Clinical study on the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy.

Objective: To explore the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy. Methods: From January 2020 to January 2022, clinical data, including blood routine, lipid profile, and renal function indicators, were gathered from a cohort consisting of 5 cases of preeclampsia and 34 cases of non-preeclampsia. The non-preeclampsia group was further categorized into 6 cases in the First trimester, 13 cases in the Second trimester, and 15 cases in the Third trimester. The data collection took place at the Obstetrics Department of the Maternal and Child Health Hospital of Hubei Province. Additionally, fecal samples were obtained from each subject for 16S rDNA gene sequencing and subsequent analysis. The clinical data and composition characteristics of the gut microbiota in each group were analyzed, and the correlation between gut microbiota and clinical data was analyzed by the Spearman correlation analysis method. Results: In comparison to pregnant women without preeclampsia, preeclampsia patients exhibited a statistically significant elevation in blood routine parameters (WBC, N, L, and PLT count), a rise in lipid-related indicators (TC, TG, and LDL-C levels), a reduction in HDL-C levels, and an increase in renal function-related indicators (Cr, BUN, UA and Pro levels). Compared with non-preeclampsia pregnant women, preeclampsia women exhibited an augmented diversity of gut microbiota. Differences in gut microbiota composition between the two groups were observed at the gate and genus levels. Moreover, there are significant differences in the composition of gut microbiota between the preeclampsia group and the third-trimester group in terms of genus and species, and this difference is mainly caused by Prevotella and s_ Bacteroides_ Uniformis and Ruminococcus_ bromii. In addition, actinobacteria, bifidobacterium at the genus level, and Ruminococcus_bromii at the species level are positively correlated with clinically relevant indicators (excluding HDL-C). Conclusion: There are significant differences in gut microbiota between preeclampsia pregnant women and late pregnancy pregnant without preeclampsia, including Prevotella and Bacteroides_ Uniformis, and Ruminococcus_ bromii. In addition, these differential bacteria are correlated with most clinical indicators. However, additional comprehensive analysis is required to ascertain the functional correlation between these bacteria and clinical indicators.

A Review of Ultrasonic Treatment in Mineral Flotation: Mechanism and Recent Development.

Ultrasonic treatment has been widely used in the mineral flotation process due to its advantages in terms of operational simplicity, no secondary pollutant formation, and safety. Currently, many studies have reported the effect of ultrasonic treatment on mineral flotation and shown excellent flotation performance. In this review, the ultrasonic mechanisms are classified into three types: the transient cavitation effect, stable cavitation effect, and acoustic radiation force effect. The effect of the main ultrasonic parameters, including ultrasonic power and ultrasonic frequency, on mineral flotation are discussed. This review highlights the uses of the application of ultrasonic treatment in minerals (such as the cleaning effect, ultrasonic corrosion, and desulfuration), flotation agents (such as dispersion and emulsification and change in properties and microstructure of pharmaceutical solution), and slurry (such formation of microbubbles and coalescence). Additionally, this review discusses the challenges and prospects of using ultrasonic approaches for mineral flotation. The findings demonstrate that the application of the ultrasonic effect yields diverse impacts on flotation, thereby enabling the regulation of flotation behavior through various treatment methods to enhance flotation indices and achieve the desired objectives.

Insights into phage-bacteria interaction in cold seep Gigantidas platifrons through metagenomics and transcriptome analyses.

Viruses are crucial for regulating deep-sea microbial communities and biogeochemical cycles. However, their roles are still less characterized in deep-sea holobionts. Bathymodioline mussels are endemic species inhabiting cold seeps and harboring endosymbionts in gill epithelial cells for nutrition. This study unveiled a diverse array of viruses in the gill tissues of Gigantidas platifrons mussels and analyzed the viral metagenome and transcriptome from the gill tissues of Gigantidas platifrons mussels collected from a cold seep in the South Sea. The mussel gills contained various viruses including Baculoviridae, Rountreeviridae, Myoviridae and Siphovirdae, but the active viromes were Myoviridae, Siphoviridae, and Podoviridae belonging to the order Caudovirales. The overall viral community structure showed significant variation among environments with different methane concentrations. Transcriptome analysis indicated high expression of viral structural genes, integrase, and restriction endonuclease genes in a high methane concentration environment, suggesting frequent virus infection and replication. Furthermore, two viruses (GP-phage-contig14 and GP-phage-contig72) interacted with Gigantidas platifrons methanotrophic gill symbionts (bathymodiolin mussels host intracellular methanotrophic Gammaproteobacteria in their gills), showing high expression levels, and have huge different expression in different methane concentrations. Additionally, single-stranded DNA viruses may play a potential auxiliary role in the virus-host interaction using indirect bioinformatics methods. Moreover, the Cro and DNA methylase genes had phylogenetic similarity between the virus and Gigantidas platifrons methanotrophic gill symbionts. This study also explored a variety of viruses in the gill tissues of Gigantidas platifrons and revealed that bacteria interacted with the viruses during the symbiosis with Gigantidas platifrons. This study provides fundamental insights into the interplay of microorganisms within Gigantidas platifrons mussels in deep sea.

