Pedagogical sentiment analysis based on the BERT-CNN-BiGRU-attention model in the context of intercultural communication barriers.

Amid the wave of globalization, the phenomenon of cultural amalgamation has surged in frequency, bringing to the fore the heightened prominence of challenges inherent in cross-cultural communication. To address these challenges, contemporary research has shifted its focus to human-computer dialogue. Especially in the educational paradigm of human-computer dialogue, analysing emotion recognition in user dialogues is particularly important. Accurately identify and understand users' emotional tendencies and the efficiency and experience of human-computer interaction and play. This study aims to improve the capability of language emotion recognition in human-computer dialogue. It proposes a hybrid model (BCBA) based on bidirectional encoder representations from transformers (BERT), convolutional neural networks (CNN), bidirectional gated recurrent units (BiGRU), and the attention mechanism. This model leverages the BERT model to extract semantic and syntactic features from the text. Simultaneously, it integrates CNN and BiGRU networks to delve deeper into textual features, enhancing the model's proficiency in nuanced sentiment recognition. Furthermore, by introducing the attention mechanism, the model can assign different weights to words based on their emotional tendencies. This enables it to prioritize words with discernible emotional inclinations for more precise sentiment analysis. The BCBA model has achieved remarkable results in emotion recognition and classification tasks through experimental validation on two datasets. The model has significantly improved both accuracy and F1 scores, with an average accuracy of 0.84 and an average F1 score of 0.8. The confusion matrix analysis reveals a minimal classification error rate for this model. Additionally, as the number of iterations increases, the model's recall rate stabilizes at approximately 0.7. This accomplishment demonstrates the model's robust capabilities in semantic understanding and sentiment analysis and showcases its advantages in handling emotional characteristics in language expressions within a cross-cultural context. The BCBA model proposed in this study provides effective technical support for emotion recognition in human-computer dialogue, which is of great significance for building more intelligent and user-friendly human-computer interaction systems. In the future, we will continue to optimize the model's structure, improve its capability in handling complex emotions and cross-lingual emotion recognition, and explore applying the model to more practical scenarios to further promote the development and application of human-computer dialogue technology.

Laryngeal leiomyoma: A case report and review of literature.

BACKGROUND: Leiomyomas (LMs) are mesenchymal tumors that arise from smooth muscle cells. LMs most commonly arise in organs with an abundance of smooth muscle such as the uterus and gastrointestinal tract. Conversely, LMs are rarely detected in the head and neck region. In this study, we report a rare case of laryngeal LM (LLM) and summarized the clinical characteristics of reported LLMs to help clinicians better understand this rare disease and improve its diagnosis, treatment, and postoperative course. CASE SUMMARY: A 49-year-old man was admitted to our ENT outpatient clinic with a chief complaint of pharynx discomfort for 2 months. Laryngoscopy performed under topical anesthesia revealed a solitary, pink mass at the tubercle of epiglottis. Surgery via laryngeal endoscopy was performed under general anesthesia, and the lesion was excised easily. Positive immunohistochemical staining for desmin and smooth-muscle actin indicated a smooth muscle origin and the diagnosis was laryngeal leiomyoma. After surgery, the patient's condition was stable, and he was discharged 2 d after surgery. During the 1-year postoperative period, the patient's condition remained stable without evidence of recurrence. CONCLUSION: Surgical resection is the preferred treatment for LLMs, its early diagnosis and differential diagnosis have important clinical significance.

