ABSTRACT
Due to the fact that more conventional heavy oil recovery methods (heating, emulsification, dilution, and other methods) have many shortcomings, they cannot meet the demand of heavy oil exploitation. Therefore, there is a need for new recovery methods. In this paper, the surface of nano SiO2 was modified with a silane coupling agent, KH-560, to prepare a nanoviscosity reducer (NRV), which has high-temperature resistance (300 °C), calcium and magnesium resistance (Ca2+ + Mg2+ > 900 mg/L) and high viscosity reduction rate (>99%). FTIR and SEM measurements showed that KH560 has been successfully connected to the surface of SiO2. The particle size distribution of NRV is mainly distributed in 50-80 nm, which matches the results of SEM. The experimental results showed that the viscosity reduction rates of 1 wt % NRV on M-1 heavy oil before and after aging were 99.73% and 99.71%, respectively. The viscosity reduction effect of 1% NRV on M-1 heavy oil and the bleeding rate of emulsion formation were investigated when the oil-water ratio ranged from 9:1 to 1:9. The results showed that when the oil-water ratio was between 7:3 and 1:9, the viscosity reduction rate was greater than 99%. Besides, the bleeding rate of emulsion increases with the decrease of the oil-water ratio. What's more, static and dynamic adsorption experiments showed that the adsorption capacity of 1 wt % NRV was 1.746 mg/g and 1.668 mg/g sand, respectively. The interfacial tension experiment showed that the interfacial tension (IFT) between 1 wt % NRV and M-1 heavy oil was 0.052 mN/m, and low interfacial tension was beneficial to displace the oil in the formation pores. At the same time, the displacement effect of NRV on M-1 heavy oil at different concentrations (0.5, 1.0, and 1.5 wt %) and temperatures (200, 250, and 300 °C) was investigated by core flooding experiments. The results showed that the recovery rate increases with the increase of NRV concentration, and 1 wt % NRV at 300 °C will improve the recovery rate of M-1 heavy oil by 27.3% compared to steam flooding. NRV could reduce the viscosity of crude oil, which provides technical guidelines for the exploitation of heavy oil and extra heavy oil.
ABSTRACT
Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.
ABSTRACT
Green manure is a crucial strategy for increasing cereal yield and mitigating environmental burden while reducing chemical N fertilizer. To effectively tackle climate change, finding ways to reduce nitrous oxide (N2O) emissions from green manuring systems is vital. Herein, field and 15N labeled microcosm experiments were arranged to investigate the effect and mechanisms of green manuring and zeolite application on N2O emission. Both experiments comprised four treatments: conventional chemical N (N100), 70â¯% chemical N (N70), N70 with green manure (N70â¯+â¯CV), and N70â¯+â¯CV combined with zeolite (N70â¯+â¯CVâ¯+â¯Z). Compared with N100, both N70â¯+â¯CV and N70â¯+â¯CVâ¯+â¯Z maintained maize yield, cumulative N2O emissions decreased by 37.7â¯% and 34.9â¯% in N70â¯+â¯CVâ¯+â¯Z in 2022-yr and 2023-yr, and by 12.8â¯% in N70â¯+â¯CV in 2022-yr. Moreover, the reduction of N2O emission primarily occurred after incorporating green manure. The N100 and N70â¯+â¯CV demonstrated a similar transformed proportion of chemical N to N2O (i.e., 4.9â¯% and 4.7â¯%) while reducing it to 2.7â¯% in N70â¯+â¯CVâ¯+â¯Z. Additionally, a mere 0.7â¯% of green manure N was transformed to N2O in both N70â¯+â¯CV and N70â¯+â¯CVâ¯+â¯Z treatments. Compared with N100, both N70â¯+â¯CV and N70â¯+â¯CVâ¯+â¯Z decreased the relative abundances of ammonia oxidation microbes, increased denitrifier and the ratios of (nirKâ¯+â¯nirS)/nosZ and norBC/nosZ. Furthermore, compared with N70â¯+â¯CV, N70â¯+â¯CVâ¯+â¯Z decreased the relative abundances of N2O-producer and the ratios of (nirKâ¯+â¯nirS)/nosZ and norBC/nosZ in denitrification. These findings revealed that the reduction of N2O emissions resulting from green manure replaced chemical N was mainly due to weakened nitrification, while zeolite reduced N2O emissions attributed to enhanced conversion of N2O to N2. Moreover, certain key N-cycling functional bacteria, such as Phycisphaerae, Rubrobacteria, and Thermoflexia, were positively correlated with N2O emission. In contrast, Dehalococcoidia, Gammaproteobacteria, and Betaproteobacteria were negatively correlated with N2O emission. This investigation uncovered the underlying mechanisms for effectively reducing N2O emissions through green manure combined with zeolite.