A Tumor Environment-Activated Photosensitized Biomimetic Nanoplatform for Precise Photodynamic Immunotherapy of Colon Cancer.

Aggressive nature of colon cancer and current imprecise therapeutic scenarios simulate the development of precise and effective treatment strategies. To achieve this, a tumor environment-activated photosensitized biomimetic nanoplatform (PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM) is fabricated by encapsulating metal-organic framework loaded with developed photosensitizer PEG2000-SiNcTI-Ph and immunoadjuvant CpG oligodeoxynucleotide within fusion cell membrane expressing programmed death protein 1 (PD-1) and cluster of differentiation 47 (CD47). By stumbling across, systematic evaluation, and deciphering with quantum chemical calculations, a unique attribute of tumor environment (low pH plus high concentrations of adenosine 5'-triphosphate (ATP))-activated photodynamic effect sensitized by long-wavelength photons is validated for PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM, advancing the precision of cancer therapy. Moreover, PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM evades immune surveillance to target CT26 colon tumors in mice mediated by CD47/signal regulatory proteins α (SIRPα) interaction and PD-1/programmed death ligand 1 (PD-L1) interaction, respectively. Tumor environment-activated photodynamic therapy realized by PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM induces immunogenic cell death (ICD) to elicit anti-tumor immune response, which is empowered by enhanced dendritic cells (DC) uptake of CpG and PD-L1 blockade contributed by the nanoplatform. The photodynamic immunotherapy efficiently combats primary and distant CT26 tumors, and additionally generates immune memory to inhibit tumor recurrence and metastasis. The nanoplatform developed here provides insights for the development of precise cancer therapeutic strategies.

Impact of Environmental Uncertainty on Depression and Anxiety Among Chinese Workers: A Moderated Mediation Model.

Purpose: Environmental uncertainty has reached unprecedented levels in recent years. While there is substantial knowledge about the connection between environmental uncertainty and organizational outcomes, limited attention has been devoted to investigating its impact on employees' depression and anxiety symptoms. Grounded in job demands-resources theory, this study aims to explore the relationship between environmental uncertainty and employees' depression and anxiety symptoms, and it further investigates the mediating role of work pressure and the moderating role of union practices. Methods: In September 2022, we undertook a cross-sectional survey study, gathering data from 1081 employees across various enterprises situated in Liaoning, China. Throughout this timeframe, notable global occurrences heightened the awareness of environmental uncertainty. Following the exclusion of participants who did not provide information on the main variables, the final valid sample comprised 940 employees. To test all hypotheses, a series of confirmatory factor analyses and path-analytic procedures were conducted using Mplus 7.0. Results: Our results confirm that environmental uncertainty, as a high job demand, increases employees' work pressure, thereby elevating rates of anxiety and depression; the indirect relationship between environmental uncertainty and employees' anxiety and depression through work pressure is stronger when union practices are lower. Conclusion: Our findings indicate the detrimental impact of environmental uncertainty on employees' mental health, and highlight the roles of work pressure and union practices. In light of this, organizations should take steps to mitigate employees' perceptions of environmental uncertainty and establish mental health programs, in cooperation with union practices, to protect employees' mental well-being.

