogramming by combining public data. CONCLUSION: This study constructs the spatial gene-metabolism map of the whole anterior tibial artery for the first time and reveals the characteristics of vascular calcification, the phenotypic transformation trend of SMCs, and the transcriptional driving network of SMCs phenotypic transformation of diabetic macrovascular disease. In the perspective of combining the transcriptome and metabolome, the study demonstrates the activated metabolic pathways in diabetic blood vessels and the key genes involved in diabetic metabolic reprogramming.

RNA modification in normal hematopoiesis and hematologic malignancies.

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotic cells. Previous studies have shown that m6A plays a critical role under both normal physiological and pathological conditions. Hematopoiesis and differentiation are highly regulated processes, and recent studies on m6A mRNA methylation have revealed how this modification controls cell fate in both normal and malignant hematopoietic states. However, despite these insights, a comprehensive understanding of its complex roles between normal hematopoietic development and malignant hematopoietic diseases remains elusive. This review first provides an overview of the components and biological functions of m6A modification regulators. Additionally, it highlights the origin, differentiation process, biological characteristics, and regulatory mechanisms of hematopoietic stem cells, as well as the features, immune properties, and self-renewal pathways of leukemia stem cells. Last, the article systematically reviews the latest research advancements on the roles and mechanisms of m6A regulatory factors in normal hematopoiesis and related malignant diseases. More importantly, this review explores how targeting m6A regulators and various signaling pathways could effectively intervene in the development of leukemia, providing new insights and potential therapeutic targets. Targeting m6A modification may hold promise for achieving more precise and effective leukemia treatments.

Heme oxygenase-1: potential therapeutic targets for periodontitis.

Periodontitis is one of the most prevalent inflammatory disease worldwide, which affects 11% of the global population and is a major cause of tooth loss. Recently, oxidative stress (OS) has been found to be the pivital pathophysiological mechanism of periodontitis, and overactivated OS will lead to inflammation, apoptosis, pyroptosis and alveolar bone resorption. Interestingly, heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme degradation, can exert antioxidant activites through its products-carbon monoxide (CO), Fe2+, biliverdin and bilirubin in the inflammatory microenvironment, thus exhibiting anti-inflammatory, anti-apoptotic, anti-pyroptosis and bone homeostasis-regulating properties. In this review, particular focus is given to the role of HO-1 in periodontitis, including the spatial-temporal expression in periodental tissues and pathophysiological mechanisms of HO-1 in periodontitis, as well as the current therapeutic applications of HO-1 targeted drugs for periodontitis. This review aims to elucidate the potential applications of various HO-1 targeted drug therapy in the management of periodontitis, investigate the influence of diverse functional groups on HO-1 and periodontitis, and pave the way for the development of a new generation of therapeutics that will benefit patients suffering from periodontitis.

Altered gut microbial profile accompanied by abnormal short chain fatty acid metabolism exacerbates nonalcoholic fatty liver disease progression.

Dysregulation of the gut microbiome has associated with the occurrence and progression of non-alcoholic fatty liver disease (NAFLD). To determine the diagnostic capacity of this association, we compared fecal microbiomes across 104 participants including non-NAFLD controls and NAFLD subtypes patients that were distinguished by magnetic resonance imaging. We measured their blood biochemical parameters, 16 S rRNA-based gut microbiota and fecal short-chain fatty acids (SCFAs). Multi-omic analyses revealed that NAFLD patients exhibited specific changes in gut microbiota and fecal SCFAs as compared to non-NAFLD subjects. Four bacterial genera (Faecalibacterium, Subdoligranulum, Haemophilus, and Roseburia) and two fecal SCFAs profiles (acetic acid, and butyric acid) were closely related to NAFLD phenotypes and could accurately distinguish NAFLD patients from healthy non-NAFLD subjects. Twelve genera belonging to Faecalibacterium, Subdoligranulum, Haemophilus, Intestinibacter, Agathobacter, Lachnospiraceae_UCG-004, Roseburia, Butyricicoccus, Actinomycetales_unclassified, [Eubacterium]_ventriosum_group, Rothia, and Rhodococcus were effective to distinguish NAFLD subtypes. Of them, combination of five genera can distinguish effectively mild NAFLD from non-NAFLD with an area under curve (AUC) of 0.84. Seven genera distinguish moderate NAFLD with an AUC of 0.83. Eight genera distinguish severe NAFLD with an AUC of 0.90. In our study, butyric acid distinguished mild-NAFLD from non-NAFLD with AUC value of 0.83. And acetic acid distinguished moderate-NAFLD and severe-NAFLD from non-NAFLD with AUC value of 0.84 and 0.70. In summary, our study and further analysis showed that gut microbiota and fecal SCFAs maybe a method with convenient detection advantages and invasive manner that are not only a good prediction model for early warning of NAFLD occurrence, but also have a strong ability to distinguish NAFLD subtypes.