ABSTRACT
BACKGROUND: Fungal skin diseases are common skin diseases with a heterogeneous distribution worldwide. OBJECTIVES: This study aimed to analyse the spatiotemporal trends in the burden of fungal skin diseases at global, regional, and national levels from 1990 to 2021. METHODS: Based on the data obtained from the Global Burden of Disease Study (GBD) 2021, we described the incident cases, prevalent cases, number of disability-adjusted life years (DALYs), and corresponding age-standardised rates (ASRs) for fungal skin diseases in 1990 and 2021 by sex, age, socio-demographic index (SDI), 21 GBD regions, and 204 countries and territories. We used Joinpoint regression analysis to assess the temporal trends in burden of fungal skin diseases during 1990 to 2021. Spearman's rank test was used to analyse the relationship between disease burden and potential factors. RESULTS: From 1990 to 2021, the incident cases, prevalent cases, and DALYs for fungal skin diseases worldwide increased by 67.93%, 67.73%, and 66.77%, respectively. Globally, the age-standardised incidence rate (ASIR), age-standardised prevalence rate (ASPR), and age-standardised DALYs rate (ASDR) for fungal skin diseases in 2021 were 21668.40 per 100,000 population (95% UI: 19601.19-23729.17), 7789.55 per 100,000 population (95% UI: 7059.28-8583.54), and 43.39 per 100,000 population (95% UI: 17.79-89.10), respectively. Between 1990 and 2021, the ASIR, ASPR, and ASDR for fungal skin diseases have modestly increased, with AAPC of 11.71% (95% confidence interval [CI]: 11.03%-12.39%), 19.24% (95% CI: 18.12%-20.36%), and 20.25% (95% CI: 19.33%-21.18%), respectively. Males experienced a higher burden of fungal skin diseases than females. The incident cases, prevalent cases, and DALYs for fungal skin diseases were highest at the age of 5-9, while the ASRs were highest among the elderly. At national level, the highest ASRs were observed in Nigeria, Ethiopia, and Mali. Overall, SDI was negatively correlated with the ASRs, whereas Global Land-Ocean Temperature Index (GLOTI) was remarkably positively correlated with the burden of fungal skin diseases. CONCLUSIONS: Between 1990 and 2021, the global burden of fungal skin diseases has increased, causing a high disease burden worldwide, particularly in underdeveloped regions and among vulnerable population such as children and the elderly. With global warming and aging of the population, the burden of fungal skin diseases may continue to increase in the future. Targeted and specific measures should be taken to address these disparities and the ongoing burden of fungal skin diseases.
Subject(s)
Dermatomycoses , Global Burden of Disease , Global Health , Humans , Male , Female , Adult , Dermatomycoses/epidemiology , Middle Aged , Prevalence , Incidence , Young Adult , Global Health/statistics & numerical data , Adolescent , Aged , Disability-Adjusted Life Years , Child, Preschool , Child , Infant , Infant, Newborn , Aged, 80 and over , Cost of IllnessABSTRACT
Endocervical adenocarcinoma (ECA) is reported increasingly often in young women, and this aggressive disease lacks effective methods of targeted therapy. Since mismatch repair deficiency (dMMR) is an important biomarker for predicting response to immune checkpoint inhibitors, it is important to investigate the clinicopathological features and immune microenvironment of dMMR ECAs. We assessed 617 ECAs from representative tissue microarray sections, gathered clinicopathologic information, reviewed histological characteristics, and performed immunohistochemical staining for MMR, programmed cell death 1 (PD-L1), and other immune markers. Of 617 ECA samples, 20 (3.2%) cases had dMMR. Among them, loss of MMR-related proteins expression was observed in 17/562 (3.0%) human papilloma virus-associated (HPVA) adenocarcinoma and 3/55 (5.5%) non-HPV-associated (NHPVA) adenocarcinoma. In NHPVA cohort, dMMR status was observed in 3 (3/14, 15.0%) patients with clear cells. dMMR ECAs had a higher tendency to have a family history of cancer, larger tumor size, p16 negative, HPV E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) negative, and lower ki-67 index. Among the morphological variables evaluated, poor differentiation, necrosis, stromal tumor-infiltrating lymphocytes, peritumoral lymphocytes, and lymphoid follicles were easily recognized in the dMMR ECAs. In addition, dMMR ECAs had higher CD3+, CD8+, CD38+, CD68+ and PD-1+ immune cells. A relatively high prevalence of PD-L1 expression was observed in dMMR ECAs. dMMR ECAs were significantly more likely to present with a tumor-infiltrating lymphocytes -high/PD-L1-positive status. In conclusion, dMMR ECAs have some specific morphological features and a critical impact on the immune microenvironment, which may provide insights into improving responses to immunotherapy-included comprehensive treatment for ECAs in the future.