Radix Rehmanniae Praeparata promoted zebrafish fin regeneration through aryl hydrocarbon receptor-dependent autophagy.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Rehmanniae Radix Praeparata (RRP), a staple in traditional Chinese medicine, is derived from Rehmannia glutinosa Libosch and is renowned for its wound-healing properties. Despite its clinical prevalence, the molecular mechanisms underlying RRP's wound-healing effects have not been fully elucidated. AIM OF THE STUDY: This research endeavored to delineate the molecular and cellular mechanisms underlying the beneficial effects of RRP on wound healing, utilizing a zebrafish model. MATERIALS AND METHODS: Zebrafish larvae at 3 days post-fertilization were amputated at the fin and subsequently treated with RRP. The pro-wound healing and regenerative effects of RRP were evaluated through morphological analysis, assessment of cell proliferation and apoptosis, Additionally, mechanistic insights were gained through a comprehensive approach encompassing network pharmacology analysis, cell tracing, RNA-sequencing, CRISPR/Cas9 gene editing, and pharmacological inhibition. RESULTS: Our findings demonstrate that RRP significantly accelerates caudal fin regeneration in zebrafish following injury by suppressing cell apoptosis, promoting cell proliferation, and upregulating the expression of regenerative-related genes. Furthermore, RRP triggers autophagy signals during the regenerative process, which is attenuated by the autophagy inhibitor chloroquine (CQ). Notably, the administration of RRP enhances the expression of ahr1 and ahr2 in the regenerating fin. Genetic knockout of ahr1a, ahr1b, or ahr2 using CRISPR/Cas9, or pharmacological blockade of AHR signals with the antagonist CH-223191, diminishes the regenerative potential of RRP. Remarkably, zebrafish lacking ahr2 completely lose their fin regeneration ability. Additionally, inhibition of AHR signaling suppresses autophagy signaling during fin regeneration. CONCLUSIONS: This study uncovers that RRP stimulates fin regeneration in zebrafish by inducing AHR signals and, at least partially, activating the autophagy process. These findings provide novel insights into the molecular mechanisms underlying the wound-healing effects of RRP and may pave the way for the development of novel therapeutic strategies.

Hyaluronic acid modified extracellular vesicles targeting hepatic stellate cells to attenuate hepatic fibrosis.

RATIONALE: Transforming growth factor-beta1 (TGF-ß1) plays a pivotal role in promoting hepatic fibrosis, pirfenidone (PFD) could inhibit TGF-ß1 signaling pathway to alleviate hepatic stellate cells (HSC) activation mediated hepatic fibrosis. The targeting delivery strategy of PFD to hepatic stellate cells is a challenge. Extracellular vesicles (EVs), cell-derived membranous particles are intraluminal nano-vesicles that play a vital role in intercellular communication, they also be considered as an ideal nano-carrier. METHODS: In this study, we developed a target strategy to deliver PFD to HSC with CD44 over-expression by EVs, hyaluronic acid (HA) modified DSPE-PEG2000 endows the active targeting ability of activated HSCs to PFD-loaded EVs. RESULTS: In both rat hepatic stellate cell line HSC-T6 and rat hepatocyte cell line BRL, HA@EVs-PFD demonstrated the capacity to down-regulate the expression of collagen-synthesis-related proteins and showed superior inhibition efficacy of HSC-T6 activation compared to free PFD. In hepatic fibrosis model, 4 weeks of HA@EVs-PFD treatment resulted in a reduction in liver collagen fibers, significant improvement in hepatic cell morphology, and amelioration of hepatic fibrosis. CONCLUSIONS: HA@EVs-PFD, as a drug delivery system that effectively targets and inhibits activated HSCs to treat hepatic fibrosis, holds promise as a potential therapeutic agent against hepatic fibrosis.

Biopolymer Meets Nanoclay: Rational Fabrication of Superb Adsorption Beads from Green Precursors for Efficient Capture of Pb(II) and Dyes.

Renewable, green, and safe natural biopolymer-derived materials are highly desired for the purification of pollutants, but significantly improving their performance without the introduction of additional harmful chemicals remains a huge challenge. Based on the concept of "structure optimization design", environment-friendly composite beads (named SA/PASP/RE) with excellent adsorption performance and recyclability were rationally constructed through a green ionic crosslinking route, using the completely green biopolymer sodium alginate (SA), sodium salt of polyaspartic acid (PASP), and the natural nanoclay rectorite (RE) as starting materials. The nano-layered RE was embedded in the polymer matrix to prevent the polymer chain from becoming over-entangled so that more adsorption sites inside the polymer network were exposed, which effectively improved the mass transfer efficiency of the adsorbent and the removal rate of contaminants. The composite beads embedded with 0.6% RE showed high adsorption capacities of 211.78, 197.13, and 195.69 mg/g for Pb(II) and 643.00, 577.80, and 567.10 mg/g for methylene blue (MB) in Yellow River water, Yangtze River water, and tap water, respectively. And the beads embedded with 43% RE could efficiently adsorb Pb(II) and MB with high capacities of 187.78 mg/g and 586.46 mg/g, respectively. This study provides a new route to design and develop a green, cost-effective, and efficient adsorbent for the decontamination of wastewater.