The association between the neutrophil-to-lymphocyte ratio and type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease often accompanied by low-grade inflammation. Recently, the neutrophil-to-lymphocyte ratio (NLR) has garnered researchers' interest as an emerging inflammation biomarker. This study aimed to comprehensively explore the relationship between NLR and T2DM using the National Health and Nutrition Examination Survey (NHANES) database. METHOD: We employed a cross-sectional study design to analyze data from five NHANES cycles from 2007 to 2016, excluding individuals with incomplete data. This study utilized a weighted logistic regression model, subgroup analyses, and restricted cubic spline (RCS) analysis to assess the potential relationship between NLR and T2DM. RESULTS: A total of 9903 participants were eligible for the analysis, of which 1280 were diagnosed with T2DM. The T2DM group exhibited significantly higher NLR levels than the non-T2DM group. After adjusting for potential confounders, elevated NLR levels were associated with an increased risk of developing T2DM, indicated by an odds ratio (OR) of 1.14, 95% CI: (1.05,1.24), P = 0.003. The results of the subgroup analyses revealed a significant interaction effect between NLR and T2DM concerning race and hypertension (P for interaction < 0.05). In contrast, no significant interactions were found for age, sex, education level, body mass index (BMI), smoking status, recreational activities, and alcohol drinker (P for interaction > 0.05). RCS analysis showed a significant non-linear relationship between NLR and T2DM, with an inflection point at 2.27 (all P for non-linearity < 0.05). CONCLUSION: Our study indicates that an elevated neutrophil-to-lymphocyte ratio is associated with a higher risk of T2DM.

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

The application of dexamethasone implants in uveitis treatment.

Uveitis refers to a group of ocular inflammatory diseases that can significantly impair vision. Although systemic corticosteroid therapy has shown substantial efficacy in treating uveitis, extensive use of corticosteroids is associated with significant adverse effects. Recently, a biodegradable, sustained-release implant, namely dexamethasone intravitreal implant (Ozurdex), has been reported for treating non-infectious and infectious uveitis. This review aims to summarize the experiences with Ozurdex treatment across various forms of uveitis and to assist readers in understanding the appropriate timing and potential side effects of Ozurdex in uveitis treatment, thereby maximizing patient benefits in uveitis management.

Molecular analysis of primary and metastatic sites in patients with renal cell carcinoma.

BACKGROUNDMetastases are the hallmark of lethal cancer, though underlying mechanisms that drive metastatic spread to specific organs remain poorly understood. Renal cell carcinoma (RCC) is known to have distinct sites of metastases, with lung, bone, liver, and lymph nodes being more common than brain, gastrointestinal tract, and endocrine glands. Previous studies have shown varying clinical behavior and prognosis associated with the site of metastatic spread; however, little is known about the molecular underpinnings that contribute to the differential outcomes observed by the site of metastasis.METHODSWe analyzed primary renal tumors and tumors derived from metastatic sites to comprehensively characterize genomic and transcriptomic features of tumor cells as well as to evaluate the tumor microenvironment at both sites.RESULTSWe included a total of 657 tumor samples (340 from the primary site [kidney] and 317 from various sites of metastasis). We show distinct genomic alterations, transcriptomic signatures, and immune and stromal tumor microenvironments across metastatic sites in a large cohort of patients with RCC.CONCLUSIONWe demonstrate significant heterogeneity among primary tumors and metastatic sites and elucidate the complex interplay between tumor cells and the extrinsic tumor microenvironment that is vital for developing effective anticancer therapies.

Potential and application of abortive transcripts as a novel molecular marker of cancers.

Abortive transcript (AT) is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage. Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments. Therefore, the distribution of AT length and the scale of abortive initiation are correlated to the promoter, discriminator, and transcription initiation sequence, and can be affected by transcription elongation factors. AT plays an important role in the occurrence and development of various diseases. Here we summarize the discovery of AT, the factors responsible for AT formation, the detection methods and biological functions of AT, to provide new clues for finding potential targets in the early diagnosis and treatment of cancers.

Molecular definition of the endogenous Toll-like receptor signalling pathways.