CFD Investigation on Combined Ventilation System for Multilayer-Caged-Laying Hen Houses.

Mechanical ventilation is an important means of environmental control in multitier laying hen cages. The mainstream ventilation mode currently in use, negative-pressure ventilation (NPV), has the drawbacks of a large temperature difference before and after adjustment and uneven air velocity distribution. To solve these problems, this study designed and analyzed a combined positive and negative-pressure ventilation system for laying hen cages. According to the principle of the conservation of mass to increase the inlet flow in the negative-pressure ventilation system on the basis of the addition of the pressure-wind body-built positive-and-negative-pressure-combined ventilation (PNCV) system, further, computational fluid dynamics (CFD) simulation was performed to analyze the distribution of environmental parameters in the chicken cage zone (CZ) with inlet angles of positive-pressure fans set at 45°, 90°, and 30°. Simulation results showed that the PNCV system increased the average air velocity in the CZ from 0.94 m/s to 1.04 m/s, 1.28 m/s, and 0.99 m/s by actively blowing air into the cage. The maximum temperature difference in the CZ with the PNCV system was 2.91 °C, 1.80 °C, and 3.78 °C, which were all lower than 4.46 °C, the maximum temperature difference in the CZ with the NPV system. Moreover, the relative humidity remained below 80% for the PNCV system and between 80% and 85% for the NPV system. Compared with the NPV system, the PNCV system increased the vertical airflow movement, causing significant cooling and dehumidifying effects. Hence, the proposed system provides an effective new ventilation mode for achieving efficient and accurate environmental control in laying hen cages.

An RNA aptamer photoelectrochemical biosensor based on the exciton energy transfer constructed for theophylline detection.

A novel photoelectrochemical (PEC) biosensor was developed incorporating a specifically designed RNA aptamer for the detection of theophylline (TP). This involved utilizing two nucleotide base aptamers with tailored sequences designed to target TP. The 3' end of a single-stranded RNA sequence (5'-GGAUACCA-(CH2)6-SH-3') and the 5' end of a complementary stranded RNA sequence (5'-HS-(CH2)6-CCUUGGAAGCC-3') were linked to gold nanoparticles (AuNPs) and CdS quantum dots (QDs), respectively. These two single-stranded RNAs (ssRNA) formed a double-stranded RNA (dsRNA) capable of recognizing TP. This major structural change altered the spacing between QDs and NPs, which signaled the presence and concentration of TP. TP was photoelectrochemical catalytic oxidation by the hole of CdS QDs under illumination, then anode photocurrent was generated. Due to the increase in surface impedance and the effect of exciton energy transfer (EET) between QDs and AuNPs, the photocurrent would undergo varying degrees of change. TP was detected by changes in photocurrent. PEC detection of TP was achieved in the range of 0.1 µM-200 µM. The detection limit was 0.033 µM. The method exhibited commendable reproducibility and remarkable selectivity. The biosensor was used to measure TP content in tea, beverages and blood samples, resulting in satisfactory recovery rates.

Electroacupuncture combined with extracorporeal shock wave lithotripsy is beneficial for the expulsion of ureteral calculi: a prospective randomized trial.