Integrated transcriptomic and metabolomic approaches reveal molecular response and potential biomarkers of the deep-sea mussel Gigantidas platifrons to copper exposure.

Metal pollution caused by deep-sea mining activities has potential detrimental effects on deep-sea ecosystems. However, our knowledge of how deep-sea organisms respond to this pollution is limited, given the challenges of remoteness and technology. To address this, we conducted a toxicity experiment by using deep-sea mussel Gigantidas platifrons as model animals and exposing them to different copper (Cu) concentrations (50 and 500 µg/L) for 7 days. Transcriptomics and LC-MS-based metabolomics methods were employed to characterize the profiles of transcription and metabolism in deep-sea mussels exposed to Cu. Transcriptomic results suggested that Cu toxicity significantly affected the immune response, apoptosis, and signaling processes in G. platifrons. Metabolomic results demonstrated that Cu exposure disrupted its carbohydrate metabolism, anaerobic metabolism and amino acid metabolism. By integrating both sets of results, transcriptomic and metabolomic, we find that Cu exposure significantly disrupts the metabolic pathway of protein digestion and absorption in G. platifrons. Furthermore, several key genes (e.g., heat shock protein 70 and baculoviral IAP repeat-containing protein 2/3) and metabolites (e.g., alanine and succinate) were identified as potential molecular biomarkers for deep-sea mussel's responses to Cu toxicity. This study contributes novel insight for assessing the potential effects of deep-sea mining activities on deep-sea organisms.

The intake of solid fat and cheese may be associated with a reduced risk of Helicobacter pylori infection status: a cross-sectional study based on NHANES 1999-2000.

BACKGROUND: Diet plays an important role in Helicobacter pylori (HP) infection, and our objective was to investigate potential connections between dietary patterns, specific food groups, and HP infection status in U.S. adults. METHODS: The data for this study was obtained from the NHANES (National Health and Nutrition Survey) database for the year 1999-2000. This cross-sectional study involved the selection of adults aged 20 years and older who had undergone dietary surveys and HP testing. Factor analysis was employed to identify dietary patterns, and logistic regression models were utilized to assess the association between these dietary patterns and specific food groups with HP infection status. RESULT: Based on the inclusion and exclusion criteria, our final analysis included 2,952 individuals. The median age of participants was 51.0 years, and 48.7% were male. In the study population, the overall prevalence of HP infection was 44.9%. Factor analysis revealed three distinct dietary patterns: High-fat and high-sugar pattern (including solid fats, refined grains, cheese, and added sugars); Vegetarian pattern (comprising fruits, juices, and whole grains); Healthy pattern (encompassing vegetables, nuts and seeds, and oils). Adjusted results showed that the high-fat and high-sugar pattern (OR = 0.689, 95% CI: 0.688-0.690), vegetarian pattern (OR = 0.802, 95% CI: 0.801-0.803), and healthy pattern (OR = 0.717, 95% CI: 0.716-0.718) were all linked to a lower likelihood of HP infection. Further analysis of the high-fat and high-sugar pattern revealed that solid fats (OR = 0.717, 95% CI: 0.716-0.718) and cheese (OR = 0.863, 95% CI: 0.862-0.864) were protective factors against HP infection, while refined grains (OR = 1.045, 95% CI: 1.044-1.046) and added sugars (OR = 1.014, 95% CI: 1.013-1.015) were identified as risk factors for HP infection. CONCLUSION: Both the Vegetarian pattern and the Healthy pattern are associated with a reduced risk of HP infection. Interestingly, the High-fat and High-sugar pattern, which is initially considered a risk factor for HP infection when the score is low, becomes a protective factor as the intake increases. Within this pattern, animal foods like solid fats and cheese play a protective role, while the consumption of refined grains and added sugars increases the likelihood of HP infection.

Construction of a prognostic model for extensive-stage small cell lung cancer patients undergoing immune therapy in northernmost China and prediction of treatment efficacy based on response status at different time points.