Innate immune pattern recognition receptors, such as the Toll-like receptors (TLRs), are key mediators of the immune response to infection and central to our understanding of health and disease1. After microbial detection, these receptors activate inflammatory signal transduction pathways that involve IκB kinases, mitogen-activated protein kinases, ubiquitin ligases and other adaptor proteins. The mechanisms that connect the proteins in the TLR pathways are poorly defined. To delineate TLR pathway activities, we engineered macrophages to enable microscopy and proteomic analysis of the endogenous myddosome constituent MyD88. We found that myddosomes form transient contacts with activated TLRs and that TLR-free myddosomes are dynamic in size, number and composition over the course of 24 h. Analysis using super-resolution microscopy revealed that, within most myddosomes, MyD88 forms barrel-like structures that function as scaffolds for effector protein recruitment. Proteomic analysis demonstrated that myddosomes contain proteins that act at all stages and regulate all effector responses of the TLR pathways, and genetic analysis defined the epistatic relationship between these effector modules. Myddosome assembly was evident in cells infected with Listeria monocytogenes, but these bacteria evaded myddosome assembly and TLR signalling during cell-to-cell spread. On the basis of these findings, we propose that the entire TLR signalling pathway is executed from within the myddosome.

Theoretical insights into the linker effects on the turn-on fluorescence behaviors in pyridazinone-containing NO probes.

Fluorescent probes with preferred photophysical properties have attracted considerable attention for their advantages in real-time and accurate detection of signalling molecules in living organisms. Nitric oxide (NO) is a ubiquitous cellular messenger closely associated with many physiological and pathological processes. A NO fluorescent probe, PYSNO, based on the pyridazinone (PY) scaffold with o-phenylenediamine as the receptor and thiophene (S) as the linker has been synthesized. Inspired by the experimental guidance, three other dyes (PYSSNO, PYSONO and PYONO) were theoretically designed by replacing the S linker with thieno[3,2-b]thiophene (SS), thieno[3,2-b]thiophene 1,1-dioxide (SO) and thiophene 1,1-dioxide (O) groups. The photophysical properties were theoretically investigated in aqueous solution, by the combined time-dependent density functional theory, polarizable continuum model and thermal vibration correlation function approaches. Our results indicate that the emission wavelengths of all the designed dyes show red shifts due to either an increase in the conjugation length or electron-accepting ability of the linkers compared to PYSNO. The photoinduced electron transfer (PET) processes are all absent in these systems. PYSSNO and PYSONO are theoretically expected to be promising candidates for novel NO fluorescent probes, but the suitability of PYONO as a NO probe is compromised by the predicted non-luminescent emission before and after reaction with NO. Our study not only offers valuable insights into the detailed structure-property relationships, but also opens a new avenue for the rational design of efficient fluorescent sensors for NO detection.

Multifaceted complications and surgical management of bronchobiliary fistula with associated pneumonia and intrahepatic stones: A case report.

Background: Bronchobiliary fistulas (BBFs), primarily stemming from choledocholithiasis, present considerable diagnostic and treatment challenges. Their prolonged nature can lead to life-threatening situations without timely management, often complicated by lung abscesses. Case presentation: A 64-year-old man, presenting with fever, chills, and a cough initially misdiagnosed as a common cold, developed severe respiratory distress and delirium upon admission. Urgent intensive care unit (ICU) admission was prompted by a computed tomography (CT) scan revealing a right lung abscess. Enhanced CT scans and elevated bilirubin levels confirmed the biliary origin of the BBFs. Comprehensive treatment included laparoscopic partial hepatectomy, choledochojejunostomy, stone extraction, choledochoscopy, T-tube drainage, and BBFs closure. The patient was discharged with a T-tube. Follow-up CT after two months showed no recurrence. Conclusions: Managing BBFs, especially with concurrent lung abscesses in choledocholithiasis patients, remains challenging but feasible. Early diagnosis and intervention are crucial to improving survival rates and quality of life, highlighting the need for vigilance. This case underscores the importance of early detection and comprehensive treatment for successful outcomes in such complex conditions.

Are different generations of female employees trapped by work-family conflicts? A study on the impact of family-supportive supervisor behavior on thriving at work.