PURPOSE: To evaluate the therapeutic efficacy and safety of electroacupuncture (EA) combined with extracorporeal shock wave lithotripsy (ESWL) in treating ureteral calculi. METHODS: This prospective randomized controlled trial included 207 patients with ureteral calculi who were randomly allocated to an experimental group that underwent EA plus ESWL (n = 95) and a control group that underwent only ESWL (n = 112). Imaging examinations were performed at 1, 2, and 4 weeks after the operation, followed by comparing the stone-clearance rate, time to first stone expulsion, and incidence of major complications between the two groups. RESULTS: The stone-clearance rates at 1 (59.1 vs. 37%, P = 0.002), 2 (86.4 vs. 59.3%, P = 0.000), and 4 (90.9 vs. 77.8%, P = 0.013) weeks after the operation in the experimental group were significantly higher than those in the control group. The time to first stone expulsion in the experimental group was significantly lower than that in the control group (1.29 ± 1.55 vs. 2.45 ± 3.11 days, respectively; P = 0.001). However, we found no difference in the incidence of major complications between the two groups (15.9 vs. 17.6%, P = 0.754). CONCLUSION: EA-assisted ESWL significantly improved stone clearance and shortened the time to stone expulsion without elevating the complication risk. However, a large-scale multicenter, prospective study is required to corroborate our conclusions.

Retroperitoneal leiomyomas with intratumoral bleeding: Presentation with multiple-organ dysfunction syndrome - A case report.

Background: Retroperitoneal leiomyomas are rare benign smooth muscle tumours. Diagnosing these tumours is often challenging due to their unique growth site and nonspecific clinical manifestations. There are a few reports of leiomyomas with intratumoral bleeding. Case presentation: A patient with a giant retroperitoneal leiomyoma presented with multiple-organ dysfunction syndrome accompanied by a progressive decrease in haemoglobin. Computed tomography (CT) revealed two cystic tumours in the abdominal cavity. The patient was underwent transabdominal retroperitoneal tumour resection. During surgery, we found two retroperitoneal tumours-one contained approximately 9000 mL of dark red fluid and the other contained 1000 mL of light brown fluid. She has recovered well without any complications. Conclusions: There have been only a few reports of retroperitoneal leiomyomas with intratumoral bleeding. This case highlights the importance of recognizing intratumoral haemorrhage in patients with large leiomyomas and a progressive decrease in haemoglobin after ruling out external haemorrhage. If necessary, dynamic monitoring via CT may help clarify the diagnosis.

A systematic review of dietary and circulating carotenoids and liver disease.

Background: due to the high incidence of liver disease and the severity of adverse outcomes, liver disease has become a serious public health problem, bringing a huge disease burden to individuals, families, and society. Most studies have shown significant differences in serum carotenoid content and dietary carotenoid intake between liver disease patients and non-liver disease patients, but some studies have reported contrary results. This paper aimed to systematically review and analyze all published epidemiological studies on carotenoids and liver disease to quantitatively assess the relationship between serum and dietary carotenoid concentrations and liver disease. Methods: by systematically searching PubMed, Web of Science, Scopus, Embase, and Cochrane databases according to pre-combined search terms from inception to July 23, 2024, 30 studies were found to meet the exclusion criteria. Finally, 3 RCT studies, 6 cohort studies, 11 case-control studies, 9 cross-sectional studies, and 1 RCT-combined cross-sectional study were included in the further analysis. Two reviewers independently scored the literature quality and extracted data, and the results were represented by the standard mean difference (SMD) with a 95% confidence interval. Cochran Q statistics and I2 statistics were used to evaluate statistical heterogeneity (defined as significant when P < 0.05 or I2 > 50%). When there was insignificant heterogeneity, a fixed effects model was selected; otherwise a random effects model was used. Publication bias was assessed by the Egger test. Results: pooled meta-analysis showed that serum α-carotene (SMD = -0.58, 95% CI (-0.83, -0.32), P < 0.001), ß-carotene (SMD = -0.81, 95% CI (-1.13, -0.49), P < 0.001), and lycopene (SMD = -1.06, 95% CI (-1.74, -0.38), P < 0.001) were negatively correlated with the risk and severity of liver disease. However, no significant difference was observed between serum ß-cryptoxanthin (SMD = 0.02, 95% CI (-0.41, 0.45), P = 0.92) and lutein/zeaxanthin (SMD = 0.62, 95% CI (-1.20, 2.45), P = 0.502). Dietary ß-carotene intake (SMD = -0.22, 95% CI (-0.31, -0.13), P < 0.001) was negatively associated with the risk of liver disease. The Egger test showed no publication bias (P > 0.05). An intake of more than 6 mg of carotenoids on an energy-restricted diet can effectively alleviate the symptoms of NAFLD. Conclusion: lower serum concentrations of α-carotene, ß-carotene, and lycopene were associated with a higher risk of liver disease. Meanwhile, dietary intake of ß-carotene could reduce the incidence of liver disease. However, for malignant diseases such as liver cancer, it did not show the significant effects of carotenoid supplementation.