BACKGROUND AND PURPOSE: Recently, the emergence of immune checkpoint inhibitors has significantly improved the survival of patients with extensive-stage small cell lung cancer. However, not all patients can benefit from immunotherapy; therefore, there is an urgent need for precise predictive markers to screen the population for the benefit of immunotherapy. However, single markers have limited predictive accuracy, so a comprehensive predictive model is needed to better enable precision immunotherapy. The aim of this study was to establish a prognostic model for immunotherapy in ES-SCLC patients using basic clinical characteristics and peripheral hematological indices of the patients, which would provide a strategy for the clinical realization of precision immunotherapy and improve the prognosis of small cell lung cancer patients. METHODS: This research retrospectively collected data from ES-SCLC patients treated with PD-1/PD-L1 inhibitors between March 1, 2019, and October 31, 2022, at Harbin Medical University Cancer Hospital. The study data was randomly split into training and validation sets in a 7:3 ratio. Variables associated with patients' overall survival were screened and modeled by univariate and multivariate Cox regression analyses. Models were presented visually via Nomogram plots. Model discrimination was evaluated by Harrell's C index, tROC, and tAUC. The calibration of the model was assessed by calibration curves. In addition, the clinical utility of the model was assessed using a DCA curve. After calculating the total risk score of patients in the training set, patients were stratified by risk using percentile partitioning. The Kaplan-Meier method was used to plot OS and PFS survival curves for different risk groups and response statuses at different milestone time points. Differences in survival time groups were compared using the chi-square test. Statistical analysis software included R 4.1.2 and SPSS 26. RESULTS: This study included a total of 113 ES-SCLC patients who received immunotherapy, including 79 in the training set and 34 in the validation set. Six variables associated with poorer OS in patients were screened by Cox regression analysis: liver metastasis (P = 0.001), bone metastasis (P = 0.013), NLR < 2.14 (P = 0.005), LIPI assessed as poor (P < 0.001), PNI < 51.03 (P = 0.002), and LDH ≥ 146.5 (P = 0.037). A prognostic model for immunotherapy in ES-SCLC patients was constructed based on the above variables. The Harrell's C-index in the training and validation sets of the model was 0.85 (95% CI 0.76-0.93) and 0.88 (95% CI 0.76-0.99), respectively; the AUC values corresponding to 12, 18, and 24 months in the tROC curves of the training set were 0.745, 0.848, and 0.819 in the training set and 0.858, 0.904 and 0.828 in the validation set; the tAUC curves show that the overall tAUC is > 0.7 and does not fluctuate much over time in both the training and validation sets. The calibration plot demonstrated the good calibration of the model, and the DCA curve indicated that the model had practical clinical applications. Patients in the training set were categorized into low, intermediate, and high risk groups based on their predicted risk scores in the Nomogram graphs. In the training set, 52 patients (66%) died with a median OS of 15.0 months and a median PFS of 7.8 months. Compared with the high-risk group (median OS: 12.3 months), the median OS was significantly longer in the intermediate-risk group (median OS: 24.5 months, HR = 0.47, P = 0.038) and the low-risk group (median OS not reached, HR = 0.14, P = 0.007). And, the median PFS was also significantly prolonged in the intermediate-risk group (median PFS: 12.7 months, HR = 0.45, P = 0.026) and low-risk group (median PFS not reached, HR = 0.12, P = 0.004) compared with the high-risk group (median PFS: 6.2 months). Similar results were obtained in the validation set. In addition, we observed that in real-world ES-SCLC patients, at 6 weeks after immunotherapy, the median OS was significantly longer in responders than in non-responders (median OS: 19.5 months vs. 11.9 months, P = 0.033). Similar results were obtained at 12 weeks (median OS: 20.7 months vs 11.9 months, P = 0.044) and 20 weeks (median OS: 20.7 months vs 11.7 months, P = 0.015). Finally, we found that in the real world, ES-SCLC patients without liver metastasis (P = 0.002), bone metastasis (P = 0.001) and a total number of metastatic organs < 2 (P = 0.002) are more likely to become long-term survivors after receiving immunotherapy. CONCLUSION: This study constructed a new prognostic model based on basic patient clinical characteristics and peripheral blood indices, which can be a good predictor of the prognosis of immunotherapy in ES-SCLC patients; in the real world, the response status at milestone time points (6, 12, and 20 weeks) can be a good indicator of long-term survival in ES-SCLC patients receiving immunotherapy.