Introduction: With women's advancement in education and status, they drive corporate and social progress. However, traditional gender roles burden female employees with more family responsibilities, challenging work-life balance and affecting job performance. Organizations should supporting female employees to address these challenges. Thriving at work, a core aspect of positive work engagement, helps maintain enthusiasm and efficiency. This study explores the impact of family-supportive supervisor behavior (FSSB) on the thriving at work of female employees in China, considering generational differences in their work-family balance needs and the mediating mechanisms involved. Methods: The methodology adopted in this study utilized Amos 26.0 and SPSS 25.0 to analyze data obtained from a sample of 279 female employees in China. Specifically, the study examined the direct impact of FSSB on thriving at work, alongside the mediating influence of work-family balance. Moreover, the research aimed to discern variations in these effects across different generational cohorts. Results: This study highlights the direct impact of FSSB on female employees' thriving at work across different generational cohorts. Notably, the "post-90s" generation displayed the strongest direct effect of FSSB on thriving at work. Additionally, the impact of FSSB on work-family balance varied by generation, with the "post-90s" generation showing the weakest effect. Furthermore, the mediating role of work-family balance differed among generations, with complete mediation observed in the "post-80s" generation but no mediating effect in the "post-90s" generation, reflecting their distinct work-life balance priorities and needs. Discussion: This study uses a generational difference perspective to explore the main and mediating effects of FSSB on thriving at work, enriching the theoretical research on generational differences and providing valuable insights for future research. Practically, organizations should focus on the needs of different generations while encouraging FSSB, fostering a supportive work environment and enhancing outcomes.

ATP6V0A1-dependent cholesterol absorption in colorectal cancer cells triggers immunosuppressive signaling to inactivate memory CD8+ T cells.

Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

Trehalose prevents the formation of aggregates of mutant ataxin-3 and reduces soluble ataxin-3 protein levels in an SCA3 cell model.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by mutant ataxin-3 with an abnormally expanded polyQ tract and is the most common dominantly inherited ataxia worldwide. There are no suitable therapeutic options for this disease. Autophagy, a defense mechanism against the toxic effects of aggregation-prone misfolded proteins, has been shown to have beneficial effects on neurodegenerative diseases. Thus, trehalose, which is an autophagy inducer, may have beneficial effects on SCA3. In the present study, we examined the effects of trehalose on an SCA3 cell model. After trehalose treatment, aggregate formation, soluble ataxin-3 protein levels and cell viability were evaluated in HEK293T cells overexpressing ataxin-3-15Q or ataxin-3-77Q. We also explored the mechanism by which trehalose affects autophagy and stress pathways. A filter trap assay showed that trehalose decreased the number of aggregates formed by mutant ataxin-3 containing an expanded polyQ tract. Western blot and Cell Counting Kit-8 (CCK-8) results demonstrated that trehalose also reduced the ataxin-3 protein levels and was safe for ataxin-3-expressing cells, respectively. Western blot and total antioxidant capacity assays suggested that trehalose had great therapeutic potential for treating SCA3, likely through its antioxidant activity. Our data indicate that trehalose plays a neuroprotective role in SCA3 by inhibiting the aggregation and reducing the protein level of ataxin-3, which is also known to protect against oxidative stress. These findings provide a new insight into the possibility of treating SCA3 with trehalose and highlight the importance of inducing autophagy in SCA3.

LASSO-derived nomogram for early identification of pediatric monogenic lupus.

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97). CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

Intensifying Salvage Therapy in Prostate-specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy with Apalutamide, Salvage Radiation, and Docetaxel: The Phase 2 STARTAR Trial.