Heteroaggregation, disaggregation, and migration of nanoplastics with nanosized activated carbon in aquatic environments: Effects of particle property, water chemistry, and hydrodynamic condition.

Nanosized activated carbon (NAC) as emerging engineered nanomaterials may interact with nanoplastics prevalent in aquatic environments to affect their fate and transport. This study investigated the effects of particle property (charge and concentration), water chemistry [electrolytes, pH, humic acid (HA), and sodium alginate (SA)], and hydrodynamic condition [wave (i.e., sonication) and turbulence (i.e., stirring)] on the heteroaggregation, disaggregation, and migration of NAC with positively charged amino-modified polystyrene (APS) or negatively charged bare polystyrene (BPS) nanoplastics. The homoaggregation rate of APS was slower than its heteroaggregation rate with NAC, with critical coagulation concentrations (CCC) decreasing at higher NAC concentrations. However, the homoaggregation rate of BPS was intermediate between its heteroaggregation rates under low (10 mg/L) and high (40 mg/L) NAC concentrations. The heteroaggregation rate of APS+NAC enhanced as pH increasing from 3 to 10, whereas the opposite trend was observed for BPS+NAC. In NaCl solution or at CaCl2 concentration below 2.5 mM, HA stabilized APS+NAC and BPS+NAC via steric hindrance more effectively than SA. Above 2.5 mM CaCl2, SA destabilized APS+NAC and BPS+NAC by calcium bridging more strongly than HA. The migration process of heteroaggregates was simulated in nearshore environments. The simulation suggests that without hydrodynamic disturbance, APS+NAC (971 m) may travel farther than BPS+NAC (901 m). Mild wave (30-s sonication) and intense turbulence (1500-rpm stirring) could induce disaggregation of heteroaggregates, thus potentially extending the migration distances of APS+NAC and BPS+NAC to 1611 and 2160 m, respectively. Conversely, intense wave (20-min sonication) and mild turbulence (150-rpm stirring) may further promote aggregation of heteroaggregates, shortening the migration distances of APS+NAC and BPS+NAC to 262 and 552 m, respectively. Particle interactions mainly involved van der Waals attraction, electrostatic repulsion, steric hindrance, calcium bridging, π-π interactions, hydrogen bonding, and hydrophobic interactions. These findings highlight the important influence of NAC on the fate, transport, and risks of nanoplastics in aquatic environments.

Nrf2-dependent hepatoprotective effect of ellagic acid in titanium dioxide nanoparticles-induced liver injury.