Identification and validation of core genes associated with intracranial aneurysms through bioinformatics analysis and Mendelian randomization.

Intracranial aneurysms (IAs) often go undetected until rupture, leading to significant morbidity and mortality. Identifying biomarkers for early detection of IAs is crucial. The current study attempted to identify core genes linked with IAs and determine their relevance through Mendelian randomization. Limma helped identify differentially expressed genes between IAs and control superficial temporal artery samples. WGCNA was utilized to find IA-related modules and associated genes, which were further evaluated using KEGG and GO analyses to ascertain their potential roles. Five highly associated genes were screened with the CytoHubba plugin of Cytoscape software. ROC curves assessed the diagnostic efficacy of these genes. A two-sample Mendelian randomization evaluated the causal relationship between the core gene PTRPC and IAs, along with its correlation with immune infiltration. WGCNA and differential expression analysis depicted 584 related genes involved in cellular metabolism and chemokine activity. PTPRC was among the top highly associated genes identified through Cytoscape. It showed significant diagnostic value for IAs. Moreover, mendelian randomization depicted that PTPRC in CD4+ T cells is related to IA risk, with an OR of 0.63538 (95 % CI = 0.41636-0.96959, p = 0.03545). No reverse causal relationship was observed between PTPRC and IAs, with an OR of 0.99947 (95 % CI = 0.99719-1.00176, p = 0.65022). Additionally, immune cell infiltration results indicated a positive correlation between PTPRC in IAs with neutrophils and unactivated dendritic cells and a negative association with regulatory T cells (Tregs). PTPRC was identified as a core gene linked with IAs, providing evidence for IA diagnosis and studying molecular mechanisms.

Toxicology assessment of deep-sea mining impacts on Gigantidas platifrons: A comparative in situ and laboratory metal exposure study.

Deep-sea toxicology is essential for deep-sea environmental impact assessment. Yet most toxicology experiments are conducted solely in laboratory settings, overlooking the complexities of the deep-sea environment. Here we carried out metal exposure experiments in both the laboratory and in situ, to compare and evaluate the response patterns of Gigantidas platifrons to metal exposure (copper [Cu] or cadmium [Cd] at 100 µg/L for 48 h). Metal concentrations, traditional biochemical parameters, and fatty acid composition were assessed in deep-sea mussel gills. The results revealed significant metal accumulation in deep-sea mussel gills in both laboratory and in situ experiments. Metal exposure could induce oxidative stress, neurotoxicity, an immune response, altered energy metabolism, and changes to fatty acid composition in mussel gills. Interestingly, the metal accumulating capability, biochemical response patterns, and fatty acid composition each varied under differing experimental systems. In the laboratory setting, Cd-exposed mussels exhibited a higher value for integrated biomarker response (IBR) while in situ the Cu-exposed mussels instead displayed a higher IBR value. This study emphasizes the importance of performing deep-sea toxicology experiments in situ and contributes valuable data to a standardized workflow for deep-sea toxicology assessment.

Multiple sarcomatoid carcinomas in the small intestine with perforation: A case report and literature review.

RATIONALE: Sarcomatoid carcinoma of the small intestine is an exceedingly rare and aggressive malignancy, often diagnosed at advanced stages with a poor prognosis. This study documents a detailed case of sarcomatoid carcinoma of the small intestine, highlighting the diagnostic challenges and treatment approaches, underscored by a comprehensive review of related literature. Given the rarity of this condition, our report aims to enrich the existing diagnostic and treatment frameworks for this malignancy, emphasizing the necessity for early detection and intervention strategies. By presenting this case in conjunction with a literature review, we seek to shed light on the elusive nature of sarcomatoid carcinoma in the small intestine and propose avenues for improving patient outcomes. PATIENT CONCERNS: Case presentation A 61-year-old male patient initially presented with recurrent abdominal pain and gastrointestinal symptoms. Initial abdominal computed tomography (CT) scans and gastrointestinal endoscopy revealed only inflammatory and hyperplastic changes in the duodenum and jejunum, with a diagnosis of intestinal obstruction. Two years later, due to gastrointestinal perforation, the patient was hospitalized again. DIAGNOSES: CT scans and other examinations revealed small intestinal lesions. Four small intestinal lesions were surgically removed, and pathology and immunohistochemistry confirmed sarcomatoid carcinoma of the small intestine. A short time later, enhanced CT scans revealed metastatic lesions in the hepatic portal and adrenal glands. INTERVENTIONS: After surgery, the gastrointestinal function gradually recovered, and the patient was discharged from the hospital on a semiliquid diet. No further treatment such as radiotherapy or chemotherapy was administered postoperatively. OUTCOMES: Five months after the surgery, the patient died due to brain metastasis. LESSONS: The study outcomes reveal the aggressive nature of sarcomatoid carcinoma of the small intestine, characterized by rapid progression and poor prognosis despite surgical interventions. The patient condition rapidly deteriorated, leading to metastasis and death within 5 months postsurgery. These findings underscore the critical need for early detection and possibly innovative treatment approaches to improve survival rates. This case also highlights the potential for gastrointestinal sarcomatoid carcinoma to metastasize to distant organs, including the brain, suggesting a propensity for hematogenous spread.