BACKGROUND AND OBJECTIVE: Androgen deprivation therapy (ADT) with salvage radiation therapy (RT) improves survival for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) for prostate cancer (PC), but many patients suffer further relapse. This study aims to determine the benefit of the combination of ADT, apalutamide, salvage RT, and docetaxel for high-risk PSA recurrent PC. METHODS: STARTAR is a multicenter, investigator-initiated phase 2 trial of men with PSA recurrent PC after RP. The key inclusion criteria included M0 by computed tomography/bone scan, Gleason 7 with either T3/positive margin/N1 disease or Gleason 8-10 prostate adenocarcinoma, PSA relapse (0.2-4 ng/ml) <4 yr after RP, and fewer than four positive resected lymph nodes. Patients received ADT with apalutamide for 9 mo, RT starting week 8, and then six cycles of docetaxel. The primary endpoint was 36-mo progression-free survival (PFS) with testosterone recovery and compared against the prior STREAM trial. KEY FINDINGS AND LIMITATIONS: We enrolled 39 men, including those with Gleason 8-10 (46%), pN1 (23%); the median PSA was 0.58 ng/ml. The median follow-up was 37 mo. All patients achieved undetectable PSA nadir. At 24 and 36 mo, PFS rates were 84% and 71%, respectively, which improved significantly over 3-yr 47% historic PFS and 54% enzalutamide/ADT/RT (STREAM) PFS rates (p = 0.004 and p = 0.039, respectively). Common any-grade adverse events included 98% hot flashes, 88% fatigue, 77% alopecia, 53% rash (10% G3), and 5% febrile neutropenia. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this phase 2 trial of ADT, apalutamide, salvage RT, and six cycles of docetaxel for high-risk PSA recurrence, the 3-yr PFS rate improved to 71%, indicating feasible and efficacious treatment intensification, with durable remissions beyond historic data. PATIENT SUMMARY: Prostate cancer recurrence after surgical removal of the tumor occurs often, and current treatment options to limit recurrence after surgery are only partially effective. In this study, we found that the addition of an androgen receptor inhibitor and docetaxel chemotherapy to standard postsurgery radiation therapy and androgen deprivation therapy significantly improved progression-free survival at 3 yr after treatment. These results suggest that intensification of treatment after surgery can provide long-term benefit to a subset of patients with high-risk prostate cancer.

Establishment and Application of Novel Hypoxia-driven Dual-reporter Model to Investigate Hypoxic Impact on Radiation Sensitivity in Human Nasopharyngeal Carcinoma Xenografts.

Background: Tumor hypoxia has been frequently detected in nasopharyngeal carcinoma (NPC) and is intently associated with therapeutic resistance. The aim of the study is to establish a clonogenically stable hypoxia-inducible dual reporter model and apply it to investigate the effect of tumor hypoxia on DNA double strand break (DSB) and synergistic effect of irradiation in combination with chemotherapy or targeted therapy. Methods: The plasmid vector consisting of hypoxia response elements to regulate HSV1-TK and GFP genes, was constructed and stably transfected into human NPC cells. The expected clone was identified and validated by in vivo and in vitro assay. DSB repair was measured by γH2AX foci formation. Tumor growth delay assay and spatial biodistribution of various biomarkers was designed to investigate the anti-tumor effect. Results: The system has the propensity of high expression of reporter genes under hypoxia and low to no expression under normoxia. Intratumoral biodistributions of GFP and classic hypoxic biomarkers were identical in poor-perfused region. Upon equilibration with 10% O2, the xenografts showed higher expression of hypoxic biomarkers. Cisplatin radiosensitized SUNE-1/HRE cells under hypoxia by suppressing DSB repair while the addition of PI3K/mTOR inhibitor further enhanced the anti-tumoral therapeutic efficacy. Combination of IR, DDP and NVP-BEZ235 exhibited most effective anti-tumor response in vivo. These observations underline the importance of dual reporter model for imaging tumor hypoxia in therapeutic study. Conclusions: Our preclinical model enables the investigation of heterogeneous tumor hypoxic regions in xenograft tissues and explores the treatment efficacy of combinations of various therapeutic approaches to overcome hypoxia.

The effects of venlafaxine on depressive-like behaviors and gut microbiome in cuprizone-treated mice.