BACKGROUND AND AIMS: Previous studies suggest that titanium dioxide nanoparticles (TiO2 NPs) induce liver injury, possibly due to oxidative stress and inflammation. Ellagic acid (EA) is a dietary polyphenol extracted from natural sources and possesses antioxidant and anti-inflammatory properties. Nonetheless, the efficacy of EA in mitigating liver injury induced by TiO2 NPs remains to be elucidated. METHODS: Primary hepatocytes and L02 cells were cultured with 45 µM EA and 10 µg/ml TiO2 NPs. Mice were orally administered TiO2 NPs (150 mg kg-1) and EA (25/50/100 mg kg-1) for eight weeks. sulforaphane (SFN) as a positive control to evaluate the inhibitory effect of EA on TiO2 NP-induced liver injury (SFN 10 mg kg-1). RNA sequencing (RNA-seq) was employed to elucidate the mechanisms underlying oxidative stress, inflammation, and liver fibrosis. RESULTS: We assessed the impact of EA on cytotoxicity, oxidative stress, inflammation, and fibrosis in both cells and mice exposed to TiO2 NPs for an extended period. Our findings indicated that EA had a protective effect on TiO2 NP-exposed hepatocytes, reducing cytotoxicity, oxidative stress, and inflammation. Furthermore, EA treatment markedly reduced serum aminotransferase levels in mice exposed to TiO2 NPs. Furthermore, EA treatment notably reduced hepatic stress response, inflammation, and fibrosis in mice. The treatment of EA demonstrates non-inferiority compared to SFN. The protective effects of EA were attributed to the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), EA promoted the translocation and phosphorylation of Nrf2, as indicated by the finding that Nfe2l2 shRNA and inhibition of Nrf2 by ML385 reversed the EA-induced hepatoprotective effects in TiO2 NP-exposed hepatocytes and mice. CONCLUSION: EA significantly mitigated liver injury induced by TiO2 NPs. Importantly, we identified that the nuclear translocation and phosphorylation of Nrf2 are the primary mechanisms through which EA alleviates liver injury resulting from exposure to TiO2 NPs. As a natural activator of Nrf2, EA emerges as a promising therapeutic candidate for treating TiO2 NPs-induced liver injury, further enhancing our understanding of its potential as a hepatoprotective agent and its underlying molecular mechanisms.

Food insecurity trends and disparities according to immigration status in the US households, 2011-2021.

BACKGROUND: Food insecurity related to immigration status remains largely underexplored. This study examined trends and disparities in household food insecurity by immigration status in the United States (US). METHODS: We analyzed data from 427,942 households from the US Current Population Survey Food Security Supplement from 2011 to 2021. Immigration status categories included recent immigrants (< 5 years), long-term immigrants (≥ 5 years), naturalized citizens, and US-born citizens. Food insecurity was assessed using validated questions on consistent access to enough food for an active and healthy life. RESULTS: From 2011 to 2021, food insecurity prevalence declined from 14.9 % (95 % CI, 14.5 %-15.3 %) to 10.2 % (95 % CI, 9.8 %-10.6 %). Among recent immigrants, prevalence decreased from 25.2 % (95 % CI, 23.1-27.4) in 2011 to 15.0 % (95 % CI, 12.8 %-17.2 %) in 2019, then increased to 17.7 % (95 % CI, 14.7 %-20.2 %) in 2020 and 17.4 % (95 % CI, 14.7 %-20.2 %) in 2021. Long-term immigrants' prevalence dropped from 20.4 % (95 % CI, 16.9 %-24.0 %) in 2011 to 10.2 % (95 % CI, 7.2 %-13.1 %) in 2018, then increased to 17.7 % (95 % CI, 13.7 %-21.7 %) in 2021. Naturalized citizens' prevalence decreased from 14.4 % (95 % CI, 12.9 %-15.9 %) to 9.5 % (95 % CI, 8.2 %-10.9 %). US-born citizens' prevalence decreased from 14.2 % (95 % CI, 13.8 %-14.6 %) to 9.7 % (95 % CI, 9.3 %-10.2 %). Compared to the US-born citizens, the adjusted prevalence ratio was 1.63 (95 % CI,1.57-1.69) for recent immigrants, 1.22 (95 % CI, 1.13-1.31) for long-term immigrants, and 0.94 (95 % CI, 0.90-0.98) for naturalized citizens. Significant disparities exist in subgroups. CONCLUSIONS: The findings provide insights for stakeholders to address food insecurity among vulnerable immigrant groups in the US.

Renal clear cell carcinoma undergoing cystic change: A cases report and review of the literature.