Flexible Supercapacitor with Wide Electrochemical Stable Window Based on Hydrogel Electrolyte.

Hydrogel electrolyte can endow supercapacitors with excellent flexibility, which has developed rapidly in recent years. However, the water-rich structures of hydrogel electrolyte are easy to freeze at subfreezing and dry at high temperatures, which will affect its energy storage characteristics. The low energy density of micro supercapacitors also hinders their development. Herein, a strategy is proposed to reduce the free water activity in the hydrogel to improve the operating voltage and the energy density of the device, which is achieved through the synergistic effect of the hydrogel skeleton, N, N'-dimethylformamide (DMF), NaClO4 and water. High concentrations of DMF and NaClO4 are introduced into sodium alginate/polyacrylamide (SA/PAAM) hydrogel through solvent exchange to obtain SA/PAAM/DMF/NaClO4 hydrogel electrolyte, which exhibited a high ionic conductivity of 82.1 mS cm-1, a high breaking strength of 563.2 kPa, and a wide voltage stability window of 3.5 V. The supercapacitor devices are assembled by the process of direct adhesion of the hydrogel electrolyte and  laser induced graphene (LIG). The micro-supercapacitor exhibited an operating voltage of 2.0 V, with a specific capacitance of 2.41 mF cm-2 and a high energy density of 1.34 µWh cm-2, and it also exhibit a high cycle stability, good flexibility, and integration performance.

The Potentiation Activity of Azithromycin in Combination with Colistin or Levofloxacin Against Pseudomonas aeruginosa Biofilm Infection.

Objective: Pseudomonas aeruginosa (PA) often displays drug resistance and biofilm-mediated adaptability. Here, we aimed to evaluate the antibiofilm efficacy of azithromycin-based combination regimens. Methods: Minimum inhibitory concentrations (MICs), minimal biofilm eradication concentrations (MBECs), and MBEC-combination of azithromycin, colistin, amikacin, and levofloxacin to bioluminescent strain PAO1 and carbapenem-resistant PAO1 (CRPAO1) were assessed. An animal biofilm infection model was established and detected using a live animal bio-photonic imaging system. Results: In vitro, PAO1 and CRPAO1 were susceptible to colistin, amikacin, and levofloxacin, while they were unsusceptible to azithromycin. The combinations based on azithromycin have no synergistic effect on biofilm in vitro. In vivo, azithromycin plus colistin or levofloxacin could shorten the PAO1 biofilm eradication time, which totally eradicates the biofilm in all mice on the 8th or 6th day, while monotherapy only eradicate biofilm in 70% or 80% mice on the 8th day. For CRPAO1 biofilm, only azithromycin-colistin combination and colistin monotherapy eradicated the bacteria in 60% and 40% of mice at the 6th day. Conclusion: Azithromycin-based combinations containing levofloxacin or colistin had no synergistic effect in vitro, and they are promising for clinical applications due to the good synergistic activity against PAO1 biofilms in vivo.

UNVEILING THE PROTECTIVE MECHANISMS OF PUERARIN AGAINST ACUTE LUNG INJURY: A COMPREHENSIVE EXPLORATION OF THE ROLES AND MECHANISMS OF MST1/ERS SIGNALING.