Background: Cuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on the gut microbiome and depressive-like behavior of CPZ-treated mice are largely unclear. Methods: Male C57BL/6J mice were fed a chow containing 0.2% cuprizone (w/w) for 5 weeks to induce a model of demyelination. Meanwhile, the gut microbiota and depressive-like behaviors were assessed after the mice were fed with Ven (20 mg/kg/day) or equal volumes of distilled water for 2 weeks by oral gavage from the third week onward during CPZ treatment. Results: CPZ treatment decreased the sucrose preference rate in the sucrose preference test and increased the immobility time in the tail-suspension test, and it also induced an abnormality in ß-diversity and changes in microbial composition. Ven alleviated the depressive-like behavior and regulated the composition of the gut microbiota, such as the increase of Lactobacillus and Bifidobacterium in CPZ-treated mice. Conclusion: The anti-depressant effects of Ven might be related to the regulation of gut microbiota in the CPZ-treated mice.

Rare taxa mediate microbial carbon and nutrient limitation in the rhizosphere and bulk soil under sugarcane-peanut intercropping systems.

Introduction: Microbial carbon (C) and nutrient limitation exert key influences on soil organic carbon (SOC) and nutrient cycling through enzyme production for C and nutrient acquisition. However, the intercropping effects on microbial C and nutrient limitation and its driving factors between rhizosphere and bulk soil are unclear. Methods: Therefore, we conducted a field experiment that covered sugarcane-peanut intercropping with sole sugarcane and peanut as controls and to explore microbial C and nutrient limitation based on the vector analysis of enzyme stoichiometry; in addition, microbial diversity was investigated in the rhizosphere and bulk soil. High throughput sequencing was used to analyze soil bacterial and fungal diversity through the 16S rRNA gene and internal transcribed spacer (ITS) gene at a phylum level. Results: Our results showed that sugarcane-peanut intercropping alleviated microbial C limitation in all soils, whereas enhanced microbial phosphorus (P) limitation solely in bulk soil. Microbial P limitation was also stronger in the rhizosphere than in bulk soil. These results revealed that sugarcane-peanut intercropping and rhizosphere promoted soil P decomposition and facilitated soil nutrient cycles. The Pearson correlation results showed that microbial C limitation was primarily correlated with fungal diversity and fungal rare taxa (Rozellomycota, Chyltridiomycota, and Calcarisporiellomycota) in rhizosphere soil and was correlated with bacterial diversity and most rare taxa in bulk soil. Microbial P limitation was solely related to rare taxa (Patescibacteria and Glomeromycota) in rhizosphere soil and related to microbial diversity and most rare taxa in bulk soil. The variation partitioning analysis further indicated that microbial C and P limitation was explained by rare taxa (7%-35%) and the interactions of rare and abundant taxa (65%-93%). Conclusion: This study indicated the different intercropping effects on microbial C and nutrient limitation in the rhizosphere and bulk soil and emphasized the importance of microbial diversity, particularly rare taxa.

H-151 attenuates lipopolysaccharide-induced acute kidney injury by inhibiting the STING-TBK1 pathway.

Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING-TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING-TBK1 signaling pathway and potential drug targets.

The cellular-centered view of hypoxia tumor microenvironment: Molecular mechanisms and therapeutic interventions.

Cancer is a profoundly dynamic, heterogeneous and aggressive systemic ailment, with a coordinated evolution of various types of tumor niches. Hypoxia plays an indispensable role in the tumor micro-ecosystem, drastically enhancing the plasticity of cancer cells, fibroblasts and immune cells and orchestrating intercellular communication. Hypoxia-induced signals, particularly hypoxia-inducible factor-1α (HIF-1α), drive the reprogramming of genetic, transcriptional, and proteomic profiles. This leads to a spectrum of interconnected processes, including augmented survival of cancer cells, evasion of immune surveillance, metabolic reprogramming, remodeling of the extracellular matrix, and the development of resistance to conventional therapeutic modalities like radiotherapy and chemotherapy. Here, we summarize the latest research on the multifaceted effects of hypoxia, where a multitude of cellular and non-cellular elements crosstalk with each other and co-evolve in a synergistic manner. Additionally, we investigate therapeutic approaches targeting hypoxic niche, encompassing hypoxia-activated prodrugs, HIF inhibitors, nanomedicines, and combination therapies. Finally, we discuss some of the issues to be addressed and highlight the potential of emerging technologies in the treatment of cancer.