INTRODUCTION: We presented a case diagnosed the renal clear cell carcinoma undergoing cystic change (RCCCC) with detailed clinical data. Along with literature review, we aimed to investigate clinical diagnosis and treatment of RCCCC and explore the differential diagnosis of RCCCC and multilocular cystic renal cell carcinoma (MCRCC). CASE PRESENTATION: The patient was diagnosed with a right renal cyst after physical examination, which was misdiagnosed as a renal cyst by imaging examination. Intraoperative surgical treatment was performed to remove the roof and decompress the renal cyst. Rapid pathology revealed MCRCC with low malignant potential during laparoscopic right renal cyst decompression. Radical nephrectomy was performed with the family's signature. The postoperative pathological diagnosis was clear cell carcinoma cystic lesion of kidney (RCCCC). No recurrence or metastasis during 1 year follow-up. CLINICAL DISCUSSION: RCCCC cases were similar to classical clear cell renal carcinoma. Radical nephrectomy should be avoided in patients with MCRCC, and radical nephrectomy should be chosen in patients with RCCCC, with postoperative and close follow-up. Unroofing decompression of renal cyst was performed during the operation, and the risk of tumor implantation and metastasis was worried after the operation. The patient agreed to receive eight cycles of immune checkpoint inhibitor therapy after surgery. Adrenal insufficiency occurred after 8 cycles of immune checkpoint inhibitor therapy(ICIs), then the immunotherapy was discontinued. CONCLUSION: RCCCC is a rare and special type of renal clear cell carcinoma, and its prognosis is the same as that of renal clear cell carcinoma. The preoperative diagnosis of RCCCC mainly depends on imaging examination (CT or B-ultrasound). The early differential diagnosis from multilocular cystic renal cell carcinoma is difficult, and the diagnosis usually depends on postoperative pathological diagnosis.

TME-NET: an interpretable deep neural network for predicting pan-cancer immune checkpoint inhibitor responses.

Immunotherapy with immune checkpoint inhibitors (ICIs) is increasingly used to treat various tumor types. Determining patient responses to ICIs presents a significant clinical challenge. Although components of the tumor microenvironment (TME) are used to predict patient outcomes, comprehensive assessments of the TME are frequently overlooked. Using a top-down approach, the TME was divided into five layers-outcome, immune role, cell, cellular component, and gene. Using this structure, a neural network called TME-NET was developed to predict responses to ICIs. Model parameter weights and cell ablation studies were used to investigate the influence of TME components. The model was developed and evaluated using a pan-cancer cohort of 948 patients across four cancer types, with Area Under the Curve (AUC) and accuracy as performance metrics. Results show that TME-NET surpasses established models such as support vector machine and k-nearest neighbors in AUC and accuracy. Visualization of model parameter weights showed that at the cellular layer, Th1 cells enhance immune responses, whereas myeloid-derived suppressor cells and M2 macrophages show strong immunosuppressive effects. Cell ablation studies further confirmed the impact of these cells. At the gene layer, the transcription factors STAT4 in Th1 cells and IRF4 in M2 macrophages significantly affect TME dynamics. Additionally, the cytokine-encoding genes IFNG from Th1 cells and ARG1 from M2 macrophages are crucial for modulating immune responses within the TME. Survival data from immunotherapy cohorts confirmed the prognostic ability of these markers, with p-values <0.01. In summary, TME-NET performs well in predicting immunotherapy responses and offers interpretable insights into the immunotherapy process. It can be customized at https://immbal.shinyapps.io/TME-NET.

Rheumatoid arthritis complicated with cervical actinomycosis and ureteral obstruction: A case report and literature review. / ç±»é£Žæ¹¿å ³èŠ‚ç‚Žåˆå¹¶å®«é¢ˆæ”¾çº¿èŒç— åŠè¾“å°¿ç®¡æ¢—é˜»1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts, often misdiagnosed due to its similarity to many infectious and non-infectious diseases. This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics, including methotrexate, leflunomide, and infliximab, leading to recurrent joint pain, poorly controlled rheumatoid arthritis activity, and persistent elevation of white blood cell counts. Abdominal CT revealed a pelvic mass and right ureteral dilation. Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules, indicating actinomycosis. The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide, hydroxychloroquine sulfate, and tofacitinib, resulting in improved joint symptoms and normalized white blood cell counts. After 2 years of follow-up, the patient remained stable with no recurrence. This case highlights the importance of clinicians being vigilant for infections, particularly chronic, occult infections from rare pathogens, in rheumatoid arthritis patients on potent immunosuppressants and biologics, advocating for early screening and diagnosis.