OBJECTIVES: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). METHODS: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines. Identification of target proteins was conducted through Western blotting. Histological alterations and apoptosis were scrutinized using H&E staining and TUNEL staining, respectively. The ultrastructure of the endoplasmic reticulum was observed via transmission electron microscopy. RESULTS: Puerarin significantly protected mice from LPS-induced ALI, reducing lung interstitial width, neutrophil and lymphocyte infiltration, pulmonary interstitial and alveolar edema, and lung apoptosis. Puerarin treatment also markedly attenuated levels of TNF-α and IL-1ß in both alveolar lavage fluid and serum. Furthermore, puerarin significantly attenuated LPS-induced increases in Mst1, GRP78, CHOP, and Caspase12 protein expression and blunted LPS-induced decrease in ZO-1 protein expression in lung tissues. Puerarin obviously reduced endoplasmic reticulum expansion and vesiculation. Similarly, puerarin significantly mitigated the LPS-induced reduction in HUVEC cell viability and ZO-1 expression. Puerarin also attenuated LPS-induced increase in apoptosis, TNF-α and IL-1ß, FD40 flux, and Mst1, GRP78, CHOP, and Caspase12 expression in HUVEC cells. Nevertheless, the inhibitory impact of puerarin on vascular endothelial cell injury, lung injury, and endoplasmic reticulum stress (ERS) was diminished by Mst1 overexpression. CONCLUSION: These findings demonstrated that the Mst1/ERS signaling pathway played a pivotal role in the development of LPS-induced vascular endothelial cell dysfunction and ALI. Puerarin exhibited the ability to attenuate LPS-induced vascular endothelial cell dysfunction and ALI by inhibiting the Mst1/ERS signaling pathway.

Reproductive outcomes in patients with high levels of sperm DNA fragmentation using testicular sperm for intracytoplasmic injection: a retrospective analysis.

This study aims to compare the embryological and clinical parameters of intracytoplasmic sperm injection (ICSI) cycles using testicular versus ejaculated sperm in male patients with elevated sperm DNA fragmentation (SDF). A total of 73 ICSI cycles were examined in couples where the male partner exhibited high levels of SDF. ICSI was performed using either ejaculated or testicular sperm. The primary outcomes were rates of blastocyst formation, high-quality embryo development, and clinical pregnancy. The DNA fragmentation index (DFI) for testicular sperm (16.81 ± 17.51) was significantly lower than that of ejaculated sperm (56.96 ± 17.56). While the blastocyst formation rate was significantly higher in the testicular sperm group compared to the ejaculated sperm group, no statistically significant differences were noted in fertilization rate (72.15% vs. 77.23%), rate of high-quality embryo formation (47.17% vs. 46.53%), clinical pregnancy (50% vs. 56.52%), Cumulative pregnancy (70.2% vs. 55.6%), or live birth rate (43.75% vs.43.48%). Testicular spermatozoa have no additional advantage over ejaculated spermatozoa except for blastocyst quality in patients with high SDF, the use of testicular spermatozoa for the first ICSI cycle in male infertility patients with high SDF should be undertaken after much consideration at present.

Bioorthogonal labeling and enrichment of histone monoaminylation reveal its accumulation and regulatory function in cancer cell chromatin.

Histone monoaminylation ( i . e ., serotonylation and dopaminylation) is an emerging category of epigenetic mark occurring on the fifth glutamine (Q5) residue of H3 N-terminal tail, which plays significant roles in gene transcription. Current analysis of histone monoaminylation is mainly based on site-specific antibodies and mass spectrometry, which either lacks high resolution or is time-consuming. In this study, we report the development of chemical probes for bioorthogonal labeling and enrichment of histone serotonylation and dopaminylation. These probes were successfully applied for the monoaminylation analysis of in vitro biochemical assays, cells, and tissue samples. The enrichment of monoaminylated histones by the probes further confirmed the crosstalk between H3Q5 monoaminylation and H3K4 methylation. Finally, combining the ex vivo and in vitro analyses based on the developed probes, we have shown that both histone serotonylation and dopaminylation are highly enriched in tumor tissues that overexpress transglutaminase 2 (TGM2) and regulate the three-dimensional architecture of cellular chromatin.

PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous tumor lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It has higher aggressiveness and metastasis than other subtypes, with limited effective therapeutic strategies, leading to a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target. This review summarizes the PI3K/AKT/mTOR signaling pathway activation mechanism in TNBC and discusses the relationship between its activation and various TNBC subtypes. We also report the latest clinical studies on kinase inhibitors related to this pathway for treating TNBC. Our review discusses the issues that need to be addressed in the clinical application of these inhibitors.