ABSTRACT
BACKGROUND: There is an increasing number of human immunodeficiency virus (HIV) reported cases among students in Southwest China. However, the data on HIV/sex-related knowledge, attitude toward sex, sexual behaviors, and correlates of pre-exposure prophylaxis (PrEP)-eligible behaviors among college students in this area is still limited. This study aimed to assess the prevalence of HIV/sex-related knowledge, sexual attitudes, sexual behaviors, and factors associated with PrEP-eligible behaviors among college students. METHOD: An online survey from 2020 to 2021 based on a multistage stratified and cluster sampling method was conducted among college students in Southwest China, and a well-designed questionnaire collected data. Propensity score matching (PSM), logistic, and log-binomial regression were used to identify the determinants of PrEP-eligible behaviors. RESULT: A total of 108,987 students participated in the survey, and 92,946 provided valid responses. 91.6% (85,145/92,946) had good HIV-related knowledge, while only 26.0% (24,137/92,946) reported awareness of sex-related knowledge. Furthermore, more than half of the participants (64.5%) held negative stances towards engaging in "one-night stand", and 58.9% (617/1,047) reported PrEP-eligible behaviors. Log-binomial regression analysis indicated that unaware of HIV-related knowledge (aPR = 1.66, 95% CI:1.22-2.26, P = 0.001), not discussing about sex with their parent(s) (aPR = 1.16, 95% CI:1.01-1.33, P = 0.021), not receiving sex-related education in school(aPR = 1.24, 95% CI: 1.07-1.45, P = 0.005), not participating in HIV/AIDS prevention activities in the past year (aPR = 1.32, 95%CI:1.09-1.60, P = 0.004), experiencing forced sex (aPR = 2.08, 95% CI: 1.19-3.63, P = 0.010), and having the drug abuse (aPR = 22.21, 95% CI:5.59-88.31, P < 0.001) were significantly associated with increased odds of PrEP-eligible behaviors. CONCLUSION: College students in Southwest China exhibited suboptimal HIV/sex-related knowledge, received limited sex education, reported conservative attitudes towards casual sex, and significant PrEP-eligible behaviors. These findings suggest that sexually experienced college students who were unaware of HIV-related knowledge, lacked sex education, experienced forced sex, and reported drug abuse were the key individuals for evaluating eligibility for PrEP initiation, and interventions aimed at increasing awareness of HIV/sex-related knowledge, promoting participation in sex education, addressing issues related to forced sex and tackling drug abuse could contribute to reducing the incidence of PrEP-eligible behaviors among college students.
Subject(s)
HIV Infections , Health Knowledge, Attitudes, Practice , Pre-Exposure Prophylaxis , Sexual Behavior , Students , Humans , Male , Female , China/epidemiology , HIV Infections/prevention & control , HIV Infections/epidemiology , Students/psychology , Students/statistics & numerical data , Cross-Sectional Studies , Young Adult , Sexual Behavior/statistics & numerical data , Universities , Surveys and Questionnaires , Adolescent , AdultABSTRACT
Talaromyces marneffei is the third most common infectious pathogen in AIDS patients and leads to the highest death rate in Guangxi, China. The lack of reliable biomarkers is one of the major obstacles in current clinical diagnosis, which largely contributes to this high mortality. Here, we present a study that aimed at identifying diagnostic biomarker candidates through genome-wide prediction and functional annotation of Talaromyces marneffei secreted proteins. A total of 584 secreted proteins then emerged, including 382 classical and 202 nonclassical ones. Among them, there were 87 newly obtained functional annotations in this study. The annotated proteins were further evaluated by combining RNA profiling and a homology comparison. Three proteins were ultimately highlighted as biomarker candidates with robust expression and remarkable specificity. The predicted phosphoinositide phospholipase C and the galactomannoprotein were suggested to play an interactive immune game through metabolism of arachidonic acid. Therefore, they hold promise in developing new tools for clinical diagnosis of Talaromyces marneffei and also possibly serve as molecular targets for future therapy.
ABSTRACT
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a new type of extracorporeal respiratory and circulatory assistance device. It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator (membrane lung) to replace lung and heart functions in a short time. ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function. CASE SUMMARY: We report a case of an 81-year-old woman who underwent whole cerebral angiography, basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO. The patient was admitted to the hospital due to myocardial infarction. Considering that the cause of the patient's disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO, the department of Radioactive Intervention performed cerebral angiography. And the result of the angiography indicated vascular occlusion. After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain, the patency of the occlusive vessel was achieved. CONCLUSION: Although the patient eventually died of circulatory failure, the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.
ABSTRACT
Intertrochanteric femur fracture is the most common hip fracture in elderly people, and the academic community has reached a consensus that early surgery is imperative. Proximal femoral nail anti-rotation (PFNA) and InterTan are the preferred internal fixation devices for intertrochanteric femur fractures in elderly individuals due to their advantages, such as a short lever arm, minimal stress shielding, and resistance to rotation. However, PFNA is associated with complications such as nail back-out and helical blade cut-out due to stress concentration. As a new internal fixation device for intertrochanteric femur fractures, the proximal femoral biodegradable nail (PFBN) addresses the issue of nail back-out and offers more stable fracture fixation, a shorter lever arm, and stress distribution compared to PFNA and InterTan. Clinical studies have shown that compared to PFNA, PFBNs lead to faster recovery of hip joint function, shorter non-weight-bearing time, and faster fracture healing. This article provides a literature review of the structural characteristics, biomechanical analysis, and clinical studies of PFBNs, aiming to provide a theoretical basis for the selection of internal fixation devices for the treatment of intertrochanteric femur fractures in elderly patients and to improve the quality of life of patients during the postoperative period.
ABSTRACT
BACKGROUND: Indeterminate dendritic cell tumor (IDCT) is a rare tumor of immune cells, and IDCT patients without skin lesions are rarely reported. Therefore, the clinical course in this type of patient is unclear, and further research on the underlying pathological mechanisms and appropriate treatments is needed. CASE SUMMARY: This study describes a female IDCT patient with bile duct lesions. The strong mimicry of IDCT lesions confused doctors, and consequently, this patient, who had no skin lesions, was first diagnosed with cholangiocarcinoma. Then, she presented with persistent abdominal distension without jaundice. Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination. However, no tumor cells or pathogens were found in the three subsequent ascites analyses. It took 2 years to reach the correct diagnosis, which was eventually obtained by performing surgery for biopsy of the patient's abdominal lymph nodes. However, by then, she was already in a cachexic state. Finally, she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases. CONCLUSION: For IDCT patients without skin lesions, early biopsy is the key to obtaining a correct diagnosis. Moreover, the collective management of IDCT patients is important. Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.
ABSTRACT
Hypertension remains a major global public health crisis due to various contributing factors, such as age and environmental exposures. This study delves into exploring the intricate association between biological aging, blood lead levels, and hypertension, along with examining the mediating role of blood lead levels in the relationship between biological aging and hypertension. We analyzed data from two cycles of the NHANES, encompassing 4473 individuals aged 18 years and older. Our findings indicate that biological aging potentially escalates the risk of hypertension and the incidences of systolic blood pressure (SBP) and diastolic blood pressure (DBP) abnormalities. Utilizing weighted quantile sum (WQS) and quantile g-computation (QGC) model analyses, we observed that exposure to heavy metal mixtures, particularly lead, may elevate the likelihood of hypertension, SBP, and DBP abnormalities. Further mediation analysis revealed that lead significantly mediated the relationship between biological aging and hypertension and between biological aging and SBP abnormalities, accounting for 64% (95% CI, 49% to 89%) and 64% (95% CI, 44% to 88%) of the effects, respectively. These outcomes emphasize the criticality of implementing environmental health measures.
Subject(s)
Aging , Blood Pressure , Hypertension , Lead , Nutrition Surveys , Humans , Hypertension/blood , Hypertension/epidemiology , Hypertension/etiology , Lead/blood , Aging/blood , Male , Adult , Female , Middle Aged , Environmental Exposure/adverse effects , Aged , Young Adult , Adolescent , United States/epidemiology , Risk Factors , Databases, FactualABSTRACT
Heart failure (HF) is a chronic condition that progressively worsens and continues to be a major financial burden and public health concern. The "gut-heart" axis provides an innovative perspective and therapeutic strategy for preventing and treating heart failure. Shenfu injection (SFI) is a Traditional Chinese Medicine-based treatment demonstrating potential as a therapeutic strategy for heart failure. However, the precise therapeutic mechanisms of SFI in heart failure are not completely characterized. In this study, HF models were established utilizing subcutaneous multipoint injection of isoproterenol (ISO) at a dosage of 5 mg kg-1·d-1 for 7 days. Serum levels of inflammatory biomarkers were quantified using protein microarrays. Rat feces were analyzed using untargeted metabolomics research and 16S rRNA sequencing. The link between gut microbiota and metabolites was examined using a MetOrigin and Spearman correlation analysis. Our results show that Shenfu injection effectively enhances cardiac function in rats with ISO-induced heart failure by potentially modulating pro-/anti-inflammatory imbalance and reducing serum and urine Trimethylamine-N-oxide (TMAO) levels. Moreover, SFI significantly increases the abundance of Bacteroidota at the phylum level, thereby improving disrupted gut microbiota composition. Additionally, SFI supplementation enriches specific genera known for their capacity to produce short-chain fatty acids. SFI was found to be associated with three key metabolic pathways, as revealed by fecal metabonomics analysis, including the pentose phosphate pathway, pyrimidine metabolism, and purine metabolism. Metabolite tracing analysis revealed that Taurine and hypotaurine metabolism was found to be specific to the microbial community. The biosynthesis of Pyrimidine metabolism, Purine metabolism, beta-alanine metabolism, Naphthalene degradation, Pantothenate, and CoA biosynthesis were identified as co-metabolic pathways between microbes and host. The Spearman correlation analysis was also significantly correlated to differentially expressed metabolites regulated by SFI and the gut microbiota. These results suggest that SFI improves ISO-induced heart failure by modulating co-metabolism and regulating the TMAO-inflammation axis.
ABSTRACT
Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.
ABSTRACT
Background: Atrial fibrillation (AF) is a common arrhythmia that can result in adverse cardiovascular outcomes but is often difficult to detect. The use of machine learning (ML) algorithms for detecting AF has become increasingly prevalent in recent years. This study aims to systematically evaluate and summarize the overall diagnostic accuracy of the ML algorithms in detecting AF in electrocardiogram (ECG) signals. Methods: The searched databases included PubMed, Web of Science, Embase, and Google Scholar. The selected studies were subjected to a meta-analysis of diagnostic accuracy to synthesize the sensitivity and specificity. Results: A total of 14 studies were included, and the forest plot of the meta-analysis showed that the pooled sensitivity and specificity were 97% (95% confidence interval [CI]: 0.94-0.99) and 97% (95% CI: 0.95-0.99), respectively. Compared to traditional machine learning (TML) algorithms (sensitivity: 91.5%), deep learning (DL) algorithms (sensitivity: 98.1%) showed superior performance. Using multiple datasets and public datasets alone or in combination demonstrated slightly better performance than using a single dataset and proprietary datasets. Conclusions: ML algorithms are effective for detecting AF from ECGs. DL algorithms, particularly those based on convolutional neural networks (CNN), demonstrate superior performance in AF detection compared to TML algorithms. The integration of ML algorithms can help wearable devices diagnose AF earlier.
ABSTRACT
The electrocatalytic nitrate reduction reaction (NO3RR) is an ideal NH3 synthesis route with ease of operation, high energy efficiency, and low environmental detriment. Electrocatalytic cathodes play a dominant role in the NO3RR. Herein, we constructed a carbon fiber paper-supported CuOx nanoarray catalyst (CP/CuOx) by an in situ electrochemical reconstruction method for NO3--to-NH3 conversion. A series of characterization techniques, such as X-ray diffraction (XRD) and in situ Raman spectroscopy, unveil that CP/CuOx is a polycrystalline-faceted composite copper nanocatalyst with a valence composition containing Cu0, Cu+ and Cu2+. CP/CuOx shows more efficient NO3--to-NH3 conversion than CP/Cu and CP/Cu2O, which indicates that the coexistence of various Cu valence states could play a dominant role. CP/CuOx with a suitable Cu2+ content obtained by adjusting the conductivity during the in situ electrochemical reconstruction process exhibited more than 90% faradaic efficiencies for the NO3RR in a broad range of -0.3 to -1.0 V vs. RHE, 28.65 mg cm-2 h-1 peak ammonia yield, and stable NO3RR efficiencies for ten cycles. These findings suggest that CP/CuOx with suitable copper valence states obtained by fine-tuning the conductivity of the electrochemical reconstruction may provide a competitive cathode catalyst for achieving excellent activity and selectivity of NO3--to-NH3 conversion.
ABSTRACT
Ulcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract. Various programmed cell death pathways in the intestinal mucosa are crucial to the pathogenesis of UC. Disulfidptosis, a recently identified form of programmed cell death, has not been extensively reported in the context of UC. This study evaluated the expression of disulfidptosis-related genes (DRGs) in UC through public databases and assessed disulfide accumulation in the intestinal mucosal tissues of UC patients and dextran sulfate sodium (DSS)-induced colitis mice via targeted metabolomics. We utilized various bioinformatics techniques to identify UC-specific disulfidptosis signature genes, analyze their potential functions, and investigate their association with immune cell infiltration in UC. The mRNA and protein expression levels of these signature genes were confirmed in the intestinal mucosa of DSS-induced colitis mice and UC patients. A total of 24 DRGs showed differential expression in UC. Our findings underscore the role of disulfide stress in UC. Four UC-related disulfidptosis signature genes-SLC7A11, LRPPRC, NDUFS1, and CD2AP-were identified. Their relationships with immune infiltration in UC were analyzed using CIBERSORT, and their expression levels were validated by quantitative real-time PCR and western blotting. This study provides further insights into their potential functions and explores their links to immune infiltration in UC. In summary, disulfidptosis, as a type of programmed cell death, may significantly influence the pathogenesis of UC by modulating the homeostasis of the intestinal mucosal barrier.
Subject(s)
Colitis, Ulcerative , Intestinal Mucosa , Colitis, Ulcerative/genetics , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , Animals , Humans , Mice , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Dextran Sulfate , Apoptosis/genetics , Male , Disease Models, Animal , Female , Gene Expression Profiling , Mice, Inbred C57BL , Computational Biology/methodsABSTRACT
Alkyllithium-activated organoboronic esters are found to undergo stereospecific phosphination with copper chloride and chlorophosphines. They also react with thiolsulfonate electrophiles under copper catalysis. These reactions enable stereospecific phosphination and thiolation of organoboronic esters, which are further applied in preparation of chiral ligands and biologically active molecules.
ABSTRACT
Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We collected pair specimens of 185 LACC patients before and after receiving NACT and conducted histological evaluation. 8 fresh tissues pre-treatment were selected from the entire cohort to conducted immune gene expression profiling. A novel pathological grading system was established by comprehensively assessing the percentages of viable tumor, inflammatory stroma, fibrotic stroma, and necrosis in the tumor bed. Then, 185 patients were categorized into either the good pathological response (GPR) group or the poor pathological response (PPR) group post-NACT, with 134 patients (72.4%, 134/185) achieving GPR. Increasing tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating lymphocytes volume (TILV) pre-treatment were correlated with GPR, with TILV emerging as an independent predictive factor for GPR. Additionally, CIBERSORT analysis revealed noteworthy differences in the expression of immune makers between cPR and non-cPR group. Furthermore, a significantly heightened density of CD8 + T cells and a reduced density of FOXP3 + T cells were observed in GPR than PPR. Importantly, patients exhibiting GPR or inflammatory type demonstrated improved overall survival and disease-free survival. Notably, stromal type was an independent prognostic factor in multivariate analysis. Our study indicates the elevated TILV in pre-treatment specimens may predict a favorable response to NACT, while identifying stromal type in post-treatment specimens as an independent prognostic factor. Moreover, we proposed this pathological grading system in NACT patients, which may offer a more comprehensive understanding of treatment response and prognosis.
Subject(s)
Lymphocytes, Tumor-Infiltrating , Neoadjuvant Therapy , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/drug therapy , Middle Aged , Lymphocytes, Tumor-Infiltrating/immunology , Adult , Treatment Outcome , Aged , Disease-Free SurvivalABSTRACT
OBJECTIVES: Few studies have been conducted on gene-environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals. METHODS: We conducted a case-control and case-only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene-environment interaction was assessed by multifactor dimensionality reduction analysis. RESULTS: Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy-Weinberg equilibrium (P > 0.05). The frequency of rs2284553-A allele and rs4263839-A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839-A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene-environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge-stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD. CONCLUSIONS: This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene-environment interaction contributes to the understanding of CD pathogenesis.