Combined effects of nitrogen limitation and overexpression of malic enzyme gene on lipid accumulation in Dunaliella parva.

Overexpression of Dunaliella parva (D. parva) malic enzyme (ME) gene (DpME) significantly increased DpME expression and ME enzyme activity in transgenic D. parva. Nitrogen limitation had an inhibitory effect on protein content, and DpME overexpression could improve protein content. Nitrogen limitation increased carbohydrate content, and Dunaliella parva overexpressing malic enzyme gene under nitrogen limitation (DpME-N-) group showed the lowest starch content among all groups. Dunaliella parva overexpressing malic enzyme gene under nitrogen sufficient condition (DpME) and DpME-N- groups showed considerably high mRNA levels of DpME. ME activity was significantly enhanced by DpME overexpression, and nitrogen limitation caused a smaller increase. DpME overexpression and nitrogen limitation obviously enhanced lipid accumulation, and DpME overexpression had more obvious effect. Compared with control (wild type), lipid content (68.97%) obviously increased in DpME-N- group. This study indicated that the combination of DpME overexpression and nitrogen limitation was favorable to the production of microalgae biodiesel.

Development and validation of a survival prediction model for patients with advanced non-small cell lung cancer based on LASSO regression.

Introduction: Lung cancer remains a significant global health burden, with non-small cell lung cancer (NSCLC) being the predominant subtype. Despite advancements in treatment, the prognosis for patients with advanced NSCLC remains unsatisfactory, underscoring the imperative for precise prognostic assessment models. This study aimed to develop and validate a survival prediction model specifically tailored for patients diagnosed with NSCLC. METHODS: A total of 523 patients were randomly divided into a training dataset (n=313) and a validation dataset (n=210). We conducted initial variable selection using three analytical methods: univariate Cox regression, LASSO regression, and random survival forest (RSF) analysis. Multivariate Cox regression was then performed on the variables selected by each method to construct the final predictive models. The optimal model was selected based on the highest bootstrap C-index observed in the validation dataset. Additionally, the predictive performance of the model was evaluated using time-dependent receiver operating characteristic (Time-ROC) curves, calibration plots, and decision curve analysis (DCA). RESULTS: The LASSO regression model, which included N stage, neutrophil-lymphocyte ratio (NLR), D-dimer, neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC), driver alterations, and first-line treatment, achieved a bootstrap C-index of 0.668 (95% CI: 0.626-0.722) in the validation dataset, the highest among the three models tested. The model demonstrated good discrimination in the validation dataset, with area under the ROC curve (AUC) values of 0.707 (95% CI: 0.633-0.781) for 1-year survival, 0.691 (95% CI: 0.616-0.765) for 2-year survival, and 0.696 (95% CI: 0.611-0.781) for 3-year survival predictions, respectively. Calibration plots indicated good agreement between predicted and observed survival probabilities. Decision curve analysis demonstrated that the model provides clinical benefit at a range of decision thresholds. CONCLUSION: The LASSO regression model exhibited robust performance in the validation dataset, predicting survival outcomes for patients with advanced NSCLC effectively. This model can assist clinicians in making more informed treatment decisions and provide a valuable tool for patient risk stratification and personalized management.

iRGD-Guided Silica/Gold Nanoparticles for Efficient Tumor-Targeting and Enhancing Antitumor Efficacy Against Breast Cancer.

Background: Breast cancer presents significant challenges due to the limited effectiveness of available treatments and the high likelihood of recurrence. iRGD possesses both RGD sequence and C-terminal sequence and has dual functions of targeting and membrane penetration. iRGD-modified nanocarriers can enhance drug targeting of tumor vascular endothelial cells and penetration of new microvessels, increasing drug concentration in tumor tissues. Methods: The amidation reaction was carried out between SiO2/AuNCs and iRGD/PTX, yielding a conjugated drug delivery system (SiO2/AuNCs-iRGD/PTX, SAIP@NPs). The assessment encompassed the characterization of the morphology, particle size distribution, physicochemical properties, in vitro release profile, cytotoxicity, and cellular uptake of SAIP@NPs. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed using a small animal in vivo imaging system and a tumor-bearing nude mice model, respectively. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed utilizing a small animal in vivo imaging system and an in situ nude mice breast cancer xenograft model, respectively. Results: The prepared SAIP@NPs exhibited decent stability and a certain slow-release effect in phosphate buffer (PBS, pH 7.4). In vitro studies had shown that, due to the dual functions of transmembrane and targeting of iRGD peptide, SAIP@NPs exhibited strong binding to integrin αvß3, which was highly expressed on the membrane of MDA-MB-231 cells, improving the uptake capacity of tumor cells, inhibiting the rapid growth of tumor cells, and promoting tumor cell apoptosis. The results of animal experiments further proved that SAIP@NPs had longer residence time in tumor sites, stronger anti-tumor effect, and no obvious toxicity to major organs of experimental animals. Conclusion: The engineered SAIP@NPs exhibited superior functionalities including efficient membrane permeability, precise tumor targeting, and imaging, thereby significantly augmenting the therapeutic efficacy against breast cancer with a favorable safety profile.

A novel temporal-frequency combination pattern optimization approach based on information fusion for motor imagery BCIs.

Motor imagery (MI) stands as a powerful paradigm within Brain-Computer Interface (BCI) research due to its ability to induce changes in brain rhythms detectable through common spatial patterns (CSP). However, the raw feature sets captured often contain redundant and invalid information, potentially hindering CSP performance. Methodology-wise, we propose the Information Fusion for Optimizing Temporal-Frequency Combination Pattern (IFTFCP) algorithm to enhance raw feature optimization. Initially, preprocessed data undergoes simultaneous processing in both time and frequency domains via sliding overlapping time windows and filter banks. Subsequently, we introduce the Pearson-Fisher combinational method along with Discriminant Correlation Analysis (DCA) for joint feature selection and fusion. These steps aim to refine raw electroencephalogram (EEG) features. For precise classification of binary MI problems, an Radial Basis Function (RBF)-kernel Support Vector Machine classifier is trained. To validate the efficacy of IFTFCP and evaluate it against other techniques, we conducted experimental investigations using two EEG datasets. Results indicate a notably superior classification performance, boasting an average accuracy of 78.14% and 85.98% on dataset 1 and dataset 2, which is better than other methods outlined in this article. The study's findings suggest potential benefits for the advancement of MI-based BCI strategies, particularly in the domain of feature fusion.

Radiomic analysis reveals diverse prognostic and molecular insights into the response of breast cancer to neoadjuvant chemotherapy: a multicohort study.

BACKGROUND: Breast cancer patients exhibit various response patterns to neoadjuvant chemotherapy (NAC). However, it is uncertain whether diverse tumor response patterns to NAC in breast cancer patients can predict survival outcomes. We aimed to develop and validate radiomic signatures indicative of tumor shrinkage and therapeutic response for improved survival analysis. METHODS: This retrospective, multicohort study included three datasets. The development dataset, consisting of preoperative and early NAC DCE-MRI data from 255 patients, was used to create an imaging signature-based multitask model for predicting tumor shrinkage patterns and pathological complete response (pCR). Patients were categorized as pCR, nonpCR with concentric shrinkage (CS), or nonpCR with non-CS, with prediction performance measured by the area under the curve (AUC). The prognostic validation dataset (n = 174) was used to assess the prognostic value of the imaging signatures for overall survival (OS) and recurrence-free survival (RFS) using a multivariate Cox model. The gene expression data (genomic validation dataset, n = 112) were analyzed to determine the biological basis of the response patterns. RESULTS: The multitask learning model, utilizing 17 radiomic signatures, achieved AUCs of 0.886 for predicting tumor shrinkage and 0.760 for predicting pCR. Patients who achieved pCR had the best survival outcomes, while nonpCR patients with a CS pattern had better survival than non-CS patients did, with significant differences in OS and RFS (p = 0.00012 and p = 0.00063, respectively). Gene expression analysis highlighted the involvement of the IL-17 and estrogen signaling pathways in response variability. CONCLUSIONS: Radiomic signatures effectively predict NAC response patterns in breast cancer patients and are associated with specific survival outcomes. The CS pattern in nonpCR patients indicates better